bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of vitamin C in ameliorating citalopram‐induced testicular toxicity via modulating nitro‐oxidative stress and apoptosis in mice
Authors: Moradi Mojtaba , Hashemian Mohammad Arshia , Fathi Mohammad , Peysokhan Mohsen , Hashemian Amir Hossein , Moradi Bahareh , Jalili Cyrus , Faramarzi Azita 
Published: October 2023

AbstractThere is a growing concern that antidepressant drugs impair sexual function and adversely impact spermatogenesis and male fertility. Vitamin C is a natural antioxidant that plays a vital role in the male reproductive system. The present study investigated the ameliorating potential of vitamin C against citalopram (CTL)‐evoked testicular toxicity and spermatogenesis impairment in mice. Mice were randomly divided into six groups: control, CTL, vitamin C 100, vitamin C 200, CTL plus vitamin C 100, and CTL plus vitamin C 200. Adult male mice were intraperitoneally (ip) injected with 10 mg/kg of CTL for 35 days with or without vitamin C. At the end of the study, body and testes weight, sperm parameters, histopathology of testes, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (TUNEL assay) were evaluated. Our findings revealed that vitamin C restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and testes histopathology were significantly improved in the vitamin C‐administrated groups. Furthermore, vitamin C administration markedly alleviated CTL‐induced nitro‐oxidative damage, enhancing TAC levels, and reducing NO and MDA levels. Whilst CTL therapy induced a significant increase in the number of TUNEL‐positive cells compared to the control, the administration of vitamin C significantly prevented the apoptotic effects of CTL. Together, vitamin C therapy protects against CTL‐induced testicular damage via mitigating nitro‐oxidative stress and apoptosis, which provides evidence for vitamin C as a beneficial therapy against antidepressant drug‐associated reproductive toxicity and male sub/infertility.
Altered 5‐methylcytosine modification of mRNA is involved in the pathogenesis of pre‐eclampsia
Authors: Tong Jing , Li Hongwanyu , Zhang Cong 
Published: October 2023

Abstract5‐Methylcytosine (m5C) is a prevalent RNA modification in messenger RNAs (mRNAs). Despite its abundance, its role in the decidua of pre‐eclampsia (PE) remains elusive. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and RNA‐sequencing (RNA‐seq) to map m5C peaks and mRNA expression profile in the decidua of human early‐onset PE (EPE), late‐onset PE (LPE), and normal pregnancy (NP). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses elucidated potential roles of the differentially methylated mRNAs (DMGs) and differentially expressed mRNAs in decidualization pathways. Integrative analysis of MeRIP‐seq and RNA‐seq data pinpointed 50 candidate genes linked to PE, marked by both differentially methylated m5C peaks and congruent expression changes. To validate these observations, we selected nine genes for verification via quantitative PCR. Our results underscore the precision and reproducibility of our bioinformatics approach. Importantly, we propose that changes in m5C modification and expression of relevant mRNA might influence the pathogenesis of PE by hampering decidualization. This work shines light on the distinct mRNA m5C modification patterns and expression profiles in the decidua of PE, implicating pivotal signaling disruptions and decidualization impediments in the onset of PE.
Structure‐based design of new N‐benzyl‐piperidine derivatives as multitarget‐directed AChE/BuChE inhibitors for Alzheimer's disease
Authors: Conceição Raissa Alves da , von Ranke Natalia , Azevedo Luciana , Franco Daiana , Nadur Nathalia Fonseca , Kummerle Arthur Eugen , Barbosa Maria Letícia de C. , Souza Alessandra M. T. 
Published: October 2023

