bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic basis of resistance in hosts facing alternative infection strategies by a virulent bacterial pathogen
Authors: Mathieu-Bégné Eglantine , Gattis Sabrina , Ebert Dieter 
Published: August 2024

AbstractHaving alternative infection routes is thought to help parasites circumvent host resistance, provided that these routes are associated with different host resistance loci. This study examines whether alternate infection routes of the parasitePasteuria ramosaare linked to distinct resistance loci in its crustacean host,Daphnia magna. We focus on theP. ramosaisolate P15, which can attach and penetrate the host through either the hindgut or the foregut. Using a global panel of 174D. magnagenotypes supplemented with breeding experiments, we analyzed resistance patterns for each of these infection routes. Our findings confirm our hypothesis: inD. magna, hindgut attachment is determined by the D locus, while foregut attachment is controlled by a newly identified G locus. We established a gene model for the G locus that indicated Mendelian segregation and epistatic interaction with at least one other resistance locus forP. ramosa, the C locus. Using genomic Pool-sequencing data, we localized the G locus within a known Pasteuria Resistance Complex on chromosome 4 ofD. magna, whereas the D locus is on chromosome 7. Two candidate genes for the G locus, belonging to the Glycosyltransferase gene family, were identified. Our study sheds new light on host–parasite coevolution and enhances our understanding of how parasites evolve infection strategies.Author summaryParasites continuously evolve strategies to overcome host resistance, including the use of alternative infection routes. However, this strategy is advantageous only if host resistance loci are specific to each entry point; otherwise, a single host gene could provide resistance to all infection routes. In this study, we tested this hypothesis using the freshwater crustaceanDaphnia magnaand a strain of the parasitePasteuria ramosathat can infect its host via the esophagus (foregut) or the hindgut. By conducting a phenotypic assay ofP. ramosaattachment on a global panel ofD. magnagenotypes, we demonstrate that foregut and hindgut infections are associated with independent genetic host resistance loci. Through a breeding experiment on a subset ofD. magnagenotypes, we were able to propose a gene model for the newly discovered G locus linked to foregut attachment, while the previously identified D locus is linked to hindgut attachment. We also discovered that the foregut infection route is influenced by an epistatic interaction between the G locus and anotherP. ramosaresistance locus, the C locus. Using genomic data, we confirmed that the G and D loci are not overlapping, with the G locus being part of the Pasteuria Resistance Complex on chromosome 4, whereas the D locus is on chromosome 7. Two potential genes involved in glycosylation processes were identified as candidates for the G locus. Overall, our study confirms a key postulate in the understanding of host–parasite co-evolution, highlighting the importance of infection strategies in host resistance.
Valine restriction extends survival in aDrosophilamodel of short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency
Authors: Mele Sarah , Martelli Felipe , Barlow Christopher K. , Jefferies Grace , Dworkin Sebastian , Christodoulou John , Schittenhelm Ralf B. , Piper Matthew D.W. , Johnson Travis K. 
Published: August 2024

SummaryShort-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare genetic disorder caused by biallelic pathogenic variants in theECHS1gene. ECHS1D is characterised by severe neurological and physical impairment that often leads to childhood mortality. Therapies such as protein and single nutrient-restricted diets show poor efficacy, whereas development of new treatments is hindered by the low prevalence of the disorder and a lack of model systems for treatment testing. Here we report on the establishment of aDrosophilamodel of ECHS1D. Flies carrying mutations inEchs1(CG6543) were characterised for their physical and metabolic phenotypes, and dietary intervention to improve fly model health was explored. TheEchs1null larvae recapitulated human ECHS1D phenotypes including elevated biomarkers (S-(2-carboxypropyl)cysteamine and 2,3-dihydroxy-2-methylbutyric acid), poor motor behaviour and early mortality, and could be rescued by expression of a humanECHS1transgene. We observed that both restriction of valine in isolation, or all branched-chain amino acids (BCAAs - leucine, isoleucine, and valine) together, extended larval survival, supporting the idea that reducing BCAA pathway catabolic flux is beneficial in this disorder. Further, metabolic profiling revealed substantial changes to carbohydrate metabolism, suggesting thatEchs1loss causes widespread metabolic dysregulation beyond valine metabolism. The similarities betweenDrosophilaand human ECHS1D suggest that the fly model is a valuable animal system in which to explore mechanisms of pathogenesis and novel treatment options for this disorder.
Epidemiology of urinary tract infection among community-living seniors aged 50 plus: population estimates and risk factors
Authors: Foxman Betsy , Bangura Marie , Kamdar Neil , Morgan Daniel M 
Published: August 2024

