bluuebunny/crossref_metadata_2025_split huggingface dataset:
The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity
Authors: Zhang Junran , Prasad Chandra , Oo Adrian , Qiu Zhaojun , Li Na , Singh Deepika , Xin Xiwen , Cho Young-Jae , Li Zaibo , Zhang Xiaoli , Yan Chunhong , Zheng Qingfei , Shao Jimin , Wang Qi-En , Kim Baek 
Published: May 2023

Abstract

Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results in preclinical studies but minimal efficacy with substantial toxicity in clinical trials. To explore novel combinational strategies that can overcome these limitations, we performed an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identified thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a novel determinant of CHK1i sensitivity. We established a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR1 inhibitor auronafin, an anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, these findings identify a new pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.
Circulation of highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in highly diverse wild bird species from Peru
Authors: Castro-Sanguinetti Gina , Gonzalez-Veliz Rosa , Callupe-Leyva Alonso , Apaza-Chiara Ana , Jara Javier , Silva Walter , Icochea Eliana , More-Bayona Juan 
Published: May 2023

Abstract
Highly pathogenic avian Influenza virus (HPAIV) has emerged in unprecedented records in recent years. Despite the large reports of cases in Asia, Europe, and North America, little is known about its circulation in South America. Here, we describe the isolation, and whole genome characterization of HPAIV obtained from sampling 26 wild bird species in Peru, representing one of the largest studies in our region. Out of 147 samples analyzed, 20 were positive for detection of avian influenza virus using a qRT-PCR-based assay. Following inoculation into embryonated chicken eggs, fourteen viral isolates were obtained from which six isolates were selected for genome characterization, based on their host relevance. Our results identified the presence of HPAIV H5N1 subtype. Phylogenetic analysis revealed that these isolates correspond to the clade 2.3.4.4b, sharing a common ancestor with North American isolates and forming a novel subclade along with isolates from Chile. Altogether, changes at the amino acid levels compared to their closest relatives indicates the virus is evolving locally, highlighting the need for constant genomic surveillance. This data evidence the chances for spillover events increases as the virus spreads into large populations of immunologically naïve avian species and adding conditions for cross species transmission.
LSTM-Based Recurrent Neural Network Provides Effective Short Term Flu Forecasting
Authors: Amendolara Alfred B , Sant David , Rotstein Horacio G. , Fortune Eric 
Published: May 2023

Abstract
Background Influenza virus is responsible for a yearly epidemic in much of the world. To better predict short-term, seasonal variations in flu infection rates and possible mechanisms of yearly infection variation, we trained a Long Short-Term Memory (LSTM)-based deep neural network on historical Influenza-Like-Illness (ILI), climate, and population data.
Methods Data were collected from the Centers for Disease Control and Prevention (CDC), the National Center for Environmental Information (NCEI), and the United States Census Bureau. The model was initially build in Python using the Keras API and tuned manually. We explored the roles of temperature, precipitation, local wind speed, population size, vaccination rate and vaccination efficacy. The model was validated using K-fold cross validation as well as forward chaining cross validation and compared to several standard algorithms. Finally, simulation data was generated in R and used for further exploration of the model.
Results We found that temperature is the strongest predictor of ILI rates, but also found that precipitation increased the predictive power of the network. The model was able to outperform comparison models at several prediction points. Additionally, the model accurately predicted simulation data. To test the role of temperature in the network, we phase-shifted temperature in time and found a predictable reduction in prediction accuracy.
Conclusions The results of this study confirm that flu forecasting may be effectively accomplished using architectures traditionally reserved for time series analysis, specifically LSTM-based neural networks. Additionally, this model provided insight into the week-to-week effects of climatic and biotic factors and revealed potential patterns in data series. Specifically, we found that temperature is the strongest predictor of seasonal flu infection rates. This information may prove to be especially important for flu forecasting given the uncertain long-term impact of the SARS-CoV-2 pandemic on seasonal influenza.
Resilience and Its Associations in Children with Systemic Lupus Erythematosus and Juvenile Idiopathic Arthritis
Authors: Trachtman Rebecca , Samuels Julie , Wojtal Emma , Feldman Brian M 
Published: May 2023

