ALBERT

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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 

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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 

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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 

Beschreibung: 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.

Beschreibung: 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 

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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.

Beschreibung: 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 

Beschreibung: Cerebral venous sinus thrombosis (CVST) is a rare and devastating complication of inflammatory bowel disease (IBD). Early diagnosis and prompt treatment could improve prognosis. The aim of our study was to investigate the clinical data and predictive factors of inflammatory bowel disease in patients with a diagnosis of CVST. All IBD patient data were collected from July 2013 and September 2020. Clinical data, predictive factors and prognosis were compared between IBD patients with CVST and the IBD control group. The incidence of CVST in our study was 0.48%. The mean age of IBD patients with CVST was 34.9 years. The average duration of IBD was 4 years when cerebrovascular events occurred. The clinical presentation of CVST included headache (73.1%), vomiting (30.8%), limb dysmetria (26.9%), speech impairment (11.5%), blurred vision (7.7%), epileptic seizures (7.7%) and drowsiness (3.8%). The most common location for CVST was the transverse sinus (61.5%) followed by the superior sagittal sinus (30.8%). Anaemia, low albumin and elevated d-dimer were independent predictors of CVST in patients with IBD. Anticoagulation therapy was effective. The prognosis of IBD patients with CVST was worse than that of IBD patients without CVST. Early identification of the risk and clinical features of CVST in IBD patients is important. Prompt antithrombotic therapy is a safe and effective treatment.

Beschreibung: Sensitive skin syndrome has a neuropathic origin, which is why it is frequently associated with irritable bowel syndrome. We have looked for a possible association with chronic cough, which is commonly maintained by neurogenic mechanisms, whatever the initial cause(s). A survey was carried out on a representative sample of the population over 15 years of age using the quota method. The questionnaire included sociodemographic data and questions about sensitive skin, the presence of chronic cough, smoking and possible causes of chronic cough. Chronic cough was assessed by the Leicester Cough Questionnaire, and 4050 subjects responded (mean age: 45 years). Overall, 12.2% of subjects with a chronic cough were compared to the 87.8% without any cough. Among them, 72.5% had sensitive skin (vs. 47.8%, p 

Beschreibung: Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage loss and reduced joint function. OA risk factors are age and obesity. Many adipokines are altered by obesity but also OA although systemic adipokine regulation in OA is not always clear. Therefore, metabolic effects of diet-induced obesity on OA development as well as the influence of obesity and OA progression on systemic vs. local adipokine expression in joints were compared. C57Bl/6-mice fed with HFD (high fat diet) or normal diet prior to destabilization of the medial meniscus (DMM) were sacrificed 4/6/8 weeks after surgery. Sera were evaluated for adiponectin, leptin, visfatin, cytokines. Liver grading and staging for non-alcoholic steatohepatitis (NASH) was performed and crown-like structures (CLS) in adipose tissue measured. OA progression was scored histologically. Adipokine-expressing cells and types were evaluated by immunohistochemistry. Time-dependent changes in DMM-progression were reflected by increased systemic adiponectin levels in DMM especially combined with HFD. While HFD increased serum leptin, DMM reduced systemic leptin significantly. OA scores correlated with bodyweight, leptin and hepatic scoring. Locally, increased numbers of adiponectin- and leptin-producing fibroblasts were observed in damaged menisci but visfatin was not changed. Local adipokine expression was independent from systemic levels, suggesting different mechanisms of action.

Beschreibung: Spontaneous intracerebral hemorrhage (ICH) is the most devastating form of stroke. To refine treatments, improved understanding of the secondary injury processes is needed. We compared energy metabolic, amyloid and neuroaxonal injury biomarkers in extracellular fluid (ECF) from the perihemorrhagic zone (PHZ) and non-injured (NCX) brain tissue, cerebrospinal fluid (CSF) and plasma. Patients (n = 11; age 61 ± 10 years) undergoing ICH surgery received two microdialysis (MD) catheters, one in PHZ, and one in NCX. ECF was analysed at three time intervals within the first 60 h post- surgery, as were CSF and plasma samples. Amyloid-beta (Aβ) 40 and 42, microtubule associated protein tau (tau), and neurofilament-light (NF-L) were analysed using Single molecule array (Simoa) technology. Median biomarker concentrations were lowest in plasma, higher in ECF and highest in CSF. Biomarker levels varied over time, with different dynamics in the three fluid compartments. In the PHZ, ECF levels of Aβ40 were lower, and tau higher when compared to the NCX. Altered levels of Aβ peptides, NF-L and tau may reflect brain tissue injury following ICH surgery. However, the dynamics of biomarker levels in the different fluid compartments should be considered in the study of pathophysiology or biomarkers in ICH patients.

Beschreibung: The aim of the study was to assess the effect of fermented dried soybean (FSBM) and/or fermented rapeseed meal (FRSM) in diets for weaned piglets on production results, nutrient digestibility, gastrointestinal tract histology, and the composition of the gut microbiota. Piglets in the control group received standard diets with soybean meal. Animals in all experimental groups received diets in which a portion of the soybean meal was replaced: in group FR—8% FRSM; in group FR/FS—6% FRSM and 2% FSBM; in group FS/FR—2% FRSM and 6% FSBM and in group FS—8% FSBM. The use of 8% FRSM or 6% FRSM and 2% FSBM in the piglet diets had a positive effect on average daily gains. Piglets from the FR and FR/FS groups had the highest feed conversion rate. Group FS/FR and FS piglets had significantly lower mortality and lower incidence of diarrhoea. Piglets fed a diet with the fermented components, in particular with 8% FRSM or 6% FRSM and 2% FSBM, exhibited a positive effect on the microbiological composition and histology of intestines, which resulted in improved nutrient digestibility coefficients (ATTD and AID).

Beschreibung: The effect of uridine on the myocardial ischemic and reperfusion injury was investigated. A possible mechanism of its cardioprotective action was established. Two rat models were used: (1) acute myocardial ischemia induced by occlusion of the left coronary artery for 60 min; and (2) myocardial ischemia/reperfusion with 30-min ischemia and 120-min reperfusion. In both models, treatment with uridine (30 mg/kg) prevented a decrease in cell energy supply and in the activity of the antioxidant system, as well as an increase in the level of lipid hydroperoxides and diene conjugates. This led to a reduction of the necrosis zone in the myocardium and disturbances in the heart rhythm. The blocker of the mitochondrial ATP-dependent potassium (mitoKATP) channel 5-hydroxydecanoate limited the positive effects of uridine. The data indicate that the cardioprotective action of uridine may be related to the activation of the mitoKATP channel. Intravenously injected uridine was more rapidly eliminated from the blood in hypoxia than in normoxia, and the level of the mitoKATP channel activator UDP in the myocardium after uridine administration increased. The results suggest that the use of uridine can be a potentially effective approach to the management of cardiovascular diseases.

