ALBERT

Description: Objectives N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. Methods Baseline data of 4598 participants aged 45–75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. Results With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. Conclusions In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.

Description: The maned wolf (Chrysocyon brachyurus) is an induced ovulator. Though the mechanism of ovulation induction remains unknown, it is suspected to be urinary chemical signals excreted by males. This study assessed volatile organic compounds (VOCs) in weekly urine samples across 5 months from 13 maned wolves (6 intact males, 1 neutered male, 6 females) with the goal of identifying VOCs that are differentially expressed across sex, reproductive status, and pairing status. Solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) were used to extract and separate VOCs that were identified via spectral matching with authentic standards, with spectral libraries, or with new software that further matches molecular fragment structures with mass spectral peaks. Two VOCs were present across all 317 urine samples: 2,5-dimethyl pyrazine and 2-methyl-6-(1-propenyl)-pyrazine. Fifteen VOCs differed significantly (Adj. P 〈 0.001 and |log2 fold change| 〉2.0) between intact males and females. Using partial least squares-discriminant analysis, the compounds with the highest importance to the sex classification were delta-decalactone, delta-dodecalactone, and bis(prenyl) sulfide. Sixty-two VOCs differed between intact males and the neutered male. Important classifier compounds were 3-ethyl 2,5-dimethyl pyrazine, 2-methyl-6-(1-propenyl)-pyrazine, and tetrahydro-2-isopentyl-5-propyl furan. Several VOCs established as important here have been implicated in reproductive communication in other mammals. This study is the most robust examination of differential expression in the maned wolf thus far and provides the most comprehensive analysis of maned wolf urinary VOCs to date, increasing the sample size substantially over previous chemical communication studies in this species. New data analysis software allowed for the identification of compounds in the hormone-producing mevalonate pathway which were previously unreported in maned wolf urine. Several putative semiochemicals were identified as good candidates for behavioral bioassays to determine their role in maned wolf reproduction, and specifically in ovulation induction.

Description: Background Patients admitted to intensive care units (ICU) are at an increased risk of developing immobility related complications. Physiotherapists are challenged to employ preventive and rehabilitative strategies to combat these effects. Passive limb range of motion (PROM) exercises- a part of early mobilization-aid in maintaining joint range of motion and functional muscle strength and forms a part of treatment for patients in ICU. However, there is a lack of evidence on practice of PROM exercises on patients admitted to ICU in the United Arab Emirates (UAE). This study aimed at exploring practices regarding the same in UAE. Methods This survey, conducted from January 2021 to February 2021 in College of Physiotherapy, Sharjah University studied practice of physiotherapists in the intensive care units. Physiotherapists currently working in ICU completed an online questionnaire composed of forty-two questions about physiotherapy service provision, assessment and intervention in the intensive care units. Results 33 physiotherapists completed the survey. 66.6% of respondents routinely assessed PROM for all the patients in ICU referred for physiotherapy. 84.8% of them assessed all the joints. More than half of the respondents (57.8%) reported that they administered PROM regularly to all the patients. According to 63.6% respondents, maintaining joint range of motion was the main reason for performing PROM. Responses pertaining to sets and repetitions of PROM were variable ranging from 1–6 sets and from 3 to 30 repetitions. Personal experience, resources/financial consideration and research findings were found to have influence on the practice. Conclusions PROM was found to be one of the frequently used mobilization techniques administered by physiotherapists in the intensive care units and was mostly performed after assessment. Maintaining joint range of motion was the main aim for performing PROM. Variability was found in the sets and repetitions of PROM administered. Various factors influenced the practice of PROM.

Description: The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p

Description: Objectives N-benzoyl-DL-arginine peptidase (trypsin-like peptidase) is specifically produced by certain strains of periodontitis-associated bacteria. We aimed to examine the effectiveness of an objectively quantified trypsin-like peptidase activity assay (TLP-AA) for detecting severe periodontitis. Methods The study population included 347 adults (108 men and 239 women; average age, 43.3 years) who underwent a full-mouth periodontal examination. Specimens for the TLP-AA were obtained using tongue swabs. Using a color reader, the TLP-AA results were obtained as a* values, with higher positive a* values indicating an increased intense enzymatic activity. The predictive validity of the TLP-AA results for severe periodontitis was assessed using receiver operating characteristic curve analysis and the periodontitis case definition provided by the Centers for Disease Control and Prevention/American Academy of Periodontology as the gold standard. Furthermore, multivariable logistic regression analyses were performed to predict severe periodontitis using the TLP-AA results and health characteristics, as the exposure variables. Results Severe periodontitis was observed in 5.2% of the participants. TLP-AA had high diagnostic accuracy for severe periodontitis, with an area under the curve of 0.83 (95% confidence interval [CI]: 0.75–0.92). The cut-off score for the a* value that best differentiated individuals with severe periodontitis was 0.09, with a sensitivity of 83% and specificity of 77%. Multivariable logistic regression analyses revealed that the TLP-AA results were significantly associated with severe periodontitis after adjusting for health characteristics (adjusted odds ratios: 1.90 [95% CI: 1.37–2.62] for the a* value). Conclusions Objectively quantified TLP-AA results are potentially useful for detecting severe periodontitis in epidemiological surveillance.

Description: Introduction Suicidality is a risk of a person committing suicide often characterized by suicidal ideation, intent or attempts. Despite the high burden of suicidality among individuals living with HIV and HAIDS, there is paucity of data on the impact of suicidality on clinical (such as CD4 counts and HIV disease progression) and behavioural outcomes (such as adherence to HIV Medications). Cross-sectional investigations of these associations are often complicated by bidirectional causal relationships and hence the need for longitudinal study designs. We conducted a cohort study to determine the impact of suicidality on clinical and behavioural outcomes among adults living with HIV/AIDS in Uganda. Materials and methods We conducted the study among 1099 ART naïve adults living with HIV/AIDS in Uganda. Data were collected at three time points: baseline, 6 and 12 months. Multiple regression and discrete time survival models were used to determine the relationship between suicidality and indices of HIV outcomes. Results Majority of the participants were female and the participant mean age was 35 years. Most of them (73%) had primary or no formal education. The proportion of participants with suicidality decreased from 2.9% at baseline to roughly 1% both at month 6 and month 12. Of the investigated clinical and behavioural outcomes, baseline suicidality only had a negative impact on missing a dose of ART where the odds of missing a dose of ART were 8.25 (95% CI 2.45–27.71, p〉0.01) times higher for participants with suicidality compared to those without suicidality. The following outcomes were not significantly impacted by baseline suicidality: HIV clinical stage, CD4 count and risky sexual behaviour. Conclusions The fact that baseline suicidality significantly negatively impacted ART adherence calls for the incorporation of psychosocial interventions to target indices of psychological distress such as suicidality to improve HIV related outcomes.

Description: Background The COVID-19 vaccination campaign in the US has been immensely successful in vaccinating those who are receptive, further increases in vaccination rates however will require more innovative approaches to reach those who remain hesitant. Developing vaccination strategies that are modelled on what people want could further increase uptake. Methods and findings To inform COVID-19 vaccine distribution strategies that are aligned with public preferences we conducted a discrete choice experiment among the US public (N = 2,895) between March 15 to March 22, 2021. We applied sampling weights, evaluated mean preferences using mixed logit models, and identified latent class preference subgroups. On average, the public prioritized ease, preferring single to two dose vaccinations (mean preference: -0.29; 95%CI: -0.37 to -0.20), vaccinating once rather than annually (mean preference: -0.79; 95%CI: -0.89 to -0.70) and reducing waiting times at vaccination sites. Vaccine enforcement reduced overall vaccine acceptance (mean preference -0.20; 95%CI: -0.30 to -0.10), with a trend of increasing resistance to enforcement with increasing vaccine hesitancy. Latent class analysis identified four distinct preference phenotypes: the first prioritized inherent “vaccine features” (46.1%), the second were concerned about vaccine “service delivery” (8.8%), a third group desired “social proof” of vaccine safety and were susceptible to enforcement (13.2%), and the fourth group were “indifferent” to vaccine and service delivery features and resisted enforcement (31.9%). Conclusions This study identifies several critical insights for the COVID-19 public health response. First, identifying preference segments is essential to ensure that vaccination services meet the needs of diverse population subgroups. Second, making vaccination easy and promoting autonomy by simplifying services and offering the public choices (where feasible) may increase uptake in those who remain deliberative. And, third vaccine mandates have the potential to increase vaccination rates in susceptible groups but may simultaneously promote control aversion and resistance in those who are most hesitant.

Description: Introduction The single-leg heel raise test (SLHR) is commonly used in clinical settings to approximate plantar flexor strength, yet this is neither validated nor supported physiologically. The purposes of this study were to: determine (1) associations between SLHR repetitions, maximal plantar flexor strength, and reductions in strength; and (2) whether sex differences exist in performance of the SLHR. Methods Twenty-eight young, healthy participants (14 males,14 females, 19–30 years) performed repeated single-leg heel raises to task failure. Pre- and post-task measures included maximal voluntary isometric contractions (MVIC), and voluntary activation and contractile properties of the plantar flexor muscles, assessed using peripheral electrical stimulation of the tibial nerve. Surface electromyography was recorded for the medial and lateral gastrocnemius, soleus, and anterior tibialis muscles. Results The SLHR resulted in 20.5% reductions in MVIC torque (p

Description: Stream temperature science and management is rapidly shifting from single-metric driven approaches to multi-metric, thermal regime characterizations of streamscapes. Given considerable investments in recovery of cold-water fisheries (e.g., Pacific salmon and other declining native species), understanding where cold water is likely to persist, and how cold-water thermal regimes vary, is critical for conservation. California’s unique position at the southern end of cold-water ecosystems in the northern hemisphere, variable geography and hydrology, and extensive flow regulation requires a systematic approach to thermal regime classification. We used publicly available, long-term (〉 8 years) stream temperature data from 77 sites across California to model their thermal regimes, calculate three temperature metrics, and use the metrics to classify each regime with an agglomerative nesting algorithm. Then, we assessed the variation in each class and considered underlying physical or anthropogenic factors that could explain differences between classes. Finally, we considered how different classes might fit existing criteria for cool- or cold-water thermal regimes, and how those differences complicate efforts to manage stream temperature through regulation. Our results demonstrate that cool- and cold-water thermal regimes vary spatially across California. Several salient findings emerge from this study. Groundwater-dominated streams are a ubiquitous, but as yet, poorly explored class of thermal regimes. Further, flow regulation below dams imposes serial discontinuities, including artificial thermal regimes on downstream ecosystems. Finally, and contrary to what is often assumed, California reservoirs do not contain sufficient cold-water storage to replicate desirable, reach-scale thermal regimes. While barriers to cold-water conservation are considerable and the trajectory of cold-water species towards extinction is dire, protecting reaches that demonstrate resilience to climate warming remains worthwhile.

