bluuebunny/crossref_metadata_2025_split huggingface dataset:
<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">Comparative analysis of virulence gene profiles of&#160;Escherichia coli&#160;from clinical and non-clinical sources&#160;in Rivers State, Nigeria
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Authors: Abeni Barira Azeez , Frank-Peterside Nnenna , Otokunefor Kome 
Published: April 2024

Traditionally, the presence of virulence features have been thought to be a key factor in differentiating pathogenic from commensal strains. An understanding of virulence potential of Escherichia coli isolates from various sources is essential to help shed light on potential contamination/transmission rates between the various sources. This study was therefore aimed at exploring the occurrence of specific virulence genes and gene profiles associated with Escherichia coli from clinical and non-clinical sources in Rivers State, Nigeria.
Two hundred samples from clinical (urine and feces) and non-clinical (soil and poultry droppings) sources (50 each) were analyzed using standard microbiological procedures. DNA was extracted from isolates presumptively identified as Escherichia coli using PrestoTM Mini gDNA Bacteria-Kit Quick protocol following the manufacturer’s instructions. Isolate identities were confirmed using E. coli specific 16S rRNA primers and confirmed isolates screened for the presence of six virulence genes (Afimbriae binding adhesin (afa), type 1 fimbriae (fimH), P-fimbrial Usher Protein (papC)), iron acquisition systems: aerobactin (aer), Cytotoxic necrotizing factor I (cnf1) and alpha hemolysin (hly).
Results showed that all isolates haboured at least one of the tested virulence genes, with fimH (97%) as the most prevalent virulence gene and papC the least commonly occurring (35%). A higher occurrence of virulence genes was noted in non-clinical isolates though hly and cnf were not detected at all in any of the isolates studied (0%). Ten different profiles were observed with the afaCc-aer-fimH profile the most commonly occurring virulence gene profile in general (33.3%). For non-clinical isolates however, the aer-afaCc-fimH-papC was the most commonly occurring profile (42.9%).
This study shows that the test Escherichia coli from clinical and non-clinical sources do not carry distinct virulence gene profiles. Studies on a larger subset of isolates would however be necessary to determine if indeed the virulence genes tested for in this study really cannot be used to tell whether an isolate is from a clinical source or not in the South-South of Nigeria.
2010 and 2013 incidence peaks in narcolepsy and idiopathic hypersomnia linked to type A H1N1 and type B Victoria influenza strains
Authors: Zhang Zhongxing , Gool Jari K. , Sirotkin Pavel , Dauvilliers Yves , Barateau Lucie , Plazzi Giuseppe , Pizza Fabio , Biscarini Francesco , Sonka Karel , Galuskova Karolina , Wierzbicka Aleksandra , Högl Birgit , Feketeova Eva , Del Río Villegas Rafael , Fronczek Rolf , Lammers Gert Jan , Khatami Ramin 
Published: April 2024

AbstractIntroductionIncreased narcolepsy type 1 (NT1) incidence rates have been reported globally in 2010, and were linked to the type A H1N1 2009-2010 influenza pandemic and Pandemrix vaccination. A European child-specific NT1 incidence peak was additionally observed in 2013 post the H1N1 pandemic. Thus, the relationship between NT1 and influenza infection remains unclear. Whether other influenza viruses may also trigger NT1 or other central disorders of hypersomnolence (CDH), is unknown. This study investigated annual European incidence patterns of all CDH in complete samples from multiple European centers, in relation to the severity of individual flu strains in preceding influenza seasons.MethodsIncidence rates of NT1 (N=981) and the combined group of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) (N=545) from eight European countries were temporally analysed to identify possible incidence peaks from 1995 to 2019. Linear mixed models and spearman correlations were conducted between hypersomnolence disorder incidence rates and the number of influenza infections of preceding influenza season, split for types A H1N1 and H3N2, and in the Netherlands also types B Victoria and Yamagata influenza.Results2010 and 2013 incidence peaks were present in NT1, and a 2010 children peak was unexpectedly found in the combined group of NT2 and IH. Both hypersomnolence groups exhibited a significantly positive relationship with preceding H1N1 influenza season severity and a negative relationship with H3N2 influenza. NT1 was additionally significantly positively correlated with influenza type B Victoria in the Netherlands and showed highest correlation in children.ConclusionsBesides H1N1 influenza, the temporal association and severity correlation suggest that influenza type B Victoria may be a novel potential trigger for NT1 that requires further investigation. We additionally provide insights into possible immune-related pathophysiologies of NT2 and IH associated with the 2009-2010 H1N1 influenza pandemic. Further immunological investigations are warranted to unravel the complexities of these relationships and their implications for CDH.
Lesion-induced impairment of therapeutic capacities of olfactory ensheathing cells in an autologous transplantation model for treatment of spinal cord injury
Authors: Delarue Quentin , Brodier Matthis , Neveu Pauline , Moncomble Laurine , Hugede Alizée , Blondin Axelle , Robac Amandine , Raimond Clémence , Lecras Pamela , Riou Gaëtan , Guérout Nicolas 
Published: April 2024

AbstractSpinal cord injury (SCI) is a serious pathology of the central nervous system that results in loss of motor, sensory and autonomic functions below the level of the lesion and for which, unfortunately, there is currently no cure. In addition to the loss of function, SCI induces a systemic inflammation that is not confined to the spinal cord and whose effects are increasingly well characterized. In particular, SCI causes cerebral inflammation, which is responsible for the impairment of hippocampal and bulbar neurogenesis. Many therapies have been tested as potential treatments for SCI. In animal models, cell therapies have shown interesting effects such as spinal scar reduction, anti-inflammatory properties, axonal regrowth or neuronal survival, allowing better functional recovery. However, in human studies, their therapeutic capacities are less significant. Beyond obvious differences in pathophysiology and cell culture procedures, a key paradigm of cell transplantation differs between humans and animals. In animal models, transplanted cells are systematically taken from healthy individuals, whereas in humans the immune incompatibility leads to the realization of autologous transplantation. Therefore, we were interested in the lesion effects on the neuro-repairing potential of olfactory ensheathing cells (OECs) harvested from olfactory bulbs.Using functional sensory-motor studies, histological and gene expression analyses, we were able to demonstrate for the first time that the lesion negatively affects the therapeutic properties of cells used to treat SCI. These innovative results shed new light on the future use of cell transplantation in autologous transplantation after SCI.
Redefining FLASH RT: the impact of mean dose rate and dose per pulse in the gastrointestinal tract
Authors: Liu Kevin , Waldrop Trey , Aguilar Edgardo , Mims Nefetiti , Neill Denae , Delahoussaye Abagail , Li Ziyi , Swanson David , Lin Steven H. , Koong Albert C. , Taniguchi Cullen M. , Loo Billy W. , Mitra Devarati , Schüler Emil 
Published: April 2024

ABSTRACTBackgroundThe understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited.PurposeWe sought to evaluate how the magnitude of radiation-induced gastrointestinal (GI) toxicity (RIGIT) depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP).MethodsC57BL/6J mice were subjected to total abdominal irradiation (11-14 Gy single fraction) under conventional irradiation (low DPP and low MDR, CONV) and various combinations of DPP and MDR up to ultra-high-dose-rate (UHDR) beam conditions. The effects of DPP were evaluated for DPPs of 1-6 Gy while the total dose and MDR were kept constant; the effects of MDR were evaluated for the range 0.3– 1440 Gy/s while the total dose and DPP were kept constant. RIGIT was quantified in non-tumor–bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay.ResultsWithin each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to better sparing of regenerating crypts, with a more prominent effect seen at 12 and 14 Gy TAI. However, at fixed DPPs >4 Gy, similar sparing of crypts was demonstrated irrespective of MDR (from 0.3 to 1440 Gy/s). At a fixed high DPP of 4.7 Gy, survival was equivalently improved relative to CONV for all MDRs from 0.3 Gy/s to 104 Gy/s, but at a lower DPP of 0.93 Gy, increasing MDR produced a greater survival effect. We also confirmed that high DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model.ConclusionsThis study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high DPP and UHDR appeared independently sufficient to produce FLASH sparing of GI toxicity, while isoeffective tumor response was maintained across all conditions.
Probing sensitivity to statistical structure in rapid sound sequences using deviant detection tasks
Authors: Milne Alice E. , Chait Maria , Conway Christopher M. 
Published: April 2024

AbstractStatistical structures and our ability to exploit them are a ubiquitous component of daily life. Yet, we still do not fully understand how we track these sophisticated statistics and the role they play in sensory processing. Predictive coding frameworks hypothesize that for stimuli that can be accurately anticipated based on prior experience, we rely more strongly on our internal model of the sensory world and are more “surprised” when that expectation is unmet. The current study used this phenomenon to probe listeners’ sensitivity to probabilistic structures generated using rapid 50 milli-second tone-pip sequences that precluded conscious prediction of upcoming stimuli. Over three experiments we measured listeners’ sensitivity and response time to deviants of a frequency outside the expected range. Predictable sequences were generated using either a triplet-based or network-style structure and deviant detection contrasted against the same set of tones but in a random, unpredictable order. All experiments found structured sequences enhanced deviant detection relative to random sequences. Additionally, Experiment 2 used three different instantiations of the community structure to demonstrate that the level of uncertainty in the structured sequences modulated deviant saliency. Finally, Experiment 3 placed the deviant within an established community or immediately after a transition between communities, where the perceptual boundary should generate momentary uncertainty. However, this manipulation did not impact performance. Together these results demonstrate that probabilistic contexts generated from statistical structures modulate the processing of an ongoing auditory signal, leading to an improved ability to detect unexpected deviant stimuli, consistent with the predictive coding framework.
Development of the pulmonary vasculature in the gray short-tailed opossum (Monodelphis domestica) – 3D reconstruction by microcomputed tomography
Authors: Ferner Kirsten 
Published: April 2024

AbstractThe marsupial gray short-tailed opossum (Monodelphis domestica) is born at the late canalicular stage of lung development and the lungs are structurally immature compared to eutherians. The majority of lung development, including the maturation of pulmonary vasculature, takes place in ventilated functioning state during the postnatal period.The current study uses X-ray computed tomography (µCT) to three-dimensionally reconstruct the vascular trees of the pulmonary artery and pulmonary vein in the marsupial gray short-tailed opossum to investigate the vascular genesis during the postnatal period. The development of the pulmonary vasculature was examined in 15 animals from neonate to postnatal day 57. The final 3-D reconstructions of the pulmonary artery and pulmonary vein in the neonate and at 21, 35 and 57 dpn were transformed into a centerline model of the vascular trees. Based on the reconstructions, the generation of end-branching vessels, the median and maximum generation and the number of vessels were calculated for the lungs.The pulmonary vasculature follows the lung anatomy with six pulmonary lobes indicated by the bronchial tree. The pulmonary arteries follow the bronchial tree closely, in contrast to the pulmonary veins, which run between the pulmonary segments. At birth the pulmonary vasculature has a simple branching pattern with a few vessel generations. Compared to the bronchial tree, the pulmonary vasculature appears to be more developed and extends to the large terminal air spaces. The pulmonary vasculature of the lungs from neonate to postnatal day 57 develops along the bronchial tree and shows a marked gain in volume and a progressive increase in vascular complexity and density. The gray short-tailed opossum resembles the assumed mammalian ancestor and is suitable to inform on the evolution of the mammalian lung. Vascular genesis in the marsupial bears resemblance to developmental patterns described in eutherians. Lung development in general seems to be highly conservative within mammalian evolution.
The impact of health inequity on regional variation of COVID-19 transmission in England
Authors: Rawson Thomas , Hinsley Wes , Sonabend Raphael , Semenova Elizaveta , Cori Anne , Ferguson Neil M 
Published: April 2024

AbstractConsiderable spatial heterogeneity has been observed in COVID-19 transmission across administrative regions of England throughout the pandemic. This study investigates what drives these differences. We constructed a probabilistic case count model for 306 administrative regions of England across 95 weeks, fit using a Bayesian evidence synthesis framework. We include the mechanistic impact of acquired immunity, of spatial exportation of cases, and 16 spatially-varying socio-economic, socio-demographic, health, and mobility variables. Model comparison assesses the relative contributions of these respective mechanisms. We find that regionally-varying and time-varying differences in week-to-week transmission were definitively associated with differences in: time spent at home, variant-of-concern proportion, and adult social care funding. However, model comparison demonstrates that the mechanistic impact of these terms was of negligible impact compared to the role of spatial exportation between regions. While these results confirm the impact of some, but not all, measures of regional inequity in England, our work corroborates the finding that observed differences in regional disease transmission during the pandemic were predominantly driven by underlying epidemiological factors rather than the demography and health inequity between regions.Author SummaryDuring the COVID-19 pandemic, different geographic areas of England saw different patterns in the number of confirmed cases over time. This study investigated whether demographic differences between these areas (such as the amount of deprivation, the age and ethnicity of the populations, or differences in where people spent their time) were linked to these differences in disease transmission. We also considered whether this was associated with the number of cases in neighbouring areas as well. Using a mathematical model fit to multiple data streams, we discovered that a statistically significant link between some demographic variables (time spent at home, COVID-19 variant, and the amount of adult social care funding) and week-to-week transmission exists, but this relationship is very small, and the influence of cases in neighbouring areas was far more impactful in explaining differences in transmission between areas over time.
A Breast Cancer Polygenic Risk Score Validation in 15,490 Brazilians using Exome Sequencing
Authors: Rius Flávia Eichemberger , Guindalini Rodrigo Santa Cruz , Viana Danilo , Salomão Júlia , Gallo Laila , Freitas Renata , Bertolacini Cláudia , Taniguti Lucas , Imparato Danilo , Antunes Flávia , Sousa Gabriel , Achjian Renan , Fukuyama Eric , Gregório Cleandra , Ventura Iuri , Gomes Juliana , Taniguti Nathália , Maistro Simone , Krieger José Eduardo , Zheng Yonglan , Huo Dezheng , Olopade Olufunmilayo I. , Koike Maria Aparecida , Schlesinger David 
Published: April 2024

AbstractBackgroundBrazil has a highly admixed population. Polygenic Risk Scores (PRS) have mostly been developed from European population studies, and their application to other populations is challenging. To assess the use of PRS for breast cancer (BC) risk in Brazil, we evaluated four PRSs in the Brazilian population.MethodsWe analyzed a Brazilian cohort composed of 6,206 women with a history of breast cancer and 8,878 unphenotyped adults as controls. Genomic variants were imputed from exomes and scores were calculated for all samples.ResultsAfter excluding individuals with known pathogenic or likely pathogenic variants inBRCA1,BRCA2,PALB2,PTEN, orTP53genes, and first-degree relatives of the probands, 5,598 cases and 8,767 controls remained. Four PRS models were compared, and PRS3820from Mavaddatet al.2019 study showed the best performance, with an Odds Ratio (OR) of 1.43 per standard deviation increase (p-value: < 0.001) and an OR of 1.88 (p-value: < 0.001) for the top decile. PRS3820also performed well for different ancestry groups: East Asian majority (OR 1.59, p-value 0.004), Non-European majority (OR 1.45, p-value: <0.001), and European majority (OR: 1.43, p-value: <0.001).ConclusionAmong different PRS, the PRS3820performed better in the highly admixed Brazilian population. This will allow a more precise BC risk assessment of mutation-negative women in Brazil.
Enhancing Genetic Association Power in Endometriosis through Unsupervised Clustering of Clinical Subtypes Identified from Electronic Health Records
Authors: Guare Lindsay , Humphrey Leigh Ann , Rush Margaret , Pollie Meredith , Luo Yuan , Weng Chunhua , Wei Wei-Qi , Kottyan Leah , Jarvik Gail , Elhadad Noemie ,   Penn Medicine Biobank,   Regeneron Genetics Center, Zondervan Krina , Missmer Stacey , Vujkovic Marijana , Velez-Edwards Digna , Senapati Suneeta , Setia-Verma Shefali 
Published: April 2024

AbstractBackgroundEndometriosis affects 10% of reproductive-age women, and yet, it goes undiagnosed for 3.6 years on average after symptoms onset. Despite large GWAS meta-analyses (N > 750,000), only a few dozen causal loci have been identified. We hypothesized that the challenges in identifying causal genes for endometriosis stem from heterogeneity across clinical and biological factors underlying endometriosis diagnosis.MethodsWe extracted known endometriosis risk factors, symptoms, and concomitant conditions from the Penn Medicine Biobank (PMBB) and performed unsupervised spectral clustering on 4,078 women with endometriosis. The 5 clusters were characterized by utilizing additional electronic health record (EHR) variables, such as endometriosis-related comorbidities and confirmed surgical phenotypes. From four EHR-linked genetic datasets, PMBB, eMERGE, AOU, and UKBB, we extracted lead variants and tag variants 39 known endometriosis loci for association testing. We meta-analyzed ancestry-stratified case/control tests for each locus and cluster in addition to a positive control (Total Nendometriosis cases= 10,108).ResultsWe have designated the five subtype clusters as pain comorbidities, uterine disorders, pregnancy complications, cardiometabolic comorbidities, and EHR-asymptomatic based on enriched features from each group. One locus,RNLS, surpassed the genome-wide significant threshold in the positive control. Thirteen more loci reached a Bonferroni threshold of 1.3 x 10-3(0.05 / 39) in the positive control. The cluster-stratified tests yielded more significant associations than the positive control for anywhere from 5 to 15 loci depending on the cluster. Bonferroni significant loci were identified for four out of five clusters, includingWNT4andGREB1for the uterine disorders cluster,RNLSfor the cardiometabolic cluster,FSHBfor the pregnancy complications cluster, andSYNE1andCDKN2B-AS1for the EHR-asymptomatic cluster. This study enhances our understanding of the clinical presentation patterns of endometriosis subtypes, showcasing the innovative approach employed to investigate this complex disease.
Heterogeneous metabolomic aging across the same age and prediction of health outcome
Authors: Jia Xueqing , Fan Jiayao , Wu Xucheng , Cao Xingqi , Ma Lina , Abdelrahman Zeinab , Bizzarri Daniele , van den Akker Erik B , Slagboom P. Eline , Deelen Joris , Zhou Dan , Liu Zuyun 
Published: April 2024

AbstractExisting metabolomic clocks exhibit deficiencies in capturing the heterogeneous aging rates among individuals with the same chronological age. Yet, the modifiable and non-modifiable factors in metabolomic aging have not been systematically studied. Here, we leveraged metabolomic profiles of 239,291 UK Biobank participants for 10-year all-cause mortality prediction to generate and validate a new aging measure--MetaboAgeMort. The MetaboAgeMort showed significant associations with all-cause mortality, cause-specific mortality, and diverse incident diseases. Adding MetaboAgeMort to conventional risk factors model improved the predictive ability of 10-year mortality. We identified 99 modifiable factors for MetaboAgeMort, where 16 factors representing pulmonary function, body composition, socioeconomic status, dietary quality, smoking status, alcohol intake, and disease status showed quantitatively stronger associations. The genetic analyses revealed 99 genomic risk loci and 271 genes associated with MetaboAgeMort. Our study illuminates heterogeneous metabolomic aging across the same age, which provides avenues for developing anti-aging therapies and personalized interventions.