bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of GIT nematodes and associated risk factors of exotic chickens in selected farm of poultry in and around Ambo, Ethiopia
Authors: Temesgen Abraham Belete , Wassie Zerihun Getie , Abebe Saleamlak 
Published: July 2024

AbstractPoultry are raised worldwide in backyards and commercial systems with fewer social and religious taboos than other livestock. However, the chicken industry faces significant challenges from nematode parasites. A cross-sectional study with a random sampling technique was conducted from April to June 2019 to estimate gastrointestinal (GI) nematode parasites in chickens in selected farms in and around Ambo, Ethiopia. The fecal analysis results revealed that out of 70 samples collected, 60% were positive for gastrointestinal (GI) nematode eggs. Prevalence varied significantly by body condition, with the highest rates in chickens in poor condition (78.57%), followed by medium (54.54%) and good condition (40%). Location also played a significant role, with Ambo University Poultry Farm having the highest prevalence (83.87%), followed by Abebe Private Farm (55%) and Guder Campus Poultry Farm (26.31%). The main nematode species identified wereAscaridia galli(57.1%) andHeterakis gallinarum(2.9%). Infestation rates differed significantly by sex, age, location, and body condition, with males having higher rates ofAscaridia galli(61.53%) than females (56.14%), andHeterakis gallinarumexclusively affecting females (3.51%). Adults showed significantly higher rates ofAscaridia galli(85.71%) than young chickens (38.09%), with some infestation ofHeterakis gallinarum(7.14%) observed in adults but absent in young chickens. This prevalence rate suggests limited awareness among chicken producers and insufficient control strategies in the study area. Hence, implementing targeted control strategies is advisable.
YAP1 Contributes to The Development of Contractile Force and Sarcomere Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Vinarsky Vladimir , Pagliari Stefania , Martino Fabiana , Mazzotti Cristina , Jirakova Katerina , Garlikova Zuzana , Iuri Enrico Di , Kytyr Daniel , Benzoni Patrizia , Arici Martina , Metallo Alessia , Zeevaert Kira , Barbuti Andrea , Wagner Wolfgang , Rocchetti Marcella , Forte Giancarlo 
Published: July 2024

AbstractBackgroundPerspective regenerative therapies for injured myocardium focus on reactivating developmental processes to regenerate damaged contractile tissue. In animal models, the Hippo pathway was shown to improve heart regeneration after myocardial infarction, possibly by expanding the pool of cardiomyocytes. We hypothesized that activating the Hippo pathway’s downstream effector, Yes Associated Protein (YAP1), may have effects beyond promoting proliferation in human cardiomyocytes. We have therefore investigated how YAP1 influences human cardiomyocyte maturation, sarcomere structure, electrophysiological properties, their response to mechanical stimuli, intracellular Ca2+″ dynamics and force development using models of cardiomyocytes derived from pluripotent stem cells.MethodsWe employed genetic models of YAP1 deficient human embryonic and induced pluripotent stem cells, cardiomyocyte differentiation, compliant cultivation substrates, mechanical actuation, ECM deposition, super resolution microscopy, electrophysiological measurements and engineered heart tissues (EHTs) to characterize the effects of YAP1 deficiency on cardiomyocytes during maturation. We also used full length YAP1 re- expression to rescue the effects of YAP1 deficiency in contracting cardiomyocytes.ResultsYAP1 contributes to cardiomyocyte maturation, participates in the formation and alignment of myofibrils, as well as in the maturation of electrophysiological properties. The net effect of YAP1 deficiency in cardiomyocytes is the inability to respond to physiological stimuli by compensatory growth resulting in reduced force development. Additionally, YAP1 reactivation in contracting cardiomyocytes leads to rescue of myofibril maturation.ConclusionsThis research demonstrates that YAP1 activity is essential to promote cardiomyocyte maturation, contractility, and response to regeneration inducing stimuli.
Self-Organization of Sinusoidal Vessels in Pluripotent Stem Cell-derived Human Liver Bud Organoids
Authors: Saiki Norikazu , Nio Yasunori , Yoneyama Yosuke , Kawamura Shuntaro , Iwasawa Kentaro , Kawakami Eri , Araki Kohei , Fukumura Junko , Sakairi Tsuyoshi , Kono Tamaki , Ohmura Rio , Koido Masaru , Funata Masaaki , Thompson Wendy L. , Cruz-Encarnacion Pamela , Chen Ya-Wen , Takebe Takanori 
Published: July 2024