Description: This paper investigated the appropriate specifications of Engel curves for non-food expenditure categories and estimated the deprivation indices of non-food needs in rural areas using a semi parametric examination of the presence of saturation points. The study used the extended partial linear model (EPLM) and adopted two estimation methods—the double residual estimator and differencing estimator—to obtain flexible shapes across different expenditure categories and estimate equivalence scales. We drew on data of the Egyptian Household Income, Expenditure, and Consumption Survey (HIEC). Our paper provides empirical evidence that the rankings of most non-food expenditure categories is of rank three at most. Rural households showed high economies of scale in non-food consumption, with child’s needs accounting for only 10% of adult’s non-food needs. Based on semi-parametrically estimated consumption behavior, the tendency of non-food expenditure categories to saturate did not emerge. While based on parametrically estimated consumption behavior, rural areas exhibited higher deprivation indices in terms of health and education expenditure categories, which indicates the need to design specific programs economically targeting such vulnerable households.

Description: Menzerath’s law is a quantitative linguistic law which states that, on average, the longer is a linguistic construct, the shorter are its constituents. In contrast, Menzerath-Altmann’s law (MAL) is a precise mathematical power-law-exponential formula which expresses the expected length of the linguistic construct conditioned on the number of its constituents. In this paper, we investigate the anatomy of MAL for constructs being word tokens and constituents being syllables, measuring its length in graphemes. First, we derive the exact form of MAL for texts generated by the memoryless source with three emitted symbols, which can be interpreted as a monkey typing model or a null model. We show that this null model complies with Menzerath’s law, revealing that Menzerath’s law itself can hardly be a criterion of complexity in communication. This observation does not apply to the more precise Menzerath-Altmann’s law, which predicts an inverted regime for sufficiently range constructs, i.e., the longer is a word, the longer are its syllables. To support this claim, we analyze MAL on data from 21 languages, consisting of texts from the Standardized Project Gutenberg. We show the presence of the inverted regime, not exhibited by the null model, and we demonstrate robustness of our results. We also report the complicated distribution of syllable sizes with respect to their position in the word, which might be related with the emerging MAL. Altogether, our results indicate that Menzerath’s law—in terms of correlations—is a spurious observation, while complex patterns and efficiency dynamics should be rather attributed to specific forms of Menzerath-Altmann’s law.

Description: Temperate grassland soils store significant amounts of carbon (C). Estimating how much livestock grazing and manuring can influence grassland soil organic carbon (SOC) is key to improve greenhouse gas grassland budgets. The Rothamsted Carbon (RothC) model, although originally developed and parameterized to model the turnover of organic C in arable topsoil, has been widely used, with varied success, to estimate SOC changes in grassland under different climates, soils, and management conditions. In this paper, we hypothesise that RothC-based SOC predictions in managed grasslands under temperate moist climatic conditions can be improved by incorporating small modifications to the model based on existing field data from diverse experimental locations in Europe. For this, we described and evaluated changes at the level of: (1) the soil water function of RothC, (2) entry pools accounting for the degradability of the exogenous organic matter (EOM) applied (e.g., ruminant excreta), (3) the month-on-month change in the quality of C inputs coming from plant residues (i.e above-, below-ground plant residue and rhizodeposits), and (4) the livestock trampling effect (i.e., poaching damage) as a common problem in areas with higher annual precipitation. In order to evaluate the potential utility of these changes, we performed a simple sensitivity analysis and tested the model predictions against averaged data from four grassland experiments in Europe. Our evaluation showed that the default model’s performance was 78% and whereas some of the modifications seemed to improve RothC SOC predictions (model performance of 95% and 86% for soil water function and plant residues, respectively), others did not lead to any/or almost any improvement (model performance of 80 and 46% for the change in the C input quality and livestock trampling, respectively). We concluded that, whereas adding more complexity to the RothC model by adding the livestock trampling would actually not improve the model, adding the modified soil water function and plant residue components, and at a lesser extent residues quality, could improve predictability of the RothC in managed grasslands under temperate moist climatic conditions.

Description: The success of unmanned car, an emerging tool of transportation with so many advantages, depends to a large extent on its user acceptability. Potential designers are both the decision makers of driverless car design and the users of driverless cars. This study aims to explore the influencing factors of the potential designers’ intention to use unmanned cars. Based on the theory of Technology Acceptance Model (TAM), this study further expanded the TAM by incorporating perceived trust, perceived enjoyment and self-efficacy, so as to explain and predict potential designers’ intention to use unmanned cars. The questionnaire is determined through theoretical literature, pre-tests, etc., and the Structural Equation Model is used to analyze the data of 202 valid survey samples to investigate the influencing factors of the willingness to use unmanned vehicles. The results show that potential designers’ intention to use unmanned cars is positively affected by perceived trust, perceived enjoyment, perceived usefulness and perceived ease of use, and perceived trust has a positive effect on perceived ease of use, self-efficacy and perceived ease of use also have a positive effect on perceived usefulness. The findings of this study can provide designers and developers of unmanned cars, policy makers and implementers with guidance in the follow-up design, policy formulation and advertising of unmanned cars.

Description: Global value chains are formed through value-added trade, and some regions promote economic integration by concluding regional trade agreements to promote these chains. However, it has not been established to quantitatively assess the scope and extent of economic integration involving various sectors in multiple countries. In this study, we used the World Input–Output Database to create a cross-border sector-wise network of trade in value-added (international value-added network) covering the period of 2000–2014 and evaluated them using network science methods. By applying Infomap to the international value-added network, we confirmed two regional communities: Europe and the Pacific Rim. We applied Helmholtz–Hodge decomposition to the value-added flows within the region into potential and circular flows, and clarified the annual evolution of the potential and circular relationships between countries and sectors. The circular flow component of the decomposition was used to define an economic integration index. Findings confirmed that the degree of economic integration in Europe declined sharply after the economic crisis in 2009 to a level lower than that in the Pacific Rim. The European economic integration index recovered in 2011 but again fell below that of the Pacific Rim in 2013. Moreover, sectoral economic integration indices suggest what Europe depends on Russia in natural resources makes the European economic integration index unstable. On the other hand, the indices of the Pacific Rim suggest the steady economic integration index of the Pacific Rim captures the stable global value chains from natural resources to construction and manufactures of motor vehicles and high-tech products.

Description: Background COPD and asthma exacerbations result in many emergency department admissions. Not all treatments are successful, often leading to hospital readmissions. Aims We sought to develop predictive models for exacerbation treatment outcome in a cohort of exacerbating asthma and COPD patients presenting to the emergency department. Methods Treatment failure was defined as the need for additional systemic corticosteroids (SCS) and/or antibiotics, hospital readmissison or death within 30 days of initial emergency department visit. We performed univariate analysis comparing characteristics of patients either given or not given SCS at exacerbation and of patients who succeeded versus failed treatment. Patient demographics, medications and exacerbation symptoms, physiology and biology were available. We developed multivariate random forest models to identify predictors of SCS prescription and for predicting treatment failure. Results Data were available for 81 patients, 43 (53%) of whom failed treatment. 64 (79%) of patients were given SCS. A random forest model using presence of wheeze at exacerbation and blood eosinophil percentage predicted SCS prescription with area under receiver operating characteristic curve (AUC) 0.69. An 11 variable random forest model (which included medication, previous exacerbations, symptoms and quality of life scores) could predict treatment failure with AUC 0.81. A random forest model using just the two best predictors of treatment failure, namely, visual analogue scale for breathlessness and sputum purulence, predicted treatment failure with AUC 0.68. Conclusion Prediction of exacerbation treatment outcome can be achieved via supervised machine learning combining different predictors at exacerbation. Validation of our predictive models in separate, larger patient cohorts is required.

Description: Introduction The concept of death is abstract, complex and has a number of meanings. Thus, its understanding and the approach taken to it depend, to a large extent, on aspects such as age, culture, training and religion. Nursing students have regular contact with the process of death and so it is of great interest to understand the attitudes they have towards it. As we live in a plural society it is even more interesting to not only understand the attitudes of Spanish students but, also, those of students coming from other countries. In the present article, we seek to identify and compare the attitudes held by nursing degree students at Hekima-Santé University (Senegal) and the University of Huelva (Spain) about end of life processes. The study identifies elements that condition attitudes and coping with death, whilst considering curricular differences with regards to specific end of life training. Method A descriptive, cross-sectional and multi-center study was conducted. The overall sample (N = 142) was divided into groups: Hekima-Santé University (Dakar, Senegal) and the University of Huelva (Huelva, Spain). The measurement instruments used were an ad-hoc questionnaire and Bugen´s Coping with Death Scale. Results Statistically significant differences (p = 0.005, 95%CI) were found in relation to overall Bugen Scale scores. We can confirm that specialized end of life training (University of Huelva, Spain) did not lead to better coping when compared with a population whose academic curriculum did not provide specific training and who engaged in more religious practices (Hekima-Santé University, Senegal). Conclusions In cultures where religion not only influences the spiritual dimension of the individual, but acts in the ethical and moral system and consequently in the economic, educational and family sphere, the accompaniment at the end of life transcends the formative plane. Considering the plural society in which we live, the training that integrates the Degree in Nursing with regard to the care of the final process, must be multidimensional in which spirituality and faith are integrated, working emotional and attentional skills, as well as cultural competence strategies in this process.

Description: Introduction Absenteeism of frontline health workers in public sector facilities is widespread in low-income countries. There is little quantitative evidence on how health worker absenteeism influences patient treatment seeking behavior, though low public sector utilization and heavy reliance on the informal sector are well documented in low-income settings. Methods Using a unique panel dataset covering health facilities and households over a 10-month period in Uganda, we investigate the extent to which health worker absenteeism (defined as zero health workers present at a health facility) impacts patient care seeking behavior, testing, and treatment. Results We find high rates of health worker absenteeism at public sector health facilities, with most of the absenteeism occurring at lower level public health clinics. On average, no health worker was present in 42% of all days monitored in lowest level public health clinics, whereas this number was less than 5% in high level public hospitals and private facilities. In our preferred empirical model with household fixed effects, we find that health worker absenteeism reduces the odds that a patient seeks care in the public sector (OR = 0.65, 95% CI = 0.44–0.95) and receives malaria testing (OR = 0.73, 95% CI = 0.53–0.99) and increases the odds of paying out-of-pocket for treatment (OR = 1.41, 95% CI = 1.10–1.80). The estimated differences in care-seeking are larger for children under-five than for the overall study population. Conclusions The impact of health worker absenteeism on the quality of care received as well as the financial burden faced by households in sub-Saharan Africa is substantial.

Description: Affective state can bias an animal’s judgement. Animals in positive affective states can interpret ambiguous cues more positively (“optimistically”) than animals in negative affective states. Thus, judgement bias tests can determine an animal’s affective state through their responses to ambiguous cues. We tested the effects of environmental complexity and stocking density on affective states of broiler chickens through a multimodal judgement bias test. Broilers were trained to approach reinforced locations signaled by one color and not to approach unreinforced locations signaled by a different color. Trained birds were tested for latencies to approach three ambiguous cues of intermediate color and location. Broilers discriminated between cues, with shorter latencies to approach ambiguous cues closest to the reinforced cue than cues closest to the unreinforced cue, validating the use of the test in this context. Broilers housed in high-complexity pens approached ambiguous cues faster than birds in low-complexity pens–an optimistic judgement bias, suggesting the former were in a more positive affective state. Broilers from high-density pens tended to approach all cues faster than birds from low-density pens, possibly because resource competition in their home pen increased food motivation. Overall, our study suggests that environmental complexity improves broilers’ affective states, implying animal welfare benefits of environmental enrichment.

Description: Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.