AbstractThe pathogenic complexity of Alzheimer's disease (AD) demands the development of multitarget‐directed agents aiming at improving actual pharmacotherapy. Based on the cholinergic hypothesis and considering the well‐established role of butyrylcholinesterase (BuChE) in advanced stages of AD, the chemical structure of the acetylcholinesterase (AChE) inhibitor drug donepezil (1) was rationally modified for the design of new N‐benzyl‐piperidine derivatives (4a−d) as potential multitarget‐direct AChE and BuChE inhibitors. The designed analogues were further studied through the integration of in silico and in vitro methods. ADMET predictions showed that 4a−d are anticipated to be orally bioavailable, able to cross the blood‐brain barrier and be retained in the brain, and to have low toxicity. Computational docking and molecular dynamics indicated the formation of favorable complexes between 4a−d and both cholinesterases. Derivative 4a presented the lowest binding free energy estimation due to interaction with key residues from both target enzymes (−36.69 ± 4.47 and −32.23 ± 3.99 kcal/mol with AChE and BuChE, respectively). The in vitro enzymatic assay demonstrated that 4a was the most potent inhibitor of AChE (IC50 2.08 ± 0.16 µM) and BuChE (IC50 7.41 ± 0.44 µM), corroborating the in silico results and highlighting 4a as a novel multitarget‐directed AChE/BuChE inhibitor.
Sweroside attenuates podocyte injury and proteinuria in part by activating Akt/BAD signaling in mice
Authors: Huang Minjiang , Yang Yang , Chen Yuefu , Li Yang , Qin Sitao , Xiao Lijun , Long Xuewen , Hu Ke , Li Yuxian , Ying Huiming , Ding Yan 
Published: October 2023

AbstractIn this study, we investigated the effects of sweroside on podocyte injury in diabetic nephropathy (DN) mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of DN to explore the effects of sweroside on proteinuria and podocyte injury in DN mice. In in vitro experiments, conditionally immortalized mouse podocytes were treated with high glucose and sweroside, and the protective effects of sweroside on podocyte injury were analyzed. In vitro, Akt/BAD pathways were detected using gene siRNA silencing assays and found to be involved in the protective roles of sweroside in high glucose‐mediated podocyte injury. In vivo, sweroside significantly decreased albuminuria in DN mice (p < 0.01). periodic acid‐Schiff staining showed that sweroside alleviated the glomerular volume and mesangium expansion in DN mice. Consistently, western blot and reverse transcription‐polymerase chain reaction analyses showed that the profibrotic molecule expression in the glomeruli declined in sweroside‐treated DN mice. Immunofluorescent results showed that sweroside preserved nephrin and podocin expression, and transmission electron microscopy showed that sweroside attenuated podocyte injury. In DN mice, sweroside decreased podocyte apoptosis, and increased nephrin, podocin expression and decreased desmin and HIF1α expression. These results confirmed that sweroside ameliorated albuminuria, glomerulomegaly, and glomerulosclerosis in these mice. Experiments in vitro revealed that sweroside improved HG‐induced podocyte injury and apoptosis. Sweroside stimulated activation of the Akt/BAD pathway and upregulated Bcl‐2‐associated death promoter (BAD) and p‐Akt. Overall, sweroside protected podocytes from injury and prevented the progression of DN, providing a novel strategy for the treatment of DN.
Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?
Authors: Rodriguez Peter , Blakely Randy D. 
Published: October 2023

AbstractReceiving a neurodegenerative disease (NDD) diagnosis, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis, is devastating, particularly given the limited options for treatment. Advances in genetic technologies have allowed for efficient modeling of NDDs in animals and brought hope for new disease‐modifying medications. The complexity of the mammalian brain and the costs and time needed to identify and develop therapeutic leads limits progress. Modeling NDDs in invertebrates, such as the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, offers orders of magnitude increases in speed of genetic analysis and manipulation, and can be pursued at substantially reduced cost, providing an important, platform complement and inform research with mammalian NDD models. In this review, we describe how our efforts to exploit C. elegans for the study of neural signaling and health led to the discovery of a paralytic phenotype (swimming‐induced paralysis) associated with altered dopamine signaling and, surprisingly, to the discovery of a novel gene and pathway whose dysfunction in glial cells triggers neurodegeneration. Research to date on swip‐10 and its putative mammalian ortholog MBLAC1, suggests that a tandem analysis will offer insights into NDD mechanisms and insights into novel, disease‐modifying therapeutics.
Disjoint cycles in tournaments and bipartite tournaments
Authors: Chen Bin , Chang An 
Published: October 2023

