bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network meta‐analysis on the mechanisms underlying alcohol augmentation of acute pancreatitis and diabetes type II
Authors: Kim Ryan J. , Bishir Muhammed , Chang Sulie L. 
Published: September 2024

AbstractBackgroundPancreatitis is a severe inflammatory pathology that occurs from pancreatic duct and exocrine acinar injury, leading to improper secretion of digestive enzymes, auto‐digestion of the pancreas, and subsequent inflammation. Clinical reports show that 60%–90% of pancreatitis patients have a history of chronic alcohol use. More recent studies reveal that exocrine pancreas disorders like acute pancreatitis can precede diabetes type II onset, though mechanisms are not yet fully known. This study identified molecules and key signaling pathways underlying alcohol‐induced acute pancreatitis and their effects on diabetes type II onset.MethodsData on human peripheral blood samples with or without acute pancreatitis were retrieved from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (accession number GSE194331). Acute pancreatitis‐mediated differentially expressed genes (DEGs) were generated from GSE194331 using CLC Genomics Workbench 12. Molecules associated with ethanol (EtOH), acute pancreatitis, and diabetes type II were collected from QIAGEN Knowledge Base (QKB). The relationship between the molecules and signaling pathways associated with EtOH, acute pancreatitis, or diabetes type II was examined using various Ingenuity Pathway Analysis (IPA) tools.ResultsOur investigation showed that acute pancreatitis‐mediated DEGs were closely associated with EtOH by revealing that EtOH‐induced acute pancreatitis appears to lead to the onset of diabetes type II. We found that diabetes type II onset was mediated by pro‐inflammatory and metabolic mechanisms underlying EtOH‐induced acute pancreatitis, involving increased expression of cytokines including macrophage migration inhibitory factor (MIF), and decreased expression of hormones such as insulin.ConclusionsExposure to alcohol may promote diabetes type II by affecting the activity of key inflammatory and metabolic mediators involved in acute pancreatitis. These findings call for further investigation into the role of pro‐inflammatory and metabolic mediators like resistin, IL‐6, and insulin in EtOH‐induced diabetes type II associated with acute pancreatitis pathologies.
Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism
Authors: Miner Martin , Wang Christina , Kaminetsky Jed , Khera Mohit , Goldstein Irwin , Carson Culley , Chidambaram Nachiappan , King Shelby , Dobs Adrian 
Published: September 2024

AbstractBackgroundTestosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations.ObjectiveThe primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality‐of‐life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie).Materials and methodsIn this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225 mg oral testosterone undecanoate twice daily, and doses were adjusted by 75 mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300–1140 ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality‐of‐life endpoints including the Short Form‐36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score.ResultsOverall mean ± SD baseline testosterone was 205.7 ± 71.6 ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24‐h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form‐36v2 Health Survey measures of mental health (2.91 vs. ‐0.10; p = 0.035), and mental component summary (3.82 vs. 0.55; p = 0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (‐0.57 vs. ‐0.20; p = 0.021). Safety endpoints were comparable between therapies. No deaths or treatment‐related serious adverse events were reported.Discussion and conclusionMale patients with hypogonadism receiving oral testosterone undecanoate 225 mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.
Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study
Authors: Mao Ruo‐Lin , Wang Xiang‐Fei , Zhou Jue‐Pu , Wang Meng , Long Rui , Jin Lei , Zhu Li‐Xia 
Published: September 2024