Description: Variable selection is crucial issue for high dimensional data modeling, where sample size is smaller compared to number of variables. Recently, majority scoring of filter measures in PLS (MS-PLS) is introduced for variable selection in high dimensional data. Filter measures are not greedy for optimal performance, hence we have proposed majority scoring with backward elimination in PLS (MSBE-PLS). In MSBE-PLS we have considered variable importance on projection (VIP) and selectivity ratio (SR). In each iteration of backward elimination in PLS variables are considered influential if they were selected by both filter indicator. The proposed method is implemented for corn’s and diesel’s content prediction. The corn contents include protein, oil, starch and moisture while diesel contents include boiling point at 50% recovery, cetane number, density, freezing temperature of the fuel, total aromatics, and viscosity. The proposed method outperforms in terms of RMSE when compared with reference methods. In addition to validating the spectrum models, data properties are also examined for explaining prediction behaviors. Moreover, MSBE-PLS select the moderate number of influential variables, hence it presents the parsimonious model for predicting contents based on spectrum data.

Description: The association between weather-related variables or seasons and the development of Bell’s palsy (BP) is controversial. This study aimed to evaluate the incidence and clinical characteristics of BP and assess the effects of meteorological factors on seasonal and monthly incidence. This retrospective population-based study used data from the Korean Health Insurance claims database (NHICD) from 2010 to 2018, in which annual, seasonal, and monthly incidence rates and age and sex distributions were calculated. A multivariate linear regression and autoregressive integrated moving average (ARIMA) model was used to determine the association between the seasonal and monthly incidence of BP and meteorological factors, including average wind speed, temperature, relative humidity, and atmospheric pressure. We also conducted a scoping review of the literature on epidemiological and seasonality studies of BP in the past 30 years and summarized them in a table for easy comparison with other studies. In this study, the incidence rate of BP increased over 9 years (from 12.86 to 19.92 per 100,000 persons) and was the highest in patients in their 60s (31.6/100,000 persons). The seasonal incidence of BP was the highest in autumn and showed a significant difference compared with spring (coefficient − 0.318, p = 0.003) and summer (coefficient − 0.463, p 

Description: This work uses a high-quality 3D seismic volume from offshore Canterbury Basin, New Zealand, to investigate how submarine canyon systems can focus sub-surface fluid. The seismic volume was structurally conditioned to improve the contrast in seismic reflections, preserving their lateral continuity. It reveals multiple pockmarks, eroded gullies and intra-slope lobe complexes occurring in association with the Waitaki Submarine Canyon. Pockmarks are densely clustered on the northern bank of the canyon and occur at a water depth of 500–900 m. In parallel, near-seafloor strata contain channel-fill deposits, channel lobes, meandering channel belts and overbank sediments deposited downslope of the submarine canyon. We propose that subsurface fluid migrates from relatively deep Cretaceous strata through shallow channel-fill deposits and lobes to latter seep out through the canyon and associated gullies. The new, reprocessed Fluid Cube meta-attribute confirms that fluids have seeped out through the eroded walls of the Waitaki Canyon, with such a seepage generating seafloor depressions in its northern bank. Our findings stress the importance of shallow reservoirs (channel-fill deposits and lobes) as potential repositories for fluid, hydrocarbons, or geothermal energy on continental margins across the world.

Description: The patterns of respiratory virus illness are expressed differently between temperate and tropical climates. Tropical outbreaks often peak in wet seasons. Temperate outbreaks typically peak during the winter. The prevailing causal hypotheses focus on sunlight, temperature and humidity variations. Yet no consistent factors have been identified to sufficiently explain seasonal virus emergence and decline at any latitude. Here we demonstrate close connections among global-scale atmospheric circulations, IgE antibody enhancement through seasonal pollen inhalation, and respiratory virus patterns at any populated latitude, with a focus on the US. Pollens emerge each Spring, and the renewed IgE titers in the population are argued to terminate each winter peak of respiratory illness. Globally circulated airborne viruses are postulated to subsequently deposit across the Southern US during lower zonal geostrophic winds each late Summer. This seasonally refreshed viral load is postulated to trigger a new influenza outbreak, once the existing IgE antibodies diminish to a critical value each Fall. Our study offers a new and consistent explanation for the seasonal diminishment of respiratory viral illnesses in temperate climates, the subdued seasonal signature in the tropics, the annually circulated virus phenotypes, and the northerly migration of influenza across the US every year. Our integrated geospatial and IgE hypothesis provides a new perspective for prediction, mitigation and prevention of the outbreak and spread of seasonal respiratory viruses including Covid-19 pandemic.

Description: Symptomatic overlap of depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) is a major diagnostic and therapeutic problem. Mania in medical history remains the only reliable distinguishing marker which is problematic given that episodes of depression compared to episodes of mania are more frequent and predominantly present at the beginning of BD. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, task-free, and well-tolerated method that may provide diagnostic markers acquired from spontaneous neural activity. Previous rs-fMRI studies focused on differentiating BD from MDD depression were inconsistent in their findings due to low sample power, heterogeneity of compared samples, and diversity of analytical methods. This meta-analysis investigated resting-state activity differences in BD and MDD depression using activation likelihood estimation. PubMed, Web of Science, Scopus and Google Scholar databases were searched for whole-brain rs-fMRI studies which compared MDD and BD currently depressed patients between Jan 2000 and August 2020. Ten studies were included, representing 234 BD and 296 MDD patients. The meta-analysis found increased activity in the left insula and adjacent area in MDD compared to BD. The finding suggests that the insula is involved in neural activity patterns during resting-state that can be potentially used as a biomarker differentiating both disorders.

Description: HBV infection is recognized as a serious global health problem, and hepatitis B virus infection is a complicated chronic disease leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). New biochemical serum markers could be used to advance the diagnosis and prognosis of HBV-associated liver diseases during the progression of chronic hepatitis B into cirrhosis and HCC. We determined whether the 4210 Da and 1866 Da polypeptides are serum metabolite biomarkers of hepatopathy with hepatitis B virus. A total of 570 subjects were divided into five groups: healthy controls, those with natural clearance, and patients with CHB, LC, and HCC. The 1866 Da and 4210 Da polypeptides were measured by Clin-ToF II MALDI-TOF–MS. There were significant differences in 4210 Da and 1866 Da levels among the five groups (P 

Description: Osteoarthritis (OA), a most common and highly prevalent joint disease, is closely associated with dysregulated expression and modification of RXRα. However, the role of RXRα in the pathophysiology of OA remains unknown. The present study aimed to investigate whether RXRα modulator, such as K-80003 can treat OA. Experimental OA was induced by intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats. Articular cartilage degeneration was assessed using Safranin-O and fast green staining. Synovial inflammation was measured using hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Expressions of MMP-13, ADAMTS-4 and ERα in joints were analyzed by immunofluorescence staining. Western blot, RT-PCR and co-Immunoprecipitation (co-IP) were used to assess the effects of K-80003 on RXRα-ERα interaction. Retinoid X receptor α (RXRα) modulator K‐80003 prevented the degeneration of articular cartilage, reduced synovial inflammation, and alleviated osteoarthritic pain in rats. Furthermore, K-80003 markedly inhibited IL-1β‐induced p65 nuclear translocation and IκBα degradation, and down-regulate the expression of HIF-2α, proteinases (MMP9, MMP13, ADAMTS-4) and pro-inflammatory factors (IL-6 and TNFα) in primary chondrocytes. Additionally, knockdown of ERα with siRNA blocked these effects of K-80003 in chondrocytes. In conclusion, RXRα modulators K-80003 suppresses inflammatory and catabolic responses in OA, suggesting that targeting RXRα‐ERα interaction by RXRα modulators might be a novel therapeutic approach for OA treatment.

Description: Perceived stress is a dimension of the maternal stress response, however little data is available on perceived stress levels and its associated psychological risk factors during labor. In this secondary data analysis from a prospective study evaluating epidural regimens, we investigated the potential associations between depressive symptomatology, anxiety, and pain catastrophizing with perceived stress during labor. Healthy nulliparous adult women with term singleton pregnancies requesting for epidural analgesia in early labor were included. Assessments were administered after epidural analgesia and adequate pain relief were achieved. Perceived stress (Perceived Stress Scale, PSS, high PSS ≥ 16), depressive symptomatology (Edinburgh Postnatal Depression Scale, EPDS, high EPDS ≥ 10), and pain catastrophizing (Pain Catastrophizing Scale, PCS, high total PCS ≥ 25) were assessed as categorical variables. Additionally, anxiety (State-trait Anxiety Inventory, STAI), PCS total and its subscales (rumination, magnification and helplessness) were analyzed as continuous variables. Univariate and multivariable logistic regression models were used to identify factors associated with high PSS. Of 801 women included, 411 (51.9%) had high PSS. High EPDS (OR 2.16, 95%CI 1.36–3.44), increasing trait anxiety (OR 1.17, 95%CI 1.14–1.20), and increasing pain magnification (OR 1.12, 95%CI 1.05–1.19) were independently associated with high PSS. Depressive symptomatology, trait anxiety, and pain magnification were associated with perceived stress during labor, providing impetus for future research aimed at detecting and alleviating stress and its psychological or pain association factors.

Description: The floatability of magnesite, dolomite and quartz is a major factor affecting the removal of silicon and calcium from magnesite ore. The effect of the regulators sodium hexametaphosphate (SH), sodium silicate (SS), trisodium phosphate (TP), tannic acid (TN) and monoammonium oxalate (OA) on the floatability of magnesite, dolomite, and quartz under the ether amine (EAH) system was studied. The results show that the five regulators have relatively little influence on the floatability of quartz and magnesite. Dolomite can be activated when the dosage of SH is less than 40 mg/L; however, dolomite can be inhibited when the SH dosage is greater than 40 mg/L. The other four regulators have inhibitory effects on dolomite, and TN and TP have strong inhibitory effects on dolomite. Under the conditions of optimum grinding fineness, pH and collector dosage, a recovery of approximately 70% and a concentrate with a grade of over 47% were obtained by three stages of reverse flotation using sodium hexametaphosphate and water glass as regulators and Haicheng magnesite ore with an SiO2 content of 2.38% and a CaO content of 0.75%. Potentiometric measurements and infrared spectroscopy analysis show that physical adsorption occurs between the three minerals and collectors, while the interaction of magnesite and dolomite with SH and SS involves both physical adsorption and chemical adsorption.

Description: Self-sealing hyaluronic acid (HA)-coated self-sealing 30-gauge needles exhibiting instant leakage prevention of intravitreal humor and injected drug were developed in this study. Ninety New Zealand rabbits were used in this study. We assessed dye regurgitation in intravitreal ICG dye injections using HA-coated needles (HA needle group) and conventional needles (control group). Vitreous humor levels of anti-vascular endothelial growth factor (VEGF) were compared between groups one, three, and seven days after intravitreal bevacizumab (0.016 mL) injections. Expression levels of inflammatory cytokines in the aqueous humor and vitreous humor, including prostaglandin E2 (PGE2), interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6, IL-17, and IL-8, were compared between HA needle, control, and normal (in which intravitreal injection was not performed) groups following 12 intravitreal injections over a period of one week. In the HA needle group, HA remained at the injection site and blocked the hole after intravitreal injection. Dye regurgitation occurred significantly less frequently in the HA needle group (16.7%) than the control group (55.6%) after intravitreal ICG dye injection. Meanwhile, vitreous anti-VEGF levels were markedly higher in the HA needle group than the control group one and three days after intravitreal bevacizumab injections. After 12 intravitreal injections, expression levels of aqueous and vitreous IL-8 significantly increased in the control group compared to the HA needle and normal groups. Conversely, there were no significant differences in the expression of the other seven cytokines among the three groups. Intravitreal injections using HA-coated self-sealing 30-gauge needles can block the outflow of vitreous humor and drugs through the needle passage.