AbstractA conjecture proposed by Bermond and Thomassen in 1981 states that every digraph with minimum out‐degree at least contains vertex disjoint directed cycles for any integer , which has received substantial attention. This conjecture has been confirmed for . In 2014, Lichiardopol raised a very related conjecture that for every integer , there exists an integer such that every digraph with minimum out‐degree at least contains vertex disjoint directed cycles of different lengths. For a digraph and a set of vertex disjoint directed cycles in , we denote to be the maximum number of directed cycles in of distinct lengths. Let . We define if has no vertex disjoint directed cycles. In this paper, we mainly investigate vertex disjoint directed cycles in tournaments and bipartite tournaments. We first show that for every tournament with minimum out‐degree at least , where . We further prove that for and , any tournament with minimum out‐degree at least satisfies that . Moreover, we deduce that for any tournament with minimum out‐degree at least 7, holds. Additionally, we classify strong bipartite tournaments with minimum out‐degree at least in which any vertex disjoint directed cycles have the same length, where . That is, for any strong bipartite tournament with minimum out‐degree at least , then if and only if is isomorphic to a member of , which is defined in the context.
Lifetime risk of liver‐related outcomes and determinants in male inactive carriers of chronic hepatitis B
Authors: Wu Wan‐Jung , Lin Chih‐Lin , Liu Chun‐Jen , Huang Yi‐Wen , Hu Jui‐Ting , Yu Ming‐Whei 
Published: October 2023

AbstractThe full spectrum of risks for the life course of inactive hepatitis B virus (HBV) carriers remains unclear. In this study, 995 untreated HBV carriers (median age: 42.8 years; median follow‐up: 30.2 years) were included. Their data were sourced from a population‐based cohort study of male civil servants recruited in 1989–1992. Outcomes were identified by active follow‐up examinations and linkage with national health insurance research database. At baseline, 483 subjects were inactive carriers, 385 with indeterminate phase, and 127 with other phases. The joint lifetime risk for incident cirrhosis, decompensation, hepatocellular carcinoma, and liver‐related deaths was lower for inactive carriers compared to subjects in other phases (p < 0.0001). There was a trend of increase in incidence among inactive carriers; the 5‐, 10‐, and 20‐year cumulative incidences were 1.86%, 6.03%, and 10.07%, respectively. Of the inactive carriers, 37.7% cleared HBsAg and 36.6% had biochemical relapse during the study. Biochemical relapse, obesity, and advanced age were predictors for disease progression in inactive carriers. Virological relapse was the predominant cause of biochemical relapse. Higher HBV‐DNA levels (≥1000 copies/mL or 200 IU/mL) and HBV genotype B (vs. C) were associated with higher virological relapse rate. After 30 years, we found that one‐time measure of inactive carrier state continued to have the lowest risk compared with other infection phases. Despite a more favorable prognosis, inactive carriers had a non‐negligible risk. Our findings of lifetime risk may provide important clues for the management of such patients and consideration of therapeutic strategies aiming to achieve functional cure.
Differential diagnosis of fever and rash cases negative for measles and rubella to complement surveillance activities
Authors: Fappani Clara , Gori Maria , Bianchi Silvia , Terraneo Mara , Bilardi Erica , Colzani Daniela , Tanzi Elisabetta , Canuti Marta , Amendola Antonella 
Published: October 2023