AbstractThe induction of tissue-specific vessels inin vitroliving tissue systems remains challenging. Here, we directly differentiated human pluripotent stem cells into CD32b+putative liver sinusoidal progenitors (iLSEP) by dictating developmental pathways. By devising an inverted multilayered air-liquid interface (IMALI) culture, hepatic endoderm, septum mesenchyme, arterial and sinusoidal quadruple progenitors self-organized to generate and sustain hepatocyte-like cells neighbored by divergent endothelial subsets composed of CD32blowCD31high, LYVE1+STAB1+CD32bhighCD31lowTHBD-vWF-, and LYVE1-THBD+vWF+cells. Wnt2 mediated sinusoidal-to-hepatic intercellular crosstalk potentiates hepatocyte differentiation and branched endothelial network formation. Intravital imaging revealed iLSEP developed fully patent human vessels with functional sinusoid-like features. Organoid-derived hepatocyte- and sinusoid-derived coagulation factors enabled correction ofin vitroclotting time with Factor V, VIII, IX, and XI deficient patients’ plasma and rescued the severe bleeding phenotype in hemophilia A mice upon transplantation. Advanced organoid vascularization technology allows for interrogating key insights governing organ-specific vessel development, paving the way for coagulation disorder therapeutics.
Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs
Authors: Dong Chuanpeng , Zhang Feifei , He Emily , Ren Ping , Verma Nipun , Zhu Xinxin , Feng Di , Zhao Hongyu , Chen Sidi 
Published: July 2024

AbstractEmerging immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy have revolutionized cancer treatment and have improved the survival of patients with multiple cancer types. Despite this success many patients are unresponsive to these treatments or relapse following treatment. CRISPR activation and knockout (KO) screens have been used to identify novel single gene targets that can enhance effector T cell function and promote immune cell targeting and eradication of tumors. However, cancer cells often employ multiple genes to promote an immunosuppressive pathway and thus modulating individual genes often has a limited effect. Paralogs are genes that originate from common ancestors and retain similar functions. They often have complex effects on a particular phenotype depending on factors like gene family similarity, each individual gene’s expression and the physiological or pathological context. Some paralogs exhibit synthetic lethal interactions in cancer cell survival; however, a thorough investigation of paralog pairs that could enhance the efficacy of cancer immunotherapy is lacking. Here we introduce a sensitive computational approach that uses sgRNA sets enrichment analysis to identify cancer-intrinsic paralog pairs which have the potential to synergistically enhance T cell-mediated tumor destruction. We have further developed an ensemble learning model that uses an XGBoost classifier and incorporates features such as gene characteristics, sequence and structural similarities, protein-protein interaction (PPI) networks, and gene coevolution data to predict paralog pairs that are likely to enhance immunotherapy efficacy. We experimentally validated the functional significance of these predicted paralog pairs using double knockout (DKO) of identified paralog gene pairs as compared to single gene knockouts (SKOs). These data and analyses collectively provide a sensitive approach to identify previously undetected paralog pairs that can enhance cancer immunotherapy even when individual genes within the pair has a limited effect.
Temporal Trends in Thromboembolic Event Hospitalizations in Patients with Atrial Fibrillation in the United States
Authors: Vasquez Moises A. , Yan Crystal Lihong , Lambrakos Litsa K. , Velasquez Alex , Goldberger Jeffrey J. , Mitrani Raul D. 
Published: July 2024

