bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation
Authors: Lazzerini Pietro Enea , Accioli Riccardo , Acampa Maurizio , Zhang Wen-Hui , Verrengia Decoroso , Cartocci Alessandra , Bacarelli Maria Romana , Xin Xiaofeng , Salvini Viola , Chen Ke-Su , Salvadori Fabio , D’errico Antonio , Bisogno Stefania , Cevenini Gabriele , Marzotti Tommaso , Capecchi Matteo , Laghi-Pasini Franco , Chen Long , Capecchi Pier Leopoldo , Boutjdir Mohamed 
Published: May 2022

BackgroundHeart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms.MethodsWe investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro.ResultsIn patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr).ConclusionFor the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.
RETRACTED: Postoperative Pulmonary Complications in Patients With Transcatheter Tricuspid Valve Implantation—Implications for Physiotherapists
Authors: Yu Peng-Ming , Wang Yu-Qiang , Luo Ze-Ruxing , Tsang Raymond C. C. , Tronstad Oystein , Shi Jun , Guo Ying-Qiang , Jones Alice Y. M. 
Published: May 2022

ObjectivesTo investigate the incidence of postoperative pulmonary complications (PPCs) and short-term recovery after transcatheter tricuspid valve implantation (TTVI).MethodsA total of 17 patients diagnosed with severe tricuspid regurgitation who received a LuX-valve TTVI were included in this study. Spirometry lung function, maximal inspiratory pressure (MIP), and 6-min walk test distance (6MWD) were recorded. Prior to surgery, patients were stratified into high or low pulmonary risk groups based on published predefined criteria. A physiotherapist provided all patients with education on thoracic expansion exercises, effective cough and an inspiratory muscle training protocol at 50% of MIP for 3 days preoperatively. All patients received standard post-operative physiotherapy intervention including positioning, thoracic expansion exercises, secretion removal techniques and mobilization. Patients were assessed for PPCs as defined by the Melbourne-Group Score-version 2. Clinical characteristics and hospital stay, cost, functional capacity, and Kansas City Cardiomyopathy Questionnaire (KCCQ) heart failure score were recorded at admission, 1-week, and 30-days post-op.ResultsThe mean (SD) age of the 17 patients was 68.4 (8.0) years and 15 (88%) were female. Pre-surgical assessment identified 8 patients (47%) at high risk of PPCs. A total of 9 patients (53%) developed PPCs between the 1st and 3rd day post-surgery, and 7 of these 9 patients were amongst the 8 predicted as “high risk” prior to surgery. One patient died before the 30 day follow up. Pre-operative pulmonary risk assessment score, diabetes mellitus, a low baseline MIP and 6MWD were associated with a high incidence of PPCs. Compared to those without PPCs, patients with PPCs had longer ICU and hospital stay, and higher hospitalization cost. At 30 days post-surgery, patients without PPCs maintained higher MIP and 6MWD compared to those with PPCs, but there were no significant between-group differences in other lung function parameters nor KCCQ.ConclusionThis is the first study to report the incidence of PPCs post TTVI. Despite a 3-day prehabilitation protocol and standard post-operative physiotherapy, PPCs were common among patients after TTVI and significantly impacted on hospital and short-term recovery and outcomes. In the majority of patients, PPCs could be accurately predicted before surgery. A comprehensive prehabilitation program should be considered for patients prior to TTVI.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2000039671].
Curcumin Improves Cardiopulmonary Resuscitation Outcomes by Modulating Mitochondrial Metabolism and Apoptosis in a Rat Model of Cardiac Arrest
Authors: Zhang Jie , Liu Siqi , Jiang Longyuan , Hou Jingying , Yang Zhengfei 
Published: May 2022