AbstractBackgroundUrinary tract infection (UTI) is common in all ages but risk factors among adults 50 and older are not well studied. One unexplored potential risk factor is constipation, a known UTI risk factor among children.ObjectiveDescribe the UTI incidence among U.S. women and men aged 50 and older and the association between constipation and other risk factors and UTI.MethodsA web interview was administered October 12-16, 2023 to U.S. adults aged 50 and older participating in a probability-based panel representative of the U.S. household population age 50 or older. The primary study outcome was self-reported healthcare provider diagnosed and treated UTI in the previous 12 months. All results were weighted to represent the U.S. household population.ResultsThe 12-month UTI incidence was 19.8% among women and 6.4% among men. Recurrence was common: 10% of women and 7% of men with a UTI had 3 more UTIs in the previous 12 months. 32% of the population reported being constipated sometimes, frequently or always. UTI incidence increased with more frequent constipation in a dose response manner among women and men. After adjusting for age, gender, having a body mass index >30 and an overnight hospital stay in the previous 12 months, those reporting sometimes being constipated were 3.69 times, and those often or always constipated were 5.48 times more likely than those never constipated to have a UTI in the previous 12 months.DiscussionThis is the first report of an association between UTI and constipation among older adults. Reducing constipation might reduce UTI incidence among older women and men.
BMI-related Genetic Factors and COPD Imaging Phenotypes
Authors: Zhang Jingzhou , Moll Matthew , Debban Catherine L. , Hobbs Brian D. , Rijhwani Heena , Washko George R. , Celli Bartolome R. , Silverman Edwin K. , Bakke Per , Oelsner Elizabeth C. , Barr R. Graham , Agustí Alvar , Faner Rosa , Bruselle Guy G. , Humphries Stephen M. , Lynch David A. , Dupuis Josée , Manichaikul Ani W. , O’Connor George T. , Cho Michael H. 
Published: August 2024

AbstractBackgroundWhile low body mass index (BMI) is associated with emphysema and obesity is associated with airway disease in chronic obstructive pulmonary disease (COPD), the underlying mechanisms are unclear.MethodsWe aggregated genetic variants from population-based genome-wide association studies to generate a polygenic score of BMI (PGSBMI). We calculated this score for participants from COPD-enriched and community-based cohorts and examined associations with automated quantification and visual interpretation of computed tomographic emphysema and airway wall thickness (AWT). We summarized the results using meta-analysis.ResultsIn the random-effects meta-analyses combining results of all cohorts (n=16,349), a standard deviation increase of the PGSBMIwas associated with less emphysema as quantified by log-transformed percent of low attenuation areas ≤ 950 Hounsfield units (β= -0.062,p<0.0001) and 15thpercentile value of lung density histogram (β=2.27,p<0.0001), and increased AWT as quantified by the square root of wall area of a 10-mm lumen perimeter airway (β=0.016,p=0.0006) and mean segmental bronchial wall area percent (β=0.26,p=0.0013). For imaging characteristics assessed by visual interpretation, a higher PGSBMIwas associated with reduced emphysema in both COPD-enriched cohorts (OR for a higher severity grade=0.89,p=0.0080) and in the community-based Framingham Heart Study (OR for the presence of emphysema=0.82,p=0.0034), and a higher risk of airway wall thickening in the COPDGene study (OR=1.17,p=0.0023).ConclusionsIn individuals with and without COPD, a higher body mass index polygenic risk is associated with both quantitative and visual decreased emphysema and increased AWT, suggesting genetic determinants of BMI affect both emphysema and airway wall thickening.
Protein Arginine Methylation of the Translation Initiation Factor eIF1A Increases Usage of a Near-cognate Start Codon
Authors: Wegman Rebecca , Langberg Michael , Davis Richoo B. , Liu Xiaozhuo , Luo Minkui , Yu Michael C. , Walker Sarah E. 
Published: August 2024

AbstractProtein arginine methylation has emerged as a key post-translational modification responsible for many facets of eukaryotic gene expression. To better understand the extent of this modification in cellular pathways, we carried out bioorthogonal methylation profiling inSaccharomyces cerevisiaeto comprehensively identify thein vivosubstrates of the major yeast protein arginine methyltransferase Hmt1. Gene ontology analysis of candidate substrates revealed an enrichment of proteins involved in the process of translation. We verified one such factor, eIF1A, byin vitromethylation. Three sites on eIF1A were found to be responsible for its methylation: R13, R14, and R62, with varied capacity by which each site contributed to the overall methylation capacityin vitro. To determine the role of methylation in eIF1A function, we used a battery of arginine-to-alanine substitution mutants to evaluate translation fidelity in these mutants. Our data show that substitution mutants at R13 and R14 in the N-terminal tail improved the fidelity of start codon recognition in an initiation fidelity assay. Overall, our data suggest that Hmt1-mediated methylation of eIF1A fine-tunes the fidelity of start codon recognition for proper translation initiation.
SARS-CoV-2 Damages Cardiomyocytes Mitochondria and Implicates Long COVID-associated Cardiovascular Manifestations
Authors: Che Wenliang , Guo Shuai , Wang Yanqun , Wan Xiaohua , Tan Bingyu , Li Hailing , Alifu Jiasuer , Zhu Mengyun , Chen Cesong , Li Peiyao , Zhang Zhaoyong , Wang Yiliang , Huang Xiaohan , Wang Xinsheng , Zhu Jian , Pan Xijiang , Zhang Fa , Wang Peiyi , Zhao Jincun , Xu Yawei , Liu Zheng 
Published: August 2024

AbstractOur study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as “Long COVID”, which has significantly affected millions globally. We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, acute inferior myocardial infarction, and acute myocarditis. All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID. Our report sheds light on the cardiovascular implications of Long COVID and underscores the importance of further research to understand its cellular underpinnings.
The First General Consent Implementation in Swiss Traditional Chinese Medicine Practices. A Prospective One-Year Study
Authors: Wang Xiaying , Lv Xiaoying , Chen Bingjun , Pradhan Saroj , Bauder Ralf , Li Yiming , Furian Michael 
Published: August 2024

SummaryBackgroundTraditional Chinese Medicine (TCM) encompasses a wide range of treatments focused on diagnosing and managing illnesses, with increasing adoption in Western countries. TCM is often applied in isolated practices, therefore, rigorous research and real-world data collection remain challenging. The implementation of the General Consent (GC) facilitates this research, therefore, the aim was to investigate the acceptance rate of the GC during the first year of its implementation in TCM practices.MethodsThis prospective cohort study was conducted from 1stJanuary to 31stDecember 2023 in five TCM practices located in Bad Zurzach, Baden, Lenzburg, Wil, and Zug in Switzerland. GC, together with other registration forms, were sent to patients prior to their appointments, collected during their first visit, and recorded by clinic secretaries. Logistic regression analysis was performed to investigate demographic factors influencing GC acceptance, considering variables such as age, sex, and practice location.ResultsThe study recorded 1,095 patients who sought TCM treatments in 2023, of which 73.6% returned a valid GC document. Overall, the GC acceptance rate was 611/1,095 (55.8%); of those returning the GC, the acceptance rate was 611/806 (75.8%). The median[IQR] age of patients was 52[37,64] years and female patients were twice as likely to seek TCM treatments compared to male patients. Logistic regression analysis, odds ratio (95%CI), revealed no difference in GC acceptance rate with older age: 1.015 (0.996 to 1.034), p=0.115; female sex: 1.847 (0.588 to 5.804), p=0.294 and age*female sex: 0.983 (0.962 to 1.004), p=0.119. Significant differences in GC acceptance rates were observed across the five TCM practices.ConclusionThe GC implementation in TCM practices was feasible, and the GC was well accepted by patients, independent of sex and age. The observed practice-related differences in GC acceptance require further investigation. More TCM practices should implement the GC to enable practice-based TCM research.
Decreased cardio-respiratory information transfer is associated with deterioration and a poor prognosis in critically ill patients with sepsis
Authors: Morandotti Cecilia , Wikner Matthew , Li Qijun , Ito Emily , Tan Calix , Chen Pin-Yu , Cawthorn Anika , Lilaonitkul Watjana , Mani Ali R 
Published: August 2024

AbstractAssessing illness severity in the ICU is crucial for early prediction of deterioration and prognosis. Traditional prognostic scores often treat organ systems separately, overlooking the body’s interconnected nature. Network physiology offers a new approach to understanding these complex interactions. This study used the concept of transfer entropy (TE) to measure information flow between heart rate (HR), respiratory rate (RR), and capillary oxygen saturation (SpO2) in critically ill sepsis patients, hypothesizing that TE between these signals would correlate with disease outcome. The retrospective cohort study utilized the MIMIC III Clinical Database, including patients who met Sepsis-3 criteria on admission and had 30 minutes of continuous HR, RR, and SpO2data. TE between the signals was calculated to create physiological network maps. Cox regression assessed the relationship between cardiorespiratory network indices and both deterioration (SOFA score increase of ≥2 points at 48 hours) and 30-day mortality. Among 164 patients, higher information flow from SpO2to HR [TE(SpO2→HR)] and reciprocal flow between HR and RR [TE(RR→HR) and TE(HR→RR)] were linked to reduced mortality, independent of age, mechanical ventilation, SOFA score, and comorbidity. Reductions in TE(HR → RR), TE(RR→HR), TE(SpO2→RR), and TE(SpO2→HR) were associated with increased risk of 48-hour deterioration. After adjustment for potential confounders, only TE(HR→RR) and TE(RR→HR) remained statistically significant. The study confirmed that physiological network mapping using routine signals in sepsis patients could indicate illness severity and that higher TE values were generally associated with improved outcomes.New & NoteworthyThis study adopts an integrative approach through physiological network analysis to investigate sepsis, with the goal of identifying differences in information transfer between physiological signals in sepsis survivors versus non-survivors. We found that greater information flow between heart rate, respiratory rate, and capillary oxygen saturation was associated with reduced mortality, independent of age, disease severity, and comorbidities. Additionally, reduced information transfer was linked to an increased risk of 48-hour deterioration in patients with sepsis.
Genetics of transient amnesia highlights a vascular role in memory
Authors: Rivas Manuel A. ,   FinnGen, Daly Mark J. 
Published: August 2024

AbstractWhere memory is stored and how it is processed is poorly understood. Traditionally, genetics of low prevalence traits have been used to get a better understanding of naturally occuring conditions across species. Here, we conduct a genome-wide association of transient global amnesia (TGA), a specific type of heritable amnesia characterized by a sudden, temporary episode of memory loss, across 4,303 patients and over 1 million controls from three population biobanks in Finland, United States, and the United Kingdom, to better understand the genetic basis of memory. We find nine loci associated with TGA (p < 5×10-8) including a missense variant inCRIP1with high posterior probability (> .9) of being the causally relevant variant using fine-mapping, replicated across 3 cohorts. Furthermore, we find enrichment for a specific cell type, pericyte cells, which are a key part of the neurovascular unit, which includes astrocytes and neurons, and control interactions between neurons and the cerebral vasculature, implicating a direct vascular role in memory formation and retrieval. We anticipate these genetic studies at a larger scale to bring new biological understanding and therapeutic insights into the brain and memory.
Penicillin Allergy as an Instrumental Variable for Estimating Antibiotic Effects on Resistance
Authors: Saciuk Yaki , Nevo Daniel , Chowers Michal , Obolski Uri 
Published: August 2024

AbstractAntibiotic resistance is influenced by prior antibiotic use, but precise causal estimates are limited. This study uses penicillin allergy as an instrumental variable (IV) to estimate the causal effect of antibiotics on resistance. A retrospective cohort of 36,351 individuals withE. colipositive urine cultures and prior outpatient antibiotic use, with outcomes assessed up to one year post-exposure, was analyzed using data from Maccabi Healthcare Services (MHS), the second-largest non-profit health fund in Israel. IV methods estimated risk differences (RD) and numbers needed to harm (NNH) for penicillin versus other antibiotics. The RD for resistance was 11.4% (95% CI: 7.6%, 15.4%) for amoxicillin/clavulanic acid, 14.1% (95% CI: 9.0%, 19.4%) for ampicillin, and 0.8% (95% CI: 0.2%, 1.4%) for piperacillin/tazobactam, with NNHs of 8.8, 7.1, and 122.0, respectively. Risks declined over time since exposure. Gentamicin, used as a negative control, showed no effect (95% CI: -2.4%, 1.8%). When directly comparing penicillin and quinolone effects on their respective AMR, penicillin use within 180 days increased resistance to amoxicillin/clavulanic acid by an RD of 17.8% (95% CI: 2.1%, 35.2%; NNH: 5.6), while quinolones raised ciprofloxacin resistance by 43.7% (95% CI: 29.9%, 59.4%; NNH: 2.3). These findings provide quantitative evidence of the impact of prior penicillin use on resistance, with implications for clinical practice and prescription policies.
Machine-Learning Enhanced Diffusion Tensor Imaging with Four Encoding Directions
Authors: Ametepe Joshua Mawuli , Gholam James , Beltrachini Leandro , Cercignani Mara , Jones Derek Kenton 
Published: August 2024

AbstractPurposeThis study aims to reduce Diffusion Tensor MRI (DT-MRI) scan time by minimizing diffusion-weighted measurements. Using machine learning, DT-MRI parameters are accurately estimated with just four tetrahedrally-arranged diffusion-encoded measurements, instead of the usual six or more. This significantly shortens scan duration and is particularly useful in ultra-low field (ULF) MRI studies and for non-compliant populations (e.g., children, the elderly, or those with movement disorders) where long scan times are impractical.MethodsTo improve upon a previous tetrahedral encoding approach, this study used a deep learning (DL) model to predict parallel and radial diffusivities and the principal eigenvector of the diffusion tensor with four tetrahedrally-arranged diffusion-weighted measurements. Synthetic data were generated for model training, covering a range of diffusion tensors with uniformly distributed eigenvectors and eigenvalues. Separate DL models were trained to predict diffusivities and principal eigenvectors, then evaluated on a digital phantom and in vivo data collected at 64 mT.ResultsThe DL models outperformed the previous tetrahedral encoding method in estimating diffusivities, fractional anisotropy, and principal eigenvectors, with significant improvements in ULF experiments, confirming the DL approach’s feasibility in low SNR scenarios. However, the models had limitations when the tensor’s principal eigenvector aligned with the scanner’s axesConclusionThe study demonstrates the potential of using DL to perform DT-MRI with only four directions in ULF environments, effectively reducing scan durations and addressing numerical instability seen in previous methods. These findings open new possibilities for ULF DT-MRI applications in research and clinical settings, particularly in pediatric neuroimaging