bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the chloride channel, leucine‐rich repeat‐containing protein 8, subfamily a (LRRC8A), in mouse cholangiocytes
Authors: Shcheynikov Nikolay , Boggs Kristy , Green Anthony , Feranchak Andrew P. 
Published: April 2022

Abstract

Background and Aims
Chloride (Cl−) channels in the apical membrane of biliary epithelial cells (BECs), also known as cholangiocytes, provide the driving force for biliary secretion. Although two Cl− channels have been identified on a molecular basis, the Cystic Fibrosis Transmembrane Conductance Regulator and Transmembrane Member 16A, a third Cl− channel with unique biophysical properties has been described. Leucine‐Rich Repeat‐Containing Protein 8, subfamily A (LRRC8A) is a newly identified protein capable of transporting Cl− in other epithelium in response to cell swelling. The aim of the present study was to determine if LRRC8A represents the volume‐regulated anion channel in mouse BECs.

Approach and Results
Studies were performed in mouse small (MSC) and large (MLC) cholangiocytes. Membrane Cl− currents were measured by whole‐cell patch‐clamp techniques and cell volume measurements were performed by calcein‐AM fluorescence. Exposure of either MSC or MLC to hypotonicity (190 mOsm) rapidly increased cell volume and activated Cl− currents. Currents exhibited outward rectification, time‐dependent inactivation at positive membrane potentials, and reversal potential at 0 mV (ECl). Removal of extracellular Cl− or specific pharmacological inhibition of LRRC8A abolished currents. LRRC8A was detected in both MSC and MLC by reverse transcription polymerase chain reaction and confirmed by western blot. Transfection with LRRC8A small interfering RNA decreased protein levels by >70% and abolished volume‐stimulated Cl− currents.

Conclusion
These results demonstrate that LRRC8A is functionally present in mouse BECs, contributes to volume‐activated Cl− secretion, and, therefore, may be a target to modulate bile formation in the treatment of cholestatic liver disorders.
First‐line therapies for hepatitis B in the United States: A 3‐year prospective and multicenter real‐world study after approval of tenofovir alefenamide
Authors: Pan Calvin Q. , Afdhal Nezam H. , Ankoma‐Sey Victor , Bae Ho , Curry Michael P. , Dieterich Douglas , Frazier Lynn , Frick Andrew , Hann Hie‐Won , Kim W. Ray , Kwo Paul , Milligan Scott , Tong Myron J. , Reddy K. Rajender 
Published: April 2022

Abstract
Real‐world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real‐world outcomes with other first‐line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively. We analyzed switching patterns of antiviral therapy and treatment outcomes of TAF, tenofovir disoproxil fumarate (TDF), and entecavir therapy. For efficacy and safety, we analyzed a subset of patients with complete data at 24 months after switching to TAF or remaining on TDF or entecavir. Among 1037 enrollees, 889 patients were analyzed. The mean age was 52%, and 72% were hepatitis B e antigen–negative. After enrollment, shifts in therapies were mostly in reduced use of TDF from 63% to 30% due to switching to TAF. Clinical parameters were compared at enrollment or initiation to measures at 24 months for patients remaining on TAF (187), TDF (229), or entecavir (181). At 24 months, a significantly higher portion of patients on TAF achieved hepatitis B virus (HBV) DNA ≤ 20 IU/ml (93% vs. 86%; p = 0.012) and normalized alanine aminotransferase (ALT) (66% vs. 56%; p = 0.031) with stable estimated glomerular filtration rates (eGFRs). However, a higher percentage of the patient with eGFR < 60 ml/mi/1.7 m2 was observed in the TDF‐treated group (9% vs. 4%; p = 0.010). In patients who remained on entecavir or TDF for 24 months, ALT and HBV‐DNA results did not differ significantly from baseline. Treatment of CHB in the United States has significantly shifted from TDF to TAF. Our data suggest that switching from TDF or entecavir to TAF may result in increased frequency of ALT normalization and potential clearance of viremia at the 24‐month time point.
What can we learn from 28 years of monitoring of fish tissue polychlorinated biphenyls in Michigan's rivers?
Authors: Shaw Emily L. , Urban Noel R. 
Published: April 2022