AbstractIntroductionPrevious studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCOS.Material and MethodsWe performed a bidirectional two‐sample Mendelian randomization (MR) analysis. Datasets were from the largest published meta‐analysis on gut microbiota composition and the FinnGen cohort of the IEU Open Genome‐Wide Association Study Project database. Inverse variance weighted (IVW), MR‐Egger, constrained maximum likelihood‐based Mendelian randomization, weighted median, weighted mode, and simple mode were used. Cochran's Q and MR‐Egger intercept tests were employed to measure the heterogeneity.ResultsA total of 211 gut microbiota taxa were identified in MR analysis. Nine taxa of bacteria, including Alphaproteobacteria (0.55, 0.30–0.99, p = 0.04), Bacilli (1.76, 1.07–2.91, p = 0.03), Bilophila (0.42, 0.23–0.77, p < 0.01), Blautia (0.16, 0.03–0.79, p = 0.02), Burkholderiales (2.37, 1.22–4.62, p = 0.01), Candidatus Soleaferrea (0.65, 0.43–0.98, p = 0.04), Cyanobacteria (0.51, 0.31–0.83, p = 0.01), Holdemania (0.53, 0.35–0.81, p < 0.01), and Lachnospiraceae (1.86, 1.04–3.35, p = 0.03), were found to be associated with PCOS in the above MR methods included at least IVW method. Cochran's Q statistics and MR‐Egger intercept test suggested no significant heterogeneity. In addition, 69 taxa were shown significant for at least the IVW method in reverse MR analysis, of these, 25 had a positive correlation, and 37 had a negative correlation. Additionally, Alphaproteobacteria and Lachnospiraceae (0.95, 0.91–0.98, p < 0.01; 0.97, 0.94–0.99, p = 0.02, respectively) were shown a bidirected causally association with PCOS.ConclusionsOur study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.
Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension
Authors: Wimmer Moritz I. , Bartolomaeus Hendrik , Anandakumar Harithaa , Chen Chia‐Yu , Vecera Valentin , Kedziora Sarah , Kamboj Sakshi , Schumacher Fabian , Pals Sidney , Rauch Ariana , Meisel Jutta , Potapenko Olena , Yarritu Alex , Bartolomaeus Theda U. P. , Samaan Mariam , Thiele Arne , Stürzbecher Lucas , Geisberger Sabrina Y. , Kleuser Burkhard , Oefner Peter J. , Haase Nadine , Löber Ulrike , Gronwald Wolfram , Forslund‐Startceva Sofia K. , Müller Dominik N. , Wilck Nicola 
Published: September 2024

AbstractAimsMetformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats.MethodsMale double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II‐dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry.ResultsMetformin treatment increased the production of short‐chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end‐diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. In vitro, acetate and propionate altered M1‐like gene expression in macrophages, reinforcing anti‐inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure.ConclusionMetformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators.
Letter: Beyond advanced fibrosis—The critical need for assessing NITs performance in identifying F2–F3 fibrosis
Authors: Yilmaz Yusuf 
Published: September 2024

LINKED CONTENTThis article is linked to McPherson et al papers. To view these articles, visit https://doi.org/10.1111/apt.18061 and https://doi.org/10.1111/apt.18209.
Physical analysis and inverse methods applied to archaeological FIRE replications on ATACAMA desert soils, northern Chile
Authors: Canot Édouard , Delannay Renaud , Santoro Calogero M. 
Published: September 2024

AbstractPhysical analysis of in situ fire experiments on soils are useful for the estimation of subsurface thermal diffusivity, which is affected by factors such as water, heterogeneity and heating conditions. To address the uncertainties due to these factors, a new data‐processing procedure based on inverse methods was developed and experimentally applied to soils from an archaeological site in the Atacama Desert, Chile. By combining experimental data and numerical simulations, we determined the dominant physical processes arising during the heating. The analysis succeeded in defining practical procedures to obtain a more accurate estimation of the diffusivities, thus reducing the above‐mentioned uncertainties.
Perivascular phosphorylated TDP‐43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin‐4
Authors: Santiago Jessica , Pocevičiūtė Dovilė ,   The Netherlands Brain Bank, Wennström Malin 
Published: September 2024

AbstractThe majority of patients with Alzheimer's disease (AD) exhibit aggregates of Trans‐active response DNA binding protein 43 (TDP‐43) in their hippocampus, which is associated with a more aggressive disease progression. The TDP‐43 inclusions are commonly found in neurons, but also in astrocytes. The impact of the inclusions in astrocytes is less known. In the current study, we investigate the presence of phosphorylated TDP‐43 (pTDP‐43) inclusions in astrocytic endfeet and their potential association with blood–brain barrier (BBB) damage, glymphatic system dysfunction, and AD pathology. By staining postmortem hippocampal sections from AD patients and non‐demented controls against TDP‐43 and pTDP‐43 together with the astrocytic markers glial fibrillary acidic protein (GFAP), astrocytic endfeet marker Aquaporin‐4 (AQP4), and markers for BBB alterations (CD146) and leakiness (Immunoglobulin A), we demonstrate a close association between perivascular pTDP‐43 or TDP‐43 inclusions and GFAP or AQP4. These perivascular inclusions were more prominent in AD and correlated with the disease severity and loss of CD146 and AQP4. The findings indicate a relationship between pTDP‐43 accumulation in astrocytic endfeet and BBB and glymphatic system dysfunction, which may contribute to the downstream pathological events seen in AD patients and the aggressive disease progression.
Echinacoside Alleviates Carbon Tetrachloride‐Induced Chronic Liver Injury by Modulating the NF‐κB/NLRP3 Inflammasome Pathway
Authors: Yang Ye‐jun , Liu Juan 
Published: September 2024