Beschreibung: Quantification of long term changes in cloud distribution and properties is critical for the proper assessment of future climate. We show contrasting trends in cloud properties and cloud radiative effects over Northwest Indian Ocean (NWIO) in south Asian summer monsoon. Cloud top height (CTH) decreases in June (− 69 ± 3 myr−1) and July (− 44 ± 3 myr−1), whereas it increases in August (106 ± 2 myr−1) and September (37 ± 1 myr−1). These contrasting trends are investigated to be due to the changes in upper tropospheric winds and atmospheric circulation pattern. Strengthening of upper tropospheric easterlies and changes in vertical wind dampen the vertical development of clouds in June and July. In contrast, weakening of upper tropospheric winds over NWIO and strengthening of updraft favour the vertical growth of clouds in August. Further, changes in horizontal winds at 450–350 hPa and strengthening of Indian Ocean Walker cell favour the westward spread of high level clouds, contributing to the increase in CTH over NWIO in August. Decrease of cloud cover and altitude in June and July and increase of the same in subsequent months would affect the monsoon rainfall over the Indian region. Proper representation of these intra-seasonal contrasting trends of clouds in climate models is important for the better prediction of regional weather.

Beschreibung: T-cell activation and cellular expansion by common gamma chain cytokines such as Interleukin-2 is necessary for adaptive immunity. However, when unregulated these same pathways promote pathologies ranging from autoimmune disorders to cancer. While the functional role of Interleukin-2 and downstream effector molecules is relatively clear, the repertoire of phosphoregulatory proteins downstream of this pathway is incomplete. To identify phosphoproteins downstream of common gamma chain receptor, YT cells were radiolabeled with [32P]-orthophosphate and stimulated with Interleukin-2. Subsequently, tyrosine phosphorylated proteins were immunopurified and subjected to tandem mass spectrometry—leading to the identification of CrkL. Phosphoamino acid analysis revealed concurrent serine phosphorylation of CrkL and was later identified as S114 by mass spectrometry analysis. S114 was inducible through stimulation with Interleukin-2 or T-cell receptor stimulation. Polyclonal antibodies were generated against CrkL phospho-S114, and used to show its inducibility by multiple stimuli. These findings confirm CrkL as an Interleukin-2 responsive protein that becomes phosphorylated at S114 by a kinase/s downstream of PI3K and MEK/ERK signaling.

Beschreibung: Rare oceanic diamonds are believed to have a mantle transition zone origin like super-deep continental diamonds. However, oceanic diamonds have a homogeneous and organic-like light carbon isotope signature (δ13C − 28 to − 20‰) instead of the extremely variable organic to lithospheric mantle signature of super-deep continental diamonds (δ13C − 25‰ to + 3.5‰). Here, we show that with rare exceptions, oceanic diamonds and the isotopically lighter cores of super-deep continental diamonds share a common organic δ13C composition reflecting carbon brought down to the transition zone by subduction, whereas the rims of such super-deep continental diamonds have the same δ13C as peridotitic diamonds from the lithospheric mantle. Like lithospheric continental diamonds, almost all the known occurrences of oceanic diamonds are linked to plume-induced large igneous provinces or ocean islands, suggesting a common connection to mantle plumes. We argue that mantle plumes bring the transition zone diamonds to shallower levels, where only those emplaced at the base of the continental lithosphere might grow rims with lithospheric mantle carbon isotope signatures.

Beschreibung: For workplaces where significant diurnal variations in radon concentrations are likely, measurements to evaluate average radon concentration during working hours could be useful for planning an optimized protection of workers according to the 2013/59/Euratom Directive. However, very few studies on this subject, generally limited to periods of few weeks, have been published. Therefore, a study has been conducted to evaluate the actual long-term radon exposure during working hours for a sample of 33 workplaces of four different types (postal offices, shops, restaurants, municipal offices), mainly located at the ground floor, and with expected considerable air exchange rate occurring during working hours due to frequent entrance/exit of persons or mechanical ventilation. The results show that the difference between the average radon level during working hours and that one during the whole day is about 20% on average and ranges from 0 to 50%. These observed differences, generally smaller compared with those found in other similar studies, are nearly the same if the analysis is restricted to workplaces with annual radon level higher than 300 Bq m–3, and therefore natural or mechanical ventilation normally present during working hours of the monitored workplaces cannot be considered an effective mitigation measure. However, the costs and time-response characteristics of the active monitors, as those used for the present study, will probably allow using more frequently a similar measurement strategy in workplaces.

Beschreibung: Airborne LiDAR bathymetry offers low cost and high mobility, making it an ideal option for shallow-water measurements. However, due to differences in the measurement environment and the laser emission channel, the received waveform is difficult to extract using a single algorithm. The choice of a suitable waveform processing method is thus of extreme importance to guarantee the accuracy of the bathymetric retrieval. In this study, we use a wavelet-denoising method to denoise the received waveform and subsequently test four algorithms for denoised-waveform processing, namely, the Richardson–Lucy deconvolution (RLD), blind deconvolution (BD), Wiener filter deconvolution (WFD), and constrained least-squares filter deconvolution (RFD). The simulation and measured multichannel databases are used to evaluate the algorithms, with focus on improving their performance after data-denoising and their capability of extracting water depth. Results show that applying wavelet denoising before deconvolution improves the extraction accuracy. The four algorithms perform better for the shallow-water orthogonal polarization channel (PMT2) than for the shallow horizontal row polarization channel (PMT1). Of the four algorithms, RLD provides the best signal-detection rate, and RFD is the most robust; BD has low computational efficiency, and WFD performs poorly in deep water (

Beschreibung: Monitoring the biodiversity of key habitats and understanding the drivers across spatial scales is essential for preserving ecosystem functions and associated services. Coralligenous reefs are threatened marine biodiversity hotspots that are challenging to monitor. As fish sounds reflect biodiversity in other habitats, we unveiled the biogeography of coralligenous reef sounds across the north-western Mediterranean using data from 27 sites covering 2000 km and 3 regions over a 3-year period. We assessed how acoustic biodiversity is related to habitat parameters and environmental status. We identified 28 putative fish sound types, which is up to four times as many as recorded in other Mediterranean habitats. 40% of these sounds are not found in other coastal habitats, thus strongly related to coralligenous reefs. Acoustic diversity differed between geographical regions. Ubiquitous sound types were identified, including sounds from top-predator species and others that were more specifically related to the presence of ecosystem engineers (red coral, gorgonians), which are key players in maintaining habitat function. The main determinants of acoustic community composition were depth and percentage coverage of coralligenous outcrops, suggesting that fish-related acoustic communities exhibit bathymetric stratification and are related to benthic reef assemblages. Multivariate analysis also revealed that acoustic communities can reflect different environmental states. This study presents the first large-scale map of acoustic fish biodiversity providing insights into the ichthyofauna that is otherwise difficult to assess because of reduced diving times. It also highlights the potential of passive acoustics in providing new aspects of the correlates of biogeographical patterns of this emblematic habitat relevant for monitoring and conservation.

