bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critically-ill COVID-19 susceptibility geneCCR3shows natural selection in sub-Saharan Africans
Authors: Sun Zewen , Pan Lin , Tian Aowen , Chen Peng 
Published: January 2024

AbstractThe prevalence of COVID-19 critical illness varies across ethnicities, with recent studies suggesting that genetic factors may contribute to this variation. The aim of this study was to investigate natural selection signals of genes associated with critically-ill COVID-19 in sub-Saharan Africans. Severe COVID-19 SNPs were obtained from the HGI website. Selection signals were assessed in 661 sub-Sahara Africans from 1000 Genomes Project using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (xpEHH), and fixation index (Fst). Allele frequency trajectory analysis of ancient DNA samples were used to validate the existing of selection in sub-Sahara Africans. We also used Mendelian randomization to decipher the correlation between natural selection and critically-ill COVID-19. We identified thatCCR3exhibited significant natural selection signals in sub-Sahara Africans. Within theCCR3gene, rs17217831-A showed both high iHS (Standardized iHS = 2) and high XP-EHH (Standardized XP-EHH = 2.5) in sub-Sahara Africans. Allele frequency trajectory ofCCR3rs17217831-A revealed natural selection occurring in the recent 1,500 years. Natural selection resulted in increasedCCR3expression in sub-Sahara Africans. Mendelian Randomization provided evidence that increased bloodCCR3expression and eosinophil counts lowered the risk of critically ill COVID-19. Our findings suggest that sub-Saharan Africans are less vulnerable to critically ill COVID-19 due to natural selection and identifyCCR3as a potential novel therapeutic target.
Limited Research Investigating the Value of MRI in Predicting Future Cognitive Morbidity in Survivors of Paediatric Brain Tumours: A Call to Action for Clinical Neuroimaging Researchers
Authors: Griffiths-King Daniel , Delivett Christopher , Peet Andrew , Waite Jane , Novak Jan 
Published: January 2024

AbstractSurvivors of pediatric brain tumour patients are at high risk of cognitive morbidity. There is clinical benefit in being able to reliably predict, at the individual patient level, whether a patient will experience these difficulties or not, the degree of impairment, and the domains affected. Whilst established risk factors exist, quantitative analysis of MRI could provide added predictive value towards this goal, above and beyond existing clinical risk models. The current systematic review aims to answer the question “Do MRI markers predict future cognitive functioning in pediatric brain tumour survivors?”. Studies of pediatric brain tumour patients which test the value of MRI variables in predicting later neuropsychological outcomes were searched up to March 2024. Only included were studies where MRI scans were acquired at an earlier timepoint and used to predict a child’s performance on cognitive tests at a later timepoint. Surprisingly few studies were identified by the systematic search process, but those that were identified specifically investigated MRI measures of cerebellar and white matter damage as features in predicting cognitive outcomes. Ultimately, the key finding of this review is that the current literature is limited. Those studies identified had small sample sizes and were rated as poor quality for the purposes of prediction. Therefore, current findings are at high risk of bias and thus the quality and conclusions are limited. Given the significant impact for this clinical population that predictive models would enable, the current review affirms the need for a ‘call to action’ for medical imaging researchers in pediatric neurooncology.
Beyond Pain Control: Exploring Regional Anaesthesia’s Potential to Improve Gastric Cancer Surgery Survival Rates: A Retrospective Cohort Study
Authors: Tatsuki Onishi , Onishi Yoshika 
Published: January 2024

AbstractBackgroundGastric cancer management remains fraught with high morbidity and mortality rates owing to surgical interventions. Postoperative complications and extended hospitalisation profoundly affect patient survival, with elderly and medically compromised patients facing greater risks. We hypothesised that regional anaesthesia may reduce the surgical stress response and thus mortality. Hence, this study was aimed at investigating whether adjunctive application of regional anaesthesia during gastric cancer surgery attenuates the stress response to surgery, thereby improving postoperative survival outcomes.MethodsIn this study, we critically examined the potential role of regional anaesthesia in modulating perioperative immune and inflammatory responses, which are vital for improving oncological outcomes. Previous studies using diverse methodologies have provided heterogeneous and inconclusive results regarding the effectiveness of regional anaesthesia in enhancing cancer-related survival. Our study addresses these inconsistencies using a robust research design that was focused on a well-defined patient cohort.ResultsPreliminary evidence suggests that regional anaesthesia can modulate immune responses. However, its clinical benefits in cancer recurrence and survival have not been consistently demonstrated. The extant literature reflects a gap between preclinical promise and clinical efficacy, with no substantial evidence supporting a reduction in cancer recurrence after gastroesophageal cancer surgery under regional anaesthesia.ConclusionThis study provides new insights into the role of regional anaesthesia in reducing the overall mortality in gastric cancer surgery. By employing stringent inclusion criteria and a well-defined patient cohort, this study aimed to provide clarity in a field marked by inconclusive evidence and guide future clinical practices and high-quality research initiatives.
Assessing Performance of Multimodal ChatGPT-4 on an image based Radiology Board-style Examination: An exploratory study
Authors: Bera Kaustav , Gupta Amit , Jiang Sirui , Berlin Sheila , Faraji Navid , Tippareddy Charit , Chiong Ignacio , Jones Robert , Nemer Omar , Nayate Ameya , Tirumani Sree Harsha , Ramaiya Nikhil 
Published: January 2024

ABSTRACTObjectiveTo evaluate the performance of multimodal ChatGPT 4 on a radiology board-style examination containing text and radiologic images.sMaterials and MethodsIn this prospective exploratory study from October 30 to December 10, 2023, 110 multiple-choice questions containing images designed to match the style and content of radiology board examination like the American Board of Radiology Core or Canadian Board of Radiology examination were prompted to multimodal ChatGPT 4. Questions were further sub stratified according to lower-order (recall, understanding) and higher-order (analyze, synthesize), domains (according to radiology subspecialty), imaging modalities and difficulty (rated by both radiologists and radiologists-in-training). ChatGPT performance was assessed overall as well as in subcategories using Fisher’s exact test with multiple comparisons. Confidence in answering questions was assessed using a Likert scale (1-5) by consensus between a radiologist and radiologist-in-training. Reproducibility was assessed by comparing two different runs using two different accounts.ResultsChatGPT 4 answered 55% (61/110) of image-rich questions correctly. While there was no significant difference in performance amongst the various sub-groups on exploratory analysis, performance was better on lower-order [61% (25/41)] when compared to higher-order [52% (36/69)] [P=.46]. Among clinical domains, performance was best on cardiovascular imaging [80% (8/10)], and worst on thoracic imaging [30% [3/10)]. Confidence in answering questions was confident/highly confident [89%(98/110)], even when incorrect There was poor reproducibility between two runs, with the answers being different in 14% (15/110) questions.ConclusionDespite no radiology specific pre-training, multimodal capabilities of ChatGPT appear promising on questions containing images. However, the lack of reproducibility among two runs, even with the same questions poses challenges of reliability.
Mendelian randomization study on the association between cheese intake and diabetes
Authors: Yang Si-Qi , Xu Yu , Zhang Yan-Bing , Wang Wei-Xing 
Published: January 2024

AbstractObjectiveTo explore whether there is a causal relationship between cheese intake and diabetes through Mendel randomization (MR).MethodsTwo samples of MR were used to verify the causal effect of cheese intake on diabetes. The analysis was conducted using inverse variance weighted (IVW), weighted median, and MR-Egger regression methods. We used a meta-analysis of publicly available genome-wide association studies (GWAS) to compile statistical datasets, and cheese intake data as exposure factors were sourced from individuals of European ancestry in the UK biobank (n=451486). At the same time, GWAS’s public summary statistical data set is also used for self reporting non cancer disease codes: diabetes data included in the Finnish database (total n=184404; case=1219, control=183185) (http://www.finngen.fi/en)as a result.ResultWe selected 108 single nucleotide polymorphisms (SNPs) with genome-wide significance as instrumental variables from the GWAS intake of cheese. IVW method results show a causal relationship between cheese intake and diabetes (β=- 1.196, SE=0.3817, P=0.001729). MR Egger regression results show that directed pleiotropy is unlikely to bias the results (intercept=0.015; P=0.58), but there is no causal relationship between cheese intake and diabetes (β=- 2.073, SE=1.621, P=0.206). The results of weighted median method also showed that there was no causal relationship between cheese intake and diabetes (β=- 0.7828, SE=0.5701, P=0.1698). Cochran’s Q-test and funnel plot indicate no evidence of heterogeneity and asymmetry, indicating the absence of directed pleiotropy.ConclusionThe results of MR analysis support that cheese intake may have a causal relationship with the reduced risk of diabetes.
The Association Between Medicare Eligibility on Elective Procedures and Hospital Transfers: A regression discontinuity design applied to the National Inpatient Sample
Authors: Swaminathan Akshay , Kumar Wasan , Jacobson Benjamin , Liou Lathan , Lopez Ivan , Yao Caroline , Shah Sarthak 
Published: January 2024

AbstractIntroductionAccess to affordable health coverage for individuals aged 51 and older, particularly those transitioning out of employer-sponsored insurance or with existing health conditions, is challenging in the United States. This study investigates the potential impact of lowering the Medicare eligibility age on healthcare utilization, focusing on elective procedures among late middle-aged individuals. Previous studies indicate significant increases in healthcare utilization around the Medicare eligibility threshold, but a national-level analysis is needed to understand the implications of policy changes in Medicare eligibility.MethodsThis retrospective cohort study utilized 2019 data from the National Inpatient Sample (NIS), encompassing over seven million hospital stays and covering more than 97% of the U.S. population. We compared two groups: uninsured patients aged 63-64 and Medicare-insured patients aged 65-66. The analysis focused on nine common elective surgical procedures, employing a regression discontinuity design to minimize confounding. Patients were exactly matched on several variables, including reason for hospitalization, sex, race, and hospitalization type (elective vs. emergent).ResultsThe matched cohort, after exact matching, included 70,916 admissions (47,262 from Medicare patients aged 65-66 and 23,654 from uninsured patients aged 63-64). The study found significantly higher utilization rates of elective procedures, including cataract surgery, glaucoma surgery, joint replacement, and spinal fusion, among the Medicare-eligible group compared to the younger, uninsured group. Rates of elective procedures approximately doubled post-eligibility for Medicare. Additionally, being below the Medicare eligibility age was associated with decreased odds of undergoing these procedures and increased odds of hospital transfers.DiscussionLowering the Medicare eligibility age could lead to increased access to elective medical procedures for late middle-aged individuals, potentially reducing delays in treatment and associated complications.
Loss of postsynaptic NMDARs drives nanoscale reorganization of Munc13-1 and PSD-95
Authors: Dharmasri Poorna A. , DeMarco Emily M. , Anderson Michael C. , Levy Aaron D. , Blanpied Thomas A. 
Published: January 2024

AbstractNanoscale protein organization within the active zone (AZ) and post-synaptic density (PSD) influences synaptic transmission. Nanoclusters of presynaptic Munc13-1 are associated with readily releasable pool size and neurotransmitter vesicle priming, while postsynaptic PSD-95 nanoclusters coordinate glutamate receptors across from release sites to control their opening probability. Nanocluster number, size, and protein density vary between synapse types and with development and plasticity, supporting a wide range of functional states at the synapse. Whether or how the receptors themselves control this critical architecture remains unclear. One prominent PSD molecular complex is the NMDA receptor (NMDAR). NMDARs coordinate several modes of signaling within synapses, giving them the potential to influence synaptic organization through direct protein interactions or through signaling. We found that loss of NMDARs results in larger synapses that contain smaller, denser, and more numerous PSD-95 nanoclusters. Intriguingly, NMDAR loss also generates retrograde reorganization of the active zone, resulting in denser, more numerous Munc13-1 nanoclusters, more of which are aligned with PSD-95 nanoclusters. Together, these changes to synaptic nanostructure predict stronger AMPA receptor-mediated transmission in the absence of NMDARs. Notably, while prolonged antagonism of NMDAR activity increases Munc13-1 density within nanoclusters, it does not fully recapitulate these trans-synaptic effects. Thus, our results confirm that NMDARs play an important role in maintaining pre- and postsynaptic nanostructure and suggest that both decreased NMDAR expression and suppressed NMDAR activity may exert distinct effects on synaptic function, yet through unique architectural mechanisms.Significance StatementSynaptic transmission is shaped by the trans-synaptic coordination of molecular ensembles required for neurotransmitter release and receptor retention, but how receptors themselves influence this critical architecture remains unclear. Using state-of-the-art super-resolution microscopy, we report that loss of NMDA receptors from excitatory synapses alters both pre- and postsynaptic nano-organizational features. Notably, pharmacological antagonism of NMDA receptors also alters presynaptic features, but without fully mimicking effects of the knockout. This suggests that both NMDA receptor activity and presence at the synapse exert retrograde influence on active zone organization. Because numerous disease and activity states decrease expression or function of NMDA receptors, our results suggest that distinct nanostructural states contribute to the unique functional status of synapses in these disorders.
Late-life dietary folate restriction reduces biosynthetic processes without compromising healthspan in mice
Authors: Blank Heidi M. , Hammer Staci E. , Boatright Laurel , Roberts Courtney , Heyden Katarina E. , Nagarajan Aravindh , Tsuchiya Mitsuhiro , Brun Marcel , Johnson Charles D. , Stover Patrick J. , Sitcheran Raquel , Kennedy Brian K. , Adams L. Garry , Kaeberlein Matt , Field Martha S. , Threadgill David W. , Andrews-Polymenis Helene L. , Polymenis Michael 
Published: January 2024

ABSTRACTFolate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual’s age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.
Discovery and characterisation of new phage targeting uropathogenicEscherichia coli
Authors: Kangachar Shahla Asgharzadeh , Logel Dominic Y. , Trofimova Ellina , Zhu Hannah X , Zaugg Julian , Schembri Mark A. , Weynberg Karen D. , Jaschke Paul R. 
Published: January 2024

ABSTRACTAntimicrobial resistance (AMR) is increasing at an escalating rate with few new therapeutic options in the pipeline. Urinary tract infections (UTIs) are one of the most prevalent bacterial infections globally and are particularly prone to becoming recurrent and antibiotic resistant. The aim of this study was to discover and characterise new bacterial viruses (phage) against uropathogenicEscherichia coli(UPEC), which is the leading cause of UTIs. Six phages from theAutographiviridaefamily andGuernseyvirinaesub-family were isolated from wastewater and sequenced. The length of the isolated phage genomes was between 39,471 bp and 45,233 bp, with a GC content between 45.0% and 51.0%, and 57 to 84 predicted coding sequences (CDS) per genome. These phages were found to infect between 25 – 75% of the twelve UPEC strains tested. Using sequence comparison and predicted structural alignments, we show a similarity between the C-terminal domain of the tail fiber proteins of two phage that correlates with their host range.In vitrocharacterisation of phage cocktails against a single bacterial strain did not perform better than the best-performing phage, but did show synergistic improvement against a mixed UPEC strain population. Lastly, we measured the effectiveness of treatment with phage with different lytic kinetics in a sequential treatment and found it was improved over single phage treatment.
FOXO-regulated Deaf1 controls muscle regeneration through autophagy
Authors: Goh Kah Yong , Lee Wen Xing , Choy Sze Mun , Krishnan Priyadarshini Gopal , Chua Kenon , Tan Qian Hui , Low Shin Yi , Chin Hui San , Wong Chee Seng , Huang Shu-Yi , Fu Nai Yang , Nishiyama Jun , Harmston Nathan , Tang Hong-Wen 
Published: January 2024

AbstractThe commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a new regulator of muscle regeneration, Deformed epidermal autoregulatory factor 1 (Deaf1) - a transcriptional factor downstream of FOXO signaling. We showed that Deaf1 is transcriptionally repressed by FOXOs and that Deaf1 targets to PI3KC3 and Atg16l1 promoter regions and suppresses their expressions.Deaf1depletion therefore induces autophagy, which in turn blocks MuSC survival and differentiation. In contrast,Deaf1overexpression inactivates autophagy in MuSCs, leading to increased protein aggregation and cell death. Interestingly,Deaf1depletion and overexpression both lead to defects in muscle regeneration, highlighting the importance of fine tuning Deaf1-regulated autophagy during muscle regeneration. We further showed thatDeaf1expression is altered in aging and cachectic MuSCs. Remarkably, manipulation ofDeaf1expression can attenuate muscle atrophy and restore muscle regeneration in aged mice or mice with cachectic cancers. Together, our findings unveil an evolutionarily conserved role for Deaf1 in muscle regeneration, providing insights into the development of new therapeutic strategies against muscle atrophy.
Automated behavioral analysis reveals that mice employ a bait-and-switch escape mechanism to de-escalate social conflict
Authors: Clein Rachel S. , Warren Megan R. , Neunuebel Joshua P. 
Published: January 2024

AbstractIntraspecies aggression has profound ecological and evolutionary consequences, as recipients can suffer injuries, decreases in fitness, and become outcasts from social groups. Although animals implement diverse strategies to avoid hostile confrontations, the extent to which social influences affect escape tactics is unclear. Here, we used computational and machine-learning approaches to analyze complex behavioral interactions as mixed-sex groups of mice,Mus musculus, freely interacted. Mice displayed a rich repertoire of behaviors marked by changes in behavioral state, aggressive encounters, and mixed-sex interactions. A prominent behavioral sequence consistently occurred after aggressive encounters, where males in submissive states quickly approached and transiently interacted with females immediately before the aggressor engaged with the same female. The behavioral sequences were also associated with substantially fewer physical altercations. Furthermore, the male’s behavioral state and the interacting partners could be predicted by distinct features of the behavioral sequence, such as kinematics and the latency to and duration of male-female interactions. More broadly, our work revealed an ethologically relevant escape strategy influenced by the presence of females that may serve as a mechanism for de-escalating social conflict and preventing consequential reductions in fitness.
A cGAS-mediated IFN-I response in human CD4+ T cells depends on productive infection and is conserved over HIV types and strains
Authors: Janevska Marija , Cammaert Timothy , Naessens Evelien , Verhasselt Bruno 
Published: January 2024

AbstractHIV type 2 is known to be better controlled by our immune system than HIV-1. The mechanism of innate sensing of HIV-2 by T cells is at present unclear. In this study we show that several primary isolates of HIV-2 (CBL20 and CI85) and HIV-1 (A8 and D2), similarly to the molecular clone HIV-1 NL4.3-GFP-I, induce a significant IFN-I response by infection of its main target, activated CD4+ T cells. However, they are unable to do so after shRNA-mediated knock-down of cGAS. In addition, HIV-1 induced IFN-I response in CD4+ T cells is dependent on productive infection and cannot be attributed to contaminating plasmid DNA present in some virus stocks. Our findings collectively showed that the cGAS-dependent innate response of CD4+ T cells to HIV infection is conserved over HIV types and critically depends on productive infection.Author SummaryOur study unveils the essential role of cGAS in sensing HIV-1 and HIV-2 infections in CD4+ T cells. By demonstrating the necessity of productive infection, we highlight the robust and specific nature of the observed cGAS-mediated innate response, dispelling concerns about contaminating plasmids triggering immune response. Our findings suggest that the lower pathogenicity of HIV-2 does not correlate to superior innate immune control mediated by cGAS. By emphasizing the importance of productive infection and cGAS activity, our research advances understanding of host-pathogen relation and informs targeted strategies for combating HIV.