BackgroundCurcumin, a diarylheptanoid chemical compound extracted from curcuma longa, exerts a variety of biological and pharmacological effects in numerous pathological conditions, including ischemia/reperfusion (I/R) injury. In this study, we investigated its role in post-resuscitation myocardial dysfunction in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) by targeting on mitochondrial metabolism and apoptosis.MethodsAnimals were randomized into three groups: sham, control and curcumin, with fifteen rats in each group. Ventricular fibrillation (VF) was induced in the rats of the control and curcumin groups. The rats in the two groups were untreated for 8 min, followed by CPR for 8 min. Placebo (saline) or curcumin was administered by intraperitoneal injection, respectively, 5 min after successful resuscitation. Myocardial function was measured at baseline and post-resuscitation for 6 h consecutively. Ten rats in each group were closely observed for an additional 66 h to analyze the survival status, and the remaining five were sacrificed for the measurement of mitochondrial parameters and cell apoptosis.ResultsCompared with the control group, myocardial function was significantly enhanced in the curcumin group, contributing to a better survival status. Curcumin treatment mitigated the depletion of superoxide dismutase (SOD) and the production of malondialdehyde (MDA). The structural damage of mitochondria was also alleviated, with improved conditions of mPTP and ΔΨm. Curcumin boosted the production of ATP and attenuated myocardial apoptosis. Cytochrome C, caspase-3 and its cleavage were suppressed by curcumin. Proteins closely related to the functional performance of mitochondria, including uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3) were downregulated, while mitochondrial transcription factor A (mtTFA) was upregulated.ConclusionCurcumin improves the outcomes of CPR via alleviating myocardial dysfunction induced by I/R injury. It exhibits anti-oxidation properties. Moreover, it is capable of ameliorating mitochondrial structure and energy metabolism, as well as inhibiting the mitochondrial apoptosis pathway. UCP2, UCP3, and mtTFA might also be involved in curcumin mediated protective effects on mitochondria.
Effectiveness of Free Bikes and E-Bikes for Commute Mode Shift: The Case of Google’s Lending Program
Authors: Fitch Dillon T. , Gao Zeyu , Noble Lucy , Mac Terry 
Published: May 2022

In 2015, Google began a new transportation demand management program designed to increase bike commuting to their two main corporate campuses in Mountain View and Sunnyvale, CA, United States by lending conventional and electric assisted bikes to employees at no cost to them. Following the lending period, Google incentivized bike purchases, among many other program co-benefits to increase bike commuting. Using a series of bivariate and multivariable analyses, we estimate the program led to average bike commute increases of approximately 1.7–2.3 days per week, roughly a tripling of prior bike commute rates for participating employees. After the program, bike rates of participants diminished slightly, but were still greater than baseline (increase of 1.3–1.9 days per week). Furthermore, nearly all the increases in bicycling are likely attributed to decreases in single occupancy vehicle (SOV) commuting. This study offers a first look at the potential for bike lending as a transportation demand management strategy for large employers in suburban settings which can help other employers design their own programs.
MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer
Authors: Wu Zhenzhen , Wang Yueyuan , Li Juan , Wang Huiling , Tuo Xunyuan , Zheng Jing 
Published: May 2022

Background: Microchromosome maintenance protein 10 (MCM10) is required for DNA replication in all eukaryotes, and it plays a key role in the development of many types of malignancies. However, we currently still do not know the relationship between MCM10 and ovarian cancer (OV) prognosis and immune checkpoints.Methods: The Gene Expression Profiling Interactive Analysis and Tumor Immunology Estimation Resource (TIMER) databases were used to investigate MCM10 expression in Fan cancer. The Kaplan-Meier Plotter and PrognoScan were used to assess the relationship between MCM10 and OV prognosis. The LinkedOmics database was used to analyze the MCM10 co-expression network and explore GO term annotation and the KEGG pathway. The relationship between MCM10 expression and immune infiltration in OV was investigated using the Tumor Immunology Estimation Resource database. cBioPortal database was used to explore the relationship between MCM10 expression and 25 immune checkpoints. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect MCM10 expression. The prognosis was also analyzed by distinguishing between high and low expression groups based on median expression values.Results: The results of the three data sets (220,651_s_at, 222,962_s_at and 223,570_at) in KM Plotter all indicated that the overall survivalof the high MCM10 expression group was lower than that of the low expression group OV, and the results of GSE9891 also reached the same conclusion. The expression level of MCM10 was negatively correlated with B cells and CD8+T cells, and positively correlated with CD4+T Cells and Macrophages. GO term annotation and KEGG pathway analysis showed that the co-expressed genes of MCM10 were mainly enriched in cell cycle and DNA replication. The alterations in MCM10 coexisted statistically with the immune checkpoints CTLA4, TNFSF4, TNFSF18, CD80, ICOSLG, LILRB1 and CD200. PCR results displayed that MCM10 was highly expressed in OV tissues, and the increased expression of MCM10 was significantly associated with poor overall survival.Conclusion: These results demonstrated that high expression of MCM10 was associated with poor prognosis in OV and correlated with immune checkpoints.
Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at the CYP2C Locus
Authors: Kee Ping Siu , Maggo Simran D. S. , Kennedy Martin A. , Barclay Murray L. , Miller Allison L. , Lehnert Klaus , Curtis Maurice A. , Faull Richard L. M. , Parker Remai , Chin Paul K. L. 
Published: May 2022

Omeprazole is extensively used to manage gastroesophageal reflux disease (GERD). It is primarily metabolized by CYP2C19. The CYP2C19*17 (rs12248560) allele and the recently described CYP2C:TG haplotype (rs11188059 and rs2860840) are associated with increased enzymatic activity, and may reduce omeprazole exposure. This observational study aimed to investigate the association between these genetic variants and omeprazole treatment failure in GERD. We recruited predominantly New Zealand European GERD patients who either did not respond to omeprazole or experienced breakthrough heartburn symptoms despite at least 8 weeks of omeprazole (≥40 mg/day). The GerdQ score was used to gauge symptomatic severity. A total of 55 cases were recruited with a median age (range) of 56 years (19–82) and GerdQ score of 11 (5–17). Of these, 19 (34.5%) were CYP2C19*17 heterozygotes and two (3.6%) were CYP2C19*17 homozygotes. A total of 30 (27.3%) CYP2C:TG haplotypes was identified in our cohort, with seven (12.7%) CYP2C:TG homozygotes, and 16 (29%) CYP2C:TG heterozygotes. No significant differences were observed for overall CYP2C19*17 alleles, CYP2C19*17/*17, overall CYP2C:TG haplotypes, and CYP2C:TG heterozygotes (p &gt; 0.05 for all comparisons). Gastroscopy and 24-h esophageal pH/impedance tests demonstrated objective evidence of GERD in a subgroup of 39 (71%) cases, in which the CYP2C:TG/TG was significantly enriched (p = 0.03) when compared with the haplotype frequencies in a predominantly (91%) New Zealand European reference population, but not the CYP2C19*17/*17 (p &gt; 0.99), when compared with the allele frequencies for the non-Finnish European subset of gnomAD. We conclude that omeprazole treatment failure in GERD is associated with CYP2C:TG/TG, but not CYP2C19*17.
Targeting Glutamine Metabolism Ameliorates Autoimmune Hepatitis via Inhibiting T Cell Activation and Differentiation
Authors: Yu Qiang , Tu Honghu , Yin Xueyi , Peng Chang , Dou Chuanyun , Yang Wenhua , Wu Wenbiao , Guan Xiaotong , Li Jia , Yan Hexin , Zang Yi , Jiang Haowen , Xia Qiang 
Published: May 2022