Beschreibung: Queen pheromones have long been studied as a major factor regulating reproductive division of labor in social insects. Hitherto, only a handful of queen pheromones were identified and their effects on workers have mostly been studied in isolation from the social context in which they operate. Our study examined the importance of behavioral and social context for the perception of queen semiochemicals by bumble bee workers. Our results indicate that a mature queen’s cuticular semiochemicals are capable of inhibiting worker reproduction only when accompanied by the queen’s visual presence and the offspring she produces, thus, when presented in realistic context. Queen’s chemistry, queen’s visual presence and presence of offspring all act to regulate worker reproduction, but none of these elements produces an inhibitory effect on its own. Our findings highlight the necessity to reconsider what constitutes a queen pheromone and suggest a new approach to the study of chemical ecology in social insects.

Beschreibung: It is a widely held assumption that the brain performs perceptual inference by combining sensory information with prior expectations, weighted by their uncertainty. A distinction can be made between higher- and lower-level priors, which can be manipulated with associative learning and sensory priming, respectively. Here, we simultaneously investigate priming and the differential effect of auditory vs. visual associative cues on visual perception, and we also examine the reliability of individual differences. Healthy individuals (N = 29) performed a perceptual inference task twice with a one-week delay. They reported the perceived direction of motion of dot pairs, which were preceded by a probabilistic visuo-acoustic cue. In 30% of the trials, motion direction was ambiguous, and in half of these trials, the auditory versus the visual cue predicted opposing directions. Cue-stimulus contingency could change every 40 trials. On ambiguous trials where the visual and the auditory cue predicted conflicting directions of motion, participants made more decisions consistent with the prediction of the acoustic cue. Increased predictive processing under stimulus uncertainty was indicated by slower responses to ambiguous (vs. non-ambiguous) stimuli. Furthermore, priming effects were also observed in that perception of ambiguous stimuli was influenced by perceptual decisions on the previous ambiguous and unambiguous trials as well. Critically, behavioural effects had substantial inter-individual variability which showed high test–retest reliability (intraclass correlation coefficient (ICC) 〉 0.78). Overall, higher-level priors based on auditory (vs. visual) information had greater influence on visual perception, and lower-level priors were also in action. Importantly, we observed large and stable differences in various aspects of task performance. Computational modelling combined with neuroimaging could allow testing hypotheses regarding the potential mechanisms causing these behavioral effects. The reliability of the behavioural differences implicates that such perceptual inference tasks could be valuable tools during large-scale biomarker and neuroimaging studies.

Beschreibung: Suppressor of Hairy wing [Su(Hw)] is an insulator protein that participates in regulating chromatin architecture and gene repression in Drosophila. In previous studies we have shown that Su(Hw) is also required for pre-replication complex (pre-RC) recruitment on Su(Hw)-bound sites (SBSs) in Drosophila S2 cells and pupa. Here, we describe the effect of Su(Hw) on developmentally regulated amplification of 66D and 7F Drosophila amplicons in follicle cells (DAFCs), widely used as models in replication studies. We show Su(Hw) binding co-localizes with all known DAFCs in Drosophila ovaries, whereas disruption of Su(Hw) binding to 66D and 7F DAFCs causes a two-fold decrease in the amplification of these loci. The complete loss of Su(Hw) binding to chromatin impairs pre-RC recruitment to all amplification regulatory regions of 66D and 7F loci at early oogenesis (prior to DAFCs amplification). These changes coincide with a considerable Su(Hw)-dependent condensation of chromatin at 66D and 7F loci. Although we observed the Brm, ISWI, Mi-2, and CHD1 chromatin remodelers at SBSs genome wide, their remodeler activity does not appear to be responsible for chromatin decondensation at the 66D and 7F amplification regulatory regions. We have discovered that, in addition to the CBP/Nejire and Chameau histone acetyltransferases, the Gcn5 acetyltransferase binds to 66D and 7F DAFCs at SBSs and this binding is dependent on Su(Hw). We propose that the main function of Su(Hw) in developmental amplification of 66D and 7F DAFCs is to establish a chromatin structure that is permissive to pre-RC recruitment.

Beschreibung: The study aims to explore the distribution characteristics and influencing factors of diabetic retinopathy (DR) in diabetes mellitus (DM) patients and association rules of eye diseases in these patients. Data were obtained from 1284 DM patients at Henan Provincial People’s Hospital. Association rules were employed to calculate the probability of the common occurrence of eye-related diseases in DM patients. A web visualization network diagram was used to display the association rules of the eye-related diseases in DM patients. DR prevalence in people aged

Beschreibung: Understanding the excitonic processes at the interfaces of fluorescent π-conjugated molecules and metal electrodes is important for both fundamental studies and emerging applications. Adsorption configurations of molecules on metal surfaces significantly affect the physical characteristics of junctions as well as molecules. Here, the electronic structures and optical properties of molecular assemblies/Au interfaces were investigated using scanning probe and photoluminescence microscopy techniques. Scanning tunneling microscopy images and tunneling conductance spectra suggested that the self-assembled molecules were physisorbed on the Au surface. Visible-range photoluminescence studies showed that Au thin films modified the emission spectra and reduced the lifetime of excitons. Surface potential maps, obtained by Kelvin probe force microscopy, could visualize electron transfer from the molecules to Au under illumination, which could explain the decreased lifetime of excitons at the molecule/Au interface.