Description: Herein we have synthesized silver nanoparticles (Ag NPs) using liquid metabolic waste of Bos taurus (A-2 type) urine. Various bio-molecules present in cow urine, are effectively used to reduce silver (Ag) ions into silver nanoparticles in one step. This is bio-inspired electron transfer to Ag ion for the formation of base Ag metal and is fairly prompt and facile. These nanoparticles act as a positive catalyst for various organic transformation reactions. The structural, morphological, and optical properties of the as-synthesized Ag NPs are widely characterized by X-ray diffraction spectroscopy, ultraviolet–visible spectroscopy, scanning electron microscope, Fourier transmission infra-red spectroscopy, and atomic force microscopy. The as-synthesized bio-mimetic Ag NPs show potential activity for several reduction reactions of nitro groups. The Ag NPs were also used for degradation of hazardous dyes such as Methylene blue and Crystal violet with good degradation rate constant.

Description: Providing clear and detailed morphological descriptions of endemic species in limited areas enables new knowledge of their biology and ecology to be obtained through citizen science. This information can be further used for their protection. Our study presents the first morphological description of the larvae of all three instars of Heterotemna tenuicornis (Brullé, 1836), an endemic species of the Canary Islands that, together with H. britoi García & Pérez, 1996 and H. figurata (Brullé, 1839), belongs to the peculiar genus Heterotemna Wollaston, 1864. Furthermore, we present the first sequences of two mitochondrial genes (COI, 16S) obtained from larval specimens, and cross reference them with sequences from an adult specimen. Phylogenetic analysis of molecular data placed the genus Heterotemna within the genus Silpha Linnaeus, 1758, suggesting paraphyly of Silpha. In our study, we underline the importance of using a combination of morphological description and molecular data, that can be used for barcoding developmental stages which could not otherwise be definitely associated.

Description: Babesia parasite invades exclusively red blood cell (RBC) in mammalian host and induces alterations to host cell for survival. Despite the importance of Babesia in livestock industry and emerging cases in humans, their basic biology is hampered by lack of suitable biological tools. In this study, we aimed to develop a synchronization method for Babesia bovis which causes the most pathogenic form of bovine babesiosis. Initially, we used compound 2 (C2), a specific inhibitor of cyclic GMP-dependent protein kinase (PKG), and a derivative of C2, ML10. While both inhibitors were able to prevent B. bovis egress from RBC and increased percentage of binary forms, removal of inhibitors from culture did not result in a synchronized egress of parasites. Because using PKG inhibitors alone was not efficient to induce a synchronized culture, we isolated viable and invasive B. bovis merozoites and showed dynamics of merozoite invasion and development in RBCs. Using isolated merozoites we showed that BbVEAP, VESA1-export associated protein, is essential for parasite development in the RBC while has no significant role in invasion. Given the importance of invasion for the establishment of infection, this study paves the way for finding novel antigens to be used in control strategies against bovine babesiosis.

Description: A new process was developed to recover high specific activity (no carrier added) 99Mo from electron-accelerator irradiated U3O8 or uranyl sulfate targets. The process leverages a novel solvent extraction scheme to recover Mo using di(2-ethylhexyl) phosphoric acid following uranium and transuranics removal with tri-n-butyl phosphate. An anion-exchange concentration column step provides a final purification, generating pure 99Mo intended for making 99Mo/99mTc generators. The process was demonstrated with irradiated uranium targets resulting in more than 95% 99Mo recovery and without presence of fission products or actinides in the product.

Description: Graphene-based photodetectors have attracted significant attention for high-speed optical communication due to their large bandwidth, compact footprint, and compatibility with silicon-based photonics platform. Large-bandwidth silicon-based optical coherent receivers are crucial elements for large-capacity optical communication networks with advanced modulation formats. Here, we propose and experimentally demonstrate an integrated optical coherent receiver based on a 90-degree optical hybrid and graphene-on-plasmonic slot waveguide photodetectors, featuring a compact footprint and a large bandwidth far exceeding 67 GHz. Combined with the balanced detection, 90 Gbit/s binary phase-shift keying signal is received with a promoted signal-to-noise ratio. Moreover, receptions of 200 Gbit/s quadrature phase-shift keying and 240 Gbit/s 16 quadrature amplitude modulation signals on a single-polarization carrier are realized with a low additional power consumption below 14 fJ/bit. This graphene-based optical coherent receiver will promise potential applications in 400-Gigabit Ethernet and 800-Gigabit Ethernet technology, paving another route for future high-speed coherent optical communication networks.

Description: Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibility remains elusive. Using RNA-Seq and ATAC-Seq we profiled differentially expressed transcripts and open chromatin regions during early dopaminergic neuron differentiation. Hierarchical clustering of differentially expressed genes, resulted in 6 groups with unique characteristics. Surprisingly, the abundance of long non-coding RNAs (lncRNAs) was high in the most downregulated transcripts, and depicted positive correlations with target mRNAs. We observed that open chromatin regions decrease upon differentiation. Enrichment analyses of accessibility depict an association between open chromatin regions and specific functional pathways and gene-sets. A bioinformatic search for motifs allowed us to identify transcription factors and structural nuclear proteins that potentially regulate dopaminergic differentiation. Interestingly, we also found changes in protein and mRNA abundance of the CCCTC-binding factor, CTCF, which participates in genome organization and gene expression. Furthermore, assays demonstrated co-localization of CTCF with Polycomb-repressed chromatin marked by H3K27me3 in pluripotent cells, progressively decreasing in neural precursor cells and differentiated neurons. Our work provides a unique resource of transcription factors and regulatory elements, potentially involved in the acquisition of human dopaminergic neuron cell identity.

Description: An overarching challenge of the electrochemical carbon dioxide reduction reaction (eCO2RR) is finding an earth-abundant, highly active catalyst that selectively produces hydrocarbons at relatively low overpotentials. Here, we report the eCO2RR performance of two-dimensional transition metal carbide class of materials. Our results indicate a maximum methane (CH4) current density of −421.63 mA/cm2 and a CH4 faradic efficiency of 82.7% ± 2% for di-tungsten carbide (W2C) nanoflakes in a hybrid electrolyte of 3 M potassium hydroxide and 2 M choline-chloride. Powered by a triple junction photovoltaic cell, we demonstrate a flow electrolyzer that uses humidified CO2 to produce CH4 in a 700-h process under one sun illumination with a CO2RR energy efficiency of about 62.3% and a solar-to-fuel efficiency of 20.7%. Density functional theory calculations reveal that dissociation of water, chemisorption of CO2 and cleavage of the C-O bond—the most energy consuming elementary steps in other catalysts such as copper—become nearly spontaneous at the W2C surface. This results in instantaneous formation of adsorbed CO—an important reaction intermediate—and an unlimited source of protons near the tungsten surface sites that are the main reasons for the observed superior activity, selectivity, and small potential.

Description: Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in  pre-clinical/Ob-T2D management.

Description: The contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.

Description: Reactive oxygen species (ROS) oxidize cellular nucleotide pools and cause double strand breaks (DSBs). Non-homologous end-joining (NHEJ) attaches broken chromosomal ends together in mammalian cells. Ribonucleotide insertion by DNA polymerase (pol) μ prepares breaks for end-joining and this is required for successful NHEJ in vivo. We previously showed that pol μ lacks discrimination against oxidized dGTP (8-oxo-dGTP), that can lead to mutagenesis, cancer, aging and human disease. Here we reveal the structural basis for proficient oxidized ribonucleotide (8-oxo-rGTP) incorporation during DSB repair by pol μ. Time-lapse crystallography snapshots of structural intermediates during nucleotide insertion along with computational simulations reveal substrate, metal and side chain dynamics, that allow oxidized ribonucleotides to escape polymerase discrimination checkpoints. Abundant nucleotide pools, combined with inefficient sanitization and repair, implicate pol μ mediated oxidized ribonucleotide insertion as an emerging source of widespread persistent mutagenesis and genomic instability.

Description: The scope of extracorporeal membrane oxygenation (ECMO) is expanding, nevertheless, pharmacokinetics in patients receiving cardiorespiratory support are fairly unknown leading to unpredictable drug concentrations. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This study aims to evaluate the pharmacokinetics (PK) of cefazolin in patients undergoing ECMO treatment. Total and unbound plasma cefazolin concentration of critically ill patients on veno-arterial ECMO were determined. Observed PK was compared to dose recommendations calculated by an online available, free dosing software. Concentration of cefazolin varied broadly despite same dosage in all patients. The mean total and unbound plasma concentration were high showing significantly (p = 5.8913 E−09) greater unbound fraction compared to a standard patient. Cefazolin clearance was significantly (p = 0.009) higher in patients with preserved renal function compared with CRRT. Based upon the calculated clearance, the use of dosing software would have led to lower but still sufficient concentrations of cefazolin in general. Our study shows that a “one size fits all” dosing regimen leads to excessive unbound cefazolin concentration in these patients. They exhibit high PK variability and decreased cefazolin clearance on ECMO appears to compensate for ECMO- and critical illness-related increases in volume of distribution.

Description: This work sought to quantify pathologists’ diagnostic bias over time in their evaluation of colorectal polyps to assess how this may impact the utility of statistical process control (SPC). All colorectal polyp specimens(CRPS) for 2011–2017 in a region were categorized using a validated free text string matching algorithm. Pathologist diagnostic rates (PDRs) for high grade dysplasia (HGD), tubular adenoma (TA_ad), villous morphology (TVA + VA), sessile serrated adenoma (SSA) and hyperplastic polyp (HP), were assessed (1) for each pathologist in yearly intervals with control charts (CCs), and (2) with a generalized linear model (GLM). The study included 64,115 CRPS. Fifteen pathologists each interpreted 〉 150 CRPS/year in all years and together diagnosed 38,813. The number of pathologists (of 15) with zero or one (p  600 CRPS each(total 52,760 CRPS), that pathologist, endoscopist, anatomical location and year were all strongly correlated (all p 

Description: The accuracy of expansion microscopy (ExM) depends on the structural preservation of samples embedded in a hydrogel. However, it has been unknown to what extent gel embedding alters the molecular positions of individual labeled sites. Here, we quantified the accuracy of gel embedding by using stochastic optical reconstruction microscopy (STORM) to image DNA origami with well-defined structures. We found that embedding in hydrogels based on polyacrylamide, the most widely used chemistry in ExM, resulted in random displacements of labeled sites with a standard deviation of ~ 16 nm. In contrast, we found that embedding in tetra-gel, a hydrogel that does not depend on free-radical chain-growth polymerization, preserved labeled sites with a standard deviation of less than 5 nm. By combining tetra-gel ExM with STORM, we were able to resolve 11-nm structural features without the loss in accuracy seen with polyacrylamide gels. Our study thus provides direct measurements of the single-molecule distortions resulting from hydrogel embedding, and presents a way to improve super-resolution microscopy through combination with tetra-gel ExM.

