bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral kinetics of sequential SARS-CoV-2 infections
Authors: Kissler Stephen M , Hay James A , Fauver Joseph R , Mack Christina , Tai Caroline G , Anderson Deverick J , Ho David D , Grubaugh Nathan D , Grad Yonatan H 
Published: March 2023

AbstractThe impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we compared the SARS-CoV-2 viral kinetics of firstvs. second infections, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a lower peak viral concentration and faster clearance time, especially in individuals who received a vaccine dose between their first and second infection. Furthermore, a person’s relative (rank-order) viral clearance time, compared to others infected with the same variant, was similar across first and second infections; that is, individuals who had a relatively fast clearance time in their first infection tended to also have a relatively fast clearance time in their second infection. These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person’s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.
Relationship between blood pressure and the risk of acute myocardial infarction in Chinese adults: a prospective study
Authors: Zhang Xin , He Xiaoyong , Mao Fan , Zhang Run , You Xiaoqing , Li Jianhong 
Published: March 2023

AbstractObjectiveTo explore the relationship between blood pressure and the risk of acute myocardial infarction (AMI) in Chinese adults.MethodsThis prospective cohort study included 26,794 participants which were recruited from 60 surveillance sites in 2010 China Chronic Disease Risk Factor Surveillance and followed-up survey was conducted from 2016 to 2017. Data were collected by questionnaires, physical measurements and laboratory tests. Blood pressure was grouped by systolic blood pressure and diastolic blood pressure, and cox proportional hazards regression models were used to analyze the relationship between blood pressure and risk of AMI.ResultsA total of 256 AMI events occurred among 160,386.38 person-years follow-up and the incidence of AMI was 159.6/100,000 person-years. After adjusting for age, sex, income, education, marital status, physical activity, drinking, abdominal obesity, BMI, dyslipidemia and diabetes, compared with normotension group, the risk of AMI onset was increased by 61% (HR=1.61, 95%CI: 1.17∼2.21), 60% (HR=1.60, 95%CI: 1.17∼2.20), 84% (HR=1.84, 95%CI: 1.26∼2.68) and 120% (HR=2.20, 95%CI: 1.43∼3.38) in systolic diastolic hypertension(SDH), hypertension grade 1(mild), hypertension grade 2(moderate), hypertension grade 3(severe), respectively. In addition, after adjusting for relevant factors, the relationship between hypertension and the risk of AMI may be influenced by abdominal obesity, diabetes and lack of physical activity.ConclusionsThe incidence of AMI appears to be considerable among Chinese adults and hypertension is an independent risk factor for its onset. The risk of AMI is higher in participants with more severe hypertension.
Stress-induced brain responses are associated with BMI in women
Authors: Kühnel Anne , Hagenberg Jonas , Knauer-Arloth Janine , Ködel Maik , Czisch Michael , Sämann Philipp G. ,   BeCOME working group, Binder Elisabeth B. , Kroemer Nils B. 
Published: March 2023