Beschreibung: Sauropod remains are abundant on the Iberian Peninsula across the Jurassic-Cretaceous transition. Where the osteological record shows a high diversity of this kind of dinosaur, the ichnological findings are mainly limited to sauropod tracks characterized by kidney-shaped manus (with or without pollex impressions) and pes impressions with three claw imprints oriented laterally. Here, we present a new sauropod ichnotaxon, Iniestapodus burgensis, found at several exposures within the Las Sereas megatracksite (Burgos, Spain). These are preserved within lacustrine limestone strata of the Rupelo Formation (Tithonian–Berriasian). Iniestapodus burgensis is characterized by: semicircular manus tracks with small pollex impressions; unusual tetradactyl pes tracks with evidence of four claws oriented anteriorly (I–II) and laterally (III–IV), of variable sizes (short claw I and IV impressions, claw II and III being the largest). The combination of features and comparison with the osteological record allows us to propose a non-titanosaurian titanosauriform as a possible trackmaker. All the Iniestapodus tracks are represented by at least two different size classes of small and medium-sized individuals, and their trackways show different multidirectional orientations. The paleoenvironmental and paleoecological data suggest that Iniestapodus trackmakers were solitary individuals, likely representing different age classes, that crossed and used the Las Sereas shallow lacustrine-palustrine areas as their preferred habitat.

Beschreibung: Modern day large-scale, high-density farming environments are inherently susceptible to viral outbreaks, inadvertently creating conditions that favor increased pathogen transmission and potential zoonotic spread. Metagenomic sequencing has proven to be a useful tool for characterizing the microbial burden in both people, livestock, and environmental samples. International efforts have been successful at characterizing pathogens in commercial farming environments, especially swine farms, however it is unclear whether the full extent of microbial agents have been adequately captured or is representative of farms elsewhere. To augment international efforts we performed metagenomic next-generation sequencing on nine swine slurry and three environmental samples from a United States of America (U.S.A.) farm operation, characterized the microbial composition of slurry, and identified novel viruses. We assembled a remarkable total of 1792 viral genomes, of which 554 were novel/divergent. We assembled 1637 Picobirnavirus genome segments, of which 538 are novel. In addition, we discovered 10 new viruses belonging to a novel taxon: porcine Statoviruses; which have only been previously reported in human, macaques, mouse, and cows. We assembled 3 divergent Posaviruses and 3 swine Picornaviruses. In addition to viruses described, we found other eukaryotic genera such as Entamoeba and Blastocystis, and bacterial genera such as Listeria, Treponema, Peptoclostridium and Bordetella in the slurry. Of these, two species Entamoeba histolytica and Listeria monocytogenes known to cause human disease were detected. Further, antimicrobial resistance genes such as tetracycline and MLS (macrolide, lincosamide, streptogramin) were also identified. Metagenomic surveillance in swine fecal slurry has great potential for novel and antimicrobial resistant pathogen detection.

Beschreibung: Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved therapy in major depressive disorder. However, its treatment efficacy on depression after traumatic brain injury (TBI) remains inconclusive. We conducted a meta-analysis to assess the effectiveness of executing rTMS over dorsolateral prefrontal cortex (DLPFC) on depression, cognitive impairment and post-concussion syndrome in individuals with traumatic brain injury. This study contained seven randomized controlled trials that published before April 5, 2020 in PubMed, Embase, Scopus, Cochrane, and Web of Science databases. The rTMS had significant anti-depressant effect (SMD = 1.03, p = 0.02), but the effects dissipated at 1-month follow-up (SMD = 0.39, p = 0.62). In the subgroup analysis, only applying rTMS to left DLPFC area of post-TBI patients showed significant anti-depressant effect (SMD = 0.98, p = 0.04). Moreover, current data observed that rTMS on post-TBI patients possessed substantial improvement in visuospatial memory (SMD = 0.39, p 

Beschreibung: The phenotype of juvenile fish is closely associated with the adult phenotype, thus consisting an important quality trait for reared fish stocks. In this study, we estimated the correlation between the juvenile and adult body-shape in Gilthead seabream, and examined the genetic basis of the ontogenetic trajectories. The body shape of 959 pit-tagged fish was periodically examined during the juvenile-to-adult period. Individual shape ontogenetic trajectories were studied in respect to the initial (juvenile) and final (adult) phenotypes, as well as to the rate that adult phenotype is attained (phenotypic integration rate). We found that the juvenile body-shape presented a rapid change up to 192.7 ± 1.9 mm standard length, followed by a phenotypically stable period (plateau). Depending on the shape component considered, body-shape correlations between juvenile and adult stages ranged from 0.22 to 0.76. Heritability estimates (h2) of the final phenotype ranged from 0.370 ± 0.077 to 0.511 ± 0.089, whereas h2 for the phenotypic integration rate was 0.173 ± 0.062. To our knowledge, this is the first study demonstrating that the variance of the ontogenetic trajectories has a substantial additive genetic component. Results are discussed in respect to their potential use in selective breeding programs of Gilthead seabream.

Beschreibung: Knowledge without awareness, or implicit knowledge, influences a variety of behaviors. It is unknown however, whether implicit knowledge of statistical structure informs visual perceptual decisions or whether explicit knowledge of statistical probabilities is required. Here, we measured visual decision-making performance using a novel task in which humans reported the orientation of two differently colored translational Glass patterns; each color associated with different orientation probabilities. The task design allowed us to assess participants’ ability to learn and use a general orientation prior as well as a color specific feature prior. Classifying decision-makers based on a questionnaire revealed that both implicit and explicit learners implemented a general orientation bias by adjusting the starting point of evidence accumulation in the drift diffusion model framework. Explicit learners additionally adjusted the drift rate offset. When subjects implemented a stimulus specific bias, they did so by adjusting primarily the drift rate offset. We conclude that humans can learn priors implicitly for perceptual decision-making and depending on awareness implement the priors using different mechanisms.

Beschreibung: Environmental DNA (eDNA) can be a powerful tool for detecting the distribution and abundance of target species. This study aimed to test the longevity of eDNA in marine sediment through a tank experiment and to use this information to reconstruct past faunal occurrence. In the tank experiment, juvenile jack mackerel (Trachurus japonicus) were kept in flow-through tanks with marine sediment for two weeks. Water and sediment samples from the tanks were collected after the removal of fish. In the field trial, sediment cores were collected in Moune Bay, northeast Japan, where unusual blooms of jellyfish (Aurelia sp.) occurred after a tsunami. The samples were analyzed by layers to detect the eDNA of jellyfish. The tank experiment revealed that after fish were removed, eDNA was not present in the water the next day, or subsequently, whereas eDNA was detectable in the sediment for 12 months. In the sediment core samples, jellyfish eDNA was detected at high concentrations above the layer with the highest content of polycyclic aromatic hydrocarbons, reflecting tsunami-induced oil spills. Thus, marine sediment eDNA preserves a record of target species for at least one year and can be used to reconstruct past faunal occurrence.