ABSTRACTThe purpose of this study was to investigate the protective effect of echinacoside (Ech) on carbon tetrachloride (CCL4)‐induced chronic liver injury in rats and its potential mechanisms. Thirty Sprague–Dawley (SD) rats were randomly divided into five groups: the Control group, the CCL4 group, the CCL4 + Ech 25 mg/kg group, the CCL4 + Ech 50 mg/kg group, and the CCL4 + Ech 100 mg/kg group. The rats were injected intraperitoneally with CCL4 solution twice a week to induce chronic liver injury, and Ech intervention lasted for 4 weeks. After the intervention, the liver and blood samples from rats were collected for subsequent analysis. Ech effectively reduced the levels of serum liver injury markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, alkaline phosphatase, and total bilirubin), attenuated the hepatocyte degeneration and necrosis, improved the severity of liver fibrosis, and inhibited the local inflammatory response of the liver in a dose‐dependent manner. Ech effectively mitigated CCL4‐induced chronic liver injury in rats by downregulating the NF‐κB/NLRP3 inflammasome pathway.
Delineating structural and metabolic abnormalities in amygdala and hippocampal subfields for different seizure‐onset patterns via stereotactic electroencephalography
Authors: Feng Tao , Yang Yanfeng , Wang Yihe , Wei Peng‐hu , Fan Xiaotong , Zhang Huaqiang , An Yang , Wang Tianren , Huang Yuda , Chen Sichang , Piao Yueshan , Xiao Fenglai , Duncan John S. , Shan Yongzhi , Zhao Guoguang 
Published: September 2024

AbstractAimsWe aimed to investigate mesial temporal lobe abnormalities in mesial temporal lobe epilepsy (MTLE) patients with hypersynchronous (HYP) and low‐voltage fast rhythms (LVF) onset identified by stereotactic electroencephalography (SEEG) and evaluate their diagnostic and prognostic value.MethodsFifty‐one MTLE patients were categorized as HYP or LVF by SEEG. High‐resolution MRI volume‐based analysis and 18F‐FDG‐PET standard uptake values of hippocampal and amygdala subfields were quantified and compared with 57 matched controls. Further analyses were conducted to delineate the distinct pathological characteristics differentiating the two groups. Diagnostic and prognostic prediction performance of these biomarkers were assessed using receiver operating characteristic curves.ResultsLVF‐onset individuals demonstrated ipsilateral amygdala enlargement (p = 0.048) and contralateral hippocampus hypermetabolism (p = 0.042), pathological results often accompany abnormalities in the temporal lobe cortex, while HYP‐onset subjects had significant atrophy (p < 0.001) and hypometabolism (p = 0.013) in ipsilateral hippocampus and its subfields, as well as amygdala atrophy (p < 0.001), pathological results are highly correlated with hippocampal sclerosis. Severe fimbria atrophy was observed in cases of HYP‐onset MTLE with poor prognosis (AUC = 0.874).ConclusionIndividuals with different seizure‐onset patterns display specific morphological and metabolic abnormalities in the amygdala and hippocampus. Identifying these subfield abnormalities can improve diagnostic and prognostic precision, guiding surgical strategies for MTLE.
Endoscopic ultrasound‐guided gastrojejunostomy with wire endoscopic simplified technique: Move towards benign indications (with video)
Authors: Gonzalez Jean‐Michel , Ouazzani Sohaib , Vanbiervliet Geoffroy , Gasmi Mohamed , Barthet Marc 
Published: September 2024