BackgroundAutoimmune hepatitis (AIH) is mediated by a cascade of T cell-mediated events directed at liver cells and persistent inflammation within the liver can eventually result in liver cirrhosis. Targeting glutamine metabolism has an impact on T cell activation and differentiation. However, the effect of glutamine metabolism blocking upon AIH remains unknown. We use glutaminase antagonist 6-diazo-5-oxo-L-norleucine (DON) for in vitro assays and its prodrug 2-(2-amino-4-methylpentanamido)-DON (JHU083) for in vivo assays to investigate the potential therapeutic effect and molecular mechanism of glutamine metabolism blocking in an AIH murine model.MethodsAIH mice were treated with JHU083 or vehicle before concanavalin A (ConA) administration, and disease severity was examined. Then activation and differentiation [including Th1/Th17 cells and cytotoxic T lymphocytes (CTL)] of T cells from Vehicle-WT, JHU083-AIH and Vehicle-AIH mice were tested. Furthermore, in vitro T cell activation and differentiation were measured using separated splenocytes stimulated with ConA with or without DON. The activation and differentiation of T cells were tested using flow cytometry, qRT-PCR and ELISA. Phosphorylation level of mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase (P70S6K) were examined by western blotting.ResultsJHU083 and DON significantly suppressed the activation of T cells and inhibited the differentiation of Th1/Th17 cells and CTL in vivo and in vitro. Besides, we demonstrated that glutamine metabolism blocking inhibited T cells activation and differentiation through decreasing the mRNA expression of amino acid transporter solute carrier family 7 member 5 (SLC7A5) and mitigating the activation of mTOR signaling.ConclusionsWe proved that targeting glutamine metabolism represents a potential new treatment strategy for patients with AIH and other T cell-mediated disease. Mechanistically, we demonstrated that glutamine metabolism blocking inhibits T cells activation and suppresses the differentiation of Th1/Th17 cells and CTL.
Plume Layer Influences the Amazon Reef Sponge Microbiome Primary Producers
Authors: Pinto Otávio H. B. , Bornemann Till L. V. , Oliveira Rafael S. , Frederico Tayna D. , Quirino Betania F. , Probst Alexander J. , de Freitas Mayanne A. M. , Thompson Fabiano L. , Kruger Ricardo H. 
Published: May 2022

Symbiont relationships between corals and photosynthetic microorganisms sustain coral reef existence. However, the Great Amazon Reef System (GARS) stays under a plume layer that attenuates the entry of light, and instead of corals, sponges are the major reef epifauna, for which little is known about the function of the associated microbiome. Here, we used genome-resolved metagenomics to investigate how the sponge microbiome supports its host and overcomes the reduced light availability, recovering 205 MAGs from Agelas and Geodia sponges with completeness &gt;70% and contamination &lt;10%. Beta diversity estimates based on the 16S rRNA genes indicated the microbiomes of Amazon and Caribbean sponges to be distinct (P&lt;0.01), with heterotrophic lifestyles being prevalent in Amazon sponge microbiomes (P&lt;0.05). Nevertheless, genes indicating the carbon fixation pathways 3-Hydroxypropionate/4-Hydroxybutyrate cycle, 3-Hydroxypropionate bicycle, Reductive Tricarboxylic Acid Cycle, and Calvin-Benson-Bassham cycle could be recovered in low abundance. The presence of Cyanobacteria, represented by both 16S rRNA analyses and low-quality MAGs indicated light incidence on the reef. The metabolic profile shows that the GARS sponge microbiome had genes for sulfate reduction, sulfur oxidation, nitric oxide reduction, ammonia oxidation, nitrate reduction, nitrite ammonification, nitrite oxidation, and nitrite reduction, indicating that the microbiome might play a role in detoxification of the holobiont. We conclude, that neither the plume-limited photosynthesis of the sponge microbiome nor the primary producers sustain the organic carbon input for the sponges, which likely live off plume-associated organic carbon and their heterotrophic microbiota.
Corrosion Inhibition and Adsorption Process of 3-Amino-5-Mercapto-1,2,4-Triazole on Aluminium Alloy: Experimental and Theoretical Studies
Authors: Guo Xin , Wang Jinke , Huang Luyao , Wang Yajie , Ma Li , Zhang Dawei , Ma Lingwei 
Published: May 2022