Beschreibung: Scaling-up supercritical fluid extraction (SFE) for the extraction of bioactive compounds from herbal plants is challenging, especially with the presence of alcohol-water as co-solvent. Hence, the main objective of this study is to validate the scale-up criteria of SFE process for Phyllanthus niruri (P. niruri), and analyse the extract safety and profitability process at the industrial scale. The study was performed by using supercritical carbon dioxide (SC-CO2) with ethanol–water co-solvent at two operating conditions (L1: 200 bar, 60 °C and L2: 262 bar, 80 °C). The solvent-to-feed ratio (S/F) scale-up validation experiments were conducted at both operating conditions with feed mass capacity of 0.5 kg. The extraction yields and overall extraction curves obtained were almost similar to the predicted ones, with error of 5.13% and 14.2%, respectively. The safety of scale-up extract was evaluated by using a toxicity test against zebrafish embryo (FETT). The extract exhibited a low toxic effect with the LD50 value of 505.71 µg/mL. The economic evaluation using a detailed profitability analysis showed that the SFE of P. niruri was an economically feasible process, as it disclosed the encouraging values of return on investment (ROI) and net present values (NPV) for all scale-up capacities.

Beschreibung: Homophily—the tendency of nodes to connect to others of the same type—is a central issue in the study of networks. Here we take a local view of homophily, defining notions of first-order homophily of a node (its individual tendency to link to similar others) and second-order homophily of a node (the aggregate first-order homophily of its neighbors). Through this view, we find a surprising result for homophily values that applies with only minimal assumptions on the graph topology. It can be phrased most simply as “in a graph of red and blue nodes, red friends of red nodes are on average more homophilous than red friends of blue nodes”. This gap in averages defies simple intuitive explanations, applies to globally heterophilous and homophilous networks and is reminiscent of but structurally distinct from the Friendship Paradox. The existence of this gap suggests intrinsic biases in homophily measurements between groups, and hence is relevant to empirical studies of homophily in networks.

Beschreibung: Susceptible-Exposed-Infected-Removed (SEIR)-type epidemiologic models, modeling unascertained infections latently, can predict unreported cases and deaths assuming perfect testing. We apply a method we developed to account for the high false negative rates of diagnostic RT-PCR tests for detecting an active SARS-CoV-2 infection in a classic SEIR model. The number of unascertained cases and false negatives being unobservable in a real study, population-based serosurveys can help validate model projections. Applying our method to training data from Delhi, India, during March 15–June 30, 2020, we estimate the underreporting factor for cases at 34–53 (deaths: 8–13) on July 10, 2020, largely consistent with the findings of the first round of serosurveys for Delhi (done during June 27–July 10, 2020) with an estimated 22.86% IgG antibody prevalence, yielding estimated underreporting factors of 30–42 for cases. Together, these imply approximately 96–98% cases in Delhi remained unreported (July 10, 2020). Updated calculations using training data during March 15-December 31, 2020 yield estimated underreporting factor for cases at 13–22 (deaths: 3–7) on January 23, 2021, which are again consistent with the latest (fifth) round of serosurveys for Delhi (done during January 15–23, 2021) with an estimated 56.13% IgG antibody prevalence, yielding an estimated range for the underreporting factor for cases at 17–21. Together, these updated estimates imply approximately 92–96% cases in Delhi remained unreported (January 23, 2021). Such model-based estimates, updated with latest data, provide a viable alternative to repeated resource-intensive serosurveys for tracking unreported cases and deaths and gauging the true extent of the pandemic.

Beschreibung: Due to urbanization and industrialization, there has been an increase in solid waste generation and has become a global concern and leakage of leachate from landfills contaminate the soil and groundwater and hence can have a severe impact on human health. The present study aimed to determine the composition of toxic metals (Cr, Mn, Cu, As) and heavy metals (Cd, Ba, Hg, Pb) in soil and water by an inductively coupled plasma optical emission spectrometer (ICP-OES). To ensure accuracy during the analysis of Cr, Mn, Cu, As, Cd, Ba, Hg, and Pb in real samples, certified reference material (CRM, SRM 2709a) of San Joaquin soil and water (SRM 1640a) were analyzed and results were presented in terms of % recovery studies. The mean concentration of all the metals in soil and water did not exceed the limit set by the European Community (EU), WHO, and US EPA except Cu where the permissible limit defined by the EU is 50–140 mg/kg in soil. The soil is uncontaminated to moderately contaminated with respect to all metals except the Cu and Pb. Among the average daily dose (ADD) of soil, ADDing and ADDinh for children had the maximum dose for all metals than adults while ADDderm was higher in adults. Hazard quotient (HQ) trend in both adults and children was found in order HQing 〉 HQderm 〉 HQinh of soil for all metals except Ba which followed HQing 〉 HQinh 〉 HQderm. Hazard index (HI) values of soil for Cr and Pb in children were 7 and 7.5 times higher than adults respectively. Lifetime cancer risk (LCR) value for Cr by different exposure pathways of soil was 5.361 × 10−4 for children which are at the lower borderline of risk for cancer.

Beschreibung: Several studies reported that mitochondrial stress induces cytosolic proteostasis in yeast and C. elegans. Notably, inhibition of mitochondrial translation with doxcycyline decreases the toxicity of β-amyloid aggregates, in a C. elegans. However, how mitochondrial stress activates cytosolic proteostasis remains unclear. Further whether doxycycline has this effect in mammals and in disease relevant tissues also remains unclear. We show here that doxycycline treatment in mice drastically reduces the accumulation of proteins destined for degradation by the proteasome in a CNS region-specific manner. This effect is associated with the activation of the ERα axis of the mitochondrial unfolded protein response (UPRmt), in both males and females. However, sexually dimorphic mechanisms of proteasome activation were observed. Doxycycline also activates the proteasome in fission yeast, where ERα is not expressed. Rather, the ancient ERα-coactivator Mms19 regulates this response in yeast. Our results suggest that the UPRmt initiates a conserved mitochondria-to-cytosol stress signal, resulting in proteasome activation, and that this signal has adapted during evolution, in a sex and tissue specific-manner. Therefore, while our results support the use of doxycycline in the prevention of proteopathic diseases, they also indicate that sex is an important variable to consider in the design of future clinical trials using doxycycline.

Beschreibung: In this paper we present, and test in two realistic environments, collaborative Brain-Computer Interfaces (cBCIs) that can significantly increase both the speed and the accuracy of perceptual group decision-making. The key distinguishing features of this work are: (1) our cBCIs combine behavioural, physiological and neural data in such a way as to be able to provide a group decision at any time after the quickest team member casts their vote, but the quality of a cBCI-assisted decision improves monotonically the longer the group decision can wait; (2) we apply our cBCIs to two realistic scenarios of military relevance (patrolling a dark corridor and manning an outpost at night where users need to identify any unidentified characters that appear) in which decisions are based on information conveyed through video feeds; and (3) our cBCIs exploit Event-Related Potentials (ERPs) elicited in brain activity by the appearance of potential threats but, uniquely, the appearance time is estimated automatically by the system (rather than being unrealistically provided to it). As a result of these elements, in the two test environments, groups assisted by our cBCIs make both more accurate and faster decisions than when individual decisions are integrated in more traditional manners.

Beschreibung: In recent years, considerable attention has been paid in time–frequency analysis (TFA) methods, which is an effective technology in processing the vibration signal of rotating machinery. However, TFA techniques are not sufficient to handle signals having a strong non-stationary characteristic. To overcome this drawback, taking short-time Fourier transform as a link, a TFA methods that using the generalized Warblet transform (GWT) in combination with the second order synchroextracting transform (SSET) is proposed in this study. Firstly, based on the GWT and SSET theories, this paper proposes a method combining the two TFA methods to improve the TFA concentration, named GWT–SSET. Secondly, the method is verified numerically with single-component and multi-component signals, respectively. Quantized indicators, Rényi entropy and mean relative error (MRE) are used to analyze the concentration of TFA and accuracy of instantly frequency (IF) estimation, respectively. Finally, the proposed method is applied to analyze nonstationary signals in variable speed. The numerical and experimental results illustrate the effectiveness of the GWT–SSET method.

Beschreibung: Hepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl4-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Liver functional indices, including serum albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in the PZH treatment group (P 

Beschreibung: A teleconnection between North Atlantic tropical storms and Amazon fires is investigated as a possible case of compound remote extreme events. The seasonal cycles of the storms and fires are in phase with a maximum around September and have significant inter-annual correlation. Years of high Amazon fire activity are associated with atmospheric conditions over the Atlantic which favour tropical cyclones. We propose that anomalous precipitation and latent heating in the Caribbean, partly caused by tropical storms, leads to a thermal circulation response which creates anomalous subsidence and enhances surface solar heating over the Amazon. The Caribbean storms and precipitation anomalies could thus promote favourable atmospheric conditions for Amazon fire.

Beschreibung: This study was aimed to investigate the air pollutants impact on heart patient's hospital admission rates in Yazd for the first time. Modeling was done by time series, multivariate linear regression, and artificial neural network (ANN). During 5 years, the mean concentrations of PM10, SO2, O3, NO2, and CO were 98.48 μg m−3, 8.57 ppm, 19.66 ppm, 18.14 ppm, and 4.07 ppm, respectively. The total number of cardiovascular disease (CD) patients was 12,491, of which 57% and 43% were related to men and women, respectively. The maximum correlation of air pollutants was observed between CO and PM10 (R = 0.62). The presence of SO2 and NO2 can be dependent on meteorological parameters (R = 0.48). Despite there was a positive correlation between age and CD (p = 0.001), the highest correlation was detected between SO2 and CD (R = 0.4). The annual variation trend of SO2, NO2, and CO concentrations was more similar to the variations trend in meteorological parameters. Moreover, the temperature had also been an effective factor in the O3 variation rate at lag = 0. On the other hand, SO2 has been the most effective contaminant in CD patient admissions in hospitals (R = 0.45). In the monthly database classification, SO2 and NO2 were the most prominent factors in the CD (R = 0.5). The multivariate linear regression model also showed that CO and SO2 were significant contaminants in the number of hospital admissions (R = 0.46, p = 0.001) that both pollutants were a function of air temperature (p = 0.002). In the ANN nonlinear model, the 14, 12, 10, and 13 neurons in the hidden layer were formed the best structure for PM, NO2, O3, and SO2, respectively. Thus, the Rall rate for these structures was 0.78–0.83. In these structures, according to the autocorrelation of error in lag = 0, the series are stationary, which makes it possible to predict using this model. According to the results, the artificial neural network had a good ability to predict the relationship between the effect of air pollutants on the CD in a 5 years' time series.

Beschreibung: Plastic pollution is a pressing issue because authorities struggle to contain and process the enormous amount of waste produced. We study the potential for reducing plastic waste by examining the efficiency with which different polyethylene terephthalate (PET) bottles deliver beverages. We find that 80% of the variation in bottle weight is explained by bottle capacity, 16% by product category, and 1% by brand. Bottle weight is quadratic and convex function of capacity, which implies that medium capacity bottles are most efficient at delivering consumable product. Local data on PET bottle sales and municipal waste recovery validate the findings. A 20% shift in consumption from smaller to larger bottles could reduce the production of PET waste by over 10,000 t annually in the U.S. alone.

Beschreibung: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Beschreibung: A Correction to this paper has been published: https://doi.org/10.1038/s41597-021-00851-9.

Beschreibung: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Beschreibung: Eucalyptus plantations around the world have been largely used by the paper industry. Optimizing the management of resources is a common practice in this highly competitive industry and new forest growth models may help to understand the impact of climate change on the decisions of the optimization processes. Current optimized management plans use empirical equations to predict future forest stands growth, and it is currently impractical to replace these empirical equations with physiological models due to data input requirements. In this paper, we present a different approach, by first carrying out a preliminary assessment with the process-based physiological model 3PG to evaluate the growth of Eucalyptus stands under climate change predictions. The information supplied by 3PG was then injected as a modifier in the projected yield that feeds the management plan optimizer allowing the interpretation of climate change impacts on the management plan. Modelling results show that although a general increase of rain with climate change is predicted, the distribution throughout the year will not favor the tree growth. On the contrary, rain will increase when it is less needed (summer) and decrease when it is most needed (winter), decreasing forest stand productivity between 3 and 5%, depending on the region and soil. Evaluation of the current optimized plan that kept constant the relation between wood price/cellulose ton shows a variation in different strategic management options and an overall increase of costs in owned areas between 2 and 4%, and a decrease of cumulated net present value, initially at 15% with later stabilization at 6–8%. This is a basic comparison to observe climate change effects; nevertheless, it provides insights into how the entire decision-making process may change due to a reduction in biomass production under future climate scenarios. This work demonstrates the use of physiological models to extract information that could be merged with existing and already implemented empirical models. The methodology may also be considered a preliminary alternative to the complete replacement of empirical models by physiological models. Our approach allows some insight into forest responses to different future climate conditions, something which empirical models are not designed for.

Beschreibung: Complete removal of cancerous tissue and preservation of breast cosmesis with a single breast conserving surgery (BCS) is essential for surgeons. New and better options would allow them to more consistently achieve this goal and expand the number of women that receive this preferred therapy, while minimizing the need for re-excision and revision procedures or more aggressive surgical approaches (i.e., mastectomy). We have developed and evaluated a regenerative tissue filler that is applied as a liquid to defects during BCS prior to transitioning to a fibrillar collagen scaffold with soft tissue consistency. Using a porcine simulated BCS model, the collagen filler was shown to induce a regenerative healing response, characterized by rapid cellularization, vascularization, and progressive breast tissue neogenesis, including adipose tissue and mammary glands and ducts. Unlike conventional biomaterials, no foreign body response or inflammatory-mediated “active” biodegradation was observed. The collagen filler also did not compromise simulated surgical re-excision, radiography, or ultrasonography procedures, features that are important for clinical translation. When post-BCS radiation was applied, the collagen filler and its associated tissue response were largely similar to non-irradiated conditions; however, as expected, healing was modestly slower. This in situ scaffold-forming collagen is easy to apply, conforms to patient-specific defects, and regenerates complex soft tissues in the absence of inflammation. It has significant translational potential as the first regenerative tissue filler for BCS as well as other soft tissue restoration and reconstruction needs.

Beschreibung: The Indian summer monsoon rainfall (ISMR) is vital for the livelihood of millions of people in the Indian region; droughts caused by monsoon failures often resulted in famines. Large volcanic eruptions have been linked with reductions in ISMR, but the responsible mechanisms remain unclear. Here, using 145-year (1871–2016) records of volcanic eruptions and ISMR, we show that ISMR deficits prevail for two years after moderate and large (VEI 〉 3) tropical volcanic eruptions; this is not the case for extra-tropical eruptions. Moreover, tropical volcanic eruptions strengthen El Niño and weaken La Niña conditions, further enhancing Indian droughts. Using climate-model simulations of the 2011 Nabro volcanic eruption, we show that eruption induced an El Niño like warming in the central Pacific for two consecutive years due to Kelvin wave dissipation triggered by the eruption. This El Niño like warming in the central Pacific led to a precipitation reduction in the Indian region. In addition, solar dimming caused by the volcanic plume in 2011 reduced Indian rainfall.

Beschreibung: In this paper, the optimal allocation of constant and switchable capacitors is presented simultaneously in two operation modes, grid-connected and islanded, for a microgrid. Different load levels are considered by employing non-dispatchable distributed generations. The objective function includes minimising the energy losses cost, the cost of peak power losses, and the cost of the capacitor. The optimization problem is solved using the spotted hyena optimizer (SHO) algorithm to determine the optimal size and location of capacitors, considering different loading levels and the two operation modes. In this study, a three-level load and various types of loads, including constant power, constant current, and constant impedance are considered. The proposed method is implemented on a 24-bus radial distribution network. To evaluate the performance of the SHO, the results are compared with GWO and the genetic algorithm (GA). The simulation results demonstrate the superior performance of the SHO in reducing the cost of losses and improving the voltage profile during injection and non-injection of reactive power by distributed generations in two operation modes. The total cost and net saving values for DGs only with the capability of active power injection is achieved 105,780 $ and 100,560.54 $, respectively and for DGs with the capability of active and reactive power injection is obtained 89,568 $ and 76,850.46 $, respectively using the SHO. The proposed method has achieved more annual net savings due to the lower cost of losses than other optimization methods.

Beschreibung: Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence the invasion capacity of ex vivo S_Typhi obtained from liver macerate in non-phagocyte cells. Finally, irregularities in the integrity of intestinal tissue evidenced ruptures in the enterocyte layer, a presence of mononuclear leukocytes in the enterocyte layer, an increase of goblet cells in the enterocyte layer and a high volume of leukocyte infiltrate in the sub-mucosa were greatly increased in coinfected animals. Increases of mononuclear leukocytes in the enterocyte layer and volume of leukocyte infiltrate in the sub-mucosa were also seen in monoinfected animals with P. berghei ANKA. Our findings suggest malaria causes a disarrangement of intestinal homeostasis, exacerbation of proinflammatory cytokines and dysfunction in neutrophils that render the host susceptible to bacteremia by Salmonella spp.

Beschreibung: CaV1.4 L-type calcium channels are predominantly expressed in photoreceptor terminals playing a crucial role for synaptic transmission and, consequently, for vision. Human mutations in the encoding gene are associated with congenital stationary night blindness type-2. Besides rod-driven scotopic vision also cone-driven photopic responses are severely affected in patients. The present study therefore examined functional and morphological changes in cones and cone-related pathways in mice carrying the CaV1.4 gain-of function mutation I756T (CaV1.4-IT) using multielectrode array, patch-clamp and immunohistochemical analyses. CaV1.4-IT ganglion cell responses to photopic stimuli were seen only in a small fraction of cells indicative of a major impairment in the cone pathway. Though cone photoreceptors underwent morphological rearrangements, they retained their ability to release glutamate. Our functional data suggested a postsynaptic cone bipolar cell defect, supported by the fact that the majority of cone bipolar cells showed sprouting, while horizontal cells maintained contacts with cones and cone-to-horizontal cell input was preserved. Furthermore a reduction of basal Ca2+ influx by a calcium channel blocker was not sufficient to rescue synaptic transmission deficits caused by the CaV1.4-IT mutation. Long term treatments with low-dose Ca2+ channel blockers might however be beneficial reducing Ca2+ toxicity without major effects on ganglion cells responses.

Beschreibung: Cyclophosphamide (CPA) dosing by body surface area (BSA, m2) has been questioned as a predictor for individual drug exposure. This study investigated phosphoramide mustard-hemoglobin (PAM-Hb, pmol g−1 Hb) as a biomarker of CPA exposure in 135 female breast cancer patients receiving CPA during three courses based on BSA: 500 mg/m2 (C500 group, n = 67) or 600 mg/m2 (C600 group, n = 68). The inter-individual difference was calculated for both groups by dividing the highest through the lowest PAM-Hb value of each course. The inter-occasion difference was calculated in percentage for each individual by dividing their PAM-Hb value through the group mean per course, and subsequently dividing this ratio of the latter through the previous course. A multivariable linear regression (MLR) was performed to identify factors that explained the variation of PAM-Hb. During the three courses, the inter-individual difference changed from 3.5 to 2.1 and the inter-occasion difference ranged between 13.3% and 11.9% in the C500 group. In the C600 group, the inter-individual difference changed from 2.7 to 2.9 and the inter-occasion difference ranged between 14.1% and 11.7%. The MLR including BSA, age, GFR, and albumin explained 17.1% of the variation of PAM-Hb and was significantly better then the model including only BSA. These factors should be considered when calculating the first dose of CPA for breast cancer patients.

Beschreibung: In several species, rank predicts access to food, and subordinates may need specific behavioural strategies to get a share of resources. This may be especially important in despotic species, where resources are strongly biased in favour of dominants and subordinates may more strongly rely on specific tactics to maximize food intake. Here, we compared three macaque species with an experimental set-up reproducing feeding competition contest. Following our predictions, more tolerant species mostly retrieved food in the presence of others and were less dependent on specific tactics. Contrarily, subordinates in more despotic species more likely collected food (1) when dominants could not see food or (2) were attacking others, (3) while “dissimulating”, or (4) “storing food”. Our study reveals that dominance styles reliably predict the probability of using specific food retrieval tactics and provides important insights on the social conditions that might have led to the emergence of tactical deception.

Beschreibung: The characteristic depth dose deposition of ion beams, with a maximum at the end of their range (Bragg peak) allows for local treatment delivery, resulting in better sparing of the adjacent healthy tissues compared to other forms of external beam radiotherapy treatments. However, the optimal clinical exploitation of the favorable ion beam ballistic is hampered by uncertainties in the in vivo Bragg peak position. Ionoacoustics is based on the detection of thermoacoustic pressure waves induced by a properly pulsed ion beam (e.g., produced by modern compact accelerators) to image the irradiated volume. Co-registration between ionoacoustics and ultrasound imaging offers a promising opportunity to monitor the ion beam and patient anatomy during the treatment. Nevertheless, the detection of the ionoacoustic waves is challenging due to very low pressure amplitudes and frequencies (mPa/kHz) observed in clinical applications. We investigate contrast agents to enhance the acoustic emission. Ultrasound microbubbles are used to increase the ionoacoustic frequency around the microbubble resonance frequency. Moreover, India ink is investigated as a possible mean to enhance the signal amplitude by taking advantage of additional optical photon absorption along the ion beam and subsequent photoacoustic effect. We report amplitude increase of up to 200% of the ionoacoustic signal emission in the MHz frequency range by combining microbubbles and India ink contrast agents.

Beschreibung: The MW 8.8 Maule earthquake is the largest well-recorded megathrust earthquake reported in South America. It is known to have had very few foreshocks due to its locking degree, and a strong aftershock activity. We analyze seismic activity in the area of the 27 February 2010, MW 8.8 Maule earthquake at different time scales from 2000 to 2019. We differentiate the seismicity located inside the coseismic rupture zone of the main shock from that located in the areas surrounding the rupture zone. Using an original spatial and temporal method of seismic comparison, we find that after a period of seismic activity, the rupture zone at the plate interface experienced a long-term seismic quiescence before the main shock. Furthermore, a few days before the main shock, a set of seismic bursts of foreshocks located within the highest coseismic displacement area is observed. We show that after the main shock, the seismic rate decelerates during a period of 3 years, until reaching its initial interseismic value. We conclude that this megathrust earthquake is the consequence of various preparation stages increasing the locking degree at the plate interface and following an irregular pattern of seismic activity at large and short time scales.

Beschreibung: Serotonin (5-HT) plays an important role in cerebrovascular homeostasis and psychiatric disorders, including suicidality. Methylation of the serotonin transporter gene (SLC6A4) is associated with 5-HT expression. However, the prognostic roles of SLC6A4 methylation and suicidal ideation (SI) in long-term outcomes of stroke have not been evaluated. We investigated the independent and interactive effects of SLC6A4 methylation and SI immediately after stroke on long-term outcomes. Blood SLC6A4 methylation status and SI based on the suicide item of the Montgomery–Åsberg Depression Rating Scale were assessed in 278 patients at 2 weeks after stroke. After the index stroke, cerebro-cardiovascular events by SLC6A4 methylation status and SI were investigated over an 8–14-year follow-up period and using Cox regression models adjusted for a range of covariates. SLC6A4 hypermethylation and SI within 2 weeks of stroke both predicted worse long-term outcomes, independent of covariates. A significant interaction effect of SI and the methylation status of CpG 4 on long-term stroke outcomes was also identified. The association between SLC6A4 methylation and long-term adverse outcomes may be strengthened in the presence of SI within 2 weeks after stroke. Evaluation of methylation and SI status during the acute phase can be helpful when assessing stroke patients.

Beschreibung: There is a growing need for surrogate biomarkers for Parkinson’s disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.

Beschreibung: The human hepatoblastoma cell line, HepG2, has been used for investigating a wide variety of physiological and pathophysiological processes. However, less information is available about the phospholipid metabolism in HepG2 cells. In the present report, to clarify the relationship between cell growth and phospholipid metabolism in HepG2 cells, we examined the phospholipid class compositions of the cells and their intracellular organelles by using enzymatic fluorometric methods. In HepG2 cells, the ratios of all phospholipid classes, but not the ratio of cholesterol, markedly changed with cell growth. Of note, depending on cell growth, the phosphatidic acid (PA) ratio increased and phosphatidylcholine (PC) ratio decreased in the nuclear membranes, the sphingomyelin (SM) ratio increased in the microsomal membranes, and the phosphatidylethanolamine (PE) ratio increased and the phosphatidylserine (PS) ratio decreased in the mitochondrial membranes. Moreover, the mRNA expression levels of enzymes related to PC, PE, PS, PA, SM and cardiolipin syntheses changed during cell growth. We suggest that the phospholipid class compositions of organellar membranes are tightly regulated by cell growth. These findings provide a basis for future investigations of cancer cell growth and lipid metabolism.

Beschreibung: Defining priority areas and risk evaluation is of utmost relevance for endangered species` conservation. For the blue whale (Balaenoptera musculus), we aim to assess environmental habitat selection drivers, priority areas for conservation and overlap with vessel traffic off northern Chilean Patagonia (NCP). For this, we implemented a single-step continuous-time correlated-random-walk model which accommodates observational error and movement parameters variation in relation to oceanographic variables. Spatially explicit predictions of whales’ behavioral responses were combined with density predictions from previous species distribution models (SDM) and vessel tracking data to estimate the relative probability of vessels encountering whales and identifying areas where interaction is likely to occur. These estimations were conducted independently for the aquaculture, transport, artisanal fishery, and industrial fishery fleets operating in NCP. Blue whale movement patterns strongly agreed with SDM results, reinforcing our knowledge regarding oceanographic habitat selection drivers. By combining movement and density modeling approaches we provide a stronger support for purported priority areas for blue whale conservation and how they overlap with the main vessel traffic corridor in the NCP. The aquaculture fleet was one order of magnitude larger than any other fleet, indicating it could play a decisive role in modulating potential negative vessel-whale interactions within NCP.