Abstract
Background: In this study, we aimed to evaluate resilience and its association with disease activity and health-related quality of life (HRQOL) in children with Systemic Lupus Erythematosus (SLE) and Juvenile Idiopathic Arthritis (JIA).
Findings: Using a cross-sectional design, patients with diagnoses of SLE or JIA were recruited between 8/2019 and 12/2022 in a pediatric rheumatology outpatient setting. At a single study visit we collected: demographic data, medical history and physical examination, physician global health assessment, patient global health assessment, Patient Reported Outcome Measurement Information System questionnaires, Connor Davidson Resilience Scale 10 (CD-RISC 10), Systemic Lupus Erythematosus Disease Activity Index, and clinical Juvenile Arthritis Disease Activity Score 10. Descriptive statistics were calculated. Using standard software, raw scores for PROMIS measures were converted to T-scores. Spearman’s correlations were performed, with statistical significance set to p<0.05.
47 study subjects were recruited. The average CD-RISC 10 score in SLE was 24.4, and in JIA was 25.2. In children with SLE, CD-RISC 10 was correlated with disease activity and inversely correlated with anxiety. In children with JIA, resilience was inversely associated with fatigue, and positively correlated with mobility and peer relationships.
Conclusions: In children with SLE and JIA, resilience is lower than in the general population. Further, our results suggest that interventions to increase resilience may improve the HRQOL of children with rheumatic disease. Ongoing study of the importance of resilience in this population, as well as interventions to increase resilience, will be an important area of future research in children with SLE and JIA.
Direct Relithiation and Efficient Regeneration of Spent LiFePO4 Materials through Thermochemical Healing
Authors: Zhu Yaunyi , Jiao Xiaojuan , Bian Haidong , Lu Xiaoying , Zhang Zheming 
Published: May 2023

Abstract
The environmentally friendly and low-cost recycling of spent LiFePO4 (LFP) cathode materials has become an urgent problem. This paper aims to employ eutectic Li+ molten-salt assisted roasting approach to relithiation and regenerating of spent LFP materials under ambient conditions. Via Li+ compensation and structure reshaping, LiFePO4 cathode material with various degradation conditions can be successfully regenerated, which enables the renovation of the electrochemical performance (the capacity, cycling stability, and rate capability) to the levels of the pristine LFP. It opens a door to the prospect of recycling and remanufacturing degraded cathode materials by this new method, having a strong potential for industrial application.
Is Heavy Metal Pollution in River Ganga: A Risk Factor for Amyotrophic Lateral sclerosis?
Authors: Mishra Bhargawi , Patil Sooraj , Gautam Geeta J. , Gautam Priyanka , Srivast Niraj Kumar , Singh Vineeta , Pathak Abhishek , Singh Varun Kumar , Kumar Anand , Chaurasia R. N. , Joshi Deepika , Mishra Vijaya Nath 
Published: May 2023

Abstract
The association between heavy metals and Amyotrophic Lateral Sclerosis (ALS) patients was explored with respect to the longest and pious Indian river Ganga. This study is designed to investigate the severity and heavy metal contamination in the blood of Gangetic (within 25 km from river Ganga) and non-Gangetic (> 25 km from river Ganga) ALS patients. Out of 65 recruited ALS patients, 36 from the Gangetic belt and 29 from the Non-Gangetic belt. Amyotrophic Lateral Sclerosis functional rating Scale (ALSFRS), Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) were calculated to study disease progression. Lead (Pb), Manganese (Mn) and Cadmium (Cd) concentrations were estimated in the whole blood of 23 subjects from Gangetic belt, 19 subjects from Non Gangetic belt and 23 heathy controls via Inductively coupled plasma mass spectrometry (ICP-MS) technique. A significantly lower FAB score was obtained in Gangetic patients. Pb concentration was significantly higher in both the diseased group than control and Cd concentration was detected significantly higher in Gangetic ALS patients than non Gangetic patients and control group.
The effect of neuter status on longevity in the Rottweiler dog
Authors: Joone Carolynne Jane , Konovalov Dmitry A. 
Published: May 2023

Abstract
Surgical sterilization or neutering of dogs is a commonly performed procedure in veterinary practices in many countries. In recent decades, concerns have been raised regarding possible side effects of neutering, including increased risk of certain neoplastic, musculoskeletal and endocrinological conditions. Considering that age serves as a significant confounding factor for some of these conditions, evaluating longevity statistics could provide valuable insights into the impact of neutering. The aim of this study was to compare longevity between neutered and sexually intact male and female Rottweilers, using electronic patient records collected by the VetCompass Australia database. Male and female Rottweilers neutered before 4.5 years of age demonstrated an expected lifespan 1.5 years and 1 year shorter, respectively, than their intact counterparts (p < 0.05).Similarly, the sub-population of male and female Rottweilers neutered at some point beyond the age of 4.5 years demonstrated reduced longevity by the age of 7 and 8 years for females and males, respectively, in comparison to their intact counterparts.These findings suggest that neutering has a negative impact on the lifespan of Rottweiler dogs, regardless of the age at which it is performed.
Prediction of osteoporosis in patients with rheumatoid arthritis using machine learning
Authors: Im Hyeonseung , Moon Ki Won , Lee Chaewon , Shin Seunghun , Joo Gihun 
Published: May 2023