The corrosion inhibition effect of 3-amino-5-mercapto-1,2,4-triazole (AMT) on AA2024 aluminium alloy in 3.5 wt.% NaCl solution was investigated, and the corrosion inhibition mechanism was revealed. The influence of AMT concentration on the corrosion inhibition performance was evaluated by potentiodynamic polarization curve and electrochemical impedance spectroscopy (EIS). Surface analysis and surface-enhanced Raman scattering (SERS) spectra were used to study the adsorption process and corrosion inhibition mechanism of AMT on the alloy surface. Polarization curve and EIS results showed that when the AMT concentration was 1.5 g/L, the corrosion current density (icorr) was the lowest and the resistance of adsorption film (Rf) was the largest, illustrating the highest corrosion inhibition efficiency. Moreover, the adsorption kinetics process of AMT was revealed by SERS measurement, and a positive correlation between the SERS intensity and Rf values of AMT after different immersion time was achieved. It indicated that the efficient adsorption of corrosion inhibitors significantly enhanced the corrosion inhibition performance. Density functional theory (DFT) and molecular dynamics simulations were used to give further insight into the adsorption and inhibition mechanism of AMT on the aluminium alloy surface.
Flexible La0.67Sr0.33MnO3:ZnO Nanocomposite Thin Films Integrated on Mica
Authors: Zhang Xiong , Yang Hui , Wang Guoliang , Zhang Yi , Huang Jijie 
Published: May 2022

The integration of functional oxide thin films on flexible substrates is critical for their application in flexible electronics. Here, to achieve flexible perovskite manganite oxide film with excellent low-field magnetoresistance (LFMR) effect, textured La0.67Sr0.33MnO3 (LSMO):ZnO nanocomposite film was deposited on a flexible mica substrate with ZnO buffer using pulsed laser deposition (PLD). Compared to the polycrystalline LSMO:ZnO nanocomposite film directly deposited on mica without buffer, the LSMO:ZnO/ZnO/mica sample exhibits larger saturation magnetization (164 emu/cm3) and higher Curie temperature (∼319 K), which results from the crystallinity and strain in the LSMO phase. In addition, the LSMO:ZnO/ZnO/mica film presents a high MR value of ∼39% at 10 K under 1 T. Furthermore, the good mechanical stretchability and property stability of the nanocomposite thin films have been demonstrated with mechanical bending.
Influenza Vaccination and Risk of Stroke in Women With Chronic Obstructive Pulmonary Disease: A Nationwide, Population-Based, Propensity-Matched Cohort Study
Authors: Chen Chun-Chao , Lin Cheng-Hsin , Chiu Chun-Chih , Yang Tsung Yeh , Hsu Min-Huei , Wang Yuan-Hung , Lei Meng-Huan , Yeh Hsien Tang , Fang Yu-Ann , Hao Wen-Rui , Liu Ju-Chi 
Published: May 2022

BackgroundsThe risk of stroke is higher among patients with chronic obstructive pulmonary disease (COPD) than among the healthy population. Moreover, women generally have worse long-term stroke outcomes than men.MethodsThe data of 6681 women with COPD (aged ≥ 65 years) registered in Taiwan’s National Health Insurance Research Database were retrospectively analyzed from January 1, 2001 to December 31, 2011. After 1:1 propensity score matching, the patients were divided into vaccinated and unvaccinated groups.ResultsIn total, 5102 women were enrolled. The vaccinated group had a significantly lower risk of total, hemorrhagic, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR]: 0.60, 95% confidence interval [CI]: 0.54–0.67; aHR: 0.59, 95% CI: 0.43–0.83; and aHR: 0.59, 95% CI: 0.52–0.68, respectively). A lower risk of stroke was observed among the women aged 65–74 and ≥75 years, and the association was dose-dependent in all types of stroke (aHR: 1.08, 95% CI: 0.92–1.26; aHR: 0.70, 95% CI: 0.60–0.82; and aHR: 0.32, 95% CI: 0.26–0.38 for those vaccinated 1, 2 to 3, and ≥4 times, respectively, during the follow-up period). Women with a CHA2DS2-VASc score (conditions and characteristics included congestive heart failure, hypertension, diabetes, stroke, vascular disease, age, and sex) of 2–3 and ≥4 had a significantly lower risk of ischemic stroke while receiving more vaccinations. A smaller significant lower risk of hemorrhagic stroke after more than 4 times of vaccination was noted in the women with a CHA2DS2-VASc score of ≥4. Both interrupted and non-interrupted vaccination was associated with lower risk of stroke occurrence.ConclusionInfluenza vaccination is associated with a lower risk of total, hemorrhagic, and ischemic stroke among women with COPD, and the association is dose-dependent. However, the findings may be limited by unmeasurable confounders. Further investigations on this subject are warranted.