Abstract
Polychlorinated biphenyls (PCBs) are an important part of chemical legacies in the Laurentian Great Lakes basin. Used in industrial products worldwide, PCBs are now extensively monitored because of their potential toxicity to humans. Fish consumption is a major pathway for exposure. Edible portion (i.e., fish fillet) data from Michigan's fish tissue PCB monitoring program were evaluated using regression statistics, principal component analysis, and t-tests to answer three questions: (1) How do fish tissue total PCB concentrations vary across Michigan's rivers? (2) Are the PCB congener patterns uniformly distributed among tested sites and species? (3) Do monitoring methods limit our ability to discern trends in fish tissue PCB concentrations? Our results indicate that although contaminated sites have been successfully identified, based on higher PCB concentrations in samples from Areas of Concern (AOCs) compared to non-AOC sites, 77% of fish samples from 2010 to 2015 exceeded the safe fish tissue PCB concentration for unrestricted consumption (97 g/day) by sensitive populations. The PCB congener profiles vary among species and locations. Results demonstrate that these data are not useful for supplementing ongoing spatial and temporal trend analysis. Only 15 of the 83 species + waterbody pairs had adequate data for evaluating temporal trends with more than three data points. In general, the trends at each location varied based on the analytical method. Conclusions from this work can inform revisions to existing monitoring programs and improve our ability to protect human health. Integr Environ Assess Manag 2023;19:152–162. © 2022 SETAC
TAZ/WWTR1 mediates liver mesothelial–mesenchymal transition induced by stiff extracellular environment, TGF‐β1, and lysophosphatidic acid
Authors: Lua Ingrid , Balog Steven , Asahina Kinji 
Published: April 2022

AbstractMesothelial cells cover the surface of the internal organs and the walls of body cavities, facilitating the movement between organs by secretion of a lubricating fluid. Upon injury, mesothelial cells undergo a mesothelial–mesenchymal transition (MMT) and give rise to myofibroblasts during organ fibrosis, including in the liver. Although transforming growth factor‐β1 (TGF‐β1) was shown to induce MMT, molecular and cellular mechanisms underlying MMT remain to be clarified. In the present study, we examined how the extracellular environment, soluble factors, and cell density control the phenotype of liver mesothelial cells by culturing them at different cell densities or on hydrogels of different stiffness. We found that TGF‐β1 does not fully induce MMT in mesothelial cells cultured at high cell density or in the absence of fetal bovine serum. Extracellular lysophosphatidic acid (LPA) synergistically induced MMT in the presence of TGF‐β1 in mesothelial cells. LPA induced nuclear localization of WW domain‐containing transcription regulator1 (WWTR1/TAZ) and knockdown of Taz, which suppressed LPA‐induced MMT. Mesothelial cells cultured on stiff hydrogels upregulated nuclear localization of TAZ and myofibroblastic differentiation. Knockdown of Taz suppressed MMT of mesothelial cells cultured on stiff hydrogels, but inhibition of TGF‐β1 signaling failed to suppress MMT. Our data indicate that TAZ mediates MMT induced by TGF‐β1, LPA, and a stiff matrix. The microenvironment of a stiff extracellular matrix is a strong inducer of MMT.
Surgical outcomes of laparoscopic versus open repeat liver resection for liver cancers: A report from a nationwide surgical database in Japan
Authors: Kaibori Masaki , Ichihara Nao , Miyata Hiroaki , Kakeji Yoshihiro , Nanashima Atsushi , Kitagawa Yuko , Yamaue Hiroki , Yamamoto Masakazu , Endo Itaru 
Published: April 2022