Abstract
Osteoporosis is a serious health concern in patients with rheumatoid arthritis (RA). Machine learning (ML) models have been increasingly incorporated into various clinical practices, including disease classification, risk prediction, and treatment response. However, only a few studies have focused on predicting osteoporosis using ML in patients with RA. We aimed to develop an ML model to predict osteoporosis using a representative Korean RA cohort database. The KORean Observational study Network for Arthritis (KORONA) database, established by the Clinical Research Center for RA in Korea, was used in this study. Among the 5,077 patients registered in KORONA, 2,374 patients were included in this study. Four representative ML algorithms were used for the prediction: logistic regression (LR), random forest, XGBoost (XGB), and LightGBM. The accuracy, F1 score, and area under the curve (AUC) of each model were measured. AUC was the highest in the LR group at 0.750, and accuracy was the highest in the XGB group at 0.682. Body mass index, age, menopause, waist and hip circumferences, RA surgery, and monthly income were risk factors of osteoporosis. In conclusion, ML algorithms are a useful option for screening for osteoporosis in patients with RA.
Perspectives of health professionals and patients on implementation of a predictive model of response to immunotherapies in advanced melanoma
Authors: Salam Rehana A , Gide Tuba N , Cust Anne E , Scolyer Richard A , Long Georgina V , Silva Ines P da , Ferguson Peter , Mann Graham J , Watts Caroline , Wilmott James S , Smith Andrea L 
Published: May 2023

Abstract
Background
Immunotherapies have significantly improved the overall survival for patients with advanced melanoma. However, almost half of such patients either do not respond to the therapy or develop resistance to it, subjecting patients to ineffective treatments and unnecessary costs. Predictive biomarker testing can ensure that the patient receives the most effective therapy thereby reducing costs and toxicities. This study was conducted prior to and alongside a clinical validation study of routine predictive biomarker testing for patients with advanced melanoma to gain an insight into the factors associated with successful implementation of this intervention.
Methods
We conducted semi-structured interviews (n=25) with health professionals and patients guided by the EPIS (Exploration, Preparation, Implementation, and Sustainment) framework to understand enablers and barriers of implementation. Data analysis involved inductive and deductive thematic analysis using the Consolidated Framework for Implementation Research (CFIR).
Results
Health providers and patients consistently reported ‘clinical utility of predictive biomarker test’ as a major enabler, recognising that an effective test would assist in identifying likely non-responders and consequently avoid the side effects and other costs of ineffective treatment. Trust in data scientists, adaptability of the test platform, pre-existing organisational infrastructure, and supportive organisational implementation culture were also identified as factors that would support implementation. Lack of validated predictive biomarkers, resources and costs required to implement the test, and health providers’ knowledge, beliefs and concerns around the test were the principal factors that would impede implementation.
Conclusion
This study identifies factors influencing implementation of biomarkers as predictors of treatment response to immunotherapy for melanoma and potential strategies to overcome barriers impeding their transition from discovery to the clinic.
Xenon postconditioning attenuates neuronal injury after spinal cord ischemia/reperfusion injury by targeting endoplasmic reticulum stress- associated apoptosis
Authors: Luo Lan , Wang Yuqing , Tong Jiaqi , Li Lu , Zhu Yanbing , Jin Mu 
Published: May 2023

Abstract
Purpose: To explore the underlying mechanisms of xenon (Xe) protect against spinal cord ischemia/reperfusion injury (SCIRI).
Materials and methods: A SCIRI rat model was induced by abdominal artery occlusion for 85 min and reperfusion. Xe postconditioning (50% Xe) was administered 1 h after 1 h of reperfusion. At reperfusion time points (2, 4, 6, and 24 h), rats were treated with spinal cord scans by MRI to assess the time of peak spinal cord injury after SCIRI. Subsequently, endoplasmic reticulum (ER) stress inhibitor sodium 4-phenylbutyrate (4-PBA) was administered by daily intraperitoneal injection (50 mg/kg) for 5 days before SCIRI. At 4 hours after reperfusion, motor function, immunofluorescence staining, hematoxylin and eosin (HE) staining, Nissl staining, TUNEL staining, real-time reverse transcription polymerase chain (RT-PCR) reaction, and Western blot analyses were performed to investigate the protective effects of Xe against SCIRI.
Results: In the rat I/R model, spinal cord edema peaked at reperfusion 4 h. SCIRI activated ER stress, which was located in neurons. Xe postconditioning remarkably alleviated hind limb motor function, reduced neuronal apoptosis rate, increased the number of normal neurons, inhibited the expression of ER stress related protein in spinal cord. Furthermore, administration of the ER stress inhibitor 4-PBA strongly decreased ER stress-induced apoptosis following SCIRI.
Conclusions: Xe postconditioning inhibits ER stress activation, which contributes to alleviate SCIRI by suppressing neuronal apoptosis.
Macrophage-derived extracellular DNA initiates heterotopic ossification
Authors: Han Xiaoxiao , Gao Changhe , Lu Weicheng , Yan Jianfei , Xu Haoqing , Guo Zhenxing , Qin Wenpin , Lu Naining , Gao Jialu , Zhu Weiwei , Fu Yutong , Jiao Kai 
Published: May 2023

