bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hernia Correction After Liver Transplantation Using Nonvascularized Fascia
Authors: Justo Iago , Caso Oscar , Marcacuzco Alberto , Rodríguez-Gil Yolanda , Jiménez-Romero Carlos 
Published: June 2024

Background.
Liver transplantation is an increasingly frequent surgical procedure, with elevated rates of postoperative incisional hernias ranging from 5% to 46%. There are numerous known risk factors for incisional hernia, including the type of incision, patient sex, and presence of comorbidities such as diabetes, ascites, older age, and the use of steroids. Most studies on the treatment of incisional hernias in patients who have undergone liver transplantation have shown consistently high rates of complications. Consequently, we propose the use of nonvascular fascia for the symptomatic treatment of incisional hernias in patients with concomitant liver transplantation.

Methods.
We performed our new technique on 8 patients, who had previously undergone liver transplantation, between January 2019 and January 2023. The patients were examined using imaging techniques during the follow-up period.

Results.
Of the 8 patients, 7 were liver transplant recipients and 1 was a combined liver-kidney transplant patient. The median donor age was 57 y (5–66 y), whereas the mean recipient age was 58 y (31–66 y). The median patient height and weight were 163 cm (117–185 cm) and 76 kg (17–104 kg), respectively. Immunosuppression did not change in fascia recipients. The median time between transplantation and hernia repair surgery was 41 mo (5–116 mo). The sizes of the aponeurotic defects varied from 6 × 6 to 25 × 20 cm. Two patients experienced complications: one experienced bulging that required reintervention and the other experienced surgical site seroma. There was no mortality related to the use of the technique, and none were reported during follow-up.

Conclusions.
With its promising results, nonvascularized fascial transplantation can be a successful treatment for incisional hernias in patients who had previously received a liver transplant.
Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal Transplantation
Authors: Wei Xinyi , Weber Sabine , Yin Decheng , Allabauer Ida , Jobst-Schwan Tilman , Wiesener Michael , Schiffer Mario , Dudziak Diana , Lehmann Christian H. K. , Woelfle Joachim , Hoerning Andre 
Published: June 2024

Background.
The mammalian target of rapamycin inhibitor (mTORi) therapy after kidney transplantation is solely monitored pharmacokinetically, not necessarily reflecting PI3K-Akt-mTOR pathway blockade efficacy leading to potential under-or overimmunosuppression.

Methods.
In this cross-sectional study, phosphoflow cytometry was used to determine the efficacy of mTOR inhibition in peripheral T- and B-lymphocyte subsets by assessing p70S6 kinase (p70S6K) phosphorylation in renal transplant recipients upon treatment with a combination of either mTORi and calcineurin inhibitors (n = 18), or mTORi with mycophenolic acid (n = 9). Nine dialysis patients with end-stage renal disease and 17 healthy age-matched volunteers served as controls.

Results.
mTORi treatment reduced p70S6K phosphorylation in CD4+, CD8+ T, and CD19+ B cells compared with healthy controls (HCs). Subpopulation analysis of CD4+ T cells and CD19+ B cells revealed a significant reduction of p70S6K phosphorylation in CD4+CD45RA−CD25− Th cells (P < 0.05), CD24hiCD38hi transitional B cells (P < 0.001), CD24+CD38− memory B cells (P < 0.001), and CD24intCD38int-naive B cells (P < 0.05) upon mTORi treatment, whereas CD4+CD45RA−CD25++CD127− regulatory T cells and CD24−CD38hi plasmablasts were not affected. Compared with mTORi + mycophenolic acid therapy, mTORi + calcineurin inhibitor treatment exhibited an even stronger inhibition of p70S6K phosphorylation in CD4+CD45RA−CD25− Th cells and CD8+ T cells. However, trough levels of mTORi did not correlate with p70S6K phosphorylation.

Conclusions.
mTORi selectively inhibited p70S6K phosphorylation in select lymphocyte subtypes. Assessing p70S6K phosphorylation by phosphoflow cytometry may serve as an approach to understand cell subset specific effects of mTORi providing detailed pharmacodynamic information for individualizing immunosuppression.
Efficacy and outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia: an updated systematic review and meta-analysis of randomized controlled trials
Authors: Goyal Aman , Shah Sangam , Dahal Krishna , Changez Mah I. Kan , Tariq Muhammad Daoud , Zuhair Varisha , Shamim Urooj , Abbasi Haleema Qayyum , Shrestha Abhigan Babu , Sah Ranjit , Sohail Amir Humza 
Published: June 2024

Introduction
Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies by Nissen et al., which boast the largest sample size.