AbstractBackground/PurposeLaparoscopic (repeat) liver resection (LRLR) is a well‐established liver tumor treatment. However, since its outcomes and comparison with open repeat liver resection (ORLR) in recurrent liver cancer remain inadequately studied, this study then aimed to compare their short‐term outcomes for liver cancers (hepatocellular carcinoma, intrahepatic cholangiocellular carcinoma, and metastatic liver cancer).MethodsRepeat liver resection cases between 2013 and 2017 from Japan’s National Clinical Database were extracted. We used propensity score matching (PSM) to compare the proportion of patients with postoperative complications of Clavien‐Dindo classification grade II or higher (CD2+) (primary endpoint), as well as the operative time, intraoperative bleeding volume, and intraoperative transfusion implementation rate (secondary endpoints).ResultsOf 2902 patients (ORLR, 2476; LRLR, 426), 712 (356 per type) with comparable backgrounds remained via PSM. Before and after PSM, the postoperative CD2+ complication rate was significantly lower in the LRLR group, who had shorter operative time, smaller intraoperative bleeding volume, and lower intraoperative transfusion rate, than in the ORLR group (after matching, 7.6% vs 18.3%, P < 0.0001).ConclusionsLRLR showed better short‐term outcomes than ORLR, making it a safer and more effective liver cancer treatment.
Performance and application evaluation of SARS‐CoV‐2 antigen assay
Authors: Ye Qing , Shao Wenxia , Meng Hanyan 
Published: April 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid detection is the gold standard for the laboratory diagnosis of coronavirus disease 2019 (COVID‐19). However, this method has high requirements for practitioners' skills and testing sites, so it is not easy to popularize and promote the application in places other than large hospitals. In addition, the detection flux of SARS‐CoV‐2 nucleic acid is small, and the whole detection process takes much time, which cannot meet the actual needs of rapid screening in large quantities. The WHO conditionally approved a batch of SARS‐CoV‐2 antigen reagents for clinical application to alleviate this contradiction. SARS‐CoV‐2 antigen detection offers a trade‐off among clinical performance, speed and accessibility. With the gradual increase in clinical application, the accumulated clinical data show that the sensitivity and specificity of the SARS‐CoV‐2 antigen assay are over 80% and 97%, respectively, which can basically meet the requirements of the WHO. However, the sensitivity of the SARS‐CoV‐2 Antigen Assay among asymptomatic people in low prevalence areas of COVID‐19 cannot meet the standard, leading to a large number of missed diagnoses. In addition, the detection ability of SARS‐CoV‐2 antigen reagent for different SARS‐CoV‐2 mutant strains differs greatly, especially for those escaping the COVID‐19 vaccines. In terms of results interpretation, it is highly reliable to exclude SARS‐CoV‐2 infection based on the high negative predictive value of the SARS‐CoV‐2 antigen assay. However, in the low prevalence environment, the probability of false positives of the SARS‐CoV‐2 antigen assay is high, so the positive results need to be confirmed by the SARS‐CoV‐2 nucleic acid reagent. The SARS‐CoV‐2 antigen assay is only a supplement to SARS‐CoV‐2 nucleic acid detection and can never completely replace it. To date, SARS‐CoV‐2 nucleic acid detection continues to be the standard laboratory method for COVID‐19 diagnosis.
SARS‐CoV‐2 Delta‐variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID‐19 vaccination
Authors: Torres Ignacio , Bellido‐Blasco Juan B. , Gimeno Concepción , Burgos Javier S. , Albert Eliseo , Moya‐Malo Raúl , Gascó‐Laborda Juan Carlos , Tornero Ana , Soriano Josefa , Meseguer‐Ferrer Noemí , Martínez‐Serrano María , Ortíz‐Rambla Javier , Buj Helena , Hernández Noelia , Peiró Salvador , Salas Dolores , Limón Ramón , Vanaclocha Hermelinda , Sánchez‐Payá José , Díez‐Domingo Javier , Comas Iñaki , González‐Candelas Fernando , Navarro David ,   the Valencian vaccine research program (ProVaVac) study group
Published: April 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID‐19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64–100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS‐CoV‐2‐Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC‐negative participants. SARS‐CoV‐2‐S‐IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS‐CoV‐2 RNA loads were quantified by real‐time polymerase chain reaction assays. Vaccine breakthrough COVID‐19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69–96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS‐CoV‐2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS‐CoV‐2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC‐positive counterparts (19/142). Among LFIC‐negative residents, a trend towards lower plasma anti‐RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS‐CoV‐2 RNA loads in nasopharyngeal specimens were lower in SARS‐CoV‐2‐experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS‐CoV‐2‐S‐reactive T cells at 3 months was similar in LFIC‐negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS‐CoV‐2 infection and detection of S‐reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta‐variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID‐19 vaccination.
ECG characteristics of COVID‐19 patient with arrhythmias: Referral hospitals data from Indonesia
Authors: Yuniadi Yoga , Yugo Dony , Fajri Muhammad , Tejo Budi Ario , Widowati Diah Retno , Hanafy Dicky Armen , Raharjo Sunu Budhi 
Published: April 2022