AbstractBackgroundStress is associated with elevated risk for overweight and obesity, especially in women. Since body mass index (BMI) is correlated with increased inflammation and reduced baseline cortisol, obesity may lead to altered stress responses. However, it is not well understood whether stress-induced changes in brain function scale with BMI and if peripheral inflammation contributes to this.MethodsWe investigated the subjective, autonomous, endocrine, and neural stress response in a transdiagnostic sample (N=192, 120 women, MBMI=23.7±4.0 kg/m2; N=148, 89 women, with cytokines). First, we used regression models to examine effects of BMI on stress reactivity. Second, we predicted BMI based on stress-induced changes in activation and connectivity using cross-validated elastic-nets. Third, to link stress responses with inflammation, we quantified the association of BMI-related cytokines with model predictions.ResultsBMI was associated with higher negative affect after stress and an increased response to stress in the substantia nigra and the bilateral posterior insula (pFWE<.05). Moreover, stress-induced changes in activation of the hippocampus, dACC, and posterior insula predicted BMI in women (pperm<.001), but not in men. BMI was associated with higher baseline cortisol while cytokines were not associated with predicted BMI scores.ConclusionsStress-induced changes in the hippocampus and posterior insula predicted BMI in women, indicating that acute brain responses to stress might be more strongly related to a higher BMI in women compared to men. Altered stress-induced changes were associated with baseline cortisol but independent of cytokines, suggesting that the endocrine system and not inflammation contributes to stress-related changes in BMI.
Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda
Authors: Sado Keina , Keenan Katherine , Manataki Areti , Kesby Mike , Mushi Martha F , Mshana Stephen E , Mwanga Joseph , Neema Stella , Asiimwe Benon , Bazira Joel , Kiiru John , Green Dominique L , Ke Xuejia , Maldonado-Barragán Antonio , Abed Al Ahad Mary , Fredricks Kathryn , Gillespie Stephen H , Sabiiti Wilber , Mmbaga Blandina T , Kibiki Gibson , Aanensen David , Smith V Anne , Sandeman Alison , Sloan Derek J , Holden Matthew TG 
Published: March 2023

AbstractAntibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviours, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce.The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from 6,827 adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Among 6,388 patients we analysed patterns of self-reported treatment seeking behaviours (‘patient pathways’) using process mining and single-channel sequence analysis. Of those with microbiologically confirmed UTI (n=1,946), we used logistic regression to assessed the relationship between treatment seeking behaviour, AB use, and likelihood of having a multi-drug resistant (MDR) UTI.The most common treatment pathways for UTI-like symptoms included attending health facilities, rather than other providers (e.g. drug sellers). Patients from the sites sampled in Tanzania and Uganda, where prevalence of MDR UTI was over 50%, were more likely to report treatment failures, and have repeated visits to clinics/other providers, than those from Kenyan sites, where MDR UTI rates were lower (33%). There was no strong or consistent relationship between individual AB use and risk of MDR UTI, after accounting for country context.The results highlight challenges East African patients face in accessing effective UTI treatment. These challenges increase where rates of MDR UTI are higher, suggesting a reinforcing circle of failed treatment attempts and sustained selection for drug resistance. Whilst individual behaviours may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of ABR.
Machines learn ecological networks: automated discovery of ecological networks based on empirical data
Authors: Ko Hongseok , Kim Ahyoung Amy , Zhang Hao Helen 
Published: March 2023

AbstractConstructing ecological networks is known to be important and challenging in community ecology. In particular, to construct the holistic structure of ecological networks, identifying species interaction is essential but often costly and impalpable. Recent studies providing major challenges in assembling ecological networks have highlighted the need of new and more powerful approaches to reconstruct biological networks, including species interaction networks. In literature, there are no promising verifications in using machine leaning (ML) approaches to reconstruct ecological networks. In this work, we develop and employ a variety of ML methods, including penalized regression and graphical tools, to reconstruct ecological networks. For evaluation, we apply the methods to empirical time series data sets of 20 species abundances collected at Lake Constance in central Europe. We use resampled data to identify highly-ranked interactions among species and measure their consistency across 7 ML methods and 5,000 learning processes. We show that the best precision, recall, and F1 score were 0.48, 0.97, and 0.64, respectively, among all penalized regression methods under comparison. In summary, our study shows that machine learning methods offer promising data-driven and automated tools for reconstructing ecological networks and discovering underlying biological interactions among species.
Using risk advancement periods to derive starting ages of colorectal cancer screening according to sex and polygenic risk score: Results from the UK Biobank
Authors: Chen Xuechen , Heisser Thomas , Cardoso Rafael , Hoffmeister Michael , Brenner Hermann 
Published: March 2023

