bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case report: Can a Titanised polypropylene mesh (TiMesh) obviate a dual mesh for sandwich technique for parastomal hernias??
Authors: Kalikar Vishakha , Patankar Roy 
Published: November 2024

Abstract
The three main surgical techniques for PSH are primary fascial repair, stoma reconstruction, and mesh reconstruction. Both open & laparoscopic repair can be done for PSH and currently mesh reinforcement is widely accepted. Polypropylene mesh permeates the ingrowth of adjacent fascia and potentially adhering onto adjacent organs, including the viscera, leading to mesh erosion and enteric fistula. Polytetrafluoroethylene (PTFE) mesh shrinks significantly in the tissue and thereby increases the chances of PSH recurrence rate. TiMesh (Healthium Medtech, Bengaluru, India) is a titanium-coated polypropylene composite mesh and is included in the guidelines for laparoscopic treatment of ventral & incisional abdominal wall hernias by International Endo hernia Society (IEHS). TiMesh can be used to repair PSH and maybe a useful alternative to dual mesh. We present a case report of a 64-year-old lady who presented with a parastomal hernia after an abdomino-perineal resection and an end sigmoid colostomy. The parastomal hernia was repaired using a laparoscopic meshplasty using TiMesh. With a Dual mesh, the polypropylene side may come in contact with the bowel with a possibility of mesh erosion and fistulation. TiMesh being a coated mesh on both sides reduces these possibilities.
Ambulatory Medication Errors and Adverse Events Involved in Medicine-Related Malpractice Cases From 2011 to 2021
Authors: Boisvert Susan , Nelson Melissa , Ross Jacqueline 
Published: November 2024

Objectives:
The aims of the study were to identify the characteristics of medication-related malpractice claims occurring in the ambulatory setting across 2 time periods.

Methods:
A retrospective, descriptive study was used. Ambulatory medication–related closed malpractice events from loss years of 2011–2021 were analyzed. Analysis included gender and age, injury severity, location, major injury, medications, primary and secondary services, roles, contributing factors, primary drivers, indemnity paid, and disposition status. Findings were analyzed using the Candello Explore tool.

Results:
Five hundred four ambulatory medication–related closed malpractice events were included. Family medicine (19.4%) and internal medicine (10.4%) services had the largest number of claims. The top medications were anti-infectants (16.4%), narcotics (15.6%), and anticoagulants (14.4%). Medication-related claims were multifactorial, averaging 4.1 contributing factors per claim. Clinical judgment issues were found in over 55% of the claims, and communication factors were observed in almost 48% of the claims. In the comparison analysis, 433 claims from 2011 to 2015 and 161 claims from 2016 to 2021 were evaluated. A statistical decrease in claims involving anticoagulants and narcotics (P = 0.01) was seen in the second period. There was a statistical increase in claims involving pharmacy dispensing errors during the 2016–2021 period (P = 0.03).

Conclusions:
Adverse drug events in ambulatory care are multifactorial. Errors in the technical process of ordering and managing medications, patient education, patient adherence, and pharmacy dispensing were the primary drivers of ambulatory medication malpractice claims in this study.
R-Spondin Mimetic, SZN-043, Induced Proliferation and Wnt Activity, Two Features Deficient in Human Alcohol-Associated Liver Disease
Authors: Fisher Trevor , Patel Mehaben , Deshmukh Shalaka , Shah Darshini , Lu Chenggang , Newman Maureen , Ye Jay , Fletcher Russell , Vanhove Geertrui F. , Tibbitts Jay , Li Yang , Skill Nicholas J , Yang Zhihong , Liangpunsakul Suthat , Baribault Helene 
Published: November 2024

ABSTRACTLiver regeneration is impaired in patients suffering from alcohol-associated liver (ALD) diseases. Wnt ligands and their FZD receptors are dysregulated in diseased livers. R-spondin and their receptors are known to regulate Wnt activity via the stabilization of FZD receptors. Here, we investigated the components of the Wnt and R-Spondin-signaling pathways and their activity in patients with ALD. We found that while hepatocytes retained high levels of differentiation markers such asASGR1andASGR2, the expression of two R-spondin co-receptors,LGR4andLGR5, and ofCYP1A2and Wnt target genes were strongly reduced.SZN-043, a hepatocyte-targeted R-Spondin mimetic, is a new investigational drug that stimulates the physiological Wnt repair pathway and proliferation of hepatocytes. Here, we show that SZN-043 induced hepatocyte proliferation in all models tested, including humanized mouse livers, a chronic-binge alcohol-induced liver injury, and a CCl4-induced fibrosis mouse model. Altogether, SZN-043 could be beneficial for the treatment of ALD.
Identification and characterization of a ubiquitin E3 RING ligase of theChlamydia-like bacteriumSimkania negevensis
Authors: Hörner Eva-Maria , Boll Vanessa , Hermanns Thomas , Moldovan Adriana , Hofmann Kay , Kozjak-Pavlovic Vera 
Published: November 2024