ABSTRACTBackgroundDirect oral anticoagulants and percutaneous left atrial appendage occlusion (LAAC) devices were approved for use in 2010 and 2015, respectively. It is unknown to what extent, if any, these new stroke preventive therapies have impacted hospitalizations for thromboembolic (TE) events in the United States.MethodsWe used the National Inpatient Sample database to describe trends over time in AF-related hospitalizations for acute ischemic stroke (AIS), transient ischemic attacks (TIA), and systemic embolic events (SEE) between 2010 and 2021. Trends in anticoagulation use (AC) and percutaneous LAAC procedures among hospitalized patients with AF were also analyzed.ResultsA total of 1,692,373 hospitalizations for TE were identified between 2010 and 2021: 798,413 from 2010 to 2015 (mean age 78.9 [standard deviation (SD) 10.7] years; 57.8% female) and 893,960 from 2016 to 2021 (mean age 77.5 [SD 10.9] years; 53.1% female). There was a significant increase in rates of AC use (21.2% of inpatients with AF in 2010 vs 42.4% of inpatients with AF in 2021; Ptrend<0.001) and rates of percutaneous LAAC procedures (0.1/100,000 US adults vs to 17.7/100,000 US adults Ptrend<0.001) among inpatients with AF. Between 2010 to 2021, age-adjusted AIS hospitalizations increased (30.8 hospitalizations /100,000 US adults vs 35.9 hospitalizations/ 100,000 US adults; Ptrend<0.001) and peaked in 2019. Age-adjusted SEE hospitalizations (2.5 hospitalizations /100,000 US adults vs 1.3 hospitalizations/ 100,000 US adults; Ptrend<0.001) and TIA hospitalization(8.5 hospitalizations /100,000 US adults vs 4.3 hospitalizations/ 100,000 US adults; Ptrend<0.001) peaked in 2011 and then decreased. Between 2016 and 2021, age-adjusted AIS hospitalizations plateaued (37.7 hospitalizations/100,000 US adults vs 35.9 hospitalizations/100,000 US adults; APC −4.7%; Ptrend= 0.197). The total of all TE hospitalizations remained stable (41.8 hospitalizations/100,000 US adults vs 41.5 hospitalizations/100,000 US adults; Ptrend0.689).ConclusionDespite increased anticoagulant and the initial use of percutaneous LAAO, AF-associated TE event hospitalizations in the US have remained stable from 2010 to 2021. Hospitalizations for AF-related TIA and SEE consistently decreased from 2010 to 2021 while AF-related AIS hospitalizations increased from 2010 to 2015 and then plateaued from 2016 to 2021.
No evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions: a Mendelian randomization study
Authors: Suri Pradeep , Tsepilov Yakov A. , Elgaeva Elizaveta E. , Williams Frances M. K. , Freidin Maxim B. , Stanaway Ian B. 
Published: July 2024

ABSTRACTObjectiveWe conducted a Mendelian randomization (MR) study to examine causal associations of C-reactive protein (CRP) with (1) spinal pain; (2) extent of multisite chronic pain; and (3) chronic widespread musculoskeletal pain.DesignTwo-sample MR study.Setting/SubjectsWe used summary statistics from publicly available genome-wide association studies (GWAS) conducted in multiple cohorts and biobanks. Genetic instrumental variables were taken from an exposure GWAS of CRP (n=204,402). Outcome GWASs examined spinal pain (n=1,028,947), extent of multisite chronic pain defined as the number of locations with chronic pain (n=387,649), and chronic widespread pain (n=249,843).MethodsWe examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis and sensitivity analyses using other methods. We calculated odds ratios (ORs), 95% confidence intervals (95% CIs), and p-values, using a Bonferroni correction (p<0.0166) to account for 3 primary comparisons.ResultsGreater serum CRP (mg/L) was not significantly causally associated with spinal pain (OR=1.04, 95% CI 1.00-1.08; p=0.07) in IVW analysis. Greater serum CRP also showed no significant causal association with extent of multisite chronic pain in IVW analysis (beta coefficient= 0.014, standard error=0.011; p=0.19). CRP also showed no significant causal association with chronic widespread pain in IVW analysis (OR=1.00, 95% CI 1.00-1.00; p=0.75). All secondary and sensitivity analyses also showed no significant associations.ConclusionsThis MR study found no causal association of CRP on spinal pain, the extent of chronic pain, or chronic widespread pain. Future studies examining mechanistic biomarkers for pain conditions should consider other candidates besides CRP.
Boosting LLM-Assisted Diagnosis: 10-Minute LLM Tutorial Elevates Radiology Residents’ Performance in Brain MRI Interpretation
Authors: Kim Su Hwan , Schramm Severin , Wihl Jonas , Raffler Philipp , Tahedl Marlene , Canisius Julian , Luiken Ina , Endrös Lukas , Reischl Stefan , Marka Alexander , Walter Robert , Schillmaier Mathias , Zimmer Claus , Wiestler Benedikt , Hedderich Dennis M. 
Published: July 2024