Description: Nanoparticulate matter activates the aryl hydrocarbon receptor (AhR) pathway in the respiratory system in a process involving the AhR nuclear translocator (ARNT) and cytochrome P450 family 1, member A1 (CYP1A1). We examined changes in AhR-related pathways following intranasal instillation of nanoparticulate matter in the olfactory bulb and cerebral cortex. Twice a day for 5 days per week for 1 week or 2 weeks, 8-week-old Sprague–Dawley rats were intranasally instilled with 10 µL nanoparticulate matter (nano group; n = 36). An equal volume of saline was intranasally instilled in control rats (n = 36). One week after intranasal instillation, olfactory function and Y-maze tests were performed. The expression levels of AhR in the olfactory bulb and temporal cortex were analyzed using western blotting and immunofluorescence assays. The expression levels of AhR, CYP1A1, inducible nitric oxide synthase (iNOS), and five genes encoding cation transporters (ARNT, ATP7B, ATPB1, OCT1, and OCT2) in the olfactory bulb were analyzed using quantitative reverse transcription. The olfactory discrimination capability was reduced in the nano group compared with the control group. Proportional changes in the Y-maze test were not significantly different between the nano and control groups. AhR mRNA and protein expression in the olfactory bulb increased 1.71-fold (P 

Description: Previous studies have suggested that PTEN loss is associated with p110β signaling dependency, leading to the clinical development of p110β-selective inhibitors. Here we use a panel pre-clinical models to reveal that PI3K isoform dependency is not governed by loss of PTEN and is impacted by feedback inhibition and concurrent PIK3CA/PIK3CB alterations. Furthermore, while pan-PI3K inhibition in PTEN-deficient tumors is efficacious, upregulation of Insulin Like Growth Factor 1 Receptor (IGF1R) promotes resistance. Importantly, we show that this resistance can be overcome through targeting AKT and we find that AKT inhibitors are superior to pan-PI3K inhibition in the context of PTEN loss. However, in the presence of wild-type PTEN and PIK3CA-activating mutations, p110α-dependent signaling is dominant and selectively inhibiting p110α is therapeutically superior to AKT inhibition. These discoveries reveal a more nuanced understanding of PI3K isoform dependency and unveil novel strategies to selectively target PI3K signaling nodes in a context-specific manner.

Description: The aim of this study is to establish prediction models for the non-destructive evaluation of the carbonization characteristics of lignin-derived hydrochars as a carbon material in real time. Hydrochars are produced via the hydrothermal carbonization of kraft lignins for 1–5 h in the temperature range of 175–250 °C, and as the reaction severity of hydrothermal carbonization increases, the hydrochar is converted to a more carbon-intensive structure. Principal component analysis using near-infrared spectra suggests that the spectral regions at 2132 and 2267 nm assigned to lignins and 1449 nm assigned to phenolic groups of lignins are informative bands that indicate the carbonization degree. Partial least squares regression models trained with near-infrared spectra accurately predicts the carbon content, oxygen/carbon, and hydrogen/carbon ratios with high coefficients of determination and low root mean square errors. The established models demonstrate better prediction than ordinary least squares regression models.

Description: Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.

Description: This 10-year retrospective observational study investigated longitudinal losses in psoas major and paraspinal muscle area in 1849 healthy individuals (1690 male, 159 female) screened using computed tomography. Logistic regression analysis revealed significant decreases in psoas major and paraspinal muscle area at 10 years relative to the baseline area regardless of age or sex, starting at 30 years of age. Only aging [≥ 50 s (odds ratio [OR]: 1.72; 95% confidence interval [CI] 1.05–2.84; p = 0.03) and ≥ 60 s (OR: 2.67; 95% CI 1.55–4.60; p  45 min daily (Calories = METs (walking: 3.0) × duration of time (h) × weight (60 kg) × 1.05) can reduce paraspinal muscle loss, which may in turn decrease the risk of falls, low-back pain, and sarcopenia.

Description: Although several prognostic factors in nivolumab therapy have been reported in recurrent or metastatic head and neck cancer (RM-HNC) patients, these factors remain controversial. Here, we conducted a multicenter retrospective cohort study to investigate the impact of clinico-hematological factors on survival in RM-HNC patients treated with nivolumab. We reviewed 126 RM-HNC patients from seven institutes. We evaluated the prognostic effects of clinico-hematological factors on survival. The median overall survival (OS) was 12.3 months, and the 1 year-OS rate was 51.2%. Patients without immune-related adverse events, lower relative eosinophil count, worse best overall response, higher performance status, and higher modified Glasgow Prognostic Score had worse survival. The score, generated by combining these factors, was associated with survival. Patients with score of 4–5 had worse survival than those with score of 2–3 and 0–1 [adjusted HR for PFS: score of 4–5, 7.77 (3.98–15.15); score of 2–3, 3.44 (1.95–6.06), compared to score of 0–1], [adjusted HR for OS: score of 4–5, 14.66 (4.28–50.22); score of 2–3, 7.63 (2.29–25.37), compared to score of 0–1]. Our novel prognostic score utilizing clinico-hematological factors might be useful to establish an individual treatment strategy in RM-HNC patients treated with nivolumab therapy.

Description: This study evaluates the ability of moderately halophilic bacterial isolates (Serratia sp., Bacillus sp., Morganella sp., Citrobacter freundii and Lysinibacillus sp.) to treat polluted wastewater in the presence of nZnO and nTiO2 nanoparticles. In this study, bacteria isolates were able to take up nZnO and nTiO2 at concentrations ranging from 1 to 50 mg/L in the presence of higher DO uptake at up to 100% and 99%, respectively, while higher concentrations triggered a significant decrease. Individual halophilic bacteria exhibited a low COD removal efficiency in the presence of both metal oxide nanoparticles concentration ranged between 1 and 10 mg/L. At higher concentrations, they triggered COD release of up to − 60% concentration. Lastly, the test isolates also demonstrated significant nutrient removal efficiency in the following ranges: 23–65% for NO3− and 28–78% for PO43−. This study suggests that moderately halophilic bacteria are good candidates for the bioremediation of highly polluted wastewater containing low metal oxide nanoparticles.

Description: The discovery of moiré superlattices (MSLs) opened an era in the research of ‘twistronics’. Engineering MSLs and realizing unique emergent properties are key challenges. Herein, we demonstrate an effective synthetic strategy to fabricate MSLs based on mechanical flexibility of WS2 nanobelts by a facile one-step hydrothermal method. Unlike previous MSLs typically created through stacking monolayers together with complicated method, WS2 MSLs reported here could be obtained directly during synthesis of nanobelts driven by the mechanical instability. Emergent properties are found including superior conductivity, special superaerophobicity and superhydrophilicity, and strongly enhanced electro-catalytic activity when we apply ‘twistronics’ to the field of catalytic hydrogen production. Theoretical calculations show that such excellent catalytic performance could be attributed to a closer to thermoneutral hydrogen adsorption free energy value of twisted bilayers active sites. Our findings provide an exciting opportunity to design advanced WS2 catalysts through moiré superlattice engineering based on mechanical flexibility.

Description: Sleep is being emphasized as a factor that improves mental health and quality of life. Here, we aimed to investigate the association between the quality and duration of sleep and subjective cognitive decline in the Korean population. We used the 2018 Korean Community Health Survey data that are nationwide representative data collected by the Korea Centers for Disease Control and Prevention. Sleep quality was measured using the Korean version of Pittsburgh Sleep Quality Index. The study population comprised 206,719 individuals aged 19 years and over. We used multiple logistic regression for the analysis. Individuals of both sexes with poor sleep quality were more likely to experience subjective cognitive decline compared with the reference group (good sleep quality) (men, odds ratio (OR) = 1.97 [95% confidence interval (CI) 1.86–2.09]; women, OR = 1.75 [95% CI 1.67–1.84]). U-shape associations were found between sleep duration and subjective cognitive decline. Additionally, the presence of depressive symptom or stress and health-related behaviors, including smoking, drinking, and not walking, were high-risk factors for subjective cognitive decline. Our results indicate that poor sleep quality might contribute to subjective cognitive decline in the Korean population. We suggest the implementation of intervention measures for poor sleep behaviors to prevent cognitive decline.

Description: Malaria is still a global health problem. Plasmodium is a single-cell protozoan parasite that causes malaria and is transmitted to humans through the female Anopheles mosquito. The previous study showed that Sonchus arvensis L. callus has antiplasmodial activity. Several treatments are needed for callus quality improvement for antimalarial compound production. This study aimed to examine the effect of dolomite [CaMg(CO3)2] on growth (morpho-anatomical structure and biomass), secondary metabolite production, and in vitro antiplasmodial activity of S. arvensis L. callus. In this study, leaf explants were grown in Murashige and Skoog medium with a combination of 2,4-dichlorophenoxyacetic acid (2,4-D, one mg/L) and 6-benzyl amino purine (BAP, 0.5 mg/L) with dolomite (50, 75, 100, 150, and 200 mg/L). The 21 days callus ethanolic and methanolic extract were analyzed by gas chromatography-mass spectrometry (GC-MS) and thin-layer chromatography (TLC). The antiplasmodial test was performed on a blood culture infected with Plasmodium falciparum strain 3D7 using the Rieckmann method. The results showed that dolomite significantly affected callus growth, metabolite profile, and in vitro antiplasmodial activity. Dolomite (150 mg/L) showed the highest biomass (0.590 ± 0.136 g fresh weight and 0.074 ± 0.008 g dry weight). GC-MS analysis detected four compounds from callus ethanolic extract. Pelargonic acid, decanoic acid, and hexadecanoic acid were major compounds. One new terpenoid compound is based on TLC analysis. S. arvensis L. callus has antiplasmodial activity with the IC50 value of 5.037 μg/mL. It was three times lower than leaf methanolic extract and five times lower than leaf ethanolic extract.

Description: Linear Parameter Varying (LPV) systems and their control have gained attraction recently as they approximate nonlinear systems with higher order than ordinary linear systems. On the other hand, time delay is an inherent part of various real-life applications. A supervisory control structure is proposed in this paper for LPV systems subject to time delays. In the proposed control structure, a supervisor selects the most suitable controller from a bank of controllers; which desires to enhance the performance of closed-loop system in contrast with using a single robust controller. The analysis is based on the celebrated Smith predictor for time delay compensation and we provide a sufficient condition to assure the stability of the closed-loop switched system in terms of dwell time. Simulations on blood pressure control of hypertension patients in postoperative scenario are used to exemplify the effectiveness of the utilized technique. The operating region of the system is partitioned into five smaller operating regions to construct corresponding robust controllers and perform hysteresis switching amongst them. Simulation results witnessed that the proposed control scheme demonstrated a pressure undershoot less than the desired value of 10 mmHg while the Mean Arterial Pressure (MAP) remains within ±5 mmHg of the desired value.