AbstractBackgroundArrhythmia is a significant clinical modifier in COVID‐19 patient outcomes. Currently, data on arrhythmia and ECG characteristics in COVID‐19 from lower middle‐income countries are limited.MethodsCOVID‐19 was confirmed by polymerase chain reaction testing of a nasopharyngeal sample. All clinical records were systematically evaluated to obtain demographic characteristics and medical comorbidities. The ECG was recorded on admission, in‐hospital, and at discharge.ResultsTotal documented arrhythmia events account for 22% of patients, comprising 6% of new‐onset arrhythmia and 16% of existing arrhythmia. Atrial fibrillation is the most common arrhythmia. The ECG changes were a decrease in heart rate (91 ± 22 vs. 83 ± 20, p < .001) and an increase in the QT interval (354.7 ± 53.70 vs. 371.4 ± 59.48 msec, p < .001) from hospital admission to hospital discharge, respectively. The in‐hospital HR of 85 bpm or higher increases the risk of death (OR = 2.69, p = .019).ConclusionThe incidence of arrhythmias in COVID‐19 patients at COVID‐19 referral hospitals in Indonesia is 22%. Atrial fibrillation is the most common arrhythmia in COVID‐19 patients. Prolongation of QRS duration from admission to discharge was related to the occurrence of new‐onset arrhythmia. The in‐hospital HR of 85 bpm or higher increased the risk of death.
Flavoring of sea salt with Mediterranean aromatic plants affects salty taste perception
Authors: Rosa Antonella , Pinna Ilenia , Piras Alessandra , Porcedda Silvia , Masala Carla 
Published: April 2022

AbstractBACKGROUNDSalt (sodium chloride) is an essential component of daily food, crucial for many physiological processes. Due to health risks related to salt over consumption, considerable interest is devoted to strategies to reduce dietary salt intake. In this work we evaluated the sensory dimensions of sea salts flavored with Mediterranean aromatic plants with the aim to confirm the role of herbs/spices in the enhancement of salty perception and to validate the use of flavored salts as a strategy to reduce salt intake. To this goal we compared taste dimensions (pleasantness, intensity, and familiarity) of solutions obtained with salt and sea salts flavored with Mediterranean herbs, spices, and fruits. Sensorial differences were analyzed using a seven‐point hedonic Likert‐type scale on 58 non‐trained judges.RESULTSMain flavor compounds, identified by gas chromatography‐flame ionization detection‐mass spectrometry (GC‐FID‐MS) analysis, were α‐pinene and 1,8‐cineole in myrtle salt (FS 1), verbenone, α‐pinene, 1,8‐cineole, and rosifoliol in herbs/plants salt (FS 2), and limonene in orange fruits/saffron salt (FS 3). At the dose of 0.04 g mL−1, saline solutions obtained with flavored salt (containing approximately 6–30% less sodium chloride) were perceived as more intense, less familiar, but equally pleasant than pure salt solution. In particular, sea salt flavored with orange fruits/saffron emerged as the most interesting in potentiating saltiness perception.CONCLUSIONOur study confirmed the important role of Mediterranean aromatic plants in the enhancement of saltiness perception and qualified the use of flavored sea salt during food preparation/cooking instead of normal salt as a potential strategy to reduce the daily salt intake. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Chronicity of posttraumatic stress disorder and comorbid pain as predictors of treatment response for trauma‐affected refugees
Authors: Nordbrandt Maja Sticker , Vindbjerg Erik , Mortensen Erik Lykke , Carlsson Jessica 
Published: April 2022