AbstractIn the arms race between a pathogen and the host, many bacteria have acquired a sizable armory to counteract or change the defense mechanisms of the host cell, including the eukaryotic ubiquitin system.Simkania negevensis, an obligate intracellularChlamydia-like bacterium, is one such example.S. negevensishas a biphasic developmental cycle, similar to other members of theChlamydialesorder. The bacterium develops inside a tubular membranous compartment calledSimkania-containing vacuole, which is in close contact with the host endoplasmic reticulum (ER) and mitochondria. It can infect a wide range of hosts, with a long infection cycle lasting up to 15 days, and is associated with respiratory tract diseases. Recently,S. negevensishas been discovered to possess an unusually large number of deubiquitinating enzymes, but not much is known about the variety of other ubiquitin-modifying enzymes in this bacterium. Our study provides an initial description of the activity of a so far uncharacterizedS. negevensisubiquitin E3 RING-ligase (SNE_A12920 or SneRING). We report that SneRING primarily generates K63- and K-11 linked ubiquitin chains and preferentially interacts with UbcH5b and UBE2T E2 ubiquitin ligases among the ones we tested. Bacteria express SneRING upon infection of various human cell lines, as well as amoeba. In addition, we demonstrate that a portion of the expressed SneRING co-localizes with mitochondria and ER. Mass spectrometry studies of the SneRING interactome show enrichment in mitochondrial and ER proteins containing a prohibitin domain and involved in organelle morphology, respiration, and stress response. Our work offers the first insights into the function of anS. negevensisRING ligase, an enzyme potentially involved in organelle remodeling to accommodate the unique lifestyle of this intracellular bacterium.
The effects of chronic neuropathic pain states on the discriminative stimulus effect of fentanyl and other MOR agonists
Authors: Burgess Gwendolyn E. , Traynor John R. , Jutkiewicz Emily M. 
Published: November 2024

AbstractPleasant subjective effects of drugs (e.g., euphoria) have been demonstrated to contribute to their abuse potential. In humans, there is some evidence that acute pain states may decrease the positive subjective effects of opioids; however, no studies have directly tested the impact of a long-lasting pain state. Therefore, the goal of this study was to directly evaluate the discriminative stimulus of mu opioid receptor (MOR) agonist, fentanyl, or the non-opioid drug of abuse, cocaine, in the presence or absence of spared nerve injury (SNI) induced chronic neuropathic pain. Prior to surgery, MOR agonists (fentanyl, morphine, nalbuphine) dose-dependently increased % fentanyl-like responding, as expected; surprisingly, after surgery, we saw small, significant rightward shifts in the fentanyl and morphine dose response curves inbothsham and SNI groups suggesting that the observed shifts were not due to chronic pain. In both sham and SNI groups, there was an increase in the generalization of nalbuphine to the fentanyl-discriminative stimulus. There was no change in the discriminative stimulus of cocaine (or amphetamine substitutions) over 4 months of SNI-induced chronic neuropathic pain or sham states, suggesting that the SNI model failed to alter the discriminative stimuli of fentanyl and cocaine. Following induction of chronic neuropathic pain, there was an observed increase in quinpirole-induced generalization to the cocaine discriminative stimulus. In the future, studies should directly examine the abuse potential of low efficacy MOR agonists and dopaminergic agonists in the presence and absence of chronic pain states.Significance StatementSubjective or interoceptive effects of drugs of abuse are known to contribute to the abuse potential. This study demonstrated that long-lasting neuropathic pain failed to alter the discriminative stimulus of mu opioid receptor agonists or cocaine; however, we observed an increase in quinpirole-induced generalization to the cocaine discriminative stimulus, suggesting the abuse potential of direct dopaminergic agonists should be further evaluated in the presence or absence of pain states.
Occurrence of Aneuploidy Across the Range of Coast Redwood (Sequoia sempervirens)
Authors: Nikolaeva Alexandra Sasha , Santangelo James , Smith Lydia , Dodd Richard , Nielsen Rasmus 
Published: November 2024