Description: Background Assessing fitness to drive and predicting driving cessation remains a challenge for primary care physicians using standard screening procedures. The objective of this study was to prospectively evaluate the properties of neuropsychological screening tests, including the Trail Making Test (TMT), Clock Drawing Test (CDT), Montreal Cognitive Assessment (MoCA), Useful Field of View (UFOV), and Timed Up and Go (TUG) test, in predicting driving cessation for health reasons in drivers older than 70 years of age. Design and methods This prospective cohort study, with a median follow-up of 4 years for drivers of 70 years old or older with an active driving license in Switzerland, included 441 participants from a driving refresher course dedicated to volunteer senior drivers. Cases were drivers reported in the national driving registry who lost their license following a health-related accident, who were reported as unfit to drive by their physician or voluntarily ceased driving for health reasons. Survival analysis was used to measure the hazard ratio of driving cessation by adjusting for age and sex and to evaluate the predictive value of combining 3 or more positive tests in predicting driving cessation during a 4-year follow-up. Results A total of 1738 person-years were followed-up in the cohort, with 19 (4.3%) having ceased driving for health reasons. We found that participants with a TMT-A 〈 54 sec and TMT-B 〈 150 sec at baseline had a significantly lower cumulative hazard of driving cessation in 4 years than those with slower performance (adjusted HR 3, 95% CI: 1.16–7.78, p = 0.023). Participants who performed a CDT ≥ 5 had a significantly lower cumulative hazard of driving cessation (adjusted HR 2.89, 95% CI: 1.01–7.71, p = 0.033). Similarly, an MoCA score ≥ 26, TUG test

Description: Host genetic background is a significant driver of the variability in neurological responses to viral infection. Here, we leverage the genetically diverse Collaborative Cross (CC) mouse resource to better understand how chronic infection by Theiler’s Murine Encephalomyelitis Virus (TMEV) elicits diverse clinical and morphologic changes in the central nervous system (CNS). We characterized the TMEV-induced clinical phenotype responses, and associated lesion distributions in the CNS, in six CC mouse strains over a 90 day infection period. We observed varying degrees of motor impairment in these strains, as measured by delayed righting reflex, paresis, paralysis, seizures, limb clasping, ruffling, and encephalitis phenotypes. All strains developed neuroparenchymal necrosis and mineralization in the brain, primarily localized to the hippocampal regions. Two of the six strains presented with axonal degeneration with myelin loss of the nerve roots in the lumbar spinal cord. Moreover, we statistically correlated lesion distribution with overall frequencies of clinical phenotypes and phenotype progression to better understand how and where TMEV targets the CNS, based on genetic background. Specifically, we assessed lesion distribution in relation to the clinical progression of these phenotypes from early to late TMEV disease, finding significant relationships between progression and lesion distribution. Finally, we identified quantitative trait loci associated with frequency of lesions in a particular brain region, revealing several loci of interest for future study: lysosomal trafficking regulator (Lyst) and nidogen 1 (Nid1). Together, these results indicate that the genetic background influences the type and severity of clinical phenotypes, phenotypic resilience to TMEV, and the lesion distribution across strains.

Description: In the field of Differential Evolution (DE), a number of measures have been used to enhance algorithm. However, most of the measures need revision for fitting ensemble of different combinations of DE operators—ensemble DE algorithm. Meanwhile, although ensemble DE algorithm may show better performance than each of its constituent algorithms, there still exists the possibility of further improvement on performance with the help of revised measures. In this paper, we manage to implement measures into Ensemble of Differential Evolution Variants (EDEV). Firstly, we extend the collecting range of optional external archive of JADE—one of the constituent algorithm in EDEV. Then, we revise and implement the Event-Triggered Impulsive (ETI) control. Finally, Linear Population Size Reduction (LPSR) is used by us. Then, we obtain Improved Ensemble of Differential Evolution Variants (IEDEV). In our experiments, good performers in the CEC competitions on real parameter single objective optimization among population-based metaheuristics, state-of-the-art DE algorithms, or up-to-date DE algorithms are involved. Experiments show that our IEDEV is very competitive.

Description: Against the background of the speed-accuracy trade-off, we explored whether the Pace of Life can be used to identify heterogeneity in the strategy to place more weight on either fast or accurate accomplishments. The Pace of Life approaches an individual’s exposure to time and is an intensively studied concept in the evolutionary biology research. Albeit overall rarely, it is increasingly used to understand human behavior and may fulfill many criteria of a personal trait. In a controlled laboratory environment, we measured the participants’ Pace of Life, as well as their performance on a real-effort task. In the real-effort task, the participants had to encode words, whereby each word encoded correctly was associated with a monetary reward. We found that individuals with a faster Pace of Life accomplished more tasks in total. At the same time, they were less accurate and made more mistakes (in absolute terms) than those with a slower Pace of Life. Thus, the Pace of Life seems to be useful to identify an individual’s stance on the speed-accuracy continuum. In our specific task, placing more weight on speed instead of accuracy paid off: Individuals with a faster Pace of Life were ultimately more successful (with regard to their monetary revenue).

Description: Predatory mites in the family Phytoseiidae (Acari: Mesostigmata) are of great importance as biological control agents of pest mites and other arthropods. Correct identification of species is crucial to implement effective biological control of target pests. Here, we provide re-descriptions of seven phytoseiid mite species collected from citrus orchards in Florida. The several important morphological features including dorsal setae lengths, dorsal solenostomes, shape of calyx of spermatheca, chelicera dentition, measurements, and shape of macrosetae on legs currently used to discriminate phytoseiid species were missing in the original descriptions and re-descriptions of these species. Additionally, we observed the presence of a previously unnoted taxonomically important character on Proprioseius meridionalis Chant. Therefore, the re-description was essential for further diagnosis of this species. Accordingly, the validity of the presence/absence of this structure as a diagnostic character to separate species groups in the genus Proprioseius should be re-considered. Furthermore, Typhlodromalus peregrinus, a species for which a series of morphological variations are reported in previous descriptions, is re-described and illustrated from Clermont, Florida, a location very close (10 km) to its type location (Minneola), and the leaves of type host citrus. The macrosetae StIV was knobbed apically in all our specimens of T. peregrinus indicating invalidity of sharp-pointed or knobbed StIV to separate this species from a closely related species, T. aripo De Leon. These re-descriptions and species are important to utilizing authentic and promising candidates for biological control.

Description: How are eyes and head adapted to meet the demands of visual exploration in different tasks and environments? In two studies, we measured the horizontal movements of the eyes (using mobile eye tracking in Studies 1 and 2) and the head (using inertial sensors in Study 2) while participants completed a walking task and a search and retrieval task in a large, outdoor environment. We found that the spread of visual exploration was greater while searching compared with walking, and this was primarily driven by increased movement of the head as opposed to the eyes. The contributions of the head to gaze shifts of different eccentricities was greater when searching compared to when walking. Findings are discussed with respect to understanding visual exploration as a motor action with multiple degrees of freedom.

Description: Background We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS). Materials and methods Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis. Results BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure–time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury. Conclusion In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in spontaneous breaths at Plow and Phigh is required to minimize VILI.

Description: Small RNAs (sRNAs) encompass a great variety of molecules of different kinds, such as microRNAs, small interfering RNAs, Piwi-associated RNA, among others. These sRNAs have a wide range of activities, which include gene regulation, protection against virus, transposable element silencing, and have been identified as a key actor in determining the development of the cell. Small RNA sequencing is thus routinely used to assess the expression of the diversity of sRNAs, usually in the context of differentially expression, where two conditions are compared. Tools that detect differentially expressed microRNAs are numerous, because microRNAs are well documented, and the associated genes are well defined. However, tools are lacking to detect other types of sRNAs, which are less studied, and whose precursor RNA is not well characterized. We present here a new method, called srnadiff, which finds all kinds of differentially expressed sRNAs. To the extent of our knowledge, srnadiff is the first tool that detects differentially expressed sRNAs without the use of external information, such as genomic annotation or additional sequences of sRNAs.

Description: In order to eliminate COVID-19, many countries provided vaccinations. However, success depends on peoples’ knowledge levels and rates of acceptance. But, previous research on this topic is currently lacking in Bangladesh. This cross-sectional study aimed at to investigate Bangladeshi peoples’ knowledge, acceptance, and perception of challenges regarding COVID-19 vaccines. Quantitative data were collected using an online survey (n = 1975) and face-to-face interviews (n = 2200) with a pre-tested structured questionnaire. In addition, seven open-ended interviews were conducted with health experts regarding challenges of vaccination. Binary logistic regression analyses were conducted to assess the association between explanatory and dependent variables. Effect size was estimated to understand the magnitude of relationship between two variables. Of 4175 respondents, 92.6% knew about COVID-19 vaccines, while only 37.4% believed vaccines to be effective in controlling COVID-19. Nearly 46% of respondents believed that COVID-19 vaccines have side-effects, and 16.4% of respondents believed that side-effects could be life-threatening. Only 60.5% of respondents indicated that they would receive the COVID-19 vaccine. Out of 1650 respondents (39.5%) who did not intend to receive the vaccine, 948 (57.4%) believed that they would be naturally protected. Regressions results indicated that men had higher rates of knowledge regarding the vaccine. In addition, rural respondents demonstrated lower knowledge regarding the vaccine. Furthermore, education had a significant association with knowledge of COVID-19 vaccines. Respondents with university education had more knowledge regarding the vaccine (Odds ratio, OR = 29.99; 95% confidence interval, CI 11.40–78.90, effect size 1.88; p = 0.01) and correct dosage (OR 27.34; 95% CI 15.25–49.00, effect size 1.83; p = 0.01). However, women (OR 1.16; 95% CI 0.96–1.40, effect size 0.08) and rural (OR 1.24; 95% CI 1.07–1.44, effect size 0.12; p = 0.01) respondents were more enthusiastic regarding receiving the COVID-19 vaccine. Higher educated respondents showed higher probability of receiving the vaccine. Those who believed in the effectiveness of the COVID-19 vaccine were 11.57 times more interested (OR 11.57; 95% CI 8.92–15.01, effect size 1.35; p = 0.01) in receiving the vaccine. Open-ended interviews identified several challenges toward successful COVID-19 vaccination. Mass awareness creation, uninterrupted supply, equitable distribution, and sectoral coordination were suggested to achieve at least 70% immunization across the country.

Description: Introduction Burnout syndrome is common among medical students, but findings about the gender differences in burnout are not consistent. The aim of this study was to assess high risk of burnout syndrome among medical students at one University in Serbia, by gender. Method A cross-sectional study was conducted at the Faculty of Medical Sciences, University of Kragujevac in 2014. The Maslach Burnout Inventory—Student Survey was used for assessment of burnout level. A questionnaire on basic socio-demographic characteristics (age, gender, marital status, habits, etc.) and academic performance (year of study, cumulative total average grade, length of study, housing, study financing, etc.) was used. The study included a total of 760 medical students (760/836 medical students; participation rate: 90.9%). Logistic regression analysis was used to determine odds ratios (OR) with 95% confidence intervals (95% CI). Results Significant gender differences were detected in prevalence of high risk of burnout syndrome (male students– 19.0% vs. female students– 12.8%, p = 0.024). A significant independent predictor of high risk for burnout syndrome in male medical students was study year (p for trend = 0.011), while in female medical students–study year (p for trend = 0.002) and use of sedatives (adjusted OR = 5.74, 95% CI = 1.96–16.77, p = 0.001). Conclusion Our results indicate the need to assess the risk of burnout syndrome at the very beginning of medical studies, in order to more effectively control the modifiable risk factors.

Description: Background Comorbidities are associated with increased mortality among patients receiving long-term kidney replacement therapy (KRT). However, it is not known whether primary kidney disease modifies the effect of comorbidities on KRT patients’ survival. Methods An incident cohort of all patients (n = 8696) entering chronic KRT in Finland in 2000–2017 was followed until death or end of 2017. All data were obtained from the Finnish Registry for Kidney Diseases. Information on comorbidities (coronary artery disease, peripheral vascular disease, left ventricular hypertrophy, heart failure, cerebrovascular disease, malignancy, obesity, underweight, and hypertension) was collected at the start of KRT. The main outcome measure was relative risk of death according to comorbidities analyzed in six groups of primary kidney disease: type 2 diabetes, type 1 diabetes, glomerulonephritis (GN), polycystic kidney disease (PKD), nephrosclerosis, and other or unknown diagnoses. Kaplan-Meier estimates and Cox regression were used for survival analyses. Results In the multivariable model, heart failure increased the risk of death threefold among PKD and GN patients, whereas in patients with other kidney diagnoses the increased risk was less than twofold. Obesity was associated with worse survival only among GN patients. Presence of three or more comorbidities increased the age- and sex-adjusted relative risk of death 4.5-fold in GN and PKD patients, but the increase was only 2.5-fold in patients in other diagnosis groups. Conclusions Primary kidney disease should be considered when assessing the effect of comorbidities on survival of KRT patients as it varies significantly according to type of primary kidney disease.

Description: New-generation migrant workers in Chinese cities are struggling with a lack of urban resources, such as capital, skills, and relationships. To cope with the pressure of these resource constraints, new-generation migrant workers obtain urban development opportunities through resource bricolage. Based on a questionnaire survey of 365 new-generation migrant workers, we used a multiple regression analysis to study the mechanism underlying the effects of resource bricolage on the city integration of new-generation migrant workers. There were four findings: (1) resource bricolage had a significant positive effect on career growth and city integration; (2) career growth had a mediation effect on the relationship between resource bricolage and city integration; (3) environmental dynamism had a positive moderating effect on the relationship between resource bricolage and city integration for new-generation migrant workers; and (4) resource bricolage and environmental dynamism had a moderating effect on city integration through the mediation effect of career growth. The results suggest that resource bricolage promotes the career growth of new-generation migrant workers and further promotes their city integration, and that the environmental dynamism faced by workers is the external condition for promoting integration through resource bricolage. The study emphasizes the importance of resource bricolage in new-generation migrant workers’ city integration.

Description: Vessel-based sonar systems that focus on the water column provide valuable information on the distribution of underwater marine organisms, but such data are expensive to collect and limited in their spatiotemporal coverage. Satellite data, however, are widely available across large regions and provide information on surface ocean conditions. If satellite data can be linked to subsurface sonar measurements, it may be possible to predict marine life over broader spatial regions with higher frequency using satellite observations. Here, we use random forest models to evaluate the potential for predicting a sonar-derived proxy for subsurface biomass as a function of satellite imagery in the California Current Ecosystem. We find that satellite data may be useful for prediction under some circumstances, but across a range of sonar frequencies and depths, overall model performance was low. Performance in spatial interpolation tasks exceeded performance in spatial and temporal extrapolation, suggesting that this approach is not yet reliable for forecasting or spatial extrapolation. We conclude with some potential limitations and extensions of this work.

Description: The area of tropical secondary forests is increasing rapidly, but data on the physical and biological structure of the canopies of these forests are limited. To obtain such data and to measure the ontogeny of canopy structure during tropical rainforest succession, we studied patch-scale (5 m2) canopy structure in three areas of 18–36 year-old secondary forest in Costa Rica, and compared the results to data from old-growth forest at the same site. All stands were sampled with a stratified random design with complete harvest from ground level to the top of the canopy from a modular portable tower. All canopies were organized into distinct high- and low-leaf-density layers (strata), and multiple strata developed quickly with increasing patch height. The relation of total Leaf Area Index (LAI, leaf area per area of ground) to patch canopy height, the existence of distinct high and low leaf- density layers (strata and free air spaces), the depth and LAI of the canopy strata and free air spaces, and the relation of the number of strata to patch canopy height were remarkably constant across the entire successional gradient. Trees were the most important contributor to LAI at all stages, while contribution of palm LAI increased through succession. We hypothesize that canopy physical structure at the patch scale is driven by light competition and discuss how this hypothesis could be tested. That canopy physical structure was relatively independent of the identity of the species present suggests that canopy physical structure may be conserved even as canopy floristics shift due to changing climate.

Description: Visual perception in football (“soccer” in the U.S.) is increasingly becoming a key area of interest for researchers and practitioners. This exploratory case study investigated a sub-set of visual perception, namely visual exploratory scanning. The aim of this study was to examine the scanning of four elite football midfield players in an 11 vs. 11 real-game environment using mobile eye-tracking technology. More specifically, we measured the duration and information (number of teammates and opponents) of the players’ scanning behavior. The results showed that the players’ scanning duration was influenced by the ball context and the action undertaken with the ball at the moment of scan initiation. Furthermore, fixations were found in only 2.3% of the scans. Additionally, the results revealed that the stop point is the most information-rich part of a scan and that the players had more opponents than teammates inside their video frame during scans. Practical applications and further research recommendations are presented.

Description: Digital mobility assessment using wearable sensor systems has the potential to capture walking performance in a patient’s natural environment. It enables monitoring of health status and disease progression and evaluation of interventions in real-world situations. In contrast to laboratory settings, real-world walking occurs in non-conventional environments and under unconstrained and uncontrolled conditions. Despite the general understanding, there is a lack of agreed definitions about what constitutes real-world walking, impeding the comparison and interpretation of the acquired data across systems and studies. The goal of this study was to obtain expert-based consensus on specific aspects of real-world walking and to provide respective definitions in a common terminological framework. An adapted Delphi method was used to obtain agreed definitions related to real-world walking. In an online survey, 162 participants from a panel of academic, clinical and industrial experts with experience in the field of gait analysis were asked for agreement on previously specified definitions. Descriptive statistics was used to evaluate whether consent (〉 75% agreement as defined a priori) was reached. Of 162 experts invited to participate, 51 completed all rounds (31.5% response rate). We obtained consensus on all definitions (“Walking” 〉 90%, “Purposeful” 〉 75%, “Real-world” 〉 90%, “Walking bout” 〉 80%, “Walking speed” 〉 75%, “Turning” 〉 90% agreement) after two rounds. The identification of a consented set of real-world walking definitions has important implications for the development of assessment and analysis protocols, as well as for the reporting and comparison of digital mobility outcomes across studies and systems. The definitions will serve as a common framework for implementing digital and mobile technologies for gait assessment and are an important link for the transition from supervised to unsupervised gait assessment.

Description: Introduction Hypertension (HT) is a major non-communicable disease worldwide and a growing global public health problem. Although several studies have investigated the independent associations of neck circumference (NC) and hypertension, no such studies have been conducted among the Thai population. Aim This study aims to identify risk factors associated with hypertension, which may be used to predict HT among asymptomatic adults residing in a remote rural community in central Thailand. Method 1,084 adults were included in this community-based cross-sectional study by a population-based total survey. The participants were included those who had been living in 6 villages in the rural community in the central area of Thailand. Anthropometric information, NC, body composition indexes such as waist circumference and blood pressure were measured. Logistic regression models were fitted to calculate the multi-variable adjusted prevalence and the association of NC with HT. Result The prevalence of HT among adults in the rural community was 27.7% (95% CI: 25.0–30.3). Of the 300 adults with HT, 164 participants (54.7%) were found within the unawareness HT category. We found that associated factors with HT were included larger neck circumference both continuous and categorical (≥ 37.5 in male, ≥ 32.5 in female), pre-existing diabetes mellitus, male, and higher body mass index. Conclusion Almost one-third of participants in the remote rural areas presented hypertension. NC was associated with HT independent from other risk factors. NC is a simple and useful anthropometric index to identify HT in rural Thai adults.

Description: This is a protocol of a review paper, and there is no abstract. This review is part of a doctoral project that aims to develop a discrete event simulation model to predict how many adolescents may become hypertensive in adulthood. We will use data from the Brazilian study of cardiovascular risks in adolescents, called ERICA (Portuguese acronym). This study may help promote adherence to disease prevention protocols.

Description: Mycobacterium tuberculosis (Mtb) infects one-quarter of the world’s population. Mtb and HIV coinfections enhance the comorbidity of tuberculosis (TB) and AIDS, accounting for one-third of all AIDS-associated mortalities. Humoral antibody to Mtb correlates with TB susceptibility, and engineering of Mtb antibodies may lead to new diagnostics and therapeutics. The characterization and validation of functional immunoglobulin (Ig) variable chain (IgV) sequences provide a necessary first step towards developing therapeutic antibodies against pathogens. The virulence-associated Mtb antigens SodA (Superoxide Dismutase), KatG (Catalase), PhoS1/PstS1 (regulatory factor), and GroES (heat shock protein) are potential therapeutic targets but lacked IgV sequence characterization. Putative IgV sequences were identified from the mRNA of hybridomas targeting these antigens and isotype-switched into a common immunoglobulin fragment crystallizable region (Fc region) backbone, subclass IgG2aκ. Antibodies were validated by demonstrating recombinant Ig assembly and secretion, followed by the determination of antigen-binding specificity using ELISA and immunoblot assay.

Description: With excellent creep resistance, good high-temperature microstructural stability and good irradiation resistance, oxide dispersion strengthened (ODS) alloys are a class of important alloys that are promising for high-temperature applications. However, plagued by a nerve-wracking fact that the oxide particles tend to aggregate at grain boundary of metal matrix, their improvement effect on the mechanical properties of metal matrix tends to be limited. In this work, we employ a unique in-house synthesized oxide@W core-shell nanopowder as precursor to prepare W-based ODS alloy. After low-temperature sintering and high-energy-rate forging, high-density oxide nanoparticles are dispersed homogeneously within W grains in the prepared alloy, accompanying with the intergranular oxide particles completely disappearing. As a result, our prepared alloy achieves a great enhancement of strength and ductility at room temperature. Our strategy using core-shell powder as precursor to prepare high-performance ODS alloy has potential to be applied to other dispersion-strengthened alloy systems.

Description: Hydrological models are widely used as simplified, conceptual, mathematical representatives for water resource management. The performance of hydrological modeling is usually challenged by model calibration and uncertainty analysis during modeling exercises. In this study, a multicriteria sequential calibration and uncertainty analysis (MS-CUA) method was proposed to improve the efficiency and performance of hydrological modeling with high reliability. To evaluate the performance and feasibility of the proposed method, two case studies were conducted in comparison with two other methods, sequential uncertainty fitting algorithm (SUFI-2) and generalized likelihood uncertainty estimation (GLUE). The results indicated that the MS-CUA method could quickly locate the highest posterior density regions to improve computational efficiency. The developed method also provided better-calibrated results (e.g., the higher NSE value of 0.91, 0.97, and 0.74) and more balanced uncertainty analysis results (e.g., the largest P/R ratio values of 1.23, 2.15, and 1.00) comparing with other traditional methods for both case studies.