ObjectivesEndoscopic ultrasound‐guided gastrojejunostomy (EUS‐GJ) is an alternative to duodenal stenting and surgical GJ (SGGJ) in malignant gastric outlet obstruction (MGOO). European Society of Gastrointestinal Endoscopy guidelines restricted EUS‐GJ for MGOO only, because of misdeployment. The aim was to evaluate its outcomes focusing on benign indications.MethodsThis was a retrospective study conducted from 2016 to 2023 in a tertiary center. Patients included had malignant or benign GOO indicated for EUS‐GJ. Techniques were the direct approach until August 2021, and the wire endoscopic simplified technique (WEST) afterwards. The main objective was to compare outcomes in benign vs. MGOO. Secondary end‐points were technical success, adverse events rates, and describing the evolution of techniques and indications.ResultsIn all, 87 patients were included, 46 men, mean age 66 ± 16.2 years. Indications were malignant in 60.1% and benign in 39.1%. The EUS‐GJ technique was direct in 33 patients (37.9%) and WEST in 54 (62.1%). No difference was found in terms of technical, clinical, or adverse events rates. The initial technical success rate was 88.5%. The final technical and clinical success rates were 96.6% and 94.25%, respectively. In the last year, benign exceeded malignant indications (70.4% vs. 29.6%, P < 0.05). Seven misdeployments occurred, six being addressed with the rescue technique. The misdeployment rate was significantly decreased using the WEST approach compared to the direct one: 3.7% vs. 18% (P < 0.05). The severe postoperative adverse events rate was 2.3%.ConclusionThis study demonstrated similar outcomes of EUS‐GJ between benign and MGOO, with a decreasing misdeployment rate (<4%) applying WEST. This represents an additional step towards recommending EUS‐GJ in benign indications.
Fentanyl self‐administration is accelerated by methamphetamine co‐use and results in worsened hypodopaminergia in male, but not female rats
Authors: Dawes Monica H. , Ortelli Olivia A. , Holleran Katherine M. , Jones Sara R. 
Published: September 2024

AbstractCombined use of fentanyl and methamphetamine (FENT + METH) has increased in recent years and has been documented in a growing number overdose deaths each year. The impact of FENT + METH on behavior and neurobiology is not well understood. In this study, male and female Long Evans rats were tested on a limited access, fixed ratio 1 self‐administration schedule for increasing doses (1.25–5 μg/kg/infusion; iv) of fentanyl, with and without a single dose (0.1 mg/kg/infusion; iv) of methamphetamine, for 15 days. FENT + METH abolished dose responsiveness to fentanyl in all rats and accelerated intake in males, resulting in patterns of responding that may be more likely to result in adverse effects. Ex vivo slice voltammetry in the nucleus accumbens core showed decreases in dopamine release and reuptake (Vmax) following FENT + METH exposure, compared with saline, fentanyl, and methamphetamine alone groups at baseline parameters. Further, significant decreases in dopamine release were observed across a range of stimulation intensities following FENT + METH exposure. Overall, male and female rats displayed sex‐specific behavioral and neurobiological responses to FENT + METH exposure, with males displaying increased vulnerability.
Nonictal electroencephalographic measures for the diagnosis of functional seizures
Authors: Hinchliffe Chloe H. L. , Yogarajah Mahinda , Elkommos Samia , Tang Hongying , Abasolo Daniel 
Published: September 2024

AbstractObjectiveFunctional seizures (FS) look like epileptic seizures but are characterized by a lack of epileptic activity in the brain. Approximately one in five referrals to epilepsy clinics are diagnosed with this condition. FS are diagnosed by recording a seizure using video‐electroencephalography (EEG), from which an expert inspects the semiology and the EEG. However, this method can be expensive and inaccessible and can present significant patient burden. No single biomarker has been found to diagnose FS. However, the current limitations in FS diagnosis could be improved with machine learning to classify signal features extracted from EEG, thus providing a potentially very useful aid to clinicians.MethodsThe current study has investigated the use of seizure‐free EEG signals with machine learning to identify subjects with FS from those with epilepsy. The dataset included interictal and preictal EEG recordings from 48 subjects with FS (mean age = 34.76 ± 10.55 years, 14 males) and 29 subjects with epilepsy (mean age = 38.95 ± 13.93 years, 18 males) from which various statistical, temporal, and spectral features from the five EEG frequency bands were extracted then analyzed with threshold accuracy, five machine learning classifiers, and two feature importance approaches.ResultsThe highest classification accuracy reported from thresholding was 60.67%. However, the temporal features were the best performing, with the highest balanced accuracy reported by the machine learning models: 95.71% with all frequency bands combined and a support vector machine classifier.SignificanceMachine learning was much more effective than using individual features and could be a powerful aid in FS diagnosis. Furthermore, combining the frequency bands improved the accuracy of the classifiers in most cases, and the lowest performing EEG bands were consistently delta and gamma.
Pricing dynamics and herding behaviour of NFTs
Authors: Fridgen Gilbert , Kräussl Roman , Papageorgiou Orestis , Tugnetti Alessandro 
Published: September 2024

AbstractThis paper analyzes the sales of 875,389 art nonfungible tokens (NFTs) on the Ethereum blockchain to identify the key determinants influencing NFT pricing and market dynamics. We find that market liquidity and trade volume are strong predictors of NFT prices. Contrarily, social media activity negatively correlates with prices. Introducing an artist ranking system, our study reveals a “superstar effect”, with a few artists dominating sales, and herding behaviour within the NFT market.