1AbstractAneuploidy, a condition characterized by an abnormal number of chromosomes, can have significant consequences for fitness of an organism, often manifesting in reduced fertility and other developmental challenges. In plants, aneuploidy is particularly complex to study, especially in polyploid species such as coast redwood (Sequoia sempervirens), which is a hexaploid conifer (2n=6x=66). This study leverages a novel Markov Chain Monte Carlo (MCMC) method based on sequence depth to investigate the occurrence of aneuploidy across the range of coast redwood.We show that aneuploidy is prevalent in second-growth redwoods, predominantly as additional chromosomes, while tissue culture plants frequently experience chromosome loss. Although our study does not directly assess the fitness of aneuploids, the frequency of chromosomal instability observed in tissue culture plants compared to second-growth and old-growth trees raises questions about their long-term developmental viability and potential to become established trees. These findings have significant implications for redwood conservation and restoration strategies, especially as tissue culture becomes the primary mode of producing nursery stock plants used in reforestation.
Quantitative contributions of hepatic and renal organic cation transporters to the clinical pharmacokinetic cimetidine-metformin interaction
Authors: Ailabouni Anoud Sameer , Singh Dilip Kumar , Thakur Aarzoo , Paine Mary F. , Boone Erin C. , Gaedigk Andrea , Prasad Bhagwat 
Published: November 2024

ABSTRACTThe widely prescribed oral anti-diabetic drug metformin is eliminated unchanged in the urine primarily through active tubular secretion. This process is mediated by organic cation transporter 2 (OCT2), an uptake transporter expressed on the basolateral membrane of renal proximal tubule cells. Metformin uptake into the liver, the site of action, is mediated by OCT1, which is expressed on the sinusoidal membrane of hepatocytes. Sixteen healthy adults participated in a clinical pharmacokinetic drug-drug interaction study in which they were orally administered metformin (50 mg) as a dual OCT1/2 substrate alone (baseline) and with cimetidine (400 mg) as an OCT inhibitor. Relative to baseline, metformin systemic plasma exposure increased by 24% (p<0.05) in the presence of cimetidine, which was accompanied by a disproportional decrease (8%) in metformin renal clearance (p=0.005). Genetic variants ofOCT1andOCT2moderately impacted the significance and magnitude of the interaction. Collectively, we hypothesized that the cimetidine-metformin interaction involves inhibition of hepatic OCT1 as well as renal OCT2. We tested this hypothesis by developing a physiologically based pharmacokinetic (PBPK) model and assessing potential OCT biomarkers in plasma and urine to gain mechanistic insight into the transporters involved in this interaction. The PBPK model predicted that cimetidine primarily inhibits hepatic OCT1 and, to a lesser extent, renal OCT2. The unchanged renal clearance of potential OCT2 biomarkers following cimetidine exposure supports a minimal role for renal OCT2 in this interaction.
Pleiotropy increases with gene age in six model multicellular eukaryotes
Authors: Martin Reese , Tate Ann T. 
Published: November 2024

AbstractFundamental traits of genes, including function, length and GC content, all vary with gene age. Pleiotropy, where a single gene affects multiple traits, arises through selection for novel traits and is expected to be removed from the genome through subfunctionalization following duplication events. It is unclear, however, how these opposing forces shape the prevalence of pleiotropy through time. We hypothesized that the prevalence of pleiotropy would be lowest in young genes, peak in middle aged genes, and then either decrease to a middling level in ancient genes or stay near the middle-aged peak, depending on the balance between exaptation and subfunctionalization. To address this question, we have calculated gene age and pleiotropic status for several model multicellular eukaryotes, includingHomo sapiens,Mus musculus,Danio rerio,Drosophila melanogaster,Caenorhabditis elegans, andArabidopsis thaliana. Gene age was determined by finding the most distantly related species that shared an ortholog using the Open Tree of Life and the Orthologous Matrix Database (OMAdb). Pleiotropic status was determined using both protein-protein interactions (STRINGdb) and associated biological processes (Gene Ontology). We found that middle-aged and ancient genes tend to be more pleiotropic than young genes, and that this relationship holds across all species evaluated and across both modalities of measuring pleiotropy. We also found absolute differences in the degree of pleiotropy based on gene functional class, but only when looking at biological process count. From these results we propose that there is a fundamental relationship between pleiotropy and gene age and further study of this relationship may shed light on the mechanism behind the functional changes genes undergo as they age.Impact statementPleiotropy, the phenomenon where a single gene acts on multiple traits, is fundamental to genomic organization and has profound consequences for fitness. This work identifies a previously unknown relationship between pleiotropy and gene age, highlighting the dynamism of pleiotropy across time. This relationship holds across six distantly related model organisms, suggesting that it could be a highly generalizable finding, at least among multicellular eukaryotes. Following from this work, future investigation into mechanisms dictating the prevalence of pleiotropy at the gene or cellular level could provide fundamental insight into the maintenance of pleiotropy despite the potential for constraining rapid adaptation.
Utility of TaqMan Array Cards for detection of Acute febrile illness etiologies in patients suspected of Viral Hemorrhagic Fever Infections in Uganda
Authors: Akurut GG , Nyakarahuka L , Whitmer S , Namanya D , Kilama K , Mulei S , Baluku J , Tumusime A , Kyondo J , Lutwama Julius J , Shoemaker Trevor , Patel K , Montgomery Joel , Klena JD , Balinandi S 
Published: November 2024

AbstractIntroductionAttributing a causative agent to acute febrile illnesses (AFI) remains a challenging diagnostic task for clinical and public health laboratories. The need for developing, validating and implementing a multi-pathogen diagnostic assay able to detect a wide range of AFI-associated pathogens should be prioritized in low-resource settings. The use of the previously developed Acute Febrile Illness TaqMan Array card (AFI-TAC), which detects 26 pathogens in less than 2 hours post-sample nucleic acid extraction, was selected for evaluation in Uganda.MethodsThis was a cross-sectional retrospective study in which archived viral hemorrhagic fever (VHF)-negative blood and plasma samples were selected. Samples were previously tested and archived at the Uganda Virus Research Institute (UVRI)-Viral Hemorrhagic Fever (UVRI-VHF) Laboratory from August 2018 to March 2019 as part of the routine surveillance program. The VHF case definition included, temperature of ≥38.0 ºC, additionally with bleeding and any other febrile symptoms. Samples were then tested using an AFI-TAC for 35 potential pathogen targets. Selected positive samples were subsequently assessed using a second, pathogen-specific simplex PCR assay. Epidemiological data were linked to the laboratory findings to assess for risk factors for infection.ResultsA total of 82 samples were selected for this study, of which 152 (83.52%) were from Uganda, 22 (12.09%) from the Democratic Republic of the Congo, 7 (3.85 %) from South Sudan, and 1 (0.55%) from Kenya. The median age of the patients was 27 years, with 145 (79.67%) samples from adults >18 years. Seven pathogens were detected with the most prevalent beingPlasmodiumspp. 26.92% (49/182) of which 69.4% (34/49) werePlasmodium falciparum, Yellow fevervirus 2 (1.10 %), non-typhoidalSalmonella3 (1.65%),Salmonella enterica serovarTyphi (1.10%),Leptospiraspp. 1 (0.54%),Streptococcus pneumonia(0.55%), andRickettsiaspp. (0.55%). Epidemiological correlation revealed a significant relationship between case fatality (p=0.002) and disease while age, occupation, sex and disease were not significant. Cough was found to be the only clinical symptom associated with being infected withPlasmodium(p=0.016).ConclusionThe use of TAC is feasible, readily adoptable diagnostic assay for use in Uganda and will be useful when incorporated into the national testing algorithm for the differential diagnosis of AFI during an outbreak and surveillance.
Negative BOLD Responses Surpass Positive Responses in Task Specificity, Reflecting Neural Reconfigurations Better Than Functional Connectivity
Authors: Gholipour Picha Saman , Hojjati Seyed Hani , Nayak Siddharth , Ozoria Sindy , Chernek Peter , Calimag Jenseric , Ghaderi Yazdi Bardiya , Razlighi Qolamreza R. 
Published: November 2024

AbstractObjectiveTo investigate whether the Negative BOLD Response (NBR) is more task-specific than the Positive BOLD Response (PBR) during cognitive tasks and to determine whether task-evoked activity reflects brain reconfigurations during different tasks better than functional connectivity.MethodsFunctional Magnetic Resonance Imaging (fMRI) data were collected from 214 participants under 50 years old (152 in Dataset 1 and 62 in Dataset 2) performing twelve cognitive tasks spanning vocabulary, speed of processing, fluid reasoning, and memory domains. Data analysis included subject-level and group-level analyses, focusing on comparing the spatial patterns and task specificity of NBR and PBR through similarity measures using Dice coefficients. Additionally, functional connectivity was assessed using the Multi-session Hierarchical Bayesian Model (MS-HBM) to evaluate its sensitivity to task-induced brain reconfigurations compared to task-evoked activity.ResultsNBR demonstrated significantly greater task specificity compared to PBR across all cognitive tasks, with lower mean Dice coefficients for NBR maps (mean: 0.44, SD: 0.13) than for PBR maps (mean: 0.67, SD: 0.09; t(65) = 18.38, p < 0.001). Functional connectivity analyses indicated that the default mode network (DMN) remained stable across tasks, suggesting that task-evoked activity reflects task-specific brain reconfigurations better than functional connectivity.ConclusionThe findings confirm that NBR is inherently more task-specific than PBR and that task-evoked activity provides a more sensitive measure of task-specific neural reconfigurations than functional connectivity. This enhances our understanding of the neural mechanisms underlying cognitive processes and highlights the importance of considering NBR in cognitive neuroscience research.
TRAIT: A Comprehensive Database for T-cell Receptor-Antigen Interactions
Authors: Wei Mengmeng , Wu Jingcheng , Bai Shengzuo , Zhou Yuxuan , Chen Yichang , Zhang Xue , Zhao Wenyi , Chi Ying , Pan Gang , Zhu Feng , Chen Shuqing , Zhou Zhan 
Published: November 2024

AbstractComprehensive and integrated resources on interactions between T-cell receptors and antigens are still lacking for adoptive T-cell-based immunotherapies, highlighting a significant gap that must be addressed to fully comprehend the mechanisms of antigen recognition by T-cells. In this study, we present TRAIT, a comprehensive database that profiles the interactions between T-cell receptors (TCRs) and antigens. TRAIT stands out due to its comprehensive description of TCR-antigen interactions by integrating sequences, structures and affinities. It provides nearly 8 million experimentally validated TCR-antigen pairs, resulting in an exhaustive landscape of antigen-specific TCRs. Notably, TRAIT emphasizes single-cell omics as a major reliable data source for TCR-antigen interactions and includes millions of reliable non-interactive TCRs. Additionally, it thoroughly demonstrates the interactions between mutations of TCRs and antigens, thereby benefiting affinity maturation of engineered TCRs as well as vaccine design. TCRs on clinical trials were innovatively provided. With the significant efforts made towards elucidating the complex interactions between TCRs and antigens, TRAIT is expected to ultimately contribute superior algorithms and substantial advancements in the field of T-cell-based immunotherapies. TRAIT is freely accessible athttps://pgx.zju.edu.cn/traitdb.
Human internal exposures of bisphenol A and six data-poor analogues predicted by physiologically based kinetic models with multimodal parameterization
Authors: Bigonne Hélène , Rolof Amrei , Potapova Inga , Sturla Shana J. , Aichinger Georg 
Published: November 2024

AbstractBackgroundBisphenols (BP) AF, B, E, F, M, and S have been introduced as substitutes for bisphenol A (BPA) and are increasingly used in consumer products. Despite widespread human exposure and potential adverse health outcomes related to BPF, BPB, BPS, and BPAF, their physiological disposition in humans is poorly characterized, which hinders assessment of associated risks.ObjectivesOur goal was to simulate the kinetic behavior of prevalent bisphenol analogs in organs of toxicological interest. To enable predictions of physiologically relevant internal concentrations of a family of structurally similar compounds with limited available human data, we aim to establish a reproducible framework using multimodal parameterization methods.MethodsHerein we developed physiologically based kinetic (PBK) models, following oral exposure. Their parametrization was primarily based on structural, physiological and experimental values, as well as quantitative structure-activity relationship (QSAR) predictions. Outputs were evaluated against available biomonitoring data for BPA and BPS. Critical parameters were identified by sensitivity analysis and iteratively re-sampled in Monte Carlo (MC) simulations to quantify uncertainties.ResultsAmong human models parametrized for males and females of different ages, we predicted that bisphenols reached the highest concentrations in 5-year-old males. Environmentally relevant exposure levels resulted in maximum concentrations in the blood and testes for BPS, and in the thyroid for BPM. After 96 hours, steady-state concentrations were not yet reached in the breasts for BPA, BPAF, BPB, BPE, BPF and BPM.ConclusionsThe data from this study suggest significant variability in internal concentrations for identical exposures to different bisphenols analogs that further depend on age, sex and organ. This diversity in toxicokinetic behavior should be considered for health risk assessment of these substitutes.