AbstractObjectivePolygenic risk scores (PRSs) derived from genome-wide association studies are strong predictors of colorectal cancer (CRC) risk. We applied the straightforward approach of risk advancement periods (RAPs) to derive risk-adapted starting ages of CRC screening according to sex and PRS in the UK Biobank.MethodsAmong 242,779 participants (40-69 years; no previous CRC screening; no family history of CRC), we assessed associations of sex and a PRS with CRC risk and mortality using Cox regression models. Hazard ratios (HRs) were translated to RAPs to quantify how many years of age earlier men and women in defined PRS deciles reach comparable risks as those in the reference group (5thand 6thPRS deciles).ResultsDuring a median follow-up of 11.2 and 12.8 years, 2,714 participants were diagnosed with CRC and 758 died from CRC, respectively. HRs (95% CIs) of CRC risk were 1.57 (1.46, 1.70) for men versus women and ranged from 0.51 (0.41, 0.62) to 2.29 (2.01, 2.62) across PRS deciles compared to the reference. RAPs (95% CI) were 5.6 (4.6, 6.6) years for men versus women, and ranged from -8.4 (-11.0, -5.9) to 10.3 (8.5, 12.1) years across PRS deciles compared to the reference. Risk-adapted starting ages would vary by 24 years between men in the highest PRS decile and women in the lowest PRS decile. Very similar results were obtained regarding CRC mortality.ConclusionConsideration of sex and a standard PRS alone could have far-reaching implications for starting ages of CRC screening in the “average risk population”.SUMMARY BOXWhat is already known on this topicPolygenic risk scores (PRSs) are strong predictors of colorectal cancer (CRC) risk.Men have substantially higher CRC incidence and mortality than women.CRC risk information from the combination of PRS and genetically determined sex, which are constant factors over lifetime, is so far not used for risk-adapted CRC screening in the “average risk population”.What this study addsRisk advancement periods (RAPs) of CRC by PRS and sex were derived at high levels of precision from the large database of the UK Biobank.By joint consideration of PRS and genetically defined sex, risk-adapted starting ages would vary by as much as 24 years between men in the highest PRS decile and women in the lowest PRS decile.How this study might affect research, practice or policyOur study demonstrates a straightforward way to translate CRC risk information from a large population-based cohort into risk-adapted starting ages of screening.Personalized, risk-adapted starting ages of CRC screening could be derived from a single blood test performed in middle adulthood.The RAP approach could be easily extended for defining personalized starting ages by incorporating additional risk factors in the regression models.
PromoR and PromoS forE. colipromoter recognition and classification
Authors: Wang Xinglong , Zhou Jingwen 
Published: March 2023

AbstractRecognition of promoters is important for novel promoter identification, which can be used for genome annotation. Classification of strong and weak promoters can be used for screening high activity promoters. This study introduced PomoR for promoter recognition and PromoS for promoter strong and weak classification. The given two network were built based on ResNet and Attention and validated by cross-validation. PromoR and PromoS displayed an accuracy of 0.887 and 0.781, respectively.
Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells
Authors: Kobia Francis M. , Castro e Almeida Luis , Carminati Francesca , Andronache Adrian , Lavezzari Francesco , Wade Mark , Vaccari Thomas 
Published: March 2023

AbstractThe evolutionarily conserved Notch pathway controls cell–cell communication during development and in adult metazoans. It influences cell fate decisions, cell proliferation and cell differentiation, and contributes to the maintenance of normal tissue homeostasis. Consequently, misregulation of the Notch pathway is associated with a wide range of diseases, including congenital disorders and cancers with little to no cure. Signaling by Notch receptors is regulated by a complex set of cellular processes that include maturation and trafficking to the plasma membrane, endocytic uptake and sorting, lysosomal and proteasomal degradation, and ligand-dependent and independent proteolytic cleavages. We devised assays to follow quantitively the lifetime of endogenous human NOTCH1 receptor in breast epithelial cells in culture. Based on such analysis, we executed a high-content screen of 2749 human genes for which modulatory compounds exist, to identify new regulators of Notch signaling activation that might be amenable to pharmacologic intervention. We uncovered 39 new NOTCH1 genetic modulators that affect different steps of NOTCH1 cellular dynamics. In particular, we find thatPTPN23andHCN2act as positive NOTCH1 regulators by promoting endocytic trafficking and NOTCH1 maturation in the Golgi apparatus, respectively, whileSGK3serves as a negative regulator that can be modulated by pharmacologic inhibition. Our findings might be relevant in the search of new strategies to counteract pathologic Notch signaling.
High-Capacity Sample Multiplexing for Single Cell Chromatin Accessibility Profiling
Authors: Booth Gregory T. , Daza Riza M. , Srivatsan Sanjay R. , McFaline-Figueroa José L. , Gladden Rula Green , Furlan Scott N. , Shendure Jay , Trapnell Cole 
Published: March 2023

ABSTRACTSingle-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe that impaired global chromatin decondensation often coincides with chemical inhibition of allogeneic T-cell activation.
Vitamin D signaling orchestrates skeletal muscle metabolic flexibility by regulating its fuel choice
Authors: Das Anamica , Jawla Neha , Gopinath Suchitra D. , Arimbasseri G. Aneeshkumar 
Published: March 2023

ABSTRACTVitamin D deficiency is associated with skeletal muscle pathologies. However, the role of vitamin D signaling in maintenance of muscle function is not well understood. Mice lacking vitamin D receptor (VDR) exhibit severe muscle wasting after weaning and this is associated with accumulation of muscle glycogen and energy deprivation. Here we show that the skeletal muscles of vdr-/- mice exhibit upregulation of fatty acid oxidation pathway and PPAR pathway and are predisposed to utilize fatty acids as the energy source even in a carbohydrate-enriched diet. As a result, fat-enriched diets could alleviate energy deprivation and atrophy of vdr-/- skeletal muscles. However, the complete restoration of muscle mass and systemic metabolism of vdr-/- mice depended on the quality of diets. Despite increasing muscle energy levels, a lard-based high-fat diet (HFD) disrupted glucose homeostasis by specifically inhibiting the insulin synthesis in pancreatic islets. Surprisingly, milk-based high-fat diets (MBD) could restore both muscle mass and pancreatic insulin response. This study reveals a micronutrient-macronutrient interaction network that connects vitamin D signaling with muscle fuel selection and pancreatic insulin response to enable energy homeostasis under different metabolic landscapes.
Modeling Biases in SARS-CoV-2 infections Prediction using Genome Copies Concentration in Wastewater
Authors: Mattei Mattia , Pinto Rosa M. , Guix Susana , Bosch Albert , Arenas Alex 
Published: March 2023

AbstractBackgroundSARS-CoV-2, the virus responsible for the COVID-19 pandemic, can be detected in stool samples and subsequently shed in the sewage system. The field of Wastewater-based epidemiology (WBE) aims to use this valuable source of data for epidemiological surveillance, as it has the potential to identify unreported infections and to anticipate the need for diagnostic tests.ObjectivesThe objectives of this study were to analyze the absolute concentration of genome copies of SARS-CoV-2 shed in Catalonia’s wastewater during the Omicron peak in January 2022, and to develop a mathematical model capable of using wastewater data to estimate the actual number of infections and the temporal relationship between reported and unreported infections.MethodsWe collected twenty-four-hour composite 1-liter samples of wastewater from 16 wastewater treatment plants (WWTPs) in Catalonia on a weekly basis. We incorporated this data into a compartmental epidemiological model that distinguishes between reported and unreported infections and uses a convolution process to estimate the genome copies shed in sewage.ResultsThe 16 WWTPs showed an average correlation of 0.88±0.08 (ranging from 0.96 to 0.71) and an average delay of 8.7±5.4 days (ranging from 0 to 20 days). Our model estimates that about 53% of the population in our study had been infected during the period under investigation, compared to the 19% of cases that were detected. This under-reporting was especially high between November and December 2021, with values up to 10. Our model also allowed us to estimate the maximum quantity of genome copies shed in a gram of feces by an infected individual, which ranged from 4.15×107gc/gto 1.33×108gc/g.DiscussionAlthough wastewater data can be affected by uncertainties and may be subject to fluctuations, it can provide useful insights into the current trend of an epidemic. As a complementary tool, WBE can help account for unreported infections and anticipate the need for diagnostic tests, particularly when testing rates are affected by human behavior-related biases.
The single item burnout measure is a reliable and valid tool to measure occupational burnout
Authors: Galanis P. , Katsiroumpa A. , Vraka I. , Siskou O. , Konstantakopoulou O. , Katsoulas T. , Gallos P. , Kaitelidou Daphne 
Published: March 2023

AbstractOBJECTIVETo estimate the reliability and the validity of the single item burnout measure in a sample of nurses in Greece.METHODWe conducted an online cross-sectional study in Greece with 963 nurses. Data were collected during October 2022. We measured demographic and work-related variables of nurses, i.e. gender, age, chronic disease, self-rated health status, years of experience, and working in COVID-19 ward/intensive care unit. We used the single item burnout (SIB) and the Copenhagen Burnout Inventory (CBI) to measure occupational burnout. Moreover, we used the COVID-19 burnout scale (COVID-19-BS) to measure nurses’ burnout during the pandemic, and the Patient Health Questionnaire-4 (PHQ-4) to measure anxiety and depression among nurses.RESULTSIntraclass correlation coefficient between the two measurements of the SIB during the test-retest study was 0.986 indicating excellent reliability of the SIB. We found a high correlation between CBI factors and SIB (p<0.001), a moderate correlation between PHQ-4 and SIB (p<0.001), and a low to moderate correlation between COVID-19-BS and SIB (p<0.001). Therefore, concurrent validity of SIB was excellent. Moreover, SIB had high discriminant validity. In particular, nurses with a chronic disease, those with a very poor/poor/moderate health status, and those working in COVID-19 ward/intensive care unit had higher levels of burnout according to the SIB (p<0.001 in all cases). Moreover, we found a positive relationship between years of experience and SIB score (r=0.13, p<0.001).CONCLUSIONSThe single item burnout measure is a brief, reliable, and valid tool that we can use as a screening measure to identify individuals at high risk of burnout.
Associative plasticity of granule cell inputs to cerebellar Purkinje cells
Authors: Conti Rossella , Auger Céline 
Published: March 2023

AbstractGranule cells of the cerebellum make up to 175 000 excitatory synapses on a single Purkinje cell, encoding the wide variety of information from the mossy fibre inputs into the cerebellar cortex. The granule cell axon is made of an ascending portion and a long parallel fibre extending at right angles, an architecture suggesting that synapses formed by the two segments of the axon could encode different information. There are controversial indications that ascending axon (AA) and parallel fibre (PF) synapse properties and modalities of plasticity are different. We tested the hypothesis that AA and PF synapses encode different information, and that association of these distinct inputs to Purkinje cells might be relevant to the circuit and trigger plasticity, similarly to the coincident activation of PF and climbing fibre inputs. Here, by recording synaptic currents in Purkinje cells from either proximal or distal granule cells (mostly AA and PF synapses respectively), we describe a new form of associative plasticity between these two distinct granule cell inputs. We show for the first time that synchronous AA and PF repetitive train stimulation, with inhibition intact, triggers long term potentiation (LTP) at AA synapses specifically. Furthermore, the timing of presentation of the two inputs controls the outcome of plasticity and induction requires NMDAR and mGluR1 activation. The long length of the PFs allows us to preferentially activate the two inputs independently, and despite a lack of morphological reconstruction of the connections, these observations reinforce the suggestion that AA and PF synapses have different coding capabilities and plasticity that is associative, enabling effective association of information transmitted via granule cells.