AbstractIn the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV‐6) and 7 (HHV‐7), parvovirus B19 (B19V), enterovirus (EV), Epstein−Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS‐CoV‐2. Differential diagnosis was carried out on 289 discarded cases by multiplex real‐time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV‐7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV‐6, EV, HAdV, and HCMV‐positive cases were found in children aged 0−4 years and HHV‐7 was most frequent in the 15−39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus‐positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities.
Using machine learning to enhance prediction of atrial fibrillation recurrence after catheter ablation
Authors: Brahier Mark S. , Zou Fengwei , Abdulkareem Musa , Kochi Shwetha , Migliarese Frank , Thomaides Athanasios , Ma Xiaoyang , Wu Colin , Sandfort Veit , Bergquist Peter J. , Srichai Monvadi B. , Piccini Jonathan P. , Petersen Steffen E. , Vargas Jose D. 
Published: October 2023

AbstractBackgroundTraditional risk scores for recurrent atrial fibrillation (AF) following catheter ablation utilize readily available clinical and echocardiographic variables and yet have limited discriminatory capacity. Use of data from cardiac imaging and deep learning may help improve accuracy and prediction of recurrent AF after ablation.MethodsWe evaluated patients with symptomatic, drug‐refractory AF undergoing catheter ablation. All patients underwent pre‐ablation cardiac computed tomography (cCT). LAVi was computed using a deep‐learning algorithm. In a two‐step analysis, random survival forest (RSF) was used to generate prognostic models with variables of highest importance, followed by Cox proportional hazard regression analysis of the selected variables. Events of interest included early and late recurrence.ResultsAmong 653 patients undergoing AF ablation, the most important factors associated with late recurrence by RSF analysis at 24 (+/−18) months follow‐up included LAVi and early recurrence. In total, 5 covariates were identified as independent predictors of late recurrence: LAVi (HR per mL/m2 1.01 [1.01–1.02]; p < .001), early recurrence (HR 2.42 [1.90–3.09]; p < .001), statin use (HR 1.38 [1.09–1.75]; p = .007), beta‐blocker use (HR 1.29 [1.01–1.65]; p = .043), and adjunctive cavotricuspid isthmus ablation [HR 0.74 (0.57–0.96); p = .02]. Survival analysis demonstrated that patients with both LAVi >66.7 mL/m2 and early recurrence had the highest risk of late recurrence risk compared with those with LAVi <66.7 mL/m2 and no early recurrence (HR 4.52 [3.36–6.08], p < .001).ConclusionsMachine learning‐derived, full volumetric LAVi from cCT is the most important pre‐procedural risk factor for late AF recurrence following catheter ablation. The combination of increased LAVi and early recurrence confers more than a four‐fold increased risk of late recurrence.
A pilot study of mitochondrial response to an in vivo prosthetic joint Staphylococcus aureus infection model
Authors: Bouji Nour , Meadows Ethan , Hollander John M. , Velayutham Murugesan , Stewart Elizabeth , Herriott Jacob , Dietz Matthew J. 
Published: October 2023