Methods
Literature search was done on Medline, EMBASE, and Cochrane Library. The primary endpoint was a change in low-density lipoprotein-cholesterol (LDL-C) levels, while secondary endpoints encompassed changes in lipid parameters, clinical endpoints, and safety endpoints. The least-square mean (LSM) percent change was utilized for lipid changes, with statistical significance set at P < 0.05.

Results
This analysis included 12 randomized control trials with 22,249 participants. BA exhibited a substantial reduction in LDL-C levels [LSM % change, −24.34; 95% confidence interval (CI), −27.80 to −20.88; P < 0.0001], total cholesterol levels (LSM % change, −16.62; 95% CI, −21.70 to −11.54; P < 0.00001) and high-density lipoprotein-cholesterol (HDL-C) levels (LSM % change, −4.22; 95% CI, −5.51 to −2.92; P < 0.00001) compared to the placebo.

Conclusions
BA significantly lowers LDL-C, total cholesterol, HDL-C, non-HDL-C, high sensitivity C reactive protein, and apolipoprotein levels.
Major depression symptom severity associations with willingness to exert effort and patch foraging strategy
Authors: Bustamante Laura A. , Barch Deanna M. , Solis Johanne , Oshinowo Temitope , Grahek Ivan , Konova Anna B. , Daw Nathaniel D. , Cohen Jonathan D. 
Published: June 2024

AbstractBackgroundIndividuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When selecting goals, people maximize ‘expected value’ by selecting actions that maximize potential reward while minimizing associated costs, including effort ‘costs’ and the opportunity cost of time. In MDD, differential weighing of costs and benefits are theorized mechanisms underlying changes in goal-directed cognition and may contribute to symptom heterogeneity.MethodsWe used the Effort Foraging Task to quantify cognitive and physical effort costs, and patch leaving thresholds in low effort conditions (reflecting perceived opportunity cost of time) and investigated their shared versus distinct relationships to clinical features in participants with MDD (N=52, 43 in-episode) and comparisons (N=27).ResultsContrary to our predictions, none of the decision-making measures differed with MDD diagnosis. However, each of the measures were related to symptom severity, over and above effects of ability (i.e., performance). Greater anxiety symptoms were selectively associated withlowercognitive effort cost (i.e. greater willingness to exert effort). Anhedonia and behavioral apathy were associated with increased physical effort costs. Finally, greater overall depression was related to decreased patch leaving thresholds.ConclusionsMarkers of effort-based decision-making may inform understanding of MDD heterogeneity. Increased willingness to exert cognitive effort may contribute to anxiety symptoms such as worry. Decreased leaving thresholds associations with symptom severity is consistent with reward rate-based accounts of reduced vigor in MDD. Future research should address subtypes of depression with or without anxiety, which may relate differentially to cognitive effort decisions.
The Transdiagnostic Connectome Project: a richly phenotyped open dataset for advancing the study of brain-behavior relationships in psychiatry
Authors: Chopra Sidhant , Cocuzza Carrisa V. , Lawhead Connor , Ricard Jocelyn A. , Labache Loïc , Patrick Lauren M. , Kumar Poornima , Rubenstein Arielle , Moses Julia , Chen Lia , Blankenbaker Crystal , Gillis Bryce , Germine Laura T. , Harpaz-Rote Ilan , Yeo BT Thomas , Baker Justin T. , Holmes Avram J. 
Published: June 2024

AbstractAn important aim in psychiatry is the establishment of valid and reliable associations linking profiles of brain functioning to clinically relevant symptoms and behaviors across patient populations. To advance progress in this area, we introduce an open dataset containing behavioral and neuroimaging data from 241 individuals aged 18 to 70, comprising 148 individuals meeting diagnostic criteria for a broad range of psychiatric illnesses and a healthy comparison group of 93 individuals. These data include high-resolution anatomical scans, multiple resting-state, and task-based functional MRI runs. Additionally, participants completed over 50 psychological and cognitive assessments. Here, we detail available behavioral data as well as raw and processed MRI derivatives. Associations between data processing and quality metrics, such as head motion, are reported. Processed data exhibit classic task activation effects and canonical functional network organization. Overall, we provide a comprehensive and analysis-ready transdiagnostic dataset, which we hope will accelerate the identification of illness-relevant features of brain functioning, enabling future discoveries in basic and clinical neuroscience.
An iPSC-based model of Jacob Syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with X aneuploid cells
Authors: Astro V. , Cardona-Londoño K. , Cortés-Medina L.V. , Alghamdi R. , Ramírez-Calderón G. , Kefalas F. , Dilmé-Capó J. , Radío S. , Adamo A. 
Published: June 2024

ABSTRACTMale sex chromosome aneuploidies are frequent genetic aberrations in humans characterized by additional Y or X chromosome complements. Jacob (JS) and Klinefelter syndromes (KS), carrying 47,XYY and 47,XXY chromosomes, respectively, share several clinical features, including sterility, hormonal deficits, neurocognitive delay, and skeletal-muscle defects. Despite the high incidence, a complete understanding of the molecular mechanisms underlying the clinical manifestations in sex aneuploid patients is still elusive. In this study, we generated and characterized the inaugural cohort of 47,XYY human induced pluripotent stem cells (iPSCs). We performed a comprehensive transcriptional analysis, including JS primary fibroblasts, iPSCs, and neural stem cells (NSCs) alongside KS cells. Our study revealed a transcriptional feedback mechanism tuning non-PAR X chromosome genes (NPX) homologs in Y supernumerary cells, a phenomenon not detected in X aneuploid iPSCs. By ectopically modulating the expression of selected NPY genes, we demonstrated a direct transcriptional link between the UTY-UTX gene pair. Furthermore, our analyses identified a shared transcriptomic signature between JS and KS, discernible already at the iPSC stage, with a notable enrichment for processes related to neurological functions. This transcriptomic convergence underscores potential commonalities in the molecular pathways underpinning the pathophysiology of male sex chromosome aneuploidies. Finally, through genome-wide DNA methylation profiling of JS iPSCs, we demonstrated that a supernumerary Y chromosome only minimally impacts the methylation status of 47,XYY cells at the pluripotent stage. Our work reveals critical transcriptional feedback mechanisms and shared gene expression signatures in male sex chromosome aneuploidies, paving the way for a better understanding of their common phenotypic features.
Human research islet cell culture outcomes at the Alberta Diabetes Institute IsletCore
Authors: Lyon James G , Carr Alice LJ , Smith Nancy P , Marfil-Garza Braulio , Spigelman Aliya F , Bautista Austin , O’Gorman Doug , Kin Tatsuya , Shapiro AM James , Senior Peter A , MacDonald Patrick E 
Published: June 2024

AbstractHuman islets from deceased organ donors have made important contributions to our understanding of pancreatic endocrine function and continue to be an important resource for research studies aimed at understanding, treating, and preventing diabetes. Understanding the impacts of isolation and culture upon the yield of human islets for research is important for planning research studies and islet distribution to distant laboratories. Here we examine islet isolation and cell culture outcomes at the Alberta Diabetes Institute (ADI) IsletCore (n=197). Research-focused isolations typically have a lower yield of islet equivalents (IEQ), with a median of 252,876 IEQ, but a higher purity (median 85%) than clinically-focused isolations before culture. The median recovery of IEQs after culture was 75%, suggesting some loss. This was associated with a shift towards smaller islet particles, indicating possible islet fragmentation, and occurred within 24 hours with no further loss after longer periods of culture (up to 136 hours). No overall change in stimulation index as a measure of islet function was seen with culture time. These findings were replicated in a representative cohort of clinical islet preparations from the Clinical Islet Transplant Program at the University of Alberta. Thus, loss of islets occurs within 24 hours of isolation and there is no further impact of extended culture prior to islet distribution for research.
No innocent bystanders: pertussis vaccination epitomizes evolutionary parallelisms betweenBordetella parapertussisandB. pertussis
Authors: Bouchez Valérie , Moreno-Mingorance Albert , Mir-Cros Alba , Landier Annie , Armatys Nathalie , Guillot Sophie , Martín-Gómez Maria Teresa , Rodrigues Carla , Toubiana Julie , Bento Ana I. , Weigand Michael R. , González-López Juan José , Brisse Sylvain 
Published: June 2024

ABSTRACTPathogens adapting to the human host and to vaccination-induced immunity may follow parallel evolutionary paths.Bordetella parapertussis(Bpp) contributes significantly to the burden of whooping cough (pertussis), shares vaccine antigens withBordetella pertussis (Bp),and both pathogens are phylogenetically related and ecological competitors.Bpvaccine antigen-coding genes have accumulated variation, including pertactin disruptions, after introduction of acellular vaccines in the 1990s. We aimed to evaluate evolutionary parallelisms inBpp, even though pertussis vaccines were designed againstBp.We investigated the temporal evolution ofBppsublineages, by sequencing 242Bppisolates collected in France, the USA and Spain between 1937 and 2019, spanning pre-vaccine and two vaccines eras.We estimated the evolutionary rate ofBppat 2.12×10−7substitutions per site·year-1, with a most recent common ancestor of all sequenced isolates around year 1877, and found that pertactin deficiencyin Bppwas driven by 18 disruptive mutations, including deletionprn:ΔG-1895 estimated to have occurred around 1998 and observed in 73.8% (149/202) of post-2007 isolates. In addition, we detected two mutations in thebvgA-fhaBintergenic region (controlling expression of the master transcriptional regulator BvgA and the filamentous hemagglutinin), that became fixed in the early 1900s.Our findings suggest early adaptation ofBppto humans through modulation of thebvgASregulon, and a rapid adaptation through the loss of pertactin expression, representing a late evolutionary parallelism concomitant with acellular vaccination against whooping cough.IMPORTANCEVaccination againstBordetella pertussis(Bp) has strongly affected the recent evolution of this main agent of whooping cough. Whether it may have done so co-incidentally onBordetella parapertussis(Bpp), which is genetically and ecologically very similar toBp,has not been described in detail. Our findings show striking evolutionary parallelisms ofBppwithBp, including early changes in a critical regulatory region, and strong evidence of adaptation to vaccine-driven population immunity, even though whooping cough vaccines were not designed explicitly againstBpp. The rapid populational loss of pertactin in countries where acellular pertussis vaccines are used may also reduce protection by vaccination againstBpp, the second agent of whooping cough.
Trapping DNA-radicals with DMPO reduced hypochlorous acid-induced 8-oxo-7,8-dihydro-2’-deoxyguanosine and mutagenesis in lung epithelial cells
Authors: Ramirez D.C. , Gomez Mejiba S.E. 
Published: June 2024

ABSTRACTIrritation causes the recruitment and activation of neutrophils in the stressed airways. This process is known as neutrophilic inflammation. This process results in myeloperoxidase (MPO), an enzyme contained inside neutrophil azurophilic granules, being released as neutrophil extracellular traps (NETs), which also contain genomic DNA, modified histones, and other proteins. In the airways, released MPO can be taken up by bystander tissue epithelial cells. MPO is the only mammalian peroxidase enzyme that under physiological conditions produces hypochlorite (HOCl). Intracellularly produced HOCl may damage the cell genome, with the intermediacy of DNA-centered free radicals, which upon reaction with molecular oxygen decay to mutagenic end-oxidation products, such as 8-oxo-7,8-dihydro-2’ –deoxyguanosine (8-oxo-dGuo). Herein, we aimed to test whether HOCl-induced DNA-centered radicals precede the oxidation of DNA and mutagenesis in A549 human lung epithelial cells as anin vitromodel that resembles neutrophilic inflammation in irritated airways. Interestingly, by trapping HOCl-induced DNA-centered radicals, the nitrone spin trap 5,5-dimethyl-1-pyrrolineN-oxide (DMPO) blocks the formation of 8-oxo-dGuo and possibly other end-oxidation products, forming DNA-DMPO nitrone adducts, thus reducing mutagenesis in the hypoxanthine phosphoribosyl transferase (hrpt)gene, one of the most sensitive genes to oxidative damage. P53 is a transcription factor known as the master regulator of the cell response to genomic damage. By trapping DNA-centered radicals, DMPO also blocks the translocation of p53 to the cell nucleus, suggesting that by trapping DNA-centered radicals with DMPO, end-oxidation products are prevented, and the cell response to genomic damage is not sensed. DMPO traps DNA-centered radicals, reduces 8-oxo-dGuo accumulation, and blockshrptgene mutation. Trapping DNA-centered radicals to reduce the accumulation of HOCl-induced mutagenic end-oxidation products in the genome of bystander cells, which have taken MPO from the inflammatory milieu, will provide new therapeutic avenues to reduce genotoxic damage at sites of neutrophilic inflammation, such as in the irritated airways.
Factors Influencing the Implementing Readiness of Shared Medical Appointments in China’s Primary Healthcare Institutions: A Mixed-Method Study Utilizing Qualitative Comparative Analysis
Authors: Yang Wei , Liu Lingrui , Chen Jiajia , Mao Run , Yang Tao , Linghu Lang , Huang Lieyu , Xu Dong (Roman) , Cai Yiyuan 
Published: June 2024

AbstractBackground and ObjectiveDiabetes mellitus (DM) is a mounting public health concern in China, home to the largest number of patients with diabetes globally. A primary challenge has been the integration of high-quality chronic disease services, with poor outcomes and inefficient health management intensifying the disease burden. Shared Medical Appointments (SMAs) offer a promising solution, yet evidence of their practical application in resource-limited settings like China’s primary healthcare institutions is scant. This study aims to evaluate the organizational readiness for change (ORC) in implementing SMA services in Guizhou province’s primary healthcare institutions and to identify determinants of high-level ORC to foster implementation success.MethodsThis study employed a mixed-method approach. The validated Chinese version of the Workplace Readiness Questionnaire (WRQ-CN) was used to assess the ORC status across 12 institutions participating in the SMART pilot trial. A Normalization Process Theory (NPT) -guided qualitative interview and quantitative survey were used to collect the conditions. Data analysis encompassed standardized descriptive statistics, Spearman correlation analysis, and qualitative comparative analysis (QCA) to discern condition variables and configurations that are favorable to high-level ORC.ResultsThe study engaged 70 institutional participants, including administrators, clinicians, and public health workers. The median ORC score was 105.20 (101.23-107.33). We identified 12 condition variables through the interview and survey. The Spearman correlation analysis highlighted a moderate correlation between Specific tasks and responsibilities (r=0.393, p=0.206) and Key participants (r=0.316, p=0.317) with ORC. QCA also revealed these condition configurations and pathways that collectively align with heightened ORC, accentuating the pivotal role of key participants.ConclusionsThis study unveiled a spectrum of dynamic conditions and pathways affecting ORC, which are consistent with the NPT-based theoretical steps. They were essential for attaining high-level ORC in rolling out health service innovations like the SMART study, especially in resource-limited settings.
Pulmonary hypertension misdiagnosis due to preventable errors in echocardiography and right heart catheterization
Authors: Saunders Alexandra , Bainey Kevin R , Varughese Rhea , Michelakis Evangelos D 
Published: June 2024

AbstractObjectivesWe hypothesized that preventable human errors in performance and reporting of transthoracic echocardiograms (TTEs) and right RHCs are common and may lead to misdiagnosis of pulmonary hypertension (PH) subgroups.BackgroundPH is a common disease, however PH subgroups have vastly different mortality and treatment. This is particularly the case for pulmonary arterial hypertension (PAH) versus PH secondary to heart failure with preserved ejection fraction (HFpEF). TTE) and RHC are needed to differentiate these two diseases. Diagnosis requires specific cut-offs for mean pulmonary artery pressure (mPAP) and pulmonary artery wedge pressure (PAWP), which can only be measured by RHC. However, TTE first identifies PH, triggering referral to specialized PH centres.MethodsWe re-analyzed TTEs and RHCs of 252 PH program referrals over 5 years. We also compared the inferred diagnosis from the original reports to the diagnosis made after error correction.ResultsWe identified numerous preventable errors in the performance and reporting of both tests, and subsequently there was a poor correlation between the parameters measured by both tests. The referral TTE reports missed or overcalled PH in 44 patients. The RHC, mostly by PAWP mistakes, led to misdiagnosis in 41 patients.ConclusionTTE errors may delay referrals, while RHC errors may lead to misdiagnosis and applying wrong therapies to patients. As PAH therapies are extremely expensive, this also impacts the health care system. Primary care physicians need to be on alert for such errors and referral centres need to promote quality improvement programs to mitigate these errors.