Description: The selection of optimal search effort for air-sea integrated search has become the most concerned issue for maritime search and rescue (MSAR) departments. Helicopters play an important role in maritime search because of their strong maneuverability and hovering ability. In this work, the requirements of maritime search were analyzed, from which a global optimization model with quantitative constraints for vessels and aircraft was developed by setting the least search time as single-objective optimization problem; then the improved Dinkelbach algorithm was used to solve the continuous programming problem, and the discrete mission planning algorithm was used to improve the calculation accuracy of search time and area. A case study shows that the errors in calculating search time and area decrease from 12–18 min to 36 s and from 76.5 to 0.45 n mile2, respectively. The results obtained from the discrete mission planning algorithm can provide better guidance for MASR departments in selecting optimal search scheme.

Description: The widespread UbiD enzyme family utilises the prFMN cofactor to achieve reversible decarboxylation of acrylic and (hetero)aromatic compounds. The reaction with acrylic compounds based on reversible 1,3-dipolar cycloaddition between substrate and prFMN occurs within the confines of the active site. In contrast, during aromatic acid decarboxylation, substantial rearrangement of the substrate aromatic moiety associated with covalent catalysis presents a molecular dynamic challenge. Here we determine the crystal structures of the multi-subunit vanillic acid decarboxylase VdcCD. We demonstrate that the small VdcD subunit acts as an allosteric activator of the UbiD-like VdcC. Comparison of distinct VdcCD structures reveals domain motion of the prFMN-binding domain directly affects active site architecture. Docking of substrate and prFMN-adduct species reveals active site reorganisation coupled to domain motion supports rearrangement of the substrate aromatic moiety. Together with kinetic solvent viscosity effects, this establishes prFMN covalent catalysis of aromatic (de)carboxylation is afforded by UbiD dynamics.

Description: Prostate cancer remains one of the most lethal cancers for men in the United States. The study aims to detect fusion transcripts in the blood samples of prostate cancer patients. We analyzed nine fusion transcripts including MAN2A1-FER, SLC45A2-AMACR, TRMT11-GRIK2, CCNH-C5orf30, mTOR-TP53BP1, KDM4-AC011523.2, TMEM135-CCDC67, LRRC59-FLJ60017 and Pten-NOLC1147 in the blood samples from 147 prostate cancer patients and 14 healthy individuals, using Taqman RT-PCR and Sanger’s sequencing. Similar analyses were also performed on 25 matched prostate cancer samples for matched-sample evaluation. Eighty-two percent blood samples from the prostate cancer patients were positive for MAN2A1-FER transcript, while 41.5% and 38.8% blood samples from the prostate cancer patients were positive for SLC45A2-AMACR and Pten-NOLC1, respectively. CCNH-c5orf30 and mTOR-TP53BP1 had low detection rates, positive in only 5.4% and 4% of the blood samples from the prostate cancer patients. Only 2 blood samples were positive for KDM4B-AC011523.2 transcript. Overall, 89.8% patients were positive for at least one fusion transcript in their blood samples. The statistical analysis showed varied sensitivity of fusion transcript detection in the blood based on the types of fusions. In contrast, the blood samples from all healthy individuals were negative for the fusion transcripts. Detection of fusion transcripts in the blood samples of the prostate cancer patients may be a fast and cost-effective way to detect prostate cancer.

Description: Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::NrasQ61K; Cdkn2a−/− melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4 knock down, as well as HDAC inhibition, promote the expression of an invasive signature, while inhibition of histone acetylation partially reverts the invasiveness program induced by SALL4 loss. Thus, SALL4 appears to regulate phenotype switching in melanoma through an HDAC2-mediated mechanism.

Description: A method was established using a scaffold-bioreactor system to examine the impact pulsatile blood flow has on the decellularized porcine kidney vascular architecture and functionality. These scaffolds were subjected to continuous arterial perfusion of whole blood at normal physiological (650 ml/min and 500 ml/min) and pathophysiological (200 ml/min) rates to examine dynamic changes in venous outflow and micro-/macrovascular structure and patency. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow over 24 h. These reductions rose from roughly 40% after 12 h to 60% after 24 h. There were no apparent signs of clotting at the renal artery, renal vein, and ureter. In comparison, venous flow rates decreased by 80% to 100% across the 24 h in acellular scaffolds hypoperfused at a rate of 200 ml/min. These kidneys also appeared intact on the surface after perfusion. However, they presented several arterial, venous, and ureteral clots. Fluoroscopic angiography confirmed substantial alterations to normal arterial branching patterns and patency, as well as parenchymal damage. Scanning electron microscopy revealed that pulsatile blood perfusion significantly disrupted glomerular microarchitecture. This study provides new insight into circumstances that limit scaffold viability and a simplified model to analyze conditions needed to prepare more durable scaffolds for long-term transplantation.

Description: The ability to predict an individual’s menstrual cycle length to a high degree of precision could help female athletes to track their period and tailor their training and nutrition correspondingly. Such individualisation is possible and necessary, given the known inter-individual variation in cycle length. To achieve this, a hybrid predictive model was built using data on 16,524 cycles collected from a sample of 2125 women (mean age 34.38 years, range 18.00–47.10, number of menstrual cycles ranging from 4 to 53). A mixed-effect state-space model was fitted to capture the within-subject temporal correlation, incorporating a Bayesian approach for process forecasting to predict the duration (in days) of the next menstrual cycle. The modelling procedure was split into three steps (1) a time trend component using a random walk with an overdispersion parameter, (2) an autocorrelation component using an autoregressive moving-average model, and (3) a linear predictor to account for covariates (e.g. injury, stomach cramps, training intensity). The inclusion of an overdispersion parameter suggested that $$26.36\%$$ 26.36 % $$[23.68\%,29.17\%]$$ [ 23.68 % , 29.17 % ] of cycles in the sample were overdispersed. The random walk standard deviation for a non-overdispersed cycle is $$27.41 pm 1.05$$ 27.41 ± 1.05 [1.00, 1.09] days while under an overdispersed cycle, the menstrual cycle variance increase in 4.78 [4.57, 5.00] days. To assess the performance and prediction accuracy of the model, each woman’s last observation was used as test data. The root mean square error (RMSE), concordance correlation coefficient and Pearson correlation coefficient (r) between the observed and predicted values were calculated. The model had an RMSE of 1.6412 days, a precision of 0.7361 and overall accuracy of 0.9871. In conclusion, the hybrid model presented here is a helpful approach for predicting menstrual cycle length, which in turn can be used to support female athlete wellness.

Description: Dental caries has been the most widespread chronic disease globally associated with significant health and financial burdens. Caries typically starts in the enamel, which is a unique tissue that cannot be healed or regrown; nonetheless, new preventive approaches have limitations and no effective care has developed yet. Since enamel is a non-renewable tissue, we believe that the intimate overlaying layer, the acquired enamel pellicle (AEP), plays a crucial lifetime protective role and could be employed to control bacterial adhesion and dental plaque succession. Based on our identified AEP whole proteome/peptidome, we investigated the bioinhibitory capacities of the native abundant proteins/peptides adsorbed in pellicle-mimicking conditions. Further, we designed novel hybrid constructs comprising antifouling and antimicrobial functional domains derived from statherin and histatin families, respectively, to attain synergistic preventive effects. Three novel constructs demonstrated significant multifaceted bio-inhibition compared to either the whole saliva and/or its native proteins/peptides via reducing biomass fouling and inducing biofilm dispersion beside triggering bacterial cell death. These data are valuable to bioengineer precision-guided enamel pellicles as an efficient and versatile prevention remedy. In conclusion, integrating complementary acting functional domains of salivary proteins/peptides is a novel translational approach to design multifunctional customizable enamel pellicles for caries prevention.

Description: One of the limiting factors of graphene integration into electronic, photonic, or sensing devices is the unavailability of large-scale graphene directly grown on the isolators. Therefore, it is necessary to transfer graphene from the donor growth wafers onto the isolating target wafers. In the present research, graphene was transferred from the chemical vapor deposited 200 mm Germanium/Silicon (Ge/Si) wafers onto isolating (SiO2/Si and Si3N4/Si) wafers by electrochemical delamination procedure, employing poly(methylmethacrylate) as an intermediate support layer. In order to influence the adhesion properties of graphene, the wettability properties of the target substrates were investigated in this study. To increase the adhesion of the graphene on the isolating surfaces, they were pre-treated with oxygen plasma prior the transfer process of graphene. The wetting contact angle measurements revealed the increase of the hydrophilicity after surface interaction with oxygen plasma, leading to improved adhesion of the graphene on 200 mm target wafers and possible proof-of-concept development of graphene-based devices in standard Si technologies.

Description: In engineering practice, the measured bearing capacity of a sand pile composite foundation in a mucky soil layer is much larger than the design value. Based on the sand pile construction and the load application process, a method of calculating the bearing capacity of the foundation based on the effective stress was proposed. Cavity diameter expansion in sand pile construction was simplified into a planar problem, and the cavity expansion theory was used to establish the expression of the rate of displacement and the horizontal stress increase. Based on the e–p curve and the calculation of the degree of consolidation, the relationships between the horizontal and vertical effective stress and the void ratio were obtained. According to the close relationship between the bearing capacity of the foundation in a mucky soil layer and the water content, an expression describing the relationships between the bearing capacity of the foundation, effective stress, void ratio, and water content was established. For the temporary engineering foundation treatment project, which needs a high bearing capacity but allows large foundation deformation, the design of sand pile composite foundations uses these relationships to take the consolidation effect of mucky soil into consideration, thereby reducing the replacement rate and lowering the construction cost.

Description: Solid iron corrosion products (FeCPs), continuously generated from iron corrosion in Fe0-based permeable reactive barriers (PRB) at pH 〉 4.5, can lead to significant porosity loss and possibility of system’s failure. To avoid such failure and to estimate the long-term performance of PRBs, reliable models are required. In this study, a mathematical model is presented to describe the porosity change of a hypothetical Fe0-based PRB through-flowed by deionized water. The porosity loss is solely caused by iron corrosion process. The new model is based on Faraday’s Law and considers the iron surface passivation. Experimental results from literature were used to calibrate the parameters of the model. The derived iron corrosion rates (2.60 mmol/(kg day), 2.07 mmol/(kg day) and 1.77 mmol/(kg day)) are significantly larger than the corrosion rate used in previous modeling studies (0.4 mmol/(kg day)). This suggests that the previous models have underestimated the impact of in-situ generated FeCPs on the porosity loss. The model results show that the assumptions for the iron corrosion rates on basis of a first-order dependency on iron surface area are only valid when no iron surface passivation is considered. The simulations demonstrate that volume-expansion by Fe0 corrosion products alone can cause a great extent of porosity loss and suggests careful evaluation of the iron corrosion process in individual Fe0-based PRB.

Description: Ultrasound-guided axillary brachial plexus block is increasingly used in preschool-age patients. However, the minimum effective volume of local anaesthetics has not been determined. With ethical committee approval and written informed consent from the guardians of all paediatric patients, we studied 27 consecutive patients aged 3 to 6 years who were scheduled for hand surgery. After general anaesthesia, eligible patients received a set volume of ultrasound-guided axillary brachial plexus block. We determined the volume of 0.2% ropivacaine for consecutive patients from the preceding patient’s outcome. The initial volume was 0.4 ml/kg. The testing interval was set at 0.05 ml/kg, and the lowest volume was 0.1 ml/kg. The following conditions were defined as a successful block: no heart rate changes, body movement, or ventilatory disorders during the operation; no use of fentanyl in the PACU; and a postoperative sensory block score