Abstract
Heterotopic ossification (HO) severely affects people's lives; however, its pathological mechanism remains poorly understood. Although extracellular DNA (ecDNA) has been shown to play important roles in pathological calcification, its effects in HO development and progression remain unknown. The in vivo rat Achilles tendon injury model and in vitro collagen I calcification model were used to evaluate the effects of ecDNA in the ectopic calcifications and the main cell types involved in those pathological process. Histology, immunofluorescent staining, reverse transcriptase-polymerase chain reaction analysis and micro-computed tomography were used to identify the distribution of macrophage-derived ecDNA and elucidate their roles in HO. The results showed that the amount of ecDNA and ectopic calcification increased significantly and exhibited a strong correlation in the injured tendons of HO model compared with those of the controls, which was accompanied by a significantly increased number of M2 macrophages in the injured tendon. During in vitro co-culture experiments, M2 macrophages calcified the reconstituted type I collagen and ectopic bone collected from the injured tendons of HO rats, while those effects were inhibited by deoxyribonuclease. More importantly, deoxyribonuclease reversed the pathological calcification in the injured rat tendon HO model. The present study showed that ecDNA from M2 macrophages initiates pathological calcification in HO, and the elimination of ecDNA might be developed into a clinical strategy to prevent ectopic mineralization diseases. The use of deoxyribonuclease for the targeted degradation of ecDNA at affected tissue sites provides a potential solution to treat diseases associated with ectopic mineralization.
Anti-leukemia effects of Omipalisib in Acute Myeloid Leukemia: inhibition of PI3K-AKT-mTOR signaling and suppression of Mitochondrial Biogenesis
Authors: Lin Liang-In , Tseng Chi-Yang , Fu Yu-Hsuan , Ou Da-Liang , Lu Jeng-Wei , Hou Hsin-An 
Published: May 2023

Abstract
Omipalisib (GSK2126458), a potent dual PI3K/mTOR inhibitor, is reported to exhibit anti-tumor effect in several kinds of cancers. More than 50% of acute myeloid leukemia (AML) patients display a hyperactivation of PI3K/AKT/mTOR signaling. We investigated the anti-proliferative effect of omipalisib in AML cell lines with varied genetic backgrounds. The OCI-AML3 and THP-1 cell lines had a significant response to omipalisib, with IC50 values of 17.45 nM and 8.93 nM, respectively. We integrated transcriptomic profile and metabolomic analyses, and followed by gene set enrichment analysis (GSEA) and metabolite enrichment analysis. Our findings showed that in addition to inhibiting PI3K/AKT/mTOR signaling and inducing cell cycle arrest at the G0/G1 phase, omipalisib also suppressed mitochondrial respiration and biogenesis. Furthermore, omipalisib downregulated several genes associated with serine, glycine, threonine, and glutathione metabolism, and decreased their protein and glutathione levels. In vivo experiments revealed that omipalisib significantly inhibited tumor growth and prolonged mouse survival without weight loss. Gedatolisib and dactolisib, another two PI3K/mTOR inhibitors, exerted similar effects without affecting mitochondria biogenesis. These results highlight the multifaceted anti-leukemic effect of omipalisib, revealing its potential as a novel therapeutic agent in AML treatment.
A novel compound heterozygous mutation in CFTR causing congenital bilateral absence of the vas deferens in a Chinese pedigree
Authors: Li Lingyi , Qu Xiaowei , Cui Chenchen , Feng Ke , Xia Yanqing , Wan Feng , Fang Yinghong , Zhang Cuilian , Guo Haibin 
Published: May 2023

Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed. In this study, whole-exome sequencing and co-segregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro