ALBERT

Description: Background Water quality monitoring at the dialysis units (DU) is essential to ensure an appropriate dialysis fluid quality and guarantee an optimal and safe dialysis treatment to patients. This paper aims to evaluate the effectiveness, economic and organizational impact of automation, digitalization and remote water quality monitoring, through a New Water Technology (NWT) at a hospital DU to produce dialysis water, compared to a Conventional Water Technology (CWT). Methods A before-and-after study was carried out at the Hospital Clínic Barcelona. Data on CWT was collected during 1-year (control) and 7-month for the NWT (case). Data on water quality, resource use and unit cost were retrospective and prospectively collected. A comparative effectiveness analysis on the compliance rate of quality water parameters with the international guidelines between the NWT and the CWT was conducted. This was followed by a cost-minimization analysis and an organizational impact from the hospital perspective. An extensive deterministic sensitivity analysis was also performed. Results The NWT compared to the CWT showed no differences on effectiveness measured as the compliance rate on international requirements on water quality (100% vs. 100%), but the NWT yielded savings of 3,599 EUR/year compared to the CWT. The NWT offered more data accuracy (daily measures: 6 vs. 1 and missing data: 0 vs. 20 days/year), optimization of the DU employees’ workload (attendance to DU: 4 vs. 19 days/month) and workflow, through the remote and continuous monitoring, reliability of data and process regarding audits for quality control. Conclusions While the compliance of international recommendations on continuous monitoring was performed with the CWT, the NWT was efficient compared to the CWT, mainly due to the travel time needed by the technical operator to attend the DU. These results were scalable to other economic contexts. Nonetheless, they should be taken with caution either when the NWT equipment/maintenance cost are largely increased, or the workforce involvement is diminished.

Description: Introduction The prevalence of oral hygiene behaviors (OHB) is very low among school children in Ethiopia. However, the determinants of student’s readiness/intention to perform those behaviors have been remained unstudied. Objective This study aimed to identify the determinants of oral hygiene behavioral intention (OHBI) among preparatory school students based on the theory of planned behavior (TPB). Methods and materials An institution-based cross-sectional study was conducted among 393 students. A 98-item self-administered questionnaire was used to evaluate oral hygiene knowledge (OHK), oral hygiene behavior (OHB), and OHBI based on TPB variables [attitude (ATT), subjective norms (SN) and perceived behavioral control (PBC)]. Descriptive statistics and structural equation modeling analysis (SEM) were employed to confirm relationships and associations among study variables. A p-value of less than 0.05 and a 95% confidence interval were used to declare statistical significance. Results A total of 393 students were participated with a response rate of 97.5%. The mean age of the participants (54% females) was 18 (± 1.3) with an age range of 16 to 24. The TPB model was well fitted to the data and explained 66% of the variance in intention. ATT (β = 0.38; 95% CI, (0.21, 0.64)), SN (β = 0.33; 95% CI, (0.05, 0.83)) and PBC (β = 0.29; 95% CI, (0.13, 0.64)) were significant predictors of OHBI, where ATT was the strongest predictor of OHBI. Conclusion The TPB model explained a large variance in the intention of students to improve their OHB. All TPB variables were significantly and positively linked to stronger intent, as the theory suggests. Furthermore, these results suggest that the model could provide a framework for oral hygiene promotion interventions in the study area. Indeed, these interventions should focus on changing the attitudes of students towards OHB, creation of positive social pressure, and enabling students to control over OHB barriers.

Description: Statins have been recommended for use in atherosclerotic cardio-cerebrovascular disease (CCVD). The purpose of this study was to investigate the efficacy of five different types of statin in the secondary prevention of CCVD in patients. This study retrospectively designed and analyzed data from the National Health Insurance Service-National Health in Korea. Participants aged 40 to 69 years were categorized into five statin groups (atorvastatin, rosuvastatin, pitavastatin, simvastatin, and pravastatin). The primary composite outcome was defined as recurrence of CCVD or all causes of death. Cox proportional hazard regression models were adopted after stepwise adjustments for confounders to investigate the difference in efficacy among the different statins. Of the 755 final participants, 48 patients experienced primary composite outcomes. After adjustments, the hazard ratios (95% confidence intervals) for primary composite outcomes of atorvastatin, pitavastatin, and rosuvastatin groups were 0.956 (0.456–2.005), 1.347 (0.354–5.116), and 0.943 (0.317–2.803), respectively, when compared with the simvastatin group. There were no significant differences between the statins in efficacy for preventing recurrence of CCVD events and/or death in CCVD patients.

Description: As a new alternative to antibody-drug conjugates, we generated “ligand-targeting” peptide-drug conjugates (PDCs), which utilize receptor-mediated endocytosis for targeted intracellular drug delivery. The PDC makes a complex with an extracellular ligand and then binds to the receptor on the cell surface to stimulate intracellular uptake via the endocytic pathway. A helix-loop-helix (HLH) peptide was designed as the drug carrier and randomized to give a conformationally constrained peptide library. The phage-displayed library was screened against vascular endothelial growth factor (VEGF) to yield the binding peptide M49, which exhibited strong binding affinity (KD = 0.87 nM). The confocal fluorescence microscopy revealed that peptide M49 formed a ternary complex with VEGF and its receptor, which was then internalized into human umbilical vein endothelial cells (HUVECs) via VEGF receptor-mediated endocytosis. The backbone-cyclized peptide M49K was conjugated with a drug, monomethyl auristatin E, to afford a PDC, which inhibited VEGF-induced HUVEC proliferation. HLH peptides and their PDCs have great potential as a new modality for targeted molecular therapy.

Description: Genetic selection in parental broiler breeders has increased their susceptibility to metabolic disorders and reproductive dysfunction. We have recently shown that maternal dietary grape seed extract (GSE) supplementation in hens improves fertility parameters, egg quality, oxidative stress in different tissues and the quality of F1 chicks. Here, we analysed the growth and fertility (both female and male) of the F1 generation animals and the quality of their offspring (F2 generation). Eggs issued from hens supplemented with GSE presented lower ROS production than control hens, suggesting a change in the embryonic environment. However, this did not affect the growth nor the body composition of male and female F1s from hatching to adulthood (37 weeks of age). At 37 weeks of age, the biochemistry analysis of the GSE-F1 muscle has revealed an increase in sensitivity to oxidative stress and a slight change in lipid composition. Both male and female F1-GSE groups presented a delay in puberty with a lower testis volume at 30 weeks of age and lower ovary development at 26 weeks of age. Adult GSE-F1 males did not present histological alterations of seminiferous tubules or semen production, but the semen quality was degraded due to higher oxidative stress and DNA-damaged spermatozoa compared with control F1 animals. In adult GSE-F1 females, despite the delay in puberty, the females laid more eggs of better quality (fewer broken eggs and a higher hatching rate). At hatching, the weight of the chicks from GSE-F1 females was reduced, and this effect was stronger in F2 male chicks (F2) compared with F2 control chicks (F2), because of the lower muscle volume. In conclusion, we can raise the hypothesis that maternal dietary GSE supplementation produces eggs with change in embryonic metabolism, which may affect in adulthood the fertility. The data obtained from the F1-GSE group pointed to a sex-specific modification with higher egg quality in females but semen sensitive to stress in males. Finally, male F2 chicks were leaner than control chicks. Thus, maternal dietary grape seed extract (GSE) supplementation in hens may impact on the fertility of the offspring in a sex-specific manner in subsequent generations.

Description: The gene SON is on human chromosome 21 (21q22.11) and is thought to be associated with hematopoietic disorders that accompany Down syndrome. Additionally, SON is an RNA splicing factor that plays a role in the transcription of leukemia-associated genes. Previously, we showed that mutations in SON cause malformations in human and zebrafish spines and brains during early embryonic development. To examine the role of SON in normal hematopoiesis, we reduced expression of the zebrafish homolog of SON in zebrafish at the single-cell developmental stage with specific morpholinos. In addition to the brain and spinal malformations we also observed abnormal blood cell levels upon son knockdown. We then investigated how blood production was altered when levels of son were reduced. Decreased levels of son resulted in lower amounts of red blood cells when visualized with lcr:GFP transgenic fish. There were also reduced thrombocytes seen with cd41:GFP fish, and myeloid cells when mpx:GFP fish were examined. We also observed a significant decrease in the quantity of T cells, visualized with lck:GFP fish. However, when we examined their hematopoietic stem and progenitor cells (HSPCs), we saw no difference in colony-forming capability. These studies indicate that son is essential for the proper differentiation of the innate and adaptive immune system, and further investigation determining the molecular pathways involved during blood development should elucidate important information about vertebrate HSPC generation, proliferation, and differentiation.

Description: Analysis with integrated assessment models (IAMs) and multisector dynamics models (MSDs) of global and national challenges and opportunities, including pursuit of Sustainable Development Goals (SDGs), requires projections of economic growth. In turn, the pursuit of multiple interacting goals affects economic productivity and growth, generating complex feedback loops among actions and objectives. Yet, most analysis uses either exogenous projections of productivity and growth or specifications endogenously enriched with a very small set of drivers. Extending endogenous treatment of productivity to represent two-way interactions with a significant set of goal-related variables can considerably enhance analysis. Among such variables incorporated in this project are aspects of human development (e.g., education, health, poverty reduction), socio-political change (e.g., governance capacity and quality), and infrastructure (e.g. water and sanitation and modern energy access), all in conditional interaction with underlying technological advance and economic convergence among countries. Using extensive datasets across countries and time, this project broadly endogenizes total factor productivity (TFP) within a large-scale, multi-issue IAM, the International Futures (IFs) model system. We demonstrate the utility of the resultant open system via comparison of new TFP projections with those produced for Shared Socioeconomic Pathways (SSP) scenarios, via integrated analysis of economic growth potential, and via multi-scenario analysis of progress toward the SDGs. We find that the integrated system can reproduce existing SSP projections, help anticipate differential economic progress across countries, and facilitate extended, integrated analysis of trade-offs and synergies in pursuit of the SDGs.

Description: Premature mortality and undernutrition rates in Pakistan are among the highest in the world. Inadequate infant and young child feeding are the major causes of premature mortality and undernutrition. Yet, very little is known about the determinants of complementary feeding practices in Pakistan. Therefore, this study aims to identify the determinants of inadequate complementary feeding practices among children aged 6 to 23 months in Pakistan by using the latest nationally representative data from the Pakistan Demographic and Health Survey (2017–18). The results show that only 12% of children consume a minimum acceptable diet, 21% achieve minimum dietary diversity, and 38% reach minimum meal frequency. Multivariate regression analysis shows that child age, child weight at birth, mother’s access to newspapers/magazines at the individual level, wealth at the household level, and prenatal visits at the community level are significant predictors of complementary feeding practices among children aged 6–23 months in Pakistan. These findings show that, in addition to poverty alleviation, raising awareness through health practitioners, increasing access to media, and expanding access to child and maternal healthcare can improve complementary feeding practices in Pakistan. This consequently reduces premature mortality and undernutrition.

Description: Background Effective management of the vaccine cold chain system at all levels is one of the crucial factors for maintaining vaccine potency. Vaccines require more complex handling and storage requirements due to increased temperature sensitivity and complicated immunization schedules. This urges adequate knowledge, attitude, and practice. This study assessed the knowledge, attitude, and practice of vaccinators and vaccine handlers’ in public health facilities. Methodology An institutional-based cross-sectional study design was used to assess the knowledge, attitude, and practice of 127 vaccinators and vaccine handlers in public health facilities of Oromia Special Zone, from September 1 to 30, 2019. Data were collected using self-administered questionnaires and a structured observation checklist. Descriptive and inferential statistics were made using the statistical package for social sciences version 20. Variables with a p-value

Description: Plant detritus represents the major source of soil carbon (C) and nitrogen (N), and changes in its quantity can influence below-ground biogeochemical processes in forests. However, we lack a mechanistic understanding of how above- and belowground detrital inputs affect soil C and N in mountain forests in an arid land. Here, we explored the effects of litter and root manipulations (control (CK), doubled litter input (DL), removal of litter (NL), root exclusion (NR), and a combination of litter removal and root exclusion (NI)) on soil C and N concentrations, enzyme activity and microbial biomass during a 2-year field experiment. We found that DL had no significant effect on soil total organic carbon (SOC) and total nitrogen (TN) but significantly increased soil dissolved organic carbon (DOC), microbial biomass C, N and inorganic N as well as soil cellulase, phosphatase and peroxidase activities. Conversely, NL and NR reduced soil C and N concentrations and enzyme activities. We also found an increase in the biomass of soil bacteria, fungi and actinomycetes in the DL treatment, while NL reduced the biomass of gram-positive bacteria, gram-negative bacteria and fungi by 5.15%, 17.50% and 14.17%, respectively. The NR decreased the biomass of these three taxonomic groups by 8.97%, 22.11% and 21.36%, respectively. Correlation analysis showed that soil biotic factors (enzyme activity and microbial biomass) and abiotic factors (soil moisture content) significantly controlled the change in soil C and N concentrations (P 〈 0.01). In brief, we found that the short-term input of plant detritus could markedly affect the concentrations and biological characteristics of the C and N fractions in soil. The removal experiment indicated that the contribution of roots to soil nutrients is greater than that of the litter.

Description: Background Although hypertension, the largest modifiable risk factor in the global burden of disease, is prevalent in sub-Saharan Africa, rates of awareness and control are low. Since 2011 village health workers (VHWs) in Kisoro district, Uganda have been providing non-communicable disease (NCD) care as part of the Chronic Disease in the Community (CDCom) Program. The VHWs screen for hypertension and other NCDs as part of a door-to-door biannual health census, and, under the supervision of health professionals from the local district hospital, also serve as the primary providers at monthly village-based NCD clinics. Objective/Methods We describe the operation of CDCom, a 10-year comprehensive program employing VHWs to screen and manage hypertension and other NCDs at a community level. Using program records we also report hypertension prevalence in the community, program costs, and results of a cost-saving strategy to address frequent medication stockouts. Results/Conclusions Of 4283 people ages 30–69 screened for hypertension, 22% had a blood pressure (BP) ≥140/90 and 5% had a BP ≥ 160/100. All 163 people with SBP ≥170 during door-to-door screening were referred for evaluation in CDCom, of which 91 (59%) had repeated BP ≥170 and were enrolled in treatment. Of 761 patients enrolled in CDCom, 413 patients are being treated for hypertension and 68% of these had their most recent blood pressure below the treatment target. We find: 1) The difference in hypertension prevalence between this rural, agricultural population and national rates mirrors a rural-urban divide in many countries in sub-Saharan Africa. 2) VHWs are able to not only screen patients for hypertension, but also to manage their disease in monthly village-based clinics. 3) Mid-level providers at a local district hospital NCD clinic and faculty from an academic center provide institutional support to VHWs, stream-line referrals for complicated patients and facilitate provider education at all levels of care. 4) Selective stepdown of medication doses for patients with controlled hypertension is a safe, cost-saving strategy that partially addresses frequent stockouts of government-supplied medications and patient inability to pay. 5) CDCom, free for village members, operates at a modest cost of 0.20 USD per villager per year. We expect that our data-informed analysis of the program will benefit other groups attempting to decentralize chronic disease care in rural communities of low-income regions worldwide.

Description: Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disorder, with a significant social and economic burden. ALS remains incurable, and the only drugs approved for its treatments confers a survival benefit of a few months for the patients. Missense mutations in superoxide dismutase 1 (SOD1), a major cytoplasmic antioxidant enzyme, has been associated with ALS development, accounting for 23% of its familial cases and 7% of all sporadic cases. This work aims to characterize in silico the structural and functional effects of SOD1 protein variants. Missense mutations in SOD1 were compiled from the literature and databases. Twelve algorithms were used to predict the functional and stability effects of these mutations. ConSurf was used to estimate the evolutionary conservation of SOD1 amino-acids. GROMACS was used to perform molecular dynamics (MD) simulations of SOD1 wild-type and variants A4V, D90A, H46R, and I113T, which account for approximately half of all ALS-SOD1 cases in the United States, Europe, Japan, and United Kingdom, respectively. 233 missense mutations in SOD1 protein were compiled from the databases and literature consulted. The predictive analyses pointed to an elevated rate of deleterious and destabilizing predictions for the analyzed variants, indicating their harmful effects. The ConSurf analysis suggested that mutations in SOD1 mainly affect conserved and possibly functionally essential amino acids. The MD analyses pointed to flexibility and essential dynamics alterations at the electrostatic and metal-binding loops of variants A4V, D90A, H46R, and I113T that could lead to aberrant interactions triggering toxic protein aggregation. These alterations may have harmful implications for SOD1 and explain their association with ALS. Understanding the effects of SOD1 mutations on protein structure and function facilitates the design of further experiments and provides relevant information on the molecular mechanism of pathology, which may contribute to improvements in existing treatments for ALS.

Description: Decision making is constantly present in agriculture. Choosing the wrong variety carries the risk that the investment in terms of sowing does not pay off at all. Therefore, it is necessary to choose the variety that gives the best results. In order to achieve this, it is necessary to apply multi-criteria decision-making of available varieties, which is, in this paper, done on the example of hybrid varieties of rapeseed that were created by selection at the Institute of Field and Vegetable Crops in Novi Sad. By applying fuzzy logic, a novel integrated Multi-Criteria Decision-Making (MCDM) model is developed and rapeseed varieties were evaluated. For determining four main and 20 subcriteria, fuzzy PIPRECIA (PIvot Pairwise RElative Criteria Importance Assessment) method has been applied based on fuzzy Bonferroni operator, while for ranking alternatives fuzzy MABAC (Multi-Attributive Border Approximation area Comparison) method has been used. The results obtained using the novel integrated fuzzy MCDM model showed that the variety A2 – Zorica has the best results, followed by A1 - NS Ras, while the worst results were seen by the variety A5 - Zlatna. These results were confirmed using other five fuzzy MCDM methods. Sensitivity analysis—changing criteria weights showed the worst results in the variety A6 - Jovana, which took last place in the application of 18 scenarios. The presented model and the results of this research will help farmers to solve this decision problem.

Description: Background Schistosoma constitutes a major public health problem and developmental challenges in the majority of developing and subtropical regions. The World Health Organization has set guidelines for the control and elimination of schistosomiasis. Ethiopia is providing school-based Mass Drug Administration (MDA) at the study areas of the Abbey and Didessa Valleys of western Ethiopian since 2015. Moreover, mass treatment was already done in the same villages 30 years ago. However, the current Schistosoma mansoni infection status among humans and snails in the study areas is not known. Hence, the present study aims to determine the current status. Methods A community-based cross-sectional study was conducted in the three communities; Chessega, Agallu Metti and Shimala in Schistosoma mansoni endemic areas of the Abbey and Didessa valleys in Western Ethiopia. Using the list of households obtained from the Kebele administration, a systematic sampling technique was used to select households in each village. Results Even though the area is under the Ethiopian national Mass Drug Administration campaign, the present study reports prevalence above 50%. Although the majority of the infections were moderate, we found that 13% had heavy infection, above 400 eggs per gram of stool, which is at the same level as before the treatment campaign 30 years ago. The infection was significantly higher among those below 12 years of age, among non-attending school-age children and daily laborers. Conclusion Schistosoma mansoni infection is still a public health problem in the study areas, despite control efforts already 30 years ago and present mass treatment in the last years. We suggest making the mass treatment campaign just early after the rainy season, when the snails are washed away. This should be supplemented with provisions of clean water, sanitation, and hygiene (WASH) and reduction of water contact and possible snail control efforts’ to prevent reinfection.

Description: Rapid urban expansion has important health implications. This study examines trends and inequalities in undernutrition and overnutrition by gender, residence (rural, urban slum, urban non-slum), and wealth among children and adults in India. We used National Family Health Survey data from 2006 and 2016 (n = 311,182 children 0-5y and 972,192 adults 15-54y in total). We calculated differences, slope index of inequality (SII) and concentration index to examine changes over time and inequalities in outcomes by gender, residence, and wealth quintile. Between 2006 and 2016, child stunting prevalence dropped from 48% to 38%, with no gender differences in trends, whereas child overweight/obesity remained at ~7–8%. In both years, stunting prevalence was higher in rural and urban slum households compared to urban non-slum households. Within-residence, wealth inequalities were large for stunting (SII: -33 to -19 percentage points, pp) and declined over time only in urban non-slum households. Among adults, underweight prevalence decreased by ~13 pp but overweight/obesity doubled (10% to 21%) between 2006 and 2016. Rises in overweight/obesity among women were greater in rural and urban slum than urban non-slum households. Within-residence, wealth inequalities were large for both underweight (SII -35 to -12pp) and overweight/obesity (+16 to +29pp) for adults, with the former being more concentrated among poorer households and the latter among wealthier households. In conclusion, India experienced a rapid decline in child and adult undernutrition between 2006 and 2016 across genders and areas of residence. Of great concern, however, is the doubling of adult overweight/obesity in all areas during this period and the rise in wealth inequalities in both rural and urban slum households. With the second largest urban population globally, India needs to aggressively tackle the multiple burdens of malnutrition, especially among rural and urban slum households and develop actions to maintain trends in undernutrition reduction without exacerbating the rapidly rising problems of overweight/obesity.

Description: The exploitation of petroleum oil generates a considerable amount of “produced water or petroleum waste effluent (PWE)” that is contaminated with polycyclic aromatic hydrocarbons (PAHs), including Benzo[a]pyrene (BaP). PWE is characterised by its high salinity, which can be as high as 30% NaCl, thus the exploitation of biodegradation to remove PAHs necessitates the use of active halophilic microbes. The strain 10SBZ1A was isolated from oil contaminated soils, by enrichment experiment in medium containing 10% NaCl (w/v). Homology analyses of 16S rRNA sequences identified 10SBZ1A as a Staphylococcus haemoliticus species, based on 99.99% homology (NCBI, accession number GI: MN388897). The strain could grow in the presence of 4–200 μmol l-1 of BaP as the sole source of carbon, with a doubling time of 17–42 h. This strain optimum conditions for growth were 37 oC, 10% NaCl (w/v) and pH 7, and under these conditions, it degraded BaP at a rate of 0.8 μmol l-1 per day. The strain 10SBZ1A actively degraded PAHs of lower molecular weights than that of BaP, including pyrene, phenanthrene, anthracene. This strain was also capable of removing 80% of BaP in the context of soil spiked with BaP (10 μmol l-1 in 100 g of soil) within 30 days. Finally, a metabolic pathway of BaP was proposed, based on the identified metabolites using liquid chromatography-high resolution tandem mass spectrometry. To the best of our knowledge, this is the first report of a halophilic BaP degrading bacterial strain at salinity 〉 5% NaCl.

Description: Algorithms play an increasingly ubiquitous and vitally important role in modern society. However, recent findings suggest substantial individual variability in the degree to which people make use of such algorithmic systems, with some users preferring the advice of algorithms whereas others selectively avoid algorithmic systems. The mechanisms that give rise to these individual differences are currently poorly understood. Previous studies have suggested two possible effects that may underlie this variability: users may differ in their predictions of the efficacy of algorithmic systems, and/or in the relative thresholds they hold to place trust in these systems. Based on a novel judgment task with a large number of within-subject repetitions, here we report evidence that both mechanisms exert an effect on experimental participant’s degree of algorithm adherence, but, importantly, that these two mechanisms are independent from each-other. Furthermore, participants are more likely to place their trust in an algorithmically managed fund if their first exposure to the task was with an algorithmic manager. These findings open the door for future research into the mechanisms driving individual differences in algorithm adherence, and allow for novel interventions to increase adherence to algorithms.

Description: Natural biopolymer-based hydrogels especially agarose and collagen gels, considering their biocompatibility with cells and their capacity to mimic biological tissues, have widely been used for in-vitro experiments and tissue engineering applications in recent years; nevertheless their mechanical properties are not always optimal for these purposes. Regarding the importance of the mechanical properties of hydrogels, many mechanical characterization studies have been carried out for such biopolymers. In this work, we have focused on understanding the mechanical role of agarose and collagen concentration on the hydrogel strength and elastic behavior. In this direction, Amirkabir Magnetic Bead Rheometry (AMBR) characterization device equipped with an optimized electromagnet, was designed and constructed for the measurement of hydrogel mechanical properties. The operation of AMBR set-up is based on applying a magnetic field to actuate magnetic beads in contact with the gel surface in order to actuate the gel itself. In simple terms the magnetic beads leads give rise to mechanical shear stress on the gel surface when under magnetic influence and together with the associated bead-gel displacement it is possible to calculate the hydrogel shear modulus. Agarose and Collagen gels with respectively 0.2–0.6 wt % and 0.2–0.5 wt % percent concentrations were prepared for mechanical characterization in terms of their shear modulus. The shear modulus values for the different percent concentrations of the agarose gel were obtained in the range 250–650 Pa, indicating the shear modulus increases by increasing in the agar gel concentration. In addition to this, the values of shear modulus for the collagen gel increase as function of concentration in the range 240–520 Pa in accordance with an approximately linear relationship between collagen concentration and gel strength.

Description: This two-part study examined the perceptions of talented Swiss soccer players about their talent development environment. The first study presented the translation and validation of the Talent Development Environment Questionnaire (TDEQ) into French using a recommended methodology for translating and culturally adapting questionnaires. Two hundred and three Swiss athletes (M = 16.99 years old) responded to the 25 items of the TDEQ-5. One item was excluded due to low factor loadings, and the descriptive statistics showed that the re-specified TDEQ-5 instrument had acceptable global model fit according to the thresholds in the literature (χ2 (df = 17) = 484.62, p

Description: With more microbiome studies being conducted by African-based research groups, there is an increasing demand for knowledge and skills in the design and analysis of microbiome studies and data. However, high-quality bioinformatics courses are often impeded by differences in computational environments, complicated software stacks, numerous dependencies, and versions of bioinformatics tools along with a lack of local computational infrastructure and expertise. To address this, H3ABioNet developed a 16S rRNA Microbiome Intermediate Bioinformatics Training course, extending its remote classroom model. The course was developed alongside experienced microbiome researchers, bioinformaticians, and systems administrators, who identified key topics to address. Development of containerised workflows has previously been undertaken by H3ABioNet, and Singularity containers were used here to enable the deployment of a standard replicable software stack across different hosting sites. The pilot ran successfully in 2019 across 23 sites registered in 11 African countries, with more than 200 participants formally enrolled and 106 volunteer staff for onsite support. The pulling, running, and testing of the containers, software, and analyses on various clusters were performed prior to the start of the course by hosting classrooms. The containers allowed the replication of analyses and results across all participating classrooms running a cluster and remained available posttraining ensuring analyses could be repeated on real data. Participants thus received the opportunity to analyse their own data, while local staff were trained and supported by experienced experts, increasing local capacity for ongoing research support. This provides a model for delivering topic-specific bioinformatics courses across Africa and other remote/low-resourced regions which overcomes barriers such as inadequate infrastructures, geographical distance, and access to expertise and educational materials.

Description: Background Early childhood dental caries (ECC), a serious public health problem lacks information on the association between ECC, risk factors and nutritional status among children in Tanzania. Therefore, this study aimed to determine the prevalence of ECC, risk factors and nutritional status among 3-5-year-old preschool children and to assess its correlation with the form, visible plaque scores in upper anterior teeth, total sugar exposure, anthropometric measures, and socio demographic attributes. Methods This cross-sectional study was conducted on 831 children registered in public preschools in Kisarawe District. Assessment of ECC used the WHO (2013) criteria and anthropometric measures used the WHO Child Growth Standards (2006). Structured questionnaires were completed by children’s parents through an interview. Collected information on socio-demographic attributes including oral hygiene and sugar exposure to their children was analyzed. Results Only 459 children (55.2%) were recognized as caries-free. Dental caries experience in terms of decayed, missing and filled teeth (dmft) index was 2.51. Children with visible plaque were the majority (56.1%). The dmft score index was negatively and significantly associated with weight-for-age z-score [Coefficient: -0.11 (95% CI: -0.76, -0.11)] and positively significantly associated with visible plaque score index [Coefficient: 0.16 (95% CI: 0.18, 0.52)] and total sugar exposure [Coefficient: 0.19 (95% CI: 0.15, 0.38)] in the adjusted model. The prevalence of underweight was 4.2% [95% CI: (3.0–5.8)] and severe underweight was 0.2% [95% CI: (0.1–0.9)] while prevalence of stunting was 1.6% [95% CI: (0.9–2.7)] and severe stunting was 0.4% [95% CI: (0.1–1.1)]. Conclusion This study demonstrated a significant negative relationship between ECC and children’s anthropometric measures indicated by weight-for-age, and positive relationship with sugar exposure and poor oral hygiene indicated by visible plaque on upper anterior teeth. Controlling risk factors will reduce the occurrence of ECC thereby catering for a healthy population of well-nourished children.

Description: Background Oral health is a less-recognized correlate of overall and mental wellbeing. This study aimed to assess the relationship between suicidal behavior (ideation and attempt) and oral health practices and status, and to determine the effect of sex on these associations among Nigerian adolescents. Methods Household survey data were collected from 10 to 19-year-old adolescents in southwestern Nigeria. Dependent variables were daily tooth brushing, daily consumption of refined carbohydrates between meals, and oral hygiene status (measured by plaque index). The independent variable was lifetime suicidal ideation/attempt, dichotomized into ‘yes’ and ‘never’. ‘Daily tooth brushing’ and ‘daily consumption of refined carbohydrates between meals’ were included in two separate logistic regression models, and ‘oral hygiene status’ was included in a linear regression model. The models were adjusted for sex, age, and socioeconomic status. The linear regression model was also adjusted for frequency of daily tooth-brushing and of consumption of refined carbohydrates between meals. Interactions between sex and suicidal ideation/suicide attempt in association with dependent variables were assessed. Significance was set at 5%. Results We recruited 1,472 participants with mean age (standard deviation) of 14.6 (2.6) years. The mean plaque index was 0.84 (0.56), and 66 (4.5%) adolescents reported ever having suicidal ideation/attempt. Suicidal ideation/attempt was associated with significantly lower likelihood of tooth brushing (OR = 0.48, 95% CI: 0.26, 0.91), higher likelihood of consuming refined carbohydrates between meals (OR = 2.30, 95% CI: 1.29, 4.10), and having poor oral hygiene (B = 0.18, 95% CI: 0.05, 0.32). Among males, suicidal ideation/attempt was associated with less likelihood of eating refined carbohydrates between meals (OR = 0.96, 95% CI: 0.35, 2.61). Conversely, it was associated with a significantly higher likelihood of this outcome (OR = 4.85, 95% CI: 2.23, 10.55) among females. Conclusion The study findings suggest that poor tooth brushing habits and poor oral hygiene are indicators for risk of suicidal behavior for adolescents in Nigeria, while high sugar consumption may be an additional risk factor for adolescent females. These findings support the role of dental practitioners as members of healthcare teams responsible for screening, identifying and referring patients at risk for suicidal ideation/attempt.

Description: The poor dynamic performance problem of a Full-Bridge converter under a traditional control strategy is investigated in this study. A new parameter adaptive terminal sliding mode control policy is developed for a Full-Bridge DC-DC converter, by combining the integral part with the power function and differential function in the design of the sliding surface. In theory, the steady-state error of the system can approach zero within a short time. To manage the un-ideal situation after using a fixed value of power γ, an improved γ adaptive algorithm is proposed. The system output is tracked and γ is adjusted in real time. The effect of the system can be guaranteed always in an optimal state. Finally, simulation results are provided to verify the performance of the proposed design method under different conditions.

Description: Objective To evaluate the retinal nerve fiber layer (RNFL) and macular thicknesses and identify systemic risk factors for thinning of these layers in patients with metabolic syndrome (MetS). Methodology A cross-sectional observational study was performed on patients diagnosed with MetS and compared to normal controls. All patients underwent ophthalmic and anthropometric examination, serological and biochemical blood investigations; and ocular imaging using spectral-domain optical coherence tomography. Patients with ocular pathology were excluded. Unpaired t-test was used to compare mean thickness between the two groups. One-way ANOVA with Bonferroni correction for multiple comparisons was used to compare mean thickness between different tertiles of MetS parameters, and a generalized estimating equation was used to correct for inter-eye correlation and to assess association between mean thickness and covariates. Results Two hundred and forty-eight eyes from 124 participants (1:1 ratio of MetS patients to controls) were included. Age ranged between 30 to 50 years old, and mean age was 40 ± 6.6 years. RNFL thickness was lower globally (93.6 ± 9.9 μm vs 99.0 ± 9.3, p

Description: Background Therapeutic hypothermia (TH) is a well-established neuroprotective therapy applied in (near) term asphyxiated infants. However, little is known regarding the effects of TH on renal and/or myocardial function. Objectives To describe the short- and long-term effects of TH on renal and myocardial function in asphyxiated (near) term neonates. Methods An electronic search strategy incorporating MeSH terms and keywords was performed in October 2019 and updated in June 2020 using PubMed and Cochrane databases. Inclusion criteria consisted of a RCT or observational cohort design, intervention with TH in a setting of perinatal asphyxia and available long-term results on renal and myocardial function. We performed a meta-analysis and heterogeneity and sensitivity analyses using a random effects model. Subgroup analysis was performed on the method of cooling. Results Of the 107 studies identified on renal function, 9 were included. None of the studies investigated the effects of TH on long-term renal function after perinatal asphyxia. The nine included studies described the effect of TH on the incidence of acute kidney injury (AKI) after perinatal asphyxia. Meta-analysis showed a significant difference between the incidence of AKI in neonates treated with TH compared to the control group (RR = 0.81; 95% CI 0.67–0.98; p = 0.03). No studies were found investigating the long-term effects of TH on myocardial function after neonatal asphyxia. Possible short-term beneficial effects were presented in 4 out of 5 identified studies, as observed by significant reductions in cardiac biomarkers and less findings of myocardial dysfunction on ECG and cardiac ultrasound. Conclusions TH in asphyxiated neonates reduces the incidence of AKI, an important risk factor for chronic kidney damage, and thus is potentially renoprotective. No studies were found on the long-term effects of TH on myocardial function. Short-term outcome studies suggest a cardioprotective effect.

Description: Understanding animals’ aversion is important to improving their welfare. Aversion is often assessed using an approach-avoidance (AA) test in which animals have to forfeit a reward if they want to avoid an event or environment presented in the same place. However, sometimes the event/environment suspected to be aversive may physically impair the animal’s ability to withdraw from that place (i.e. its ability to express aversion), leading to incorrect interpretations. Combining AA with a Conditioned-Stimulus that predicts the event/environment may overcome this problem by allowing animals to demonstrate aversion without exposure to the stimulus. We aimed to validate this paradigm for testing aversion in chickens. Seven Hyline-Brown chickens were trained to obtain a food reward from a coloured bowl located in the test chamber (TC) of a two-chambered box; the reward was presented in a green bowl with an inactivated air canister or a red bowl with the canister activated to deliver an air puff. Two 5-minute tests were conducted, one with each bowl colour and both with the canister inactivated. All chickens entered TC with the green bowl. With the red bowl, two chickens entered on their first attempt, one fully entered after a partial entry (3/7 fully entered), two made only partial entries and two made no attempts to enter. Chickens spent less time in the TC with the red bowl (median 31s, IQR 7–252) compared to the green bowl (293s, IQR 290–294; p = 0.008). The higher ratio of partial to full entries, failure to enter the TC and less time spent in TC reflected chickens’ aversion to the air puff, signalled by the red bowl. The paradigm allowed chickens to demonstrate aversion without exposure to the aversive stimulus during testing.

Description: Background Abdominal obesity predict metabolic syndrome parameters at low levels of waist circumference (WC) in Africans. At the same time, the African lipid profile phenotype of low high-density lipoprotein (HDL) cholesterol without concomitant elevated triglyceride levels renders high triglyceride levels detrimental to cardiometabolic health unsuitable for identifying cardiometabolic risk in black African populations. Objectives We aimed to identify simple clinical measures for cardiometabolic risk based on WC and HDL in an adult Kenyan population in order to determine which of the two predictors had the strongest impact. Methods We used linear regression analyses to assess the association between the two exposure variables WC and HDL with cardiometabolic risk factors including ultrasound-derived visceral (VAT) and subcutaneous adipose tissue (SAT) accumulation, fasting and 2-h venous glucose, fasting insulin, fasting lipid profile, and blood pressure in adult Kenyans (n = 1 370), and a sub-population with hyperglycaemia (diabetes and pre-diabetes) (n = 196). The same analyses were performed with an interaction between WC and HDL to address potential effect modification. Ultrasound-based, semi-quantitative hepatic steatosis assessment was used as a high-risk measure of cardiometabolic disease. Results Mean age was 38.2 (SD 10.7) (range 17–68) years, mean body mass index was 22.3 (SD 4.5) (range 13.0–44.8) kg/m2, and 57.8% were women. Cardiometabolic risk was found in the association between both WC and HDL and all outcome variables (p

Description: Objective To find preoperative screening criteria for dry eye syndrome (DES) that present after successful endoscopic dacryocystorhinostomy (EDCR). Methods We retrospectively analyzed medical records of 110 patients who underwent EDCR for nasolacrimal duct obstruction. DES diagnostic criteria were defined as tear break-up time (TBUT) less than 10 seconds, and ocular surface disease index (OSDI) score greater than 13 points. After EDCR, patients were divided into DES group and control group according to the DES diagnostic criteria. Preoperative OSDI score alone or in combination of preoperative TBUT and OSDI score were used to find screening criteria, which could discriminate the two groups preoperatively with a high positive predictive value (PPV). Criteria A was set same as the diagnostic criteria of DES, and Criteria B and C were set to improve PPV by increasing specificity while maintaining similar sensitivity to Criteria A. Results Thirty patients (27.3%) were diagnosed with DES after EDCR, while 80 patients (72.7%) were normal. In patients with DES, preoperative TBUT was not different (p = 0.851), but OSDI score was significantly higher (p

Description: Introduction The intestinal microbiota comprises bacteria, fungi, archaea, protists, helminths and viruses that symbiotically inhabit the digestive system. To date, research has provided limited data on the possible association between an active lifestyle and a healthy composition of human microbiota. This review was aimed to summarize the results of human studies comparing the microbiome of healthy individuals with different physical activity amounts. Methods We searched Medline/Ovid, NIH/PubMed, and Academic Search Complete between August–October 2020. Inclusion criteria comprised: (a) cross-sectional studies focused on comparing gut microbiome among subjects with different physical activity levels; (b) studies describing human gut microbiome responses to any type of exercise stimulus; (c) studies containing healthy adult women and men. We excluded studies containing diet modifications, probiotic or prebiotic consumption, as well as studies focused on diabetes, hypertension, cancer, hormonal dysfunction. Methodological quality and risk of bias for each study were assessed using the Risk Of Bias In Non-randomized Studies—of Interventions tool. The results from cross-sectional and longitudinal studies are shown independently. Results A total of 17 articles were eligible for inclusion: ten cross-sectional and seven longitudinal studies. Main outcomes vary significantly according to physical activity amounts in longitudinal studies. We identified discrete changes in diversity indexes and relative abundance of certain bacteria in active people. Conclusion As literature in this field is rapidly growing, it is important that studies incorporate diverse methods to evaluate other aspects related to active lifestyles such as sleep and dietary patterns. Exploration of other groups such as viruses, archaea and parasites may lead to a better understanding of gut microbiota adaptation to physical activity and sports and its potentially beneficial effects on host metabolism and endurance.

Description: During the Natufian period, more than 12,000 years ago, Eynan (Ain Mallaha) was an important human settlement in the Hula Valley, Israel. This study concentrates on the anuran and squamate assemblage from the ultimate stage of the Natufian period at the site, the Final Natufian. Over five thousand bones assigned to at least sixteen taxa were studied from a sampled segment of the excavated open-air site. Relative species abundance, spatial distribution, taphonomic observations and ecological considerations all pointed to the conclusion that the inhabitants of Eynan intensively exploited three large “colubrine” snakes species: the Large Whip Snake (Dolichophis jugularis), the Eastern Montpellier Snake (Malpolon insignitus) and an Eastern Four-lined Ratsnake (Elaphe cf. sauromates). These snakes were the most desired and were intensively gathered, while other snakes and lizards could have been opportunistically collected when encountered. We raise questions about whether the large “colubrines” exploitation should be interpreted as additional evidence of increasing diet breadth. We suggest challenging this line of reasoning and offer possible alternative motives.

Description: We performed whole-genome multi-locus sequence typing for 2554 genes in a large and heterogenous panel of 180 Listeria monocytogenes strains having diverse geographical and temporal origins. The subtyping data was used for characterizing genetic variation and evaluating patterns of linkage disequilibrium in the pan-genome of L. monocytogenes. Our analysis revealed the presence of strong linkage disequilibrium in L. monocytogenes, with ~99% of genes showing significant non-random associations with a large majority of other genes in the genome. Twenty-seven loci having lower levels of association with other genes were considered to be potential “hot spots” for horizontal gene transfer (i.e., recombination via conjugation, transduction, and/or transformation). The patterns of linkage disequilibrium in L. monocytogenes suggest limited exchange of foreign genetic material in the genome and can be used as a tool for identifying new recombinant strains. This can help understand processes contributing to the diversification and evolution of this pathogenic bacteria, thereby facilitating development of effective control measures.

Description: The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science.

Description: Understanding the functionality of proteins has emerged as a critical problem in recent years due to significant roles of these macro-molecules in biological mechanisms. However, in-laboratory techniques for protein function prediction are not as efficient as methods developed and processed for protein sequencing. While more than 70 million protein sequences are available today, only the functionality of around one percent of them are known. These facts have encouraged researchers to develop computational methods to infer protein functionalities from their sequences. Gene Ontology is the most well-known database for protein functions which has a hierarchical structure, where deeper terms are more determinative and specific. However, the lack of experimentally approved annotations for these specific terms limits the performance of computational methods applied on them. In this work, we propose a method to improve protein function prediction using their sequences by deeply extracting relationships between Gene Ontology terms. To this end, we construct a conditional generative adversarial network which helps to effectively discover and incorporate term correlations in the annotation process. In addition to the baseline algorithms, we compare our method with two recently proposed deep techniques that attempt to utilize Gene Ontology term correlations. Our results confirm the superiority of the proposed method compared to the previous works. Moreover, we demonstrate how our model can effectively help to assign more specific terms to sequences.

Description: Pulsed-electromagnetic-field (PEMF) treatment was found to enhance cellular differentiation of the mouse preosteoblast, MC3T3-E1, to a more osteoblastic phenotype. Differentiation genes such as Alp, BSPI, cFos, Ibsp, Osteocalcin, Pthr1 and Runx2 showed increased expression in response to PEMF stimulation. Detailed molecular mechanisms linking PEMF to the activation of these genes are limited. Two adenosine receptors known to be modulated in response to PEMF, Adora2A and Adora3, were functionally impaired by CRISPR-Cas9-mediated gene disruption, and the consequences of which were studied in the context of PEMF-mediated osteoblastic differentiation. Disruption of Adora2A resulted in a delay of Alp mRNA expression, but not alkaline phosphatase protein expression, which was similar to that found in wild type cells. However, Adora3 disruption resulted in significantly reduced responses at both the alkaline phosphatase mRNA and protein levels throughout the PEMF stimulation period. Defects observed in response to PEMF were mirrored using a chemically defined growth and differentiation-inducing media (DM). Moreover, in cells with Adora2A disruption, gene expression profiles showed a blunted response in cFos and Pthr1 to PEMF treatment; whereas cells with Adora3 disruption had mostly blunted responses in AlpI, BSPI, Ibsp, Osteocalcin and Sp7 gene activation. To demonstrate specificity for Adora3 function, the Adora3 open reading frame was inserted into the ROSA26 locus in Adora3 disrupted cells culminating in rescued PEMF responsiveness and thereby eliminating the possibility of off-target effects. These results lead us to propose that there are complementary and parallel positive roles for adenosine receptor A2A and A3 in PEMF-mediated osteoblast differentiation.

Description: Increased availability of drug response and genomics data for many tumor cell lines has accelerated the development of pan-cancer prediction models of drug response. However, it is unclear how much between-tissue differences in drug response and molecular characteristics may contribute to pan-cancer predictions. Also unknown is whether the performance of pan-cancer models could vary by cancer type. Here, we built a series of pan-cancer models using two datasets containing 346 and 504 cell lines, each with MEK inhibitor (MEKi) response and mRNA expression, point mutation, and copy number variation data, and found that, while the tissue-level drug responses are accurately predicted (between-tissue ρ = 0.88–0.98), only 5 of 10 cancer types showed successful within-tissue prediction performance (within-tissue ρ = 0.11–0.64). Between-tissue differences make substantial contributions to the performance of pan-cancer MEKi response predictions, as exclusion of between-tissue signals leads to a decrease in Spearman’s ρ from a range of 0.43–0.62 to 0.30–0.51. In practice, joint analysis of multiple cancer types usually has a larger sample size, hence greater power, than for one cancer type; and we observe that higher accuracy of pan-cancer prediction of MEKi response is almost entirely due to the sample size advantage. Success of pan-cancer prediction reveals how drug response in different cancers may invoke shared regulatory mechanisms despite tissue-specific routes of oncogenesis, yet predictions in different cancer types require flexible incorporation of between-cancer and within-cancer signals. As most datasets in genome sciences contain multiple levels of heterogeneity, careful parsing of group characteristics and within-group, individual variation is essential when making robust inference.

Description: Background The WHO African region frequently experiences outbreaks and epidemics of infectious diseases often exacerbated by weak health systems and infrastructure, late detection, and ineffective outbreak response. To address this, the WHO Regional Office for Africa developed and began implementing the Integrated Disease Surveillance and Response strategy in 1998. Objectives This systematic review aims to document the identified successes and challenges surrounding the implementation of IDSR in the region available in published literature to highlight areas for prioritization, further research, and to inform further strengthening of IDSR implementation. Methods A systematic review of peer-reviewed literature published in English and French from 1 July 2012 to 13 November 2019 was conducted using PubMed and Web of Science. Included articles focused on the WHO African region and discussed the use of IDSR strategies and implementation, assessment of IDSR strategies, or surveillance of diseases covered in the IDSR framework. Data were analyzed descriptively using Microsoft Excel and Tableau Desktop 2019. Results The number of peer-reviewed articles discussing IDSR remained low, with 47 included articles focused on 17 countries and regional level systems. Most commonly discussed topics were data reporting (n = 39) and challenges with IDSR implementation (n = 38). Barriers to effective implementation were identified across all IDSR core and support functions assessed in this review: priority disease detection; data reporting, management, and analysis; information dissemination; laboratory functionality; and staff training. Successful implementation was noted where existing surveillance systems and infrastructure were utilized and streamlined with efforts to increase access to healthcare. Conclusions and implications of findings These findings highlighted areas where IDSR is performing well and where implementation remains weak. While challenges related to IDSR implementation since the first edition of the technical guidelines were released are not novel, adequately addressing them requires sustained investments in stronger national public health capabilities, infrastructure, and surveillance processes.

Description: Few studies have assessed HIV incidence in men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA). We assessed HIV incidence and its correlates among MSM and TGW in SSA enrolled in the prospective, multi-country HIV Prevention Trials Network (HPTN) 075 study, conducted from 2015 to 2017. Participants were enrolled at four sites in SSA (Kisumu, Kenya; Blantyre, Malawi; Cape Town and Soweto, South Africa). Eligible participants reported male sex assignment at birth, were 18 to 44 years of age, and had engaged in anal intercourse with a man in the preceding three months. Participation involved five study visits over 12 months. Visits included behavioral assessments and testing for HIV and sexually transmitted infections. Twenty-one of 329 persons acquired HIV during the study [incidence rate: 6.96/100 person-years (PY) (95% CI: 4.3, 10.6)]. Among TGW, HIV incidence was estimated to be 8.4/100 PY (95% CI: 2.3, 21.5). Four participants were found to have acute HIV infection at their first HIV-positive visit. HIV incidence varied among the four study sites, ranging from 1.3/100 PY to 14.4/100 PY. In multivariate longitudinal analysis, factors significantly associated with HIV acquisition were engagement in unprotected receptive anal intercourse [adjusted hazard ratio (AHR) 5.8, 95% confidence interval (CI): 2.4, 14.4] and incident rectal gonorrhea and/or chlamydia (AHR: 2.7, 95% CI: 1.1, 6.8). The higher HIV incidence in Cape Town compared to Blantyre could be explained by the higher prevalence of several risk factors for HIV infection among participants in Cape Town. Annual HIV incidence observed in this study is substantially higher than reported HIV incidence in the general populations in the respective countries and among MSM in the United States. Intensification of HIV prevention efforts for MSM and TGW in SSA is urgently needed.

Description: Male lower urinary tract symptoms (LUTS) comprise a common syndrome of aging that negatively impacts quality of life. The etiology of LUTS is multifactorial, involving benign prostatic hyperplasia, smooth muscle and neurologic dysfunction, inflammation, sexually transmitted infections, fibrosis, and potentially dysbiosis, but this aspect remains poorly explored. We investigated whether the presence of infectious agents in urine might be associated with LUTS by combining next-generation DNA sequencing for virus discovery, microbiome analysis for characterization of bacterial communities, and mass spectrometry-based metabolomics. In urine from 29 LUTS cases and 9 controls from Wisconsin, we found a statistically significant association between a diagnosis of LUTS and the presence of JC virus (JCV), a common neurotropic human polyomavirus (Polyomaviridae, Betapolyomavirus) linked to severe neurologic disease in rare cases. This association (based on metagenomics) was not borne out when specific polymerase chain reaction (PCR) testing was applied to this set of samples, likely due to the greater sensitivity of PCR. Interestingly, urine metabolomics analysis identified dysregulation of metabolites associated with key LUTS processes. Microbiome analysis found no evidence of microbial community dysbiosis in LUTS cases, but JCV-positive samples contained more Anaerococcus species, which are involved in polymicrobial infections of the urinary tract. Neither age nor body mass index were significantly associated with the presence of urinary JCV—in the initial group or in an additional, regionally distinct group. These data provide preliminary support the hypothesis that viruses such as JCV may play a role in the development or progression of LUTS, together with other infectious agents and host metabolic responses.

Description: Background There are gaps in our understanding of how non-specialists, such as lay health workers, can achieve core competencies to deliver psychosocial interventions in low- and middle-income countries. Methods We conducted a 12-month mixed-methods study alongside the Rehabilitation Intervention for people with Schizophrenia in Ethiopia (RISE) pilot study. We rated a total of 30 role-plays and 55 clinical encounters of ten community-based rehabilitation (CBR) lay workers using an Ethiopian adaptation of the ENhancing Assessment of Common Therapeutic factors (ENACT) structured observational rating scale. To explore factors influencing competence, six focus group discussions and four in-depth interviews were conducted with 11 CBR workers and two supervisors at three time-points. We conducted a thematic analysis and triangulated the qualitative and quantitative data. Results There were improvements in CBR worker competence throughout the training and 12-month pilot study. Therapeutic alliance competencies (e.g., empathy) saw the earliest improvements. Competencies in personal factors (e.g., substance use) and external factors (e.g., assessing social networks) were initially rated lower, but scores improved during the pilot. Problem-solving and giving advice competencies saw the least improvements overall. Multimodal training, including role-plays, field work and group discussions, contributed to early development of competence. Initial stigma towards CBR participants was reduced through contact. Over time CBR workers occupied dual roles of expert and close friend for the people with schizophrenia in the programme. Competence was sustained through peer supervision, which also supported wellbeing. More intensive specialist supervision was needed. Conclusion It is possible to equip lay health workers with the core competencies to deliver a psychosocial intervention for people with schizophrenia in a low-income setting. A prolonged period of work experience is needed to develop advanced skills such as problem-solving. A structured intervention with clear protocols, combined with peer supervision to support wellbeing, is recommended for good quality intervention delivery. Repeated ENACT assessments can feasibly and successfully be used to identify areas needing improvement and to guide on-going training and supervision.

Description: Background/Aims Post-filter ionized calcium (iCa) measured on a blood gas analyzer (BGA) during regional citrate anticoagulated continuous renal replacement therapy (CRRT) are needed to control the regime. This increases the workload and requires attention including interpretation of blood analyses. Two algorithms were developed to calculate the post-filter iCa instead. The first algorithm used measured systemic total calcium and the second used a selected set of values from an initial blood gas sample as input. Methods Calculated post-filter iCa values were compared to real blood gas analyses. 57 patients treated at the intensive care unit at Skåne University Hospital in Lund during 2010–2017 were included after applying inclusion and exclusion criteria. Clinical and machine parameters were collected from the electronic medical records. Non-quality checked data contained 1240 measurements and quality checked data contained 1034 measurements. Results The first algorithm using measured systemic total calcium resulted in slightly better precision and trueness with an average difference between the predicted and measured post-filter iCa concentration of 0.0185±0.0453 mmol/L for quality checked data, p

Description: Adult T-cell leukemia/lymphoma (ATLL) is virus-caused cancer that originates from the infection by human T-cell leukemia virus type 1. ATLL dysregulates various biological pathways related to the viral infection and cancer progression through the dysexpression of miRNAs and mRNAs. In this study, the potential regulatory subnetworks were constructed aiming to shed light on the pathogenesis mechanism of ATLL. For this purpose, two mRNA and one miRNA expression datasets were firstly downloaded from the GEO database. Next, the differentially expressed genes and miRNAs (DEGs and DE-miRNAs, respectively), as well as differentially co-expressed gene pairs (DCGs), were determined. Afterward, common DEGs and DCGs targeted by experimentally validated DE-miRNAs were explored. The oncogenic and anti-oncogenic miRNA-mRNA regulatory subnetworks were then generated. The expression levels of four genes and two miRNAs were examined in the blood samples by qRT-PCR. The members of three oncogenic/anti-oncogenic subnetworks were generally enriched in immune, virus, and cancer-related pathways. Among them, FZD6, THBS4, SIRT1, CPNE3, miR-142-3p, and miR-451a were further validated by real-time PCR. The significant up-regulation of FZD6, THBS4, and miR-451a as well as down-regulation of CPNE3, SIRT1, and miR-142-3p were found in ATLL samples than normal samples. The identified oncogenic/anti-oncogenic subnetworks are pieces of the pathogenesis puzzle of ATLL. The ultimate winner is probably an oncogenic network that determines the final fate of the disease. The identified genes and miRNAs are proposed as novel prognostic biomarkers for ATLL.

Description: Introduction The work environment of healthcare professionals is important for good patient care and is receiving increasing attention in scientific research. A clear and unambiguous understanding of a positive work environment, as perceived by healthcare professionals, is crucial for gaining systematic objective insights into the work environment. The aim of this study was to gain consensus on the concept of a positive work environment in the hospital. Methods This was a three-round Delphi study to establish consensus on what defines a positive work environment. A literature review and 17 semi-structured interviews with experts (transcribed and analyzed by open and thematic coding) were used to generate items for the Delphi study. Results The literature review revealed 228 aspects that were clustered into 48 work environment elements, 38 of which were mentioned in the interviews also. After three Delphi rounds, 36 elements were regarded as belonging to a positive work environment in the hospital. Discussion The work environment is a broad concept with several perspectives. Although all 36 elements are considered important for a positive work environment, they have different perspectives. Mapping the included elements revealed that no one work environment measurement tool includes all the elements. Conclusion We identified 36 elements that are important for a positive work environment. This knowledge can be used to select the right measurement tool or to develop interventions for improving the work environment. However, the different perspectives of the work environment should be considered.

Description: Knowing how many donkeys there are in specific countries where welfare is compromised is a key concern for targeting efforts to improve donkey welfare. Additionally, accurate population estimates are vital for providing evidence and addressing the impact of population threats. The FAO annually report the number of donkeys and mules in each country. The last paper to investigate global and region trends dates back to 2000 and used FAO data from 1961 to 1997. This paper is an update focusing on global, regional and country level donkey and mule populations to understand if there have been any changes in the trends reported by the previous study between 1997 and 2018. Results show that the general trend identified between 1961 and 1997 is continuing with the number of donkeys globally increasing at a rate of ~1% per annum whilst mule populations are in decline at a rate of ~2% per annum. Results also suggest that the trend identified in the original paper are still evident today with the largest increases in donkey population seen in the sub-Saharan African region and greatest reduction noted in Eastern Europe with these two regions having different socio-economic drivers influencing these changes. These results highlight the multifaceted socio-economic drivers influence changes in donkey and mule populations demonstrating the complexity of designing targeted one-welfare approaches. Whilst the FAO donkey and mule datasets are the best available for understanding spatial-temporal distributions in populations there needs to be greater effort to promote the communication of information from the country level to the FAO. This can be directly supported by NGO’s by promoting the robustness of the FAO process for collating and disseminating this information. NGO’s should also seek to highlight the importance of this information for understanding global regional and country level drivers for equid population changes and potential threats to welfare as well as using this information to facilitate projects that support one-welfare approaches.

Description: Human coronaviruses (HCoVs) cause mild to severe respiratory infection. Most of the common cold illnesses are caused by one of four HCoVs, namely HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43. Several studies have applied global transcriptomic methods to understand host responses to HCoV infection, with most studies focusing on the pandemic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and the newly emerging SARS-CoV-2. In this study, Next Generation Sequencing was used to gain new insights into cellular transcriptomic changes elicited by alphacoronavirus HCoV-229E. HCoV-229E-infected MRC-5 cells showed marked downregulation of superpathway of cholesterol biosynthesis and eIF2 signaling pathways. Moreover, upregulation of cyclins, cell cycle control of chromosomal replication, and the role of BRCA1 in DNA damage response, alongside downregulation of the cell cycle G1/S checkpoint, suggest that HCoV-229E may favors S phase for viral infection. Intriguingly, a significant portion of key factors of cell innate immunity, interferon-stimulated genes (ISGs) and other transcripts of early antiviral response genes were downregulated early in HCoV-229E infection. On the other hand, early upregulation of the antiviral response factor Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) was observed. APOBEC3B cytidine deaminase signature (C-to-T) was previously observed in genomic analysis of SARS-CoV-2 but not HCoV-229E. Higher levels of C-to-T mutations were found in countries with high mortality rates caused by SARS-CoV-2. APOBEC activity could be a marker for new emerging CoVs. This study will enhance our understanding of commonly circulating HCoVs and hopefully provide critical information about still-emerging coronaviruses.

Description: With the exponential increase in heterogeneous wireless networks today, there has been a growing interest from the academic community for issues related to handover problems. The main objective of this paper is to evaluate the quality of service and performance of a device with a dual interface that connects simultaneously to two heterogeneous networks with no competition in the exchange of packets between them. It is a proposal to solve the mitigation of handover impacts. The tool used for evaluation was the Network Simulator 2. The results showed a better use of the band in comparison to the scenario using a traditional mobile device.

Description: Background/Objective High tibial osteotomy (HTO) is a common treatment for medial knee arthrosis. However, a high rate of complications associated with a plate and a significant loss of correction have been reported. Therefore, an internal support block (ISB) is designed to enhance the initial stability of the fixation device that is important for successful bone healing and maintenance of the correction angle of the osteotomy site. The purpose of this study was performed to examine if an internal support block combined with a plate reduces the stress on the plate and screw area. Methods Finite element models were reconstructed following three different implant combinations. Two loading conditions were applied to simulate standing and initial sit-to-stand postures. Data analysis was conducted to evaluate the axial displacement of the posteromedial tibial plateau, which represents the loss of the posteromedial tibial plateau in clinical observation. Moreover, the stresses on the bone plate and locking screws were evaluated. Results Compared to the TomoFix plate, the ISB reduced the axial displacement by 73% and 76% in standing and initial sit-to-stand loading conditions, respectively. The plate with an ISB reduced stress by 90% on the bone plate and by 73% on the locking screw during standing compared to the standalone TomoFix plate. During the initial sit-to-stand loading condition, the ISB reduced the stress by 93% and 77% on the bone plate and the locking screw, respectively. Conclusion The addition of the PEEK block showed a benefit for structural stability in the osteotomy site. However, further clinical trials are necessary to evaluate the clinical benefit of reduced implant stress and the internal support block on the healing of the medial bone tissue.

Description: The spread of Covid-19 has resulted in worldwide health concerns. Social media is increasingly used to share news and opinions about it. A realistic assessment of the situation is necessary to utilize resources optimally and appropriately. In this research, we perform Covid-19 tweets sentiment analysis using a supervised machine learning approach. Identification of Covid-19 sentiments from tweets would allow informed decisions for better handling the current pandemic situation. The used dataset is extracted from Twitter using IDs as provided by the IEEE data port. Tweets are extracted by an in-house built crawler that uses the Tweepy library. The dataset is cleaned using the preprocessing techniques and sentiments are extracted using the TextBlob library. The contribution of this work is the performance evaluation of various machine learning classifiers using our proposed feature set. This set is formed by concatenating the bag-of-words and the term frequency-inverse document frequency. Tweets are classified as positive, neutral, or negative. Performance of classifiers is evaluated on the accuracy, precision, recall, and F1 score. For completeness, further investigation is made on the dataset using the Long Short-Term Memory (LSTM) architecture of the deep learning model. The results show that Extra Trees Classifiers outperform all other models by achieving a 0.93 accuracy score using our proposed concatenated features set. The LSTM achieves low accuracy as compared to machine learning classifiers. To demonstrate the effectiveness of our proposed feature set, the results are compared with the Vader sentiment analysis technique based on the GloVe feature extraction approach.

Description: During formation of the Hedgehog (Hh) signaling proteins, cooperative activities of the Hedgehog INTein (Hint) fold and Sterol Recognition Region (SRR) couple autoproteolysis to cholesterol ligation. The cholesteroylated Hh morphogens play essential roles in embryogenesis, tissue regeneration, and tumorigenesis. Despite the centrality of cholesterol in Hh function, the full structure of the Hint-SRR (“Hog”) domain that attaches cholesterol to the last residue of the active Hh morphogen remains enigmatic. In this work, we combine molecular dynamics simulations, photoaffinity crosslinking, and mutagenesis assays to model cholesterolysis intermediates in the human Sonic Hedgehog (hSHH) protein. Our results provide evidence for a hydrophobic Hint-SRR interface that forms a dynamic, non-covalent cholesterol-Hog complex. Using these models, we suggest a unified mechanism by which Hh proteins can recruit, sequester, and orient cholesterol, and offer a molecular basis for the effects of disease-causing hSHH mutations.

Description: Objectives In Jang-jeom, a small village in Hamra-myeon, Iksan-si, Jeollabuk-do, South Korea, residents raised concerns about a suspected cancer cluster that they attributed to a fertilizer plant near the village. We aimed to investigate whether the cancer incidence in the village was higher than that in the general Korean population when the factory was in operation (2001–2017) and whether living in the village was associated with a higher risk of cancer. Methods Using national population data and cancer registration data of South Korea, we estimated the standardized incidence ratios (SIRs) in the village to investigate whether more cancer cases occurred in the village compared to other regions. The SIRs were standardized by age groups of 5 years and sex. In order to investigate whether residence in the village increased the risk of cancer, a retrospective cohort was constructed using National Health Insurance Service (NHIS) databases. We estimated the cancer hazard ratios (HRs) using the Cox proportional hazard model, and defined the exposed area as the village of Jang-jeom, and the unexposed or control area as the village neighborhood in Hamra-myeon. We considered potential confounding variables such as age, sex, and income index in the models. Additionally, we measured polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines (TSNAs), suspected carcinogens that may have caused the cancer cluster, in samples collected from the plant and the village. Results Twenty-three cancer cases occurred in Jang-jeom from 2001 to 2017. Between 2010 and 2016, the incidence rates of all cancers (SIR: 2.05, except thyroid cancer: 2.22), non-melanoma skin cancer (SIR: 21.14, female: 25.41), and gallbladder (GB) and biliary tract cancer in men (SIR: 16.01) in the village were higher than those in the national population in a way that was statistically significant. In our cohort analysis that included only Hamra-myeon residents who have lived there for more than 7 years, we found a statistically significant increase in the risk of all cancers (HR: 1.99, except thyroid cancer: 2.20), non-melanoma skin cancer (HR: 11.60), GB and biliary tract cancer (HR: 15.24), liver cancer (HR: 6.63), and gastric cancer (HR: 3.29) for Jang-jeom residents compared to other Hamra area residents. We identified PAHs and TSNAs in samples of deposited dust and residual fertilizer from the plant and TSNAs in dust samples from village houses. Conclusions The results of the SIR calculation and cancer risk analyses of Jang-jeom village residents from the retrospective cohort design showed consistency in the effect size and direction, suggesting that there was a cancer cluster in Jang-jeom. This study would be a good precedent for cancer cluster investigation.

Description: Childhood trauma is associated with an increased risk of psychosis, but the mechanisms that mediate this relationship are unknown. Exposure to trauma has been hypothesised to lead to cognitive biases that might have causal effects on psychotic symptoms. The literature on whether childhood trauma is associated with psychosis-related cognitive biases has not been comprehensively reviewed. A systematic review and meta-analysis or narrative synthesis of studies examining the association between childhood trauma and the following biases: external locus of control (LOC), external attribution, probabilistic reasoning, source monitoring, top-down processing, and bias against disconfirmatory evidence. Studies were assessed for quality, and sources of heterogeneity were explored. We included 25 studies from 3,465 studies identified. Individuals exposed to childhood trauma reported a more external LOC (14 studies: SMD Median = 0.40, Interquartile range 0.07 to 0.52), consistent with a narrative synthesis of 11 other studies of LOC. There was substantial heterogeneity in the meta-analysis (I2 = 93%) not explained by study characteristics examined. Narrative syntheses for other biases showed weaker, or no evidence of association with trauma. The quality of included studies was generally low. Our review provides some evidence of an association between childhood trauma and a more external LOC, but not with the other biases examined. The low quality and paucity of studies for most of the cognitive biases examined highlights the need for more rigorous studies to determine which biases occur after trauma, and whether they mediate an effect of childhood trauma on psychosis.

Description: The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N’-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p

Description: Background Hypoxic perinatal brain injury is caused by lack of oxygen to baby’s brain and can lead to death or permanent brain damage. However, the effectiveness of therapeutic hypothermia in birth asphyxiated infants with encephalopathy is uncertain. This systematic review and meta-analysis was aimed to estimate the pooled relative risk of mortality among birth asphyxiated neonates with hypoxic-ischemic encephalopathy in a global context. Methods We used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to search randomized control trials from electronic databases (PubMed, Cochrane library, Google Scholar, MEDLINE, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and meta register of Current Controlled Trials (mCRT)). The authors extracted the author’s name, year of publication, country, method of cooling, the severity of encephalopathy, the sample size in the hypothermic, and non-hypothermic groups, and the number of deaths in the intervention and control groups. A weighted inverse variance fixed-effects model was used to estimate the pooled relative risk of mortality. The subgroup analysis was done by economic classification of countries, methods of cooling, and cooling devices. Publication bias was assessed with a funnel plot and Eggers test. A sensitivity analysis was also done. Results A total of 28 randomized control trials with a total sample of 35, 92 (1832 hypothermic 1760 non-hypothermic) patients with hypoxic-ischemic encephalopathy were used for the analysis. The pooled relative risk of mortality after implementation of therapeutic hypothermia was found to be 0.74 (95%CI; 0.67, 0.80; I2 = 0.0%; p

Description: Background Inequality is rife throughout South Africa. The first wave of COVID-19 may have affected people in lower socioeconomic groups worse than the affluent. The SARS-CoV-2 seroprevalence and the specificity of anti-SARS-CoV-2 antibody tests in South Africa is not known. Methods We tested 405 volunteers representing all socioeconomic strata from the workforce of a popular shopping and tourist complex in central Cape Town with the Abbott SARS-CoV-2 IgG assay. We assessed the association between antibody positivity and COVID-19 symptom status, medical history, and sociodemographic variables. We tested 137 serum samples from healthy controls collected in Cape Town prior to the COVID-19 pandemic, to confirm the specificity of the assay in the local population. Results Of the 405 volunteers tested one month after the first peak of the epidemic in Cape Town, 96(23.7%) were SARS-CoV-2 IgG positive. Of those who tested positive, 46(47.9%) reported no symptoms of COVID-19 in the previous 6 months. Seropositivity was significantly associated with living in informal housing, residing in a subdistrict with low income-per household, and having a low-earning occupation. The specificity of the assay was 98.54%(95%CI 94.82%-99.82%) in the pre-COVID controls. Conclusions There is a high background seroprevalence in Cape Town, particularly in people of lower socioeconomic status. Almost half of cases are asymptomatic, and therefore undiagnosed by local testing strategies. These results cannot be explained by low assay specificity.

Description: Introduction Pre-exposure prophylaxis (PrEP) is effective in reducing HIV transmission among key populations. In India, where PrEP is not currently part of the national HIV program, little is known about PrEP awareness, willingness to use PrEP, and barriers to uptake among people who inject drugs (PWID) and men who have sex with men (MSM). Methods We used respondent-driven sampling to accrue PWID and MSM in 22 sites from August 2016 to May 2017. Participants were asked about awareness of PrEP, willingness to use PrEP (following a brief description) and reasons why they might not be willing to use PrEP. Participants were also queried on preferences for PrEP delivery modality (oral vs. injectable). Multi-level logistic regression models were used to determine participant correlates of willingness to use PrEP. Estimates were weighted for the sampling method. Results A total of 10,538 PWID and 8,621 MSM who self-reported being HIV-negative were included in the analysis. Only 6.1% (95% confidence interval [CI]: 5.9, 6.3) of PWID and 8.0% of MSM (95% CI: 7.7, 8.4) were aware of PrEP. However, willingness to use PrEP was substantially higher in both groups: 52.4% of PWID and 67.6% of MSM. Participants commonly cited a perceived low risk for acquiring HIV infection, being perceived by others as being HIV-positive, and side effects as reasons why they would be unwilling to use PrEP. Among PWID, sharing needles and hazardous alcohol use were associated with increased willingness to use PrEP. Among MSM, having a main male partner and injection drug use were associated with increased willingness to use PrEP. Preference for daily oral or monthly injectable PrEP was similar among MSM (39.6%% vs. 41.7%,), while PWID were more likely to prefer oral to injectable administration routes (56.3% vs. 31.1%). Conclusions As India plans to roll-out of PrEP in the public sector, our multi-city survey of PWID and MSM highlights the need for key population-focused education campaigns about PrEP and self-assessment of risk.

Description: Scientific collections such as the U.S. National Museum (USNM) are critical to filling knowledge gaps in molecular systematics studies. The global taxonomic impediment has resulted in a reduction of expert taxonomists generating new collections of rare or understudied taxa and these large historic collections may be the only reliable source of material for some taxa. Integrated systematics studies using both morphological examinations and DNA sequencing are often required for resolving many taxonomic issues but as DNA methods often require partial or complete destruction of a sample, there are many factors to consider before implementing destructive sampling of specimens within scientific collections. We present a methodology for the use of archive specimens that includes two crucial phases: 1) thoroughly documenting specimens destined for destructive sampling—a process called electronic vouchering, and 2) the pipeline used for whole genome sequencing of archived specimens, from extraction of genomic DNA to assembly of putative genomes with basic annotation. The process is presented for eleven specimens from two different insect subfamilies of medical importance to humans: Anophelinae (Diptera: Culicidae)—mosquitoes and Triatominae (Hemiptera: Reduviidae)—kissing bugs. Assembly of whole mitochondrial genome sequences of all 11 specimens along with the results of an ortholog search and BLAST against the NCBI nucleotide database are also presented.

Description: Plant phenotyping is a central task in crop science and plant breeding. It involves measuring plant traits to describe the anatomy and physiology of plants and is used for deriving traits and evaluating plant performance. Traditional methods for phenotyping are often time-consuming operations involving substantial manual labor. The availability of 3D sensor data of plants obtained from laser scanners or modern depth cameras offers the potential to automate several of these phenotyping tasks. This automation can scale up the phenotyping measurements and evaluations that have to be performed to a larger number of plant samples and at a finer spatial and temporal resolution. In this paper, we investigate the problem of registering 3D point clouds of the plants over time and space. This means that we determine correspondences between point clouds of plants taken at different points in time and register them using a new, non-rigid registration approach. This approach has the potential to form the backbone for phenotyping applications aimed at tracking the traits of plants over time. The registration task involves finding data associations between measurements taken at different times while the plants grow and change their appearance, allowing 3D models taken at different points in time to be compared with each other. Registering plants over time is challenging due to its anisotropic growth, changing topology, and non-rigid motion in between the time of the measurements. Thus, we propose a novel approach that first extracts a compact representation of the plant in the form of a skeleton that encodes both topology and semantic information, and then use this skeletal structure to determine correspondences over time and drive the registration process. Through this approach, we can tackle the data association problem for the time-series point cloud data of plants effectively. We tested our approach on different datasets acquired over time and successfully registered the 3D plant point clouds recorded with a laser scanner. We demonstrate that our method allows for developing systems for automated temporal plant-trait analysis by tracking plant traits at an organ level.

Description: Given the pressure on healthcare authorities to assess whether hospital capacity allows properly responding to outbreaks such as COVID-19, there is a need for simple, data-driven methods that may provide accurate forecasts of hospital bed demand. This study applies growth models to forecast the demand for Intensive Care Unit admissions in Italy during COVID-19. We show that, with only some mild assumptions on the functional form and using short time-series, the model fits past data well and can accurately forecast demand fourteen days ahead (the mean absolute percentage error (MAPE) of the cumulative fourteen days forecasts is 7.64). The model is then applied to derive regional-level forecasts by adopting hierarchical methods that ensure the consistency between national and regional level forecasts. Predictions are compared with current hospital capacity in the different Italian regions, with the aim to evaluate the adequacy of the expansion in the number of beds implemented during the COVID-19 crisis.

Description: Introduction Low anterior resection (LAR) for rectal cancer affects bowel function after the operation, causing a group of symptoms known as LAR Syndrome (LARS). LARS score is a patient-reported questionnaire to assess bowel dysfunction after the LAR operation. This study performed to validate the Persian (Farsi) translation of the LARS score and to investigate the psychometric properties of the score. The impact of LARS on the Quality of Life (QoL) of patients was also assessed. Materials and methods The LARS score was translated into Persian. Participants with a history of rectal cancer and low anterior resection were asked to complete the LARS score questionnaire. They were also asked a single question evaluating the impact of bowel function on QoL. Discriminative validity, convergent validity, sensitivity, and specificity of the questionnaire were calculated. A group of patients completed the score twice to assess the reliability of the questionnaire. Results From 358 patients with rectal cancer, 101 participants completed the Persian questionnaire. Answers of a high fraction of participants showed a moderate/perfect fit between their LARS score and their QoL. The Persian score demonstrated good convergent validity. It was able to differentiate between participants in terms of gender and T staging of the primary tumor. The score had high reliability. Conclusion The Persian translation of the LARS score has excellent psychometric properties compared to previous translations in other languages. Therefore, it is a valid and reliable questionnaire to assess LARS.

Description: Background Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. Methods The nationwide incidence of sarcoma or TIM (2013–2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. Results Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1–0.1/106, or 〈 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p

Description: The Hippo-YAP pathway responds to diverse environmental cues to manage tissue homeostasis, organ regeneration, tumorigenesis, and immunity. However, how phosphatase(s) directly target Yes-associated protein (YAP) and determine its physiological activity are still inconclusive. Here, we utilized an unbiased phosphatome screening and identified protein phosphatase magnesium-dependent 1A (PPM1A/PP2Cα) as the bona fide and physiological YAP phosphatase. We found that PPM1A was associated with YAP/TAZ in both the cytoplasm and the nucleus to directly eliminate phospho-S127 on YAP, which conferring YAP the nuclear distribution and transcription potency. Accordingly, genetic ablation or depletion of PPM1A in cells, organoids, and mice elicited an enhanced YAP/TAZ cytoplasmic retention and resulted in the diminished cell proliferation, severe gut regeneration defects in colitis, and impeded liver regeneration upon injury. These regeneration defects in murine model were largely rescued via a genetic large tumor suppressor kinase 1 (LATS1) deficiency or the pharmacological inhibition of Hippo-YAP signaling. Therefore, we identify a physiological phosphatase of YAP/TAZ, describe its critical effects in YAP/TAZ cellular distribution, and demonstrate its physiological roles in mammalian organ regeneration.

Description: There has been a relative reduction of tobacco consumption between Global Adult Tobacco Survey-India (GATS-India) 2009–10 and GATS-India 2016–17. However, in terms of absolute numbers, India still has the highest number of tobacco consumers. Therefore, this paper aims to examine the socioeconomic correlates and delineate the factors contributing to a change in smoking and smokeless tobacco use from GATS (2009–10) to GATS (2016–17) in India. We used multivariable binary logistic regressions to examine the demographic and socioeconomic correlates of smoking and smokeless tobacco use for both the rounds of the survey. Further decomposition analysis has been applied to examine the specific contribution of factors in the decline of tobacco consumption over a period from 2009 to 2016. Results indicated that the propensity component was primarily responsible for major tobacco consumption decline (smoking- 41%, smokeless tobacco use- 81%). Most of the decrease in propensity to smoke has been explained by residential type and occupation of the respondent. Age of the respondent contribute significantly in reducing the prevalence of smokeless tobacco consumption during the seven-year period, regardless of change in the composition of population. To achieve the National Health Policy, 2017 aim of reducing tobacco use up to 15% by 2020 and up to 30% by 2025, targeted policies and interventions addressing the inequalities identified in this study, must be developed and implemented.

Description: The objective of this study is to verify the feasibility of using biochar made from crop straw as a bitumen additive to improve some properties of bitumen. The differences between crop straw biochar prepared in a laboratory and commercial charcoal were investigated through scanning electron microscopy and laser particle size analyses. Furthermore, biochar-modified asphalt was prepared using the high-speed shear method, and the penetration, softening point, ductility at 15°C, and apparent viscosity of the asphalt binder with 6% biochar were measured at 120, 135, 150, 160, and 175°C. It was found that both the crop straw biochar and the commercial charcoal consist mainly of C, O, Si, and K, but the C content of crop straw biochar is slightly higher than that of commercial charcoal. The particle size of biochar is smaller than that of commercial charcoal, while the specific surface area is larger. It was determined that the addition of crop straw biochar significantly improved the high-temperature performance of asphalt, and that biochar and commercial charcoal have a similar influence on the high temperature performance of asphalt.

Description: The aim of this study was to investigate the effects of ankle and hip muscle fatigue on motor adjustments (experiment 1) and symmetry (experiment 2) of postural control during a quiet standing task. Twenty-three young adults performed a bipedal postural task on separate force platforms, before and after a bilateral ankle and hip muscle fatigue protocol (randomized). Ankle and hip muscles were fatigued separately using a standing calf raise protocol (ankle fatigue) on a step and flexion and extension of the hip (hip fatigue) sitting on a chair, at a controlled movement frequency (0.5Hz), respectively. In both experiments, force, center of pressure, and electromyography parameters were measured. The symmetry index was used in experiment 2 to analyze the postural asymmetry in the parameters. Our main findings showed that muscle fatigue impaired postural stability, regardless of the fatigued muscle region (i.e., ankle or hip). In addition, young adults used an ankle motor strategy (experiment 1) before and after both the ankle and hip muscle fatigue protocols. Moreover, we found increased asymmetry between the lower limbs (experiment 2) during the quiet standing task after muscle fatigue. Thus, we can conclude that the postural motor strategy is not muscle fatigue joint-dependent and a fatigue task increases postural asymmetry, regardless of the fatigued region (hip or ankle). These findings could be applied in sports training and rehabilitation programs with the objective of reducing the fatigue effects on asymmetry and improving balance.

Description: The prospect of utilizing CRISPR-based gene-drive technology for controlling populations has generated much excitement. However, the potential for spillovers of gene-drive alleles from the target population to non-target populations has raised concerns. Here, using mathematical models, we investigate the possibility of limiting spillovers to non-target populations by designing differential-targeting gene drives, in which the expected equilibrium gene-drive allele frequencies are high in the target population but low in the non-target population. We find that achieving differential targeting is possible with certain configurations of gene drive parameters, but, in most cases, only under relatively low migration rates between populations. Under high migration, differential targeting is possible only in a narrow region of the parameter space. Because fixation of the gene drive in the non-target population could severely disrupt ecosystems, we outline possible ways to avoid this outcome. We apply our model to two potential applications of gene drives—field trials for malaria-vector gene drives and control of invasive species on islands. We discuss theoretical predictions of key requirements for differential targeting and their practical implications.

Description: The human auditory system often relies on relative pitch information to extract and identify auditory objects; such as when the same melody is played in different keys. The current study investigated the mental chronometry underlying the active discrimination of unfamiliar melodic six-tone patterns by measuring behavioural performance and event-related potentials (ERPs). In a roving standard paradigm, such patterns were either repeated identically within a stimulus train, carrying absolute frequency information about the pattern, or shifted in pitch (transposed) between repetitions, so only relative pitch information was available to extract the pattern identity. Results showed that participants were able to use relative pitch to detect when a new melodic pattern occurred. Though in the absence of absolute pitch sensitivity significantly decreased and behavioural reaction time to pattern changes increased. Mismatch-Negativity (MMN), an ERP indicator of auditory deviance detection, was elicited at approximately 206 ms after stimulus onset at frontocentral electrodes, even when only relative pitch was available to inform pattern discrimination. A P3a was elicited in both conditions, comparable in amplitude and latency. Increased latencies but no differences in amplitudes of N2b, and P3b suggest that processing at higher levels is affected when, in the absence of absolute pitch cues, relative pitch has to be extracted to inform pattern discrimination. Interestingly, the response delay of approximately 70 ms on the behavioural level, already fully manifests at the level of N2b. This is in accordance with recent findings on implicit auditory learning processes and suggests that in the absence of absolute pitch cues a slowing of target selection rather than a slowing of the auditory pattern change detection process causes the deterioration in behavioural performance.

Description: Background Diabetes is one of the most prevalent non-communicable diseases globally, which rapidly is increasing in developing countries. Ethiopia is also facing growing morbidity and mortality related to diabetes complications. Thus, dealing with glycemic control is essential for controlling the development of devastating acute and chronic complications related to diabetes. Therefore, this study aims to assess the magnitude and predictors of poor glycemic control among diabetic patients in western Ethiopia. Methods The cross-sectional study design was employed on a sample of 423 diabetic patients. A systematic random sampling method was employed. An interviewer-administered structured questionnaire was used. The data entered into Epi data version 3.1 and exported into Statistical Package for the Social Sciences window version 24 for analysis. All variables significant at p-

Description: The first case of Coronavirus Disease 2019 in Italy was detected on February the 20th in Lombardy region. Since that date, Lombardy has been the most affected Italian region by the epidemic, and its healthcare system underwent a severe overload during the outbreak. From a public health point of view, therefore, it is fundamental to provide healthcare services with tools that can reveal possible new health system stress periods with a certain time anticipation, which is the main aim of the present study. Moreover, the sequence of law decrees to face the epidemic and the large amount of news generated in the population feelings of anxiety and suspicion. Considering this whole complex context, it is easily understandable how people “overcrowded” social media with messages dealing with the pandemic, and emergency numbers were overwhelmed by the calls. Thus, in order to find potential predictors of possible new health system overloads, we analysed data both from Twitter and emergency services comparing them to the daily infected time series at a regional level. Particularly, we performed a wavelet analysis in the time-frequency plane, to finely discriminate over time the anticipation capability of the considered potential predictors. In addition, a cross-correlation analysis has been performed to find a synthetic indicator of the time delay between the predictor and the infected time series. Our results show that Twitter data are more related to social and political dynamics, while the emergency calls trends can be further evaluated as a powerful tool to potentially forecast new stress periods. Since we analysed aggregated regional data, and taking into account also the huge geographical heterogeneity of the epidemic spread, a future perspective would be to conduct the same analysis on a more local basis.

Description: Background The long-term clinical and physiological consequences of COVID-19 infection remain unclear. While fatigue has emerged as a common symptom following infection, little is known about its links with autonomic dysfunction. SARS-CoV-2 is known to infect endothelial cells in acute infection, resulting in autonomic dysfunction. Here we set out to test the hypothesis that this results in persistent autonomic dysfunction and is associated with post-COVID fatigue in convalescent patients. Methods We recruited 20 fatigued and 20 non-fatigued post-COVID patients (median age 44.5 years, 36/40 (90%) female, median time to follow up 166.5 days). Fatigue was assessed using the Chalder Fatigue Scale. These underwent the Ewing’s autonomic function test battery, including deep breathing, active standing, Valsalva manoeuvre and cold-pressor testing, with continuous electrocardiogram and blood pressure monitoring, as well as near-infrared spectroscopy-based cerebral oxygenation. 24-hour ambulatory blood pressure monitoring was also conducted, and patients completed the generalised anxiety disorder-7 questionnaire. We assessed between-group differences in autonomic function test results and used unadjusted and adjusted linear regression to investigate the relationship between fatigue, anxiety, and autonomic test results. Results We found no pathological differences between fatigued and non-fatigued patients on autonomic testing or on 24-hour blood pressure monitoring. Symptoms of orthostatic intolerance were reported by 70% of the fatigued cohort at the time of active standing, with no associated physiological abnormality detected. Fatigue was strongly associated with increased anxiety (p

Description: Animal carcasses are often brought into tidal flats where they are at the boundary between terrestrial and marine ecosystems. Since these carcasses act as microhabitats with large amounts of energy and nutrients, they likely develop unique bacterial assemblages in the ambient sediment, which in turn may stimulate colonization of other organisms such as protozoans. However, little is known about the microbial assemblages colonized in sediment around animal carcasses in the tidal zone. Herein we examined the bacterial and ciliophoran assemblages developed in association with fish carcasses by incubating the carcasses in the Higashiyachi tidal flat (Sendai, Japan). We collected sediment samples at 2, 9, and 42 days of incubation and analyzed the bacterial and ciliophoran assemblages by 16S and 18S rRNA gene amplicon sequencing. We observed significant differences in the composition and relative abundance of bacterial and ciliophoran operational taxonomic units (OTUs) between the sediments with and without the carcasses. Our analyses suggest that these unique assemblages were created through the direct effects of the carcass and indirect effects through interactions between bacteria and ciliophorans. These results also suggest that animal carcasses developed a temporally unique microbial food web in the sediments close to the carcasses, although it disappeared for several weeks.

Description: The suppression of distracting information in order to focus on an actual cognitive goal is a key feature of executive functions. The use of brain imaging methods to investigate the underlying neurobiological brain activations that occur during conflict processing have demonstrated a strong involvement of the fronto-parietal attention network (FPAN). Surprisingly, the directional interconnections, their time courses and activations at different frequency bands remain to be elucidated, and thus, this constitutes the focus of this study. The shared information flow between brain areas of the FPAN is provided for frequency bands ranging from the theta to the lower gamma band (4–40 Hz). We employed an adaptation of the Simon task utilizing Magnetoencephalography (MEG). Granger causality was applied to investigate interconnections between the active brain regions, as well as their directionality. Following stimulus onset, the middle frontal precentral cortex and superior parietal cortex were significantly activated during conflict processing in a time window of between 300 to 600ms. Important differences in causality were found across frequency bands between processing of conflicting stimuli in the left as compared to the right visual hemifield. The exchange of information from and to the FPAN was most prominent in the beta band. Moreover, the anterior cingulate cortex and the anterior insula represented key areas for conflict monitoring, either by receiving input from other areas of the FPAN or by generating output themselves. This indicates that the salience network is at least partly involved in processing conflict information. The present study provides detailed insights into the underlying neural mechanisms of the FPAN, especially regarding its temporal characteristics and directional interconnections.

Description: Introduction Medicines used at Danish public hospitals are purchased through tendering. Together with drug shortage, tendering result in drug changes, known to compromise patient safety, increase medicine errors and to be resource demanding for healthcare personnel. Details on actual resources required in the clinic setting to manage drug changes are unknown. The aim of the study is to explore time spend by hospital personnel in a drug change situation when dispensing medicine to in- and outpatients in a hospital setting in the Capital Region of Denmark. Method A time and motion study, using direct observation combined with time-registration tools, such as eye-tracking, video recording and manual time tracking. Data were obtained from observing nurses and social and health care assistants with dispensing authority while dispensing or extraditing medicine before and after the implementation of drug changes in two clinical setting; a cardiology ward and a rheumatology outpatient clinic. Results Hospital personnel at the cardiology inpatient ward spent 20.5 seconds on dispensing a drug, which was increased up to 28.4 seconds by drug changes. At the rheumatology outpatient clinic, time to extradite medicine increased from 8 minutes and 6 seconds to 15 minutes and 36 seconds by drug changes due to tender. Similarly, drug changes due to drug shortage prolonged the extradition time to 16 minutes and 54 seconds. Statistical analysis reveal that drug changes impose a significant increase in time to dispense a drug for both in- and outpatients. Conclusion Clinical hospital personnel spent significantly longer time on drug change situations in the dispensing of medicine to in- and outpatients in a hospitals. This study emphasizes that implementing drug changes do require extra time, thus, the hospital management should encounter this and ensure that additional time is available for the hospital personnel to ensure a safe drug dispensing process.

Description: In Spanish causative constructions with dejar ‘let’ and hacer ‘make’ the subject of the embedded infinitive verb can appear in the accusative or the dative case. This case alternation has been accounted for by resorting to the notion of direct vs. indirect causation. Under this account, the accusative clitic with a transitive verb denotes direct causation while the dative clitic with an intransitive verb expresses indirect causation. The problem with this account is that we lack an independent definition of (in)direct causation in this context and so this approach suffers from circularity: the case of the clitic is used to determine causation type and causation type implies use of one or the other grammatical case. Therefore, a more objective way to account for clitic case alternation is needed. In this paper, I offer one possible solution in this direction by investigating clitic case alternation against Hopper and Thompson’s Transitivity parameters and a small number of other linguistic variables. The novelty of this approach is that I operationalise Transitivity as a weighted continuous measure (which I call the Transitivity Index) and use it to predict the case of the clitic. The results indicate that the transitivity of the infinitive verb, the animacy of the object and the agentivity of the subject are strong predictors of clitic case. Moreover, the Transitivity Index clearly shows that higher levels of Transitivity are associated with the dative clitic contrary to other contexts in which accusative is said to be more transitive. The findings in this paper allow us to arrive at a finer-grained characterization of the contexts in which each clitic case is more likely to occur and provide further evidence of the pervasiveness of Transitivity in natural language.

Description: Background After the Chernobyl accident on 26 April 1986, a drop in birth-rate was found in several European countries in the first quarter of 1987. The objective of the present study was to investigate whether a similar drop in live births occurred in Japan after the Fukushima nuclear accident. Data and methods A study region was defined consisting of Fukushima prefecture plus 10 nearby prefectures. The observed monthly numbers of live births (LB) in October 2011 through December 2012 were compared with the predicted numbers determined from the trend of live births in the remaining months from January 2006 through December 2018. The study region was divided into Fukushima plus three adjacent prefectures (Area A, assumed effective mean dose in the first year 1 mSv) and seven surrounding prefectures (Area B, 0.5 mSv). The rest of Japan (Area C) served as the comparison (control) region (0.1 mSv). A combined regression of live births (LB) in areas A, B, C was conducted with individual trend parameters but common parameters for monthly variations. Results In the study region as a whole (areas A and B combined) a highly significant 9.1% (95% CI: -12.2%, -6.0%) drop in LB was found in December 2011. Reduced numbers of live births were also observed in October-November 2011 (-3.3%, p = 0.006), i.e. in births exposed early in pregnancy. In the second quarter of 2012, i.e. in live births conceived more than 3 months after the Fukushima accident, the decrease was greater (-4.3%, p

Description: Background To suppress the COVID-19 outbreak, the Norwegian government closed all schools on March 13, 2020. The kindergartens reopened on April 20, and the schools on April 27 and May 11 of 2020. The effect of these measures is largely unknown since the role of children in the spread of the SARS-CoV-2 virus is still unclear. There are only a few studies of school closures as a separate intervention to other social distancing measures, and little research exists on the effect of school opening during a pandemic. Objective This study aimed to model the effect of opening kindergartens and the schools in Norway in terms of a change in the reproduction number (R). A secondary objective was to assess if we can use the estimated R after school openings to infer the rates of transmission between children in schools. Methods We used an individual-based model (IBM) to assess the reopening of kindergartens and schools in two Norwegian cities, Oslo, the Norwegian capital, with a population of approximately 680 000, and Tromsø, which is the largest city in Northern Norway, with a population of approximately 75 000. The model uses demographic information and detailed data about the schools in both cities. We carried out an ensemble study to obtain robust results in spite of the considerable uncertainty that remains about the transmission of SARS-CoV-2. Results We found that reopening of Norwegian kindergartens and schools are associated with a change in R of 0.10 (95%CI 0.04–0.16) and 0.14 (95%CI 0.01–0.25) in the two cities under investigation if the in-school transmission rates for the SARS-CoV-2 virus are equal to what has previously been estimated for influenza pandemics. Conclusion We found only a limited effect of reopening schools on the reproduction number, and we expect the same to hold true in other countries where nonpharmaceutical interventions have suppressed the pandemic. Consequently, current R-estimates are insufficiently accurate for determining the transmission rates in schools. For countries that have closed schools, planned interventions, such as the opening of selected schools, can be useful to infer general knowledge about children-to-children transmission of SARS-CoV-2.

Description: Alginates gel rapidly under ambient conditions and have widely documented potential to form protective matrices for sensitive bioactive cargo. Most commonly, alginate gelation occurs via calcium mediated electrostatic crosslinks between the linear polyuronic acid polymers. A recent breakthrough to form crosslinked alginate microcapsules (CLAMs) by in situ gelation during spray drying (“CLAMs process”) has demonstrated applications in protection and controlled delivery of bioactives in food, cosmetics, and agriculture. The extent of crosslinking of alginates in CLAMs impacts the effectiveness of its barrier properties. For example, higher crosslinking extents can improve oxidative stability and limit diffusion of the encapsulated cargo. Crosslinking in CLAMs can be controlled by varying the calcium to alginate ratio; however, the choice of alginates used in the process also influences the ultimate extent of crosslinking. To understand how to select alginates to target crosslinking in CLAMs, we examined the roles of alginate molecular properties. A surprise finding was the formation of alginic acid gelling in the CLAMs that is a consequence of simultaneous and rapid pH reduction and moisture removal that occurs during spray drying. Thus, spray dried CLAMs gelation is due to calcium crosslinking and alginic acid formation, and unlike external gelation methods, is insensitive to the molecular composition of the alginates. The ‘extent of gelation’ of spray dried CLAMs is influenced by the molecular weights of the alginates at saturating calcium concentrations. Alginate viscosity correlates with molecular weight; thus, viscosity is a convenient criterion for selecting commercial alginates to target gelation extent in CLAMs.

Description: The hepatopulmonary syndrome (HPS) is defined by the presence of pulmonary gas exchange abnormalities due to intrapulmonary vascular dilatations in patients with chronic liver disease. Changes in DNA methylation reflect the genomic variation. Since liver transplant (LT) reverts HPS we hypothesized that it may be associated with specific liver epigenetic changes. Thus, the aim of this study was to investigate the role of the liver epigenome in patients with HPS. We extracted DNA from paraffin embedded liver tissue samples from 10 patients with HPS and 10 age-, sex- and MELD (Model for End-stage Liver Disease)-matched controls. DNA methylation was determined using the 850K array (Illumina). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules related to defining physiologic characteristics of HPS. Only 12 out of the 20 liver biopsies (7 HPS and 5 controls) had sufficient quality to be analyzed. None of the 802,688 DNA probes analyzed in the case control comparison achieved a significant False Discovery Rate (FDR). WGCNA identified 5 co-methylated gene-modules associated to HPS markers, mainly related to nervous and neuroendocrine system, apoptotic processes, gut bacterial translocation, angiogenesis and vascular remodeling ontologies. To conclude, HPS is associated with nervous/neuroendocrine system and vascular remodeling related liver epigenetic changes.

Description: Workflow management systems represent, manage, and execute multistep computational analyses and offer many benefits to bioinformaticians. They provide a common language for describing analysis workflows, contributing to reproducibility and to building libraries of reusable components. They can support both incremental build and re-entrancy—the ability to selectively re-execute parts of a workflow in the presence of additional inputs or changes in configuration and to resume execution from where a workflow previously stopped. Many workflow management systems enhance portability by supporting the use of containers, high-performance computing (HPC) systems, and clouds. Most importantly, workflow management systems allow bioinformaticians to delegate how their workflows are run to the workflow management system and its developers. This frees the bioinformaticians to focus on what these workflows should do, on their data analyses, and on their science. RiboViz is a package to extract biological insight from ribosome profiling data to help advance understanding of protein synthesis. At the heart of RiboViz is an analysis workflow, implemented in a Python script. To conform to best practices for scientific computing which recommend the use of build tools to automate workflows and to reuse code instead of rewriting it, the authors reimplemented this workflow within a workflow management system. To select a workflow management system, a rapid survey of available systems was undertaken, and candidates were shortlisted: Snakemake, cwltool, Toil, and Nextflow. Each candidate was evaluated by quickly prototyping a subset of the RiboViz workflow, and Nextflow was chosen. The selection process took 10 person-days, a small cost for the assurance that Nextflow satisfied the authors’ requirements. The use of prototyping can offer a low-cost way of making a more informed selection of software to use within projects, rather than relying solely upon reviews and recommendations by others.

Description: Although most fatalities in tsunami-related disasters are conjectured to be a result of drowning, injury risk owing to collision with other floating debris or fixed buildings has not been studied sufficiently. In this study, the impact force corresponding to the collision of a concrete block and drifting test body in a tsunami wave was experimentally investigated, and the injury risk was evaluated in terms of different biomechanical indexes; specifically, maximum acceleration, head injury criterion, and impact force. The injury risk indicated by the considered indexes was reasonably low. It was noted that if a healthy adult collided with a concrete wall under a velocity of 2.5 m s-1 and wave height of 0.59 m, the adult would likely not be critically injured. However, a similar collision impact poses considerable risk to infants and children, as well as the more sensitive regions of the adult body. Moreover, in the case of large tsunamis, such as that in the 2011 Great East Japan Earthquake, a drifting person may be at considerable risk for injuries. The collision impact occurring on the tip of a surge flow is notably significantly larger than that on a bore flow. This is because a surge flow, which arrives at the concrete block earlier than a bore flow, forms a certain water layer along the concrete wall and that layer acts as a cushion for any body drifting on the bore flow, indicating the importance of such a buffering effect. These findings can provide practical guidance regarding the formulation of effective tsunami-protection measures.

Description: The aim of the study is to evaluate the progression of visual field (VF) defects over 16 years of observation and to assess abnormalities in vessels and retinal nerve fibre layer (RNFL) thickness in patients with optic disc drusen (ODD). Both static automated perimetry (SAP) and semi-automated kinetic perimetry (SKP) were performed in 16 eyes of 8 patients (mean age 54 years) with ODD among 26 eyes of 13 patients examined 16 years before. The area of I2e, I4e, III4e, and V4e isopters was measured in deg2. The MD and PSD parameters were estimated using SAP. Optical coherence tomography angiography (OCT-A) was additionally performed in 16 ODD eyes and 16 eyes of 8 healthy subjects to estimate the RNFL thickness and vessel density of the optic nerve disc and the macula. The differences in all isopter areas of SKP and SAP parameters after 16 years were not significant. The analysis of OCT-A showed a significant reduction of the vessel density and RNFL of the peripapillary area in each segment in patients with ODD, compared with the control group. The highest reduction of RNFL was observed in the superior segment of the optic disc area (92.56μm vs 126.63μm) also the macular thickness was decreased in ODD patients, compared with the control group. In the macula, there was a significant vascular defect in the whole superficial layer and in the parafoveal deep layer. A strong significant correlation of the parafoveal deep plexus with MD and PSD parameters was detected. In conclusion, VF loss due to ODD after 16 years of the follow-up was not significant both in SKP and SAP. ODD caused a reduced vessel density and RNFL, as well as macular thickness in OCT-A. SAP parameters were influenced by parafoveal deep plexus.

Description: Genome-wide association studies (GWASs) have identified multiple susceptibility loci for Alzheimer’s disease (AD), which is characterized by early and progressive damage to the hippocampus. However, the association of hippocampal gene expression with AD and the underlying neurobiological pathways remain largely unknown. Based on the genomic and transcriptomic data of 111 hippocampal samples and the summary data of two large-scale meta-analyses of GWASs, a transcriptome-wide association study (TWAS) was performed to identify genes with significant associations between hippocampal expression and AD. We identified 54 significantly associated genes using an AD-GWAS meta-analysis of 455,258 individuals; 36 of the genes were confirmed in another AD-GWAS meta-analysis of 63,926 individuals. Fine-mapping models further prioritized 24 AD-related genes whose effects on AD were mediated by hippocampal expression, including APOE and two novel genes (PTPN9 and PCDHA4). These genes are functionally related to amyloid-beta formation, phosphorylation/dephosphorylation, neuronal apoptosis, neurogenesis and telomerase-related processes. By integrating the predicted hippocampal expression and neuroimaging data, we found that the hippocampal expression of QPCTL and ERCC2 showed significant difference between AD patients and cognitively normal elderly individuals as well as correlated with hippocampal volume. Mediation analysis further demonstrated that hippocampal volume mediated the effect of hippocampal gene expression (QPCTL and ERCC2) on AD. This study identifies two novel genes associated with AD by integrating hippocampal gene expression and genome-wide association data and reveals candidate hippocampus-mediated neurobiological pathways from gene expression to AD.

Description: Athletes undergoing energy restriction for weight/fat reduction sometimes apply ‘diet breaks’ involving increased energy intake, but there is little empirical evidence of effects on outcomes. Twenty-six resistance-trained athletes (11/26 or 42% female) who had completed 12 weeks of intermittent energy restriction participated in this study. Participants had a mean (SD) age of 29.3 (6.4) years, a weight of 72.7 (15.9) kg, and a body fat percentage of 21.3 (7.5) %. During the 1-week diet break, energy intake was increased (by means of increased carbohydrate intake) to predicted weight maintenance requirements. While the 1-week diet break had no significant effect on fat mass, it led to small but significant increases in mean body weight (0.6 kg, P

Description: Sugi (Cryptomeria japonica D. Don) is an important conifer used for afforestation in Japan. As the genome of this species is 11 Gbps, it is too large to assemble within a short timeframe. Transcriptomics is one approach that can address this deficiency. Here we designed a workflow consisting of three stages to de novo assemble transcriptome using Oases and Trinity. The three transcriptomic stage used were independent assembly, automatic and semi-manual integration, and refinement by filtering out potential contamination. We identified a set of 49,795 cDNA and an equal number of translated proteins. According to the benchmark set by BUSCO, 87.01% of cDNAs identified were complete genes, and 78.47% were complete and single-copy genes. Compared to other full-length cDNA resources collected by Sanger and PacBio sequencers, the extent of the coverage in our dataset was the highest, indicating that these data can be safely used for further studies. When two tissue-specific libraries were compared, there were significant expression differences between male strobili and leaf and bark sets. Moreover, subtle expression difference between male-fertile and sterile libraries were detected. Orthologous genes from other model plants and conifer species were identified. We demonstrated that our transcriptome assembly output (CJ3006NRE) can serve as a reference transcriptome for future functional genomics and evolutionary biology studies.

Description: Background Understanding patients’ trust in health information sources is critical to designing work systems in healthcare. Patient-centered communication during the visit might be a major factor in shaping patients’ trust in information sources. Objective The purpose of this paper is to explore relationships between patient ratings of clinician communication during the visit and patient trust in health information sources. Methodology We conducted a secondary analysis of the nationally-representative Health Information National Trends Surveys; HINTS4 Cycle1 (2011), HINTS4 Cycle4 (2014), and HINTS5 Cycle1 (2017), and HINTS5 Cycle2 (2018). We created a composite score of patient-centered communication from five questions and dichotomized at the median. We created multivariable logistic regression models to see how patient-centered communication influenced trust in different information sources across cycles. Consecutively, we used hierarchical analysis for aggregated data. Results We analyzed data from 14,425 individuals. In the adjusted logistic models for each cycle and the hierarchical model, clinicians’ perceived patient-centered communication skills were significantly associated with increased trust in the clinicians as an information source. Conclusion Clinicians still represent an essential source of trustworthy information reinforced by patient-centered communication skills. Given that trust helps build healing relationships that lead to better healthcare outcomes, communication sets an essential foundation to establish necessary trust. Interpreting information from the internet sources for patients is likely to remain a vital clinician function.

Description: Rice (Oryza sativa L.) feeds to two-third of the global population by serving as staple food. It is the main export commodity of several countries; thus, contributes towards foreign exchange earnings. Unfortunately, average global rice yield is far below than its genetic potential. Low nitrogen (N) use efficiency (NUE) is among the major reasons for low average yield. Current study evaluated the impact of nitrogen fertilizer application methods (conventional and deep placement) on growth, yield-related traits, chlorophyll contents, photosynthesis rate, agronomic N-use efficiency (ANUE), partial factors productivity of applied N (PFP) and economic returns of two different transplanted rice varieties (Basmati-515 and Super-Basmati). Fertilizer application methods significantly affected allometry, yield-related traits, chlorophyll contents, photosynthesis rate, ANUE, PFP and economic returns. Deep placement of N-fertilizer (DPNF) observed better allometric traits, high chlorophyll contents, photosynthesis rate, ANUE, PFP, yield attributes and economic returns compared to conventional application of N-fertilizer (CANF). Similarly, Basmati-515 had better allometric and yield-related traits, chlorophyll contents, photosynthesis rate, ANUE, PFP and economic returns than Super-Basmati. Regarding interactions among N-fertilizer application methods and rice varieties, Basmati-515 with DPNF resulted in higher chlorophyll contents, photosynthesis rate, ANUE, PFP, allometric and yield related traits and economic returns than CANF. The lowest values of these traits were observed for Super-Basmati with no application of N-fertilizer. Both varieties had better yield and economic returns with DPNF compared to CANF. It is concluded that DPNF improved yield, ANUE and economic returns; therefore, should be opted to improve productivity of transplanted fine rice. Nonetheless, lower nitrogen doses need to be tested for DPNF to infer whether it could lower N use in rice crop.

Description: Identifying barriers and facilitators in HIV-indicator reporting contributes to strengthening HIV monitoring and evaluation efforts by acknowledging contributors to success, as well as identifying weaknesses within the system that require improvement. Nonetheless, there is paucity in identifying and comparing barriers and facilitators in HIV-indicator data reporting among facilities that perform well and those that perform poorly at meeting reporting completeness and timeliness requirements. Therefore, this study aims to use a qualitative approach in identifying and comparing the current state of barriers and facilitators in routine reporting of HIV-indicators by facilities performing well, and those performing poorly in meeting facility reporting completeness and timeliness requirements to District Health Information Software2 (DHIS2). A multiple qualitative case study design was employed. The criteria for case selection was based on performance in HIV-indicator facility reporting completeness and timeliness. Areas of interest revolved around reporting procedures, organizational, behavioral, and technical factors. Purposive sampling was used to identify key informants in the study. Data was collected using semi-structured in-depth interviews with 13 participants, and included archival records on facility reporting performance, looking into documentation, and informal direct observation at 13 facilities in Kenya. Findings revealed that facilitators and barriers in reporting emerged from the following factors: interrelationship between workload, teamwork and skilled personnel, role of an EMRs system in reporting, time constraints, availability and access-rights to DHIS2, complexity of reports, staff rotation, availability of trainings and mentorship, motivation, availability of standard operating procedures and resources. There was less variation in barriers and facilitators faced by facilities performing well and those performing poorly. Continuous evaluations have been advocated within health information systems literature. Therefore, continuous qualitative assessments are also necessary in order to determine improvements and recurring of similar issues. These assessments have also complemented other quantitative analyses related to this study.

Description: EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees & Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1–12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 μM, similar to positive control benznidazole (18.7 μM). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 μM, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi.