bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between role conflict and ambiguity and stress among nurses in primary health care centers in Saudi Arabia during the coronavirus disease 2019 pandemic
Authors: Alyahya Saad A. , Al-Mansour Khalid A. , Alkohaiz Mohammed A. , Almalki Mansour A. 
Published: September 2021

Abstract
This study aimed to assess the association between role conflict and ambiguity among nurses in primary healthcare centers (PHCs) in Saudi Arabia and their stress levels during the coronavirus disease 2019 (COVID-19) pandemic.
In this online cross-sectional study, sociodemographic and occupational characteristics, role conflict, and ambiguity of 432 nurses were assessed using the Bowling Scale for Role Conflict and Ambiguity and stress was assessed using the 10-item Perceived Stress Scale from September 27 to October 17, 2020. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for above-median stress levels of nurses with average and high (2nd and 3rd tertiles) role conflict and ambiguity compared with nurses with low role conflict and ambiguity (1st tertile).
The mean (standard deviation) age of the nurses was 36.5 ± 6.6 years, and 25.9% of them were males. After adjusting for PHC type and working hours, nurses with average and high role conflict had significantly higher stress rates than those with low role conflict, with ORs (95% CIs) of 2.69 (1.62–4.46) and 6.31 (3.78–10.53), respectively. Similarly, nurses with average- and high-role ambiguity had significantly higher stress than those with low role ambiguity, with ORs (95% CIs) of 2.15 (1.30–3.55) and 7.68 (4.54–13.01), respectively. Increasing stress rates were detected across increasing categories of role conflict and ambiguity (P values for trend <.001).
We found that role conflict and ambiguity were associated with stress among nurses in PHCs in Saudi Arabia during the COVID-19 pandemic.
Emerging therapeutic and preventive approaches to transplant-associated thrombotic microangiopathy
Authors: Schoettler Michelle , Chonat Satheesh , Williams Kirsten , Lehmann Leslie 
Published: September 2021

Purpose of review
Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication that can occur in both allogeneic and autologous haematopoietic cellular therapy (HCT) recipients and is associated with significant morbidity and mortality. Although TA-TMA is a complex disease, there is emerging evidence that complement activation and endothelial dysfunction play a key role in the pathophysiology of the disease. The use of eculizumab has improved survival in patients with high risk and severe disease, but mortality rates in treated patients still exceed 30%, highlighting the need for novel approaches.

Recent findings
There are multiple ongoing and planned clinical trials investigating novel complement agents in TA-TMA and other TMAs. Drugs vary by targets of the complement system, mechanism, and form of administration. Clinical trial designs include single arm studies that span across multiple age groups including children, and double-blind, randomized, placebo-controlled studies. These studies will provide robust data to inform the care of patients with TA-TMA in the future. In addition to multiple promising therapeutic agents, preventing TA-TMA is an emerging strategy. Agents known to protect the endothelium from damage and augment endothelial function by promoting anti-inflammatory and antithrombotic effects may have a role in preventing TA-TMA or ameliorating the severity, though additional studies are needed.

Summary
Novel therapeutic agents for TA-TMA inhibition of the complement system are under investigation and prophylactic strategies of endothelial protection are emerging. Further understanding of the pathophysiology of the disease may identify additional therapeutic targets. Multiinstitutional, collaborative clinical trials are needed to determine the safety and efficacy of these agents going forward.
Racial Disparities in Stroke Readmissions Reduced in Hospitals With Better Nurse Staffing
Authors: Carthon J. Margo Brooks , Brom Heather , McHugh Matthew , Daus Marguerite , French Rachel , Sloane Douglas M. , Berg Robert , Merchant Raina , Aiken Linda H. 
Published: September 2021

Background
Racial minorities are disproportionately affected by stroke, with Black patients experiencing worse poststroke outcomes than White patients. A modifiable aspect of acute stroke care delivery not yet examined is whether disparities in stroke outcomes are related to hospital nurse staffing levels.

Objectives
The aim of this study was to determine whether 7- and 30-day readmission disparities between Black and White patients were associated with nurse staffing levels.

Methods
We conducted a secondary analysis of 542 hospitals in four states. Risk-adjusted, logistic regression models were used to determine the association of nurse staffing with 7- and 30-day all-cause readmissions for Black and White ischemic stroke patients.

Results
Our sample included 98,150 ischemic stroke patients (87% White, 13% Black). Thirty-day readmission rates were 10.4% (12.7% for Black patients, 10.0% for White patients). In models accounting for hospital and patient characteristics, the odds of 30-day readmissions were higher for Black than White patients. A significant interaction was found between race and nurse staffing, with Black patients experiencing higher odds of 30- and 7-day readmissions for each additional patient cared for by a nurse. In the best-staffed hospitals (less than three patients per nurse), Black and White stroke patients’ disparities were no longer significant.

Discussion
Disparities in readmissions between Black and White stroke patients may be linked to the level of nurse staffing in the hospitals where they receive care. Tailoring nurse staffing levels to meet the needs of Black ischemic stroke patients represents a promising intervention to address systemic inequities linked to readmission disparities among minority stroke patients.
Long-term Effects of Perceived Stress, Anxiety, and Anger on Hospitalizations or Death and Health Status in Heart Failure Patients
Authors: Dimond Andrew J. , Krantz David S. , Waters Andrew J. , Liew Keen Seong , Gottlieb Stephen S. 
Published: September 2021

ABSTRACTBackgroundChronic and acute stress and emotion predict incidence/recurrence of CHD, but long-term effects on HF exacerbations are poorly understood. This study determined long-term chronic and episodic effects of stress, anxiety, and anger on hospitalizations or death, and worsened health status in HF.Methods and Results147 patients with heart failure and reduced ejection fraction (HFrEF) completed measures of perceived stress (Perceived Stress Scale; PSS), state anxiety (STAI), recent anger (RA), and HF-related health status (Kansas City Cardiomyopathy Questionnaire; KCCQ) every 6 months for up to 39 months. Relationships of chronic (Mean) stress and emotion and episodic changes (Deviation) to subsequent hospitalizations or death and health status were determined utilizing Generalized Estimating Equation models. All-cause hospitalizations were predicted by chronic (Mean) PSS (OR=1.06, 95% CI 1.02-1.11, p=0.004), Mean STAI (OR=1.06, 95% CI=1.03, 1.10, p<0.001), and episodic (Deviation) PSS (OR=1.03, 95% CI 1.01-1.06, p=0.022). Mean PSS and Mean STAI also predicted cardiovascular hospitalizations. Each 1 standard deviation increase in Mean PSS and Mean STAI was associated, respectively, with a 61% and 79% increase in hospitalization or death. Anger was not associated with hospitalizations. Poorer KCCQ health status was related to higher Mean and Deviation PSS, STAI, and RA. Relationships to hospitalizations and health status were significant for Anxiety and Perceived Stress, independently of the other psychological measures.ConclusionsIn HF patients, chronic perceived stress and anxiety and episodic stress increases are predictive of hospitalizations or death and worsened health status over a >3-year period. Mechanisms may involve sympathetic activation, and/or exacerbations of perceived symptoms or health behaviors.
Quantitative drug susceptibility testing for M. tuberculosis using unassembled sequencing data and machine learning
Authors:   The CRyPTIC consortium, Lachapelle Alexander S 
Published: September 2021

AbstractThere remains a clinical need for better approaches to rapid drug susceptibility testing in view of the increasing burden of multidrug resistant tuberculosis. Binary susceptibility phenotypes only capture changes in minimum inhibitory concentration when these cross the critical concentration, even though other changes may be clinically relevant. We developed a machine learning system to predict minimum inhibitory concentration from unassembled whole-genome sequencing data for 13 anti-tuberculosis drugs. We trained, validated and tested the system on 10,859 isolates from the CRyPTIC dataset. Essential agreement rates (predicted MIC within one doubling dilution of observed MIC) were above 92% for first-line drugs, 91% for fluoroquinolones and aminoglycosides, and 90% for new and repurposed drugs, albeit with a significant drop in performance for the very few phenotypically resistant isolates in the latter group. To further validate the model in the absence of external MIC datasets, we predicted MIC and converted values to binary for an external set of 15,239 isolates with binary phenotypes, and compare their performance against a previously validated mutation catalogue, the expected performance of existing molecular assays, and World Health Organization Target Product Profiles. The sensitivity of the model on the external dataset was greater than 90% for all drugs except ethionamide, clofazimine and linezolid. Specificity was greater than 95% for all drugs except ethambutol, ethionamide, bedaquiline, delamanid and clofazimine. The proposed system can provide quantitative susceptibility phenotyping to help guide antimicrobial therapy, although further data collection and validation are required before machine learning can be used clinically for all drugs.
Long-term meditation training is associated with enhanced attention and stronger posterior cingulate – rostrolateral prefrontal cortex resting connectivity
Authors: Kral Tammi RA , Lapate Regina , Imhoff-Smith Ted , Patsenko Elena , Grupe Daniel W , Goldman Robin , Rosenkranz Melissa A , Davidson Richard J 
Published: September 2021

AbstractMindfulness meditation has been shown to increase resting state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC–DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC – DLPFC rsFC in a sample of 40 long-term meditators (average practice= 3759 hours) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in inter-regional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (PFC) rsFC, lower connector hub strength across the default mode network (DMN) relative to other functional networks, and better attention to task, compared to 124 meditation-naïve controls. Orienting attention positively correlated with PCC– rostrolateral PFC connectivity, and negatively correlated with DMN connector hub strength. These findings provide novel evidence that posterior cingulate – rostrolateral PFC rsFC may support attention orienting, consistent with a role for rostrolateral PFC in meta-cognitive background awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.
The polyol pathway is an evolutionarily conserved system for sensing glucose uptake
Authors: Sano Hiroko , Nakamura Akira , Yamane Mariko , Niwa Hitoshi , Nishimura Takashi , Araki Kimi , Takemoto Kazumasa , Ishiguro Kei-ichiro , Aoki Hiroki , Kojima Masayasu 
Published: September 2021

SummaryCells must adjust the expression levels of metabolic enzymes in response to fluctuating nutrient supply. For glucose, such metabolic remodeling is highly dependent on a master transcription factor ChREBP/MondoA. However, it remains elusive how glucose fluctuations are sensed by ChREBP/MondoA despite the stability of major glycolytic pathways. Here we show that in both flies and mice, ChREBP/MondoA activation in response to glucose ingestion depends on an evolutionarily conserved glucose-metabolizing pathway: the polyol pathway. The polyol pathway converts glucose to fructose via sorbitol. It has been believed that this pathway is almost silent, and its activation in hyperglycemic conditions has deleterious effects on human health. We show that the polyol pathway is required for the glucose-induced nuclear translocation of Mondo, a Drosophila homologue of ChREBP/MondoA, which directs gene expression for organismal growth and metabolism. Likewise, inhibition of the polyol pathway in mice impairs ChREBP’s nuclear localization and reduces glucose tolerance. We propose that the polyol pathway is an evolutionarily conserved sensing system for the glucose uptake that allows metabolic remodeling.
NLRP3 activation in response to disrupted endocytic traffic
Authors: Lee Bali , Hoyle Christopher , Green Jack P. , Wellens Rose , Martin-Sanchez Fatima , Williams Daniel , Seoane Paula I. , Bennett Hayley , Adamson Antony , Lopez-Castejon Gloria , Lowe Martin , Brough David 
Published: September 2021

AbstractInflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and with a poorly defined regulation by sub-cellular organelles. Here, we tested the hypothesis that NLRP3 senses disrupted endosome trafficking to trigger inflammasome formation and inflammatory cytokine secretion. NLRP3-activating stimuli disrupted endosome trafficking and triggered localization of NLRP3 to vesicles positive for endosome markers and the inositol lipid PtdIns4P. Chemical disruption of endosome trafficking sensitized macrophages to the NLRP3 activator imiquimod driving enhanced inflammasome activation and cytokine secretion. Together these data suggest that NLRP3 is capable of sensing disruptions in the trafficking of endosomal cargoes, and that this may explain in part the spatial activation of the NLRP3 inflammasome complex. These data highlight new mechanisms amenable for the therapeutic targeting of NLRP3.One-Sentence SummaryNLRP3 senses disruptions in endosome trafficking to trigger the formation of an inflammasome complex and initiate an inflammatory response.
Physical geography, isolation by distance and environmental variables shape genomic variation of wild barley (Hordeum vulgare L. ssp. spontaneum) in the Southern Levant
Authors: Chang Che-Wei , Fridman Eyal , Mascher Martin , Himmelbach Axel , Schmid Karl 
Published: September 2021

AbstractDetermining the extent of genetic variation that reflects local adaptation in crop wild relatives is of interest to discovering useful genetic diversity for plant breeding. We investigated the association of genomic variation with geographical and environmental factors in wild barley (Hordeum vulgare L. ssp. spontaneum) populations of the Southern Levant using genotyping-by-sequencing (GBS) of 244 accessions of the Barley1K+ collection. Inference of population structure resulted in four genetic clusters that corresponded to eco-geographical habitats and a significant association of lower gene flow rates with geographical barriers, e.g. the Judaean Mountains and the Sea of Galilee. Redundancy analysis (RDA) revealed that spatial autocorrelation explained 45% and environmental variables explained 15% of total genomic variation. Only 4.5% of genomic variation was exclusively attributed to environmental variation if the component confounded with spatial autocorrelation was excluded. A synthetic environmental variable combining latitude, solar radiation, and accumulated precipitation explained the highest proportion of genomic variation (3.9%). After correcting for population structure, soil water capacity was the most important environmental variable explaining 1.18% of genomic variation. Genome scans with outlier analysis and genome-environment association studies were conducted to identify signatures of adaptation. RDA and outlier methods jointly detected selection signatures in the pericentromeric regions of chromosome 3H, 4H, and 5H, but they mostly disappeared after correction for population structure. In conclusion, adaptation to the highly diverse environments of the Southern Levant over short geographical ranges has a small effect on the genomic diversity of wild barley highlighting the importance of non-selective forces in genetic differentiation.
Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice
Authors: Vaughan Owen R. , Rosario Fredrick J. , Chan Jeannie , Cox Laura A. , Ferchaud-Roucher Veronique , Zemski-Berry Karin A. , Reusch Jane E.B. , Keller Amy C. , Powell Theresa L. , Jansson Thomas 
Published: September 2021

ABSTRACTObesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk but its effect on myocardial metabolism is unknown. We hypothesised that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day, E18.5; term≈E21) and offspring were studied at 3, 6, 9 or 24 months postnatally. Maternal obesity increased heart weight and peroxisome proliferator activated receptor γ (Pparg) expression in female and male fetuses and caused left ventricular diastolic dysfunction in the adult offspring. Cardiac dysfunction progressively worsened with age in female, not male, offspring of obese dams, compared to age-matched controls. In 6-month-old offspring, exposure to maternal obesity increased cardiac palmitoyl carnitine-supported mitochondrial respiration in males and reduced myocardial 18F-fluorodeoxyglucose uptake in females. Cardiac Pparg expression remained higher in adult offspring of obese than control dams and correlated with contractile and metabolic function. Maternal obesity did not affect cardiac palmitoyl carnitine respiration in females or 18F-fluorodeoxyglucose uptake in males, or alter cardiac 3H-oleic acid uptake, pyruvate respiration, lipid content or fatty acid/glucose transporter abundance in offspring of either sex. The results support our hypothesis and show that maternal obesity affects offspring cardiac metabolism in a sex-dependent manner. Persistent upregulation of Pparg expression in response to overnutrition in utero may mechanistically underpin programmed cardiac impairments and contribute to cardiovascular disease risk in children of women with obesity.
Effect of Endoplasmic Reticulum Stress on Human Trophoblast Cells: Survival Triggering or Catastrophe Resulting in Death
Authors: Garip Gurur , Ozdil Berrin , Calik-Kocaturk Duygu , Oltulu Fatih , Eroglu Fatma Zuhal , Aktug Huseyin , Uysal Aysegul 
Published: September 2021

ABSTRACTAlthough in vitro endoplasmic reticulum (ER) stress studies have been carried out using Tunicamycin in human trophoblast cell lines in recent years, the effect of calcium homeostasis impaired by the effect of Thapsigargin on cell survival - death pathways have not been clearly demonstrated.Here, the effects of ER stress and impaired calcium homeostasis on cell death pathways such as apoptosis and autophagy in 2-dimensional and 3-dimensional cell cultures were investigated using the HTR8 / SVneo cell line representing human trophoectoderm cells and the ER stressor Thapsigargin. By using Real Time PCR, gene and immunofluorescence analyzes were studied at the protein level.In this study, it has been established that the Thapsigargin creates ER stress by increasing the level of GRP78 gene and protein in 2 and 3 dimensions of human trophoectoderm cells and that cells show different characterization properties in 2 and 3 dimensions. It has been determined that while it moves in the direction of EIF2A and IRE1A mechanisms in 2 dimensions, it proceeds in the direction of EIF2A and ATF6 mechanisms in 3 dimensions and creates different responses in survival and programmed cell death mechanisms such as apoptosis and autophagy.With forthcoming studies, it is thought that the effects of Thapsigargin on the intrinsic pathway of apoptosis and the linkage of the autophagy mechanism, the examination of the survival-death pathways in the co-culture model with endometrial cells, therapeutic target molecules that will contribute to the elucidation of intracellular cell dynamics may increase the success of implantation.
Conserved induction of distinct antiviral signalling kinetics by primate interferon lambda 4 proteins
Authors: Guo Cuncai , Reuss Dorothee , Coey Jonathon D. , Sukumar Swathi , Lang Benjamin , McLauchlan John , Boulant Steeve , Stanifer Megan L. , Bamford Connor G. G. 
Published: September 2021

AbstractInterferon lambdas (IFNλ) (also known as type III IFNs) are critical cytokines that combat infection predominantly at barrier tissues, such as the lung, liver and gastrointestinal tract. Humans have four IFNλs (1-4) where IFNλ1-3 show ∼80-95% homology and IFNλ4 is the most divergent displaying only ∼30% sequence identity. Variants in IFNλ4 in humans are associated with the outcome of infection, such as with hepatitis C virus. However, how IFNλ4 variants impact cytokine signalling in other tissues and how well this is conserved is largely unknown. In this study we address whether differences in antiviral signalling exist between IFNλ4 variants in human hepatocyte and intestinal cells, comparing them to IFNλ3. We demonstrate that compared to IFNλ3, wild-type human IFNλ4 induces a signalling response with distinct magnitudes and kinetics, which is modified by naturally-occurring variants P70S and K154E in both cell types. IFNλ4’s distinct antiviral response was more rapid yet transient compared to IFNλ1 and 3. Additionally, divergent antiviral kinetics were also observed using non-human primate IFNλs and cell lines. Furthermore, an IFNλ4-like receptor-interacting interface failed to alter IFNλ1’s kinetics. Together our data provide further evidence that major functional differences exist within the IFNλ gene family. These results highlight the possible tissue specialisation of IFNλs and encourage further investigation of the divergent, non-redundant activities of IFNλ4 and other IFNλs.Contribution to the FieldViral infections remain major causes of death and disease in humans and other animals. Interferons (IFNs) are a diverse group of host signalling proteins that can induce a potent antiviral state in cells and are intimately involved in the outcome of infection. Genetic variants within one IFN (interferon lambda 4, IFNλ4) are associated with the outcome of hepatitis C infection in humans. However, how IFNλ4 functions – and how natural variants affect its activity - remains poorly understood. Comparing how the antiviral activity changes over time following stimulation with different IFNλs, we identified that IFNλ4 induces a more rapid antiviral state compared to other IFNλs in liver and intestinal cells. Importantly, this response was conserved within human variants and between humans and non-human primates (chimpanzee and Rhesus macaque). Our results shed light on the unique functions of the divergent IFNλ4 protein.