AbstractPurposeTo evaluate the impact of a structured tutorial on the use of a large language model (LLM)-based search engine on radiology residents’ performance in LLM-assisted brain MRI differential diagnosis.Materials & MethodsIn this retrospective study, nine radiology residents determined the three most likely differential diagnoses for three sets of ten brain MRI cases with a challenging yet definite diagnosis. Each set of cases was assessed 1) with the support of conventional internet search, 2) using an LLM-based search engine (© Perplexity AI) without prior training, or 3) with LLM assistance after a structured 10-minute tutorial on how to effectively use the tool for differential diagnosis. The tutorial content was based on the results of two studies on LLM-assisted radiological diagnosis and included a prompt template. Reader responses were rated using a binary and numeric scoring system. Reading times were tracked and confidence levels were recorded on a 5-point Likert scale. Binary and numeric scores were analyzed using chi-square tests and pairwise Mann-Whitney U tests each. Search engine logs were examined to quantify user interaction metrics, and to identify hallucinations and misinterpretations in LLM responses.ResultsRadiology residents achieved the highest accuracy when employing the LLM-based search engine following the tutorial, indicating the correct diagnosis among the top three differential diagnoses in 62.5% of cases (55/88). This was followed by the LLM-assisted workflow before the tutorial (44.8%; 39/87) and the conventional internet search workflow (32.2%; 28/87). The LLM tutorial led to significantly higher performance (binary scores: p = 0.042, numeric scores: p = 0.016) and confidence (p = 0.006) but resulted in no relevant differences in reading times. Hallucinations were found in 5.1% of LLM queries.ConclusionA structured 10-minute LLM tutorial increased performance and confidence levels in LLM-assisted brain MRI differential diagnosis among radiology residents.Clinical Relevance StatementOur findings highlight the considerable benefits that even low-cost, low-effort educational interventions on LLMs can provide. Integrating LLM education in radiology training programs could augment practitioners’ capacity to harness AI technologies effectively.
Bladder-resident bacteria associated with increased risk of recurrence after electrofulguration in women with antibiotic-recalcitrant urinary tract infection
Authors: Gadhvi Jashkaran G. , Kenee Parker R.M. , Lutz Kevin C. , Khan Fatima , Li Qiwei , Zimmern Philippe E. , De Nisco Nicole J. 
Published: July 2024

AbstractBackgroundAntibiotic-recalcitrant recurrent urinary tract infection (rUTI) is has become increasingly observed in postmenopausal women. Therefore, when standard antibiotic therapies have failed, some elect electrofulguration (EF) of areas of chronic cystitis when detected on office cystoscopy. EF is thought to remove tissue-resident bacteria that have been previously detected in the bladder walls of postmenopausal women with rUTI. We hypothesized that increased bladder bacterial burden may be associated with incomplete rUTI resolution following EF.MethodsFollowing IRB approval, bladder biopsies were obtained from 34 consenting menopausal women electing EF for the advanced management of rUTI. 16S rRNA FISH was performed using both universal andEscherichiaprobes and tissue-resident bacterial load was quantified. Time to UTI relapse after EF was recorded during a six-month follow-up period and the association of bladder bacterial burden and clinical covariates with UTI relapse was assessed.ResultsWe observed bladder-residentEscherichiain 52% of all participants and in 92% of participants with recentE. coliUTI. Time-to-relapse analysis revealed that women with high bladder bacterial burden as detected by the universal probe had a significantly (p=0.035) higher risk of UTI within six months of EF (HR=3.15, 95% CI: 1.09-9.11). Interestingly, bladder-residentEscherichiawas not significantly associated (p=0.26) with a higher risk of UTI relapse (HR= 2.14, 95% CI: 0.58-7.90).ConclusionsWe observed that total bladder bacterial burden was associated with a 3.1x increased risk of rUTI relapse within six months. Continued analysis of the relationship between bladder bacterial burden and rUTI outcomes may provide insight into the management of these challenging patients.
PGAP3 regulates human bronchial epithelial cell mRNAs present in asthma and respiratory virus reference data sets
Authors: Leslie Eric , Miller Marina , Lafuze Allison , Svyatskaya Sofya , Choi Gil-Soon , Broide David H. 
Published: July 2024