AbstractProsthetic joint infections (PJI) are associated with orthopaedic morbidity and mortality. Mitochondria, the “cell's powerhouses,” are thought to play crucial roles in infection response and in increased risk of sepsis mortality. No current research discusses PJI's effect on mitochondrial function and a lack of understanding of immune‐infection interactions potentially hinders patient care. The purpose of this pilot study was to evaluate the impact of simulated PJI on local tissue mitochondrial function. Using an established prosthetic implant‐associated in vivo model, tissues were harvested from the surgical limb of a methicillin‐sensitive Staphylococcus aureus implant‐associated infection group (n = 6) and compared to a noninfected group (n = 6) at postoperative day (POD) 21. Using mitochondrial coupling assays, oxygen consumption rate and extracellular acidification rate were assessed in each group. Electron flow through mitochondrial complexes reflected group activity. Electron Paramagnetic Resonance (EPR) spectrometry measured the oxidizing potential of serum samples from infected versus noninfected groups. On POD21, colony‐forming units per gram of tissue showed 5 × 109 in the infected group and 101 in the noninfected group (p < 0.0001). Maximal respiration and oxygen consumption due to adenosine triphosphate synthesis were significantly lower in isolated mitochondria from infected limbs (p = 0.04). Both groups had similar complex I, III, IV, and V activity (p > 0.1). Infected group EPR signal intensity reflecting reactive oxygen species levels was 1.31 ± 0.30 compared to 1.16 ± 0.28 (p = 0.73) in the noninfected group. This study highlights PJI's role in mammalian cell mitochondrial dysfunction and oxidative tissue damage, which can help develop interventions to combat PJI.
Current clinical practice in the management of Brazilian patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC)
Authors: de Jesus Victor Hugo Fonseca , Peixoto Renata D'Alpino , Ribeiro Héber Salvador de Castro , Pinheiro Rodrigo Nascimento , Oliveira Alexandre Ferreira , Anghinoni Marciano , Torres Silvio Melo , Boff Márcio Fernando , Weschenfelder Rui , Prolla Gabriel , Riechelmann Rachel P. 
Published: October 2023

AbstractBackground and ObjectivesWe aimed to describe the routine clinical practice of physicians involved in the treatment of patients with localized pancreatic ductal adenocarcinoma (PDAC) in Brazil.MethodsPhysicians were invited through email and text messages to participate in an electronic survey sponsored by the Brazilian Gastrointestinal Tumor Group (GTG) and the Brazilian Society of Surgical Oncology (SBCO). We evaluated the relationship between variable categories numerically with false discovery rate‐adjusted Fisher's exact test p values and graphically with Multiple Correspondence Analysis.ResultsOverall, 255 physicians answered the survey. Most (52.5%) were medical oncologists, treated patients predominantly in the private setting (71.0%), and had access to multidisciplinary tumor boards (MTDTB; 76.1%). Medical oncologists were more likely to describe neoadjuvant therapy as beneficial in the resectable setting and surgeons in the borderline resectable setting. Most physicians would use information on risk factors for early recurrence, frailty, and type of surgery to decide treatment strategy. Doctors working predominantly in public institutions were less likely to have access to MTDTB and to consider FOLFIRINOX the most adequate regimen in the neoadjuvant setting.ConclusionsConsiderable differences exist in the management of localized PDAC, some of them possibly explained by the medical specialty, but also by the funding source of health care.
Primary sarcoma of the liver: A nationwide analysis of a rare mesenchymal tumor
Authors: Finney Nicole , Tran Tu , Hasjim Bima J. , Jakowatz James , Chiao Elaine , Eng Oliver , Wolf Ronald , Jutric Zeljika , Yamamoto Maki , Tran Thuy B. 
Published: October 2023

AbstractBackground and ObjectivesPrimary liver sarcomas are rare malignancies. Prognostic factors associated with long‐term survival remain poorly understood. The objective of this study is to determine factors associated with long‐term survival.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with visceral sarcoma arising from the liver. Demographic factors, tumor characteristics, resection status, and survival were evaluated. Multivariate Cox regression analysis was performed to determine predictors of survival.ResultsA total of 743 patients with primary hepatic sarcoma were identified. The median tumor size was 10 cm. Only 30% (n = 221) of patients in the cohort underwent surgery. The 5‐year overall survival rates were 47.9% for localized disease, 29.5% for regional disease, and 16.5% for distant disease, p < 0.001. Among patients who underwent surgical resection, patients with embryonal sarcoma had better 5‐year survival compared with angiosarcoma and other histologic subtypes. On multivariate analysis, surgery was associated with improved survival, while older age, higher stage, and angiosarcoma histology were the strongest independent predictors of poor survival.ConclusionsSurgery remains the mainstay of treatment for this rare malignancy but is performed in less than one‐third of patients. Angiosarcoma histology is associated with worse overall survival, while surgical resection remains the strongest predictor of improved overall survival.