AbstractPredictors of treatment outcomes have received limited attention in the field of trauma‐affected refugees. Symptom chronicity is potentially a particularly relevant predictor, as it would instruct earlier interventions for a population less familiar with psychiatric treatment options, and its identification may also reduce or delay the onset of comorbidities, such as chronic pain. Accordingly, this study examined the impacts of posttraumatic stress disorder (PTSD) chronicity and baseline comorbid pain on treatment response in trauma‐affected refugees. Multiple regression was used to analyze data from a randomized controlled trial of 318 trauma‐affected refugees with PTSD that was conducted at a specialized psychiatric clinic in Denmark. Treatment response was measured by changes in symptoms of PTSD (Harvard Trauma Questionnaire) and depression (Hopkins Symptom Checklist–25). Duration of functional impairment was found to be a significant predictor of PTSD outcomes, p = .003, ΔR2 = .02, f2 = .03; it was not predictive of outcomes for depression. Baseline pain severity was a significant predictor of outcomes for both PTSD, p = .009, ΔR2 = .02, f2 = .02, and depression, p = .041, ΔR2 = .01, f2 = .01. These findings suggest that trauma‐affected refugees with long‐lasting functional impairment and a high pain score are likely to show less improvement from treatments for PTSD and depression. This points to a need for early intervention to prevent chronic functional impairment and suggests comorbid pain is an important therapeutic target.
Spectral optimization for Robin Laplacian on domains admitting parallel coordinates
Authors: Exner Pavel , Lotoreichik Vladimir 
Published: April 2022

AbstractIn this paper we deal with spectral optimization for the Robin Laplacian on a family of planar domains admitting parallel coordinates, namely a fixed‐width strip built over a smooth closed curve and the exterior of a convex set with a smooth boundary. We show that if the curve length is kept fixed, the first eigenvalue referring to the fixed‐width strip is for any value of the Robin parameter maximized by a circular annulus. Furthermore, we prove that the second eigenvalue in the exterior of a convex domain Ω corresponding to a negative Robin parameter does not exceed the analogous quantity for the exterior of a disk whose boundary has a curvature larger than or equal to the maximum of that for .
Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity
Authors: Jiang Zhongyi , Zhu Haitao , Wang Pusen , Que Weitao , Zhong Lin , Li Xiao‐Kang , Du Futian 
Published: April 2022

AbstractCD4+CD25+ regulatory T cells (Tregs), a subpopulation of naturally CD4+ T cells that characteristically express transcription factor Forkhead box P3 (FOXP3), play a pivotal role in the maintenance of immune homeostasis and the prevention of autoimmunity. With the development of biological technology, the understanding of plasticity and stability of Tregs has been further developed. Recent studies have suggested that human Tregs are functionally and phenotypically diverse. The functions and mechanisms of different phenotypes of Tregs in different disease settings, such as tumor microenvironment, autoimmune diseases, and transplantation, have gradually become hot spots of immunology research that arouse extensive attention. Among the complex functions, CD4+CD25+FOXP3+ Tregs possess a potent immunosuppressive capacity and can produce various cytokines, such as IL‐2, IL‐10, and TGF‐β, to regulate immune homeostasis. They can alleviate the progression of diseases by resisting inflammatory immune responses, whereas promoting the poor prognosis of diseases by helping cells evade immune surveillance or suppressing effector T cells activity. Therefore, methods for targeting Tregs to regulate their functions in the immune microenvironment, such as depleting them to strengthen tumor immunity or expanding them to treat immunological diseases, need to be developed. Here, we discuss that different subpopulations of Tregs are essential for the development of immunotherapeutic strategies involving Tregs in human diseases.
Mid‐infrared multiline absorption tomography for in situ analysis of thermochemical structure in natural gas‐fired cooker flame
Authors: Sheng Gang , Han Jie , Ma Liuhao , Wang Wei , Wang Yu 
Published: April 2022

AbstractA mid‐infrared laser absorption tomography technique was developed to quantify the nonuniform thermochemical structures of flames stabilized on a natural gas‐fired cooker. Multispectral absorption spectroscopy coupled with Tikhonov‐regularized three‐point Abel inversion was used to resolve the spatially resolved temperature and species concentration. A tunable interband cascade laser (ICL) near 4.2 μm was used to access multiple CO2 absorption lines in the fundamental vibration band. Multiline Voigt fitting strategy was used to improve the fitting of the overlap absorption features. Comprehensive measurements at a different height above the cooker were performed and assembled to display the contour of temperature and CO2 concentrations, resolving the nonuniform thermochemical structure of the high‐temperature combustion field. The measurement uncertainty analysis for temperature and CO2 concentration was also discussed. The current technique is demonstrated to be capable of quantitatively distinguishing flame conditions under different fuel supply modes.