AbstractPGAP3 is a glycosylphosphatidylinositol (GPI) phospholipase gene localized within chromosome 17q12-21, a region highly linked to asthma. Although much is known about the function of other chromosome 17q12-21 genes expressed at increased levels in bronchial epithelium such as ORMDL3 and GSDMB, little is known about the function of increased PGAP3 expression in bronchial epithelium in the context of asthma. The aim of this study was therefore to determine whether increased PGAP3 expression in human bronchial epithelial cells regulated expression of mRNA pathways important to the pathogenesis of asthma by utilizing RNA-sequencing and bioinformatic analysis. We performed RNA-sequencing on normal human bronchial epithelial cells transfected with PGAP3 for 24 and 48 hours. PGAP3 regulated genes were compared to asthma and respiratory virus (influenza A, rhinovirus, respiratory syncytial virus) reference data sets to identify PGAP3 target genes and pathways. Approximately 9% of the upregulated PGAP3-induced genes were found in an asthma reference data set, 41% in a rhinovirus reference data set, 33% in an influenza A reference data set, and 3% in a respiratory syncytial virus reference data set. PGAP3 significantly upregulated the expression of several genes associated with the innate immune response and viral signatures of respiratory viruses associated with asthma exacerbations. Two of the highest expressed genes induced by PGAP3 are RSAD2, OASL, and IFN-λ, which are anti-viral genes associated with asthma. PGAP3 also upregulated the antiviral gene BST2, which like PGAP3 is a GPI-anchored protein. We conclude that PGAP3 expression in human bronchial epithelial cells regulates expression of genes known to be linked to asthma, and also regulates the bronchial epithelial expression of genes pertinent to the pathogenesis of respiratory viral triggered asthma exacerbations.
Female fruit flies use social cues to make egg clustering decisions
Authors: Churchill Emily R. , Fowler Emily K. , Friend Lucy A. , Archetti Marco , Yu Douglas W. , Bourke Andrew F. G. , Chapman Tracey , Bretman Amanda 
Published: July 2024

AbstractBackgroundThe ability to respond plastically to environmental variation is a key determinant of fitness. Females may use cues to strategically place their eggs, for example adjusting the number or location of eggs according to whether other females are present, driving the dynamics of local competition or cooperation. The expression of plasticity in egg laying patterns within individual patches, i.e., in contact clusters or not, represents an additional, under-researched and potentially important opportunity for fitness gains. Clustered eggs might benefit from increased protection or defence, and clustering could facilitate cooperative feeding. However, increased clustering is also expected to increase the risk of over-exploitation through direct competition. These potential benefits and costs likely covary with the number of individuals present, hence egg clustering behaviour within resource patches should be socially responsive. We investigate this new topic using the fruit flyDrosophila melanogaster.ResultsOur mathematical model, parameterised by data, verified that females cluster their eggs non-randomly, and increase clustering as group size increases. We also showed that, as the density of adult females increased, females laid more eggs, laid them faster, and laid more eggs in clusters. Females also preferred to place eggs within existing clusters. Most egg clusters were of mixed maternity.ConclusionsCollectively, the results reveal that females actively express plasticity in egg clustering according to social environment cues and prefer to lay in clusters of mixed maternity, despite the potential for increased competition. These findings are consistent with egg clustering plasticity being selected due to public goods-related benefits.