bluuebunny/crossref_metadata_2025_split huggingface dataset:
Definition and measurement of alcohol-associated insight in early liver transplantation for acute alcohol-associated hepatitis: A systematic review
Authors: Winder Gerald Scott , Clifton Erin G. , Fernandez Anne C. , MacEachern Mark , Andrews Sarah , Perumalswami Ponni , DiMartini Andrea F. , Mellinger Jessica L. 
Published: April 2023

Background:
Alcohol accounts for a large disease burden in hepatology and liver transplantation (LT) and across the globe. Clinical evaluations and decisions about LT candidacy are challenging because they rely on detailed psychosocial assessments and interpretations of psychiatric and substance use disorder data, which often must occur rapidly according to the acuity of end-stage liver disease. Such difficulties commonly occur during the process of candidate selection and liver allocation, particularly during early LT (eLT) in patients with acute alcohol-associated hepatitis (AAH). Patients with AAH commonly have very recent or active substance use, high short-term mortality, psychiatric comorbidities, and compressed evaluation and treatment timetables. LT clinicians report that patients’ alcohol-associated insight (AAI) is among the most relevant psychosocial data in this population, yet no studies exist examining how LT teams define and use AAI in eLT or its effect on clinical outcomes. In April 2022, we searched Ovid MEDLINE, Elsevier Embase, EBSCOhost PsycInfo and CINAHL, and Wiley Cochrane Central Register of Controlled Trials for reports describing AAH populations who underwent eLT, which also described psychosocial evaluation parameters. The searches retrieved 1603 unique reports. After eligibility screening, 8 were included in the qualitative analysis. This systematic review reveals that AAI is a poorly defined construct that is not measured in a standardized way. Yet it is a commonly cited parameter in articles that describe the psychosocial evaluation and decision-making of patients undergoing eLT for AAH. This article also discusses the general challenges of assessing AAI during eLT for AAH, existing AAI definitions and rating scales, how AAI has been used to date in the broader hepatology and LT literature, and future areas for clinical and research progress.
Cell polarity linked to gravity sensing is generated by protein translocation from statoliths to the plasma membrane
Authors: Nishimura Takeshi , Mori Shogo , Shikata Hiromasa , Nakamura Moritaka , Hashiguchi Yasuko , Abe Yoshinori , Hagihara Takuma , Yoshikawa Hiroshi Y. , Toyota Masatsugu , Higaki Takumi , Morita Miyo Terao 
Published: April 2023

AbstractOrganisms have evolved under the gravitational force and sense the direction of gravity via statoliths in specialized cells. In the gravitropism of flowering plants, the starch-accumulating plastids, amyloplasts, in gravity sensing cells act as statoliths. The gravity sensing mechanism has long been considered a mechanosensing process by which amyloplasts transmit forces to intracellular structures, but the molecular support has not been reported. This study revealed that LAZY1-LIKE family proteins involved in gravity signaling in statocytes are localized to the amyloplast periphery and its proximal plasma membrane, resulting in polar localization according to the direction of gravity. We propose a gravity sensing mechanism by which LZY transmits the positional information of amyloplasts, i.e., the direction of gravity, by translocating to the plasma membrane.
Evaluation of Xpert®MTB/XDR test for susceptibility testing ofMycobacterium tuberculosisto first and second-line drugs in Uganda
Authors: Katamba Achilles , Ssengooba Willy , Sserubiri James , Semugenze Derrick , William Kasule George , Abdunoor Nyombi , Byaruhanga Raymond , Turyahabwe Stavia , Joloba Moses L 
Published: April 2023

AbstractBackgroundDrug-Resistant Tuberculosis (DR-TB) is one of the key challenges toward TB control. There is an urgent need for rapid and accurate drug susceptibility tests (DST) for the most commonly used 1stand 2ndline TB drugs.Design and MethodsIn a blinded, laboratory-based cross-sectional study, we set out to validate the performance of the Xpert®MTB/XDR test for DST ofM. tuberculosis. Sputum samples or culture isolates collected between January 2020 and December 2021 from patients with rifampicin resistance –TB and/or with higher suspicion index for isoniazid (INH) resistance and/or 2ndline fluoroquinolones (FQ) and injectable agents (IAs) were tested using the Xpert®MTB/XDR test from 11/September 2021 to 26/May /2022. Diagnostic accuracy and factors for laboratory uptake of Xpert®MTB/XDR test were compared to MGIT960 and the Hain Genotype® MTBDRplusand MDRsl assays (LPA) as reference DST methods.ResultsA total of 100 stored sputum samples were included in this study. Of the samples tested using MGIT960, 65/99 (65.6%) were resistant to INH, 5/100 (5.0%) resistant to FQ and none were resistant to IAs. The sensitivity and specificity, n (%; 95%Confidence Interval, CI) of Xpert®MTB/XDR test for; INH were 58 (89.2; 79.1-95.5) and 30 (88.2; 72.5-96.6), FQ; 4 (80.0; 28.3-99.4) and 95 (100; 96.2-100), respectively. The specificity for AIs was 100 (100; 96.3-100).Using LPA as a reference standard, a total of 52/98 (53.1%) were resistant to INH, 3/100 (3.0%) to FQ, and none to IA. The sensitivity and specificity, n (%; 95%CI) of Xpert®MTB/XDR test compared to LPA for; INH was 50 (96.1; 86.7-99.5) and 34 (74.0; 58.8-85.7) and FQ 3 (100; 29.2-100) and 96 (99.0; 94.3-99.9) respectively. The specificity of IAs was 96 (100; 96.2-100).The factors for laboratory uptake and roll-out included; no training needed for technicians with previous Xpert-ultra experience and one day for those without, recording and reporting needs were not different from those of Xpert ultra, the error rate was 4/100 (4%), no uninterpretable results reported, test turn-around-time was 1hr/45 minutes and workflow similar to that of the Xpert-ultra test.ConclusionThere is high sensitivity and specificity of Xpert®MTB/XDR test for isoniazid, fluoroquinolones, and Injectable agents. There are acceptable Xpert®MTB/XDR test attributes for test uptake and roll-out.
Stricturing Crohn’s disease single-cell RNA sequencing reveals fibroblast heterogeneity and intercellular interactions
Authors: Mukherjee Pranab K. , Nguyen Quang Tam , Li Jiannan , Zhao Shuai , Christensen Stephen M. , West Gail A. , Chandra Jyotsna , Gordon Ilyssa O. , Lin Sinan , Wang Jie , Mao Ren , Czarnecki Douglas , Rayan Carla , Kotak Prerna , Plesec Thomas , Lal Samir , Fabre Thomas , Asano Shoh , Bound Kathryn , Hart Kevin , Park Chanyoung , Martinez Robert , Dower Ken , Wynn Thomas A. , Hu Shaomin , Naydenov Nayden , Decaris Martin , Turner Scott , Holubar Stefan D. , Steele Scott R. , Fiocchi Claudio , Ivanov Andrei I. , Kravarik Kellie M. , Rieder Florian 
Published: April 2023

ABSTRACTBackgroundFibroblasts play a key role in stricture formation in Crohn’s disease (CD) but understanding it’s pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation.MethodsWe performed scRNAseq of 13 fresh full thickness CD resections containing non-involved, inflamed non-strictured, and strictured segments as well as 7 normal non-CD bowel segments. Each segment was separated into mucosa/submucosa or muscularis propria and analyzed separately for a total of 99 tissue samples and 409,001 cells. We validated cadherin-11 (CDH11) as a potential therapeutic target by using whole tissues, isolated intestinal cells, NanoString nCounter, next generation sequencing, proteomics and animal models.ResultsOur integrated dataset revealed fibroblast heterogeneity in strictured CD with the majority of stricture-selective changes detected in the mucosa/submucosa, but not the muscle layer. Cell-cell interaction modeling revealed CXCL14+ as well as MMP/WNT5A+ fibroblasts displaying a central signaling role in CD strictures. CDH11, a fibroblast cell-cell adhesion molecule, was broadly expressed and upregulated, and its pro-fibrotic function was validated by NanoString nCounter, RNA sequencing, tissue target expression,in vitrogain- and loss-of-function experiments, proteomics, and two animal models of experimental colitis.ConclusionA full-thickness bowel scRNAseq atlas revealed previously unrecognized fibroblast heterogeneity and interactions in CD strictures and CDH11 was validated as a potential therapeutic target. These results provide a new resource for a better understanding of CD stricture formation and opens potential therapeutic developments.
Genetic contributions of noncognitive skills to academic development
Authors: Malanchini Margherita , Allegrini Andrea G. , Nivard Michel G. , Biroli Pietro , Rimfeld Kaili , Cheesman Rosa , Stumm Sophie von , Demange Perline A. , Bergen Elsje van , Grotzinger Andrew D. , Raffington Laurel , Fuente Javier De la , Pingault Jean-Baptiste , Harden K. Paige , Tucker-Drob Elliot M. , Plomin Robert 
Published: April 2023

AbstractNoncognitive skills such as motivation and self-regulation, are partly heritable and predict academic achievement beyond cognitive skills. However, how the relationship between noncognitive skills and academic achievement changes over development is unclear. The current study examined how cognitive and noncognitive skills contribute to academic achievement from ages 7 to 16 in a sample of over 10,000 children from England and Wales. Noncognitive skills were increasingly predictive of academic achievement across development. Twin and polygenic scores analyses found that the contribution of noncognitive genetics to academic achievement became stronger over the school years. Results from within-family analyses indicated that associations with noncognitive genetics could not simply be attributed to confounding by environmental differences between nuclear families and are consistent with a possible role for evocative/active gene-environment correlations. By studying genetic effects through a developmental lens, we provide novel insights into the role of noncognitive skills in academic development.
Functional genomics identifies extension of complex N-glycans as a mechanism to evade lysis by natural killer cells
Authors: Zhuang Xiaoxuan , Woods James , Ji Yanlong , Scheich Sebastian , Mo Fei , Voss Matthias , Urlaub Henning , Pan Kuan-Ting , Long Eric O. 
Published: April 2023

AbstractSomatic mutations can lead to the transformation of healthy cells into malignant cells and allow their evasion from immune surveillance. To uncover genes that play a role in the detection and lysis of tumor cells by natural killer (NK) cells, a B lymphoblastoid cell line was subjected to a genome-wide CRISPR screen. Among the top hits that facilitated NK evasion wasSPPL3, which encodes an intramembrane protease that cleaves transmembrane glycosyltransferases in the Golgi apparatus.SPPL3-deficient cells accumulated glycosyltransferases, such as acetylglucosaminyltransferase 5 (MGAT5), and displayed increased N-glycosylation. Binding of NK receptors NKG2D and CD2 to their corresponding ligands MICB and CD58, and binding of rituximab to CD20, was disrupted bySPPL3-deletion. Inhibition of N-glycan maturation restored receptor binding and sensitivity to NK cells. To elucidate the mechanism of this resistant phenotype, a secondary CRISPR screen was performed inSPPL3-deficient cells. This screen identified glycosyltransferases that catalyze the formation of highly branched N-glycans and N-acetyl-lactosamine (LacNAc) extensions as key regulators that prevent killing. A significant enrichment of poly-LacNAc-containing tetra-antennary species was confirmed by glycoproteomic analysis. These findings provide mechanistic insight into howSPPL3deletions have been linked to cancer.
Structural and neurophysiological alterations in Parkinson’s disease are aligned with cortical neurochemical systems
Authors: Wiesman Alex I. , Silva Castanheira Jason da , Fon Edward A. , Baillet Sylvain ,   PREVENT-AD Research Group,   Quebec Parkinson Network
Published: April 2023

SummaryParkinson’s disease (PD) affects cortical structures and neurophysiology. How these deviations from normative variants relate to the neurochemical systems of the cortex in a manner corresponding to motor and cognitive symptoms is unknown. We measured cortical thickness and spectral neurophysiological alterations from structural magnetic resonance imaging and task-free magnetoencephalography in patients with idiopathic PD (NMEG= 79; NMRI= 65), contrasted with similar data from matched healthy controls (NMEG= 65; NMRI= 37). Using linear mixed-effects models and cortical atlases of 19 neurochemical systems, we found that the structural and neurophysiological alterations of PD align with several receptor and transporter systems (acetylcholine, serotonin, glutamate, and noradrenaline) albeit with different implications for motor and non-motor symptoms. Some neurophysiological alignments are protective of cognitive functions: the alignment of broadband power increases with acetylcholinergic systems is related to better attention function. However, neurochemical alignment with structural and other neurophysiological alterations is associated with motor and psychiatric impairments, respectively. Collectively, the present data advance understanding of the association between the nature of neurophysiological and structural cortical alterations in PD and the symptoms that are characteristic of the disease. They also demonstrate the value of a new nested atlas modeling approach to advance research on neurological and neuropsychiatric diseases.
Impact of Cardiac Troponin Release and Fluid Resuscitation on Outcomes of Patients with Sepsis
Authors: Ma Zhiyuan , Krishnamurthy Mahesh , Modi Vivek , Allen David , Shirani Jamshid 
Published: April 2023

ABSTRACTBackgroundSeptic patients are predisposed to myocardial injury manifested as cardiac troponin release (TnR). Prognostic significance and management implications of TnR and its relationship to fluid resuscitation and outcomes in the intensive care unit (ICU) setting has not been fully elucidated.MethodsA total of 24,778 patients with sepsis from eICU-CRD (n=11,992), MIMIC-III (n=6,638) and MIMIC-IV (n=6,148) databases were included in this retrospective study. In-hospital mortality and survival at 1 year were examined using multivariable logistic, Cox regression analysis, or Kaplan-Meier survival analysis with overlap weighting adjustment, as well as generalized additive models for fluid resuscitation.ResultsTnR on admission was associated with higher in-hospital mortality [adjusted odds ratios (OR)=1.33; 95% confidence interval (CI)=1.23-1.43; p<0.001 in unweighted analysis and adjusted OR=1.39; 95% CI=1.29-1.50; p< 0.001 with overlap weighting]. One-year survival was lower in patients with admission TnR (Kaplan-Meier survival analysis; p=0.002). A trend was noted for association between admission TnR and 1-year mortality [adjusted OR=1.16; 95% CI=0.99-1.37; p=0.067 in unweighted analysis] while the association was statistically significant after overlap weighting (adjusted OR=1.25; 95% CI=1.06-1.47; p=0.008). We also found that patients with admission TnR were less likely to benefit from more liberal fluid resuscitation. Adequate fluid resuscitation within a range of 70 to 90 ml/kg in the first 24 hours of ICU stay was associated with lower in-hospital mortality in septic patients without TnR but not in those with admission TnR.ConclusionsAdmission TnR was significantly associated with higher in-hospital mortality and worse 1-year survival among septic patients. Adequate fluid resuscitation improved in-hospital mortality in septic patients without but not with admission TnR.
A novel tablet-based software for the acquisition and analysis of gaze and eye movement parameters: a preliminary validation study in Parkinson’s disease
Authors: de Villers-Sidani Étienne , Voss Patrice , Guitton Daniel , Cisneros-Franco J. Miguel , Ducharme Simon 
Published: April 2023

AbstractThe idea that eye movements can reflect certain aspects of brain function and inform on the presence of neurodegeneration is not a new one. Indeed, a growing body of research has shown that several neurodegenerative disorders, such as Alzheimer’s and Parkinson’s Disease, present characteristic eye movement anomalies and that specific gaze and eye movement parameters correlate with disease severity. The use of detailed eye movement recordings in research and clinical settings, however, has been limited due to the expensive nature and limited scalability of the required equipment. Here we test a novel technology that can track and measure eye movement parameters using the embedded camera of a mobile tablet. We show that using this technology can replicate several well-known findings regarding oculomotor anomalies in Parkinson’s disease, and furthermore show that several parameters significantly correlate with disease severity as assessed with the MDS-UPDRS motor subscale. This tablet-based tool has the potential to accelerate eye movement research via affordable and scalable eye-tracking and aid with the identification of disease status and monitoring of disease progression in clinical settings.
Tristetraprolin promotes survival of mammary progenitor cells by restraining TNFα levels
Authors: Micaela Stedile , Angela Lara Montero , Emilio García Solá Martín , Victoria Goddio María , Inés Beckerman , Emilia Bogni , Marina Ayre , Zaira Naguila , Omar Coso , Kordon Edith C. 
Published: April 2023

SUMMARYTristetraprolin (TTP) is a RNA binding protein that destabilizes mRNA of factors that up-regulate proliferation, invasiveness and inflammation. Here we show that TTP expression is higher in mammary progenitor cells than in other cell populations, and that reducing its levels impairs mammary gland morphogenesisin vivoand mammosphere formation in culture. Knocking down TTP in stem-like HC11 mouse mammary cell line increased inflammatory cytokine mRNAs and signaling cascades involving NFκB, STAT3 and MAPK p38 activation, which led to apoptosis. Importantly, TNFα overexpression and the consequent p38 phosphorylation would be the leading cause of progenitor cell death upon TTP expression restriction. Taken together, our results reveal the relevance of negative posttranscriptional regulation on TNFα, exerted by TTP, for the maintenance of the progenitor cell compartment in the mammary gland.
Spatial and temporal metagenomics of river compartments reveals viral community dynamics in an urban impacted stream
Authors: Rodríguez-Ramos Josué , Oliverio Angela , Borton Mikayla A. , Danczak Robert , Mueller Birgit M. , Schulz Hanna , Ellenbogen Jared , Flynn Rory M. , Daly Rebecca A. , Schopflin LeAundra , Shaffer Michael , Goldman Amy , Lewandowski Joerg , Stegen James C. , Wrighton Kelly C. 
Published: April 2023

AbstractAlthough river ecosystems comprise less than 1% of Earth’s total non-glaciated area, they are critical modulators of microbially and virally orchestrated global biogeochemical cycles. However, most studies either use data that is not spatially resolved or is collected at timepoints that do not reflect the short life cycles of microorganisms. As a result, the relevance of microbiome interactions and the impacts they have over time on biogeochemical cycles are poorly understood. To assess how viral and microbial communities change over time, we sampled surface water and pore water compartments of the wastewater-impacted River Erpe in Germany every 3 hours over a 48-hour period resulting in 32 metagenomes paired to geochemical and metabolite measurements. We reconstructed 6,500 viral and 1,033 microbial genomes and found distinct communities associated with each river compartment. We show that 17% of our vMAGs clustered to viruses from other ecosystems like wastewater treatment plants and rivers. Our results also indicated that 70% of the viral community was persistent in surface waters, whereas only 13% were persistent in the pore waters taken from the hyporheic zone. Finally, we predicted linkages between 73 viral genomes and 38 microbial genomes. These putatively linked hosts included members of theCompetibacteraceae,which we suggest are potential contributors to carbon and nitrogen cycling. Together, these findings demonstrate that microbial and viral communities in surface waters of this urban river can exist as stable communities along a flowing river; and raise important considerations for ecosystem models attempting to constrain dynamics of river biogeochemical cycles.
Approach-avoidance reinforcement learning as a translational and computational model of anxiety-related avoidance
Authors: Yamamori Yumeya , Robinson Oliver J , Roiser Jonathan P 
Published: April 2023

AbstractAlthough avoidance is a prevalent feature of anxiety-related psychopathology, differences in the measurement of avoidance between humans and non-human animals hinder our progress in its theoretical understanding and treatment. To address this, we developed a novel translational measure of anxiety-related avoidance in the form of an approach-avoidance reinforcement learning task, by adapting a paradigm from the non-human animal literature to study the same cognitive processes in human participants. We used computational modelling to probe the putative cognitive mechanisms underlying approach-avoidance behaviour in this task and investigated how they relate to subjective task-induced anxiety. In a large online study (n = 372), participants who experienced greater task-induced anxiety avoided choices associated with punishment, even when this resulted in lower overall reward. Computational modelling revealed that this effect was explained by greater individual sensitivities to punishment relative to rewards. We replicated these findings in an independent sample (n = 627) and we also found fair-to-excellent reliability of measures of task performance in a sub-sample retested one week later (n = 57). Our findings demonstrate the potential of approach-avoidance reinforcement learning tasks as translational and computational models of anxiety-related avoidance. Future studies should assess the predictive validity of this approach in clinical samples and experimental manipulations of anxiety.
Harmonized diffusion MRI data and white matter measures from the Adolescent Brain Cognitive Development Study
Authors: Cetin-Karayumak Suheyla , Zhang Fan , Billah Tashrif , Zekelman Leo , Makris Nikos , Pieper Steve , O’Donnell Lauren J. , Rathi Yogesh 
Published: April 2023

AbstractThe Adolescent Brain Cognitive Development (ABCD) study has collected data from over 10,000 children across 21 sites, providing valuable insights into adolescent brain development. However, site-specific scanner variability has made it challenging to use diffusion MRI (dMRI) data from this study. To address this, a database of harmonized and processed ABCD dMRI data has been created, comprising quality-controlled imaging data from 9345 subjects. This resource required significant computational effort, taking ∼50,000 CPU hours to harmonize the data, perform white matter parcellation, and run whole brain tractography. The database includes harmonized dMRI data, 800 white matter clusters, 73 anatomically labeled white matter tracts both in full-resolution (for analysis) and low-resolution (for visualization), and 804 different dMRI-derived measures per subject. It is available via the NIMH Data Archive and offers tremendous potential for scientific discoveries in structural connectivity studies of neurodevelopment in children and adolescents. Additionally, several post-harmonization experiments were conducted to demonstrate the success of the harmonization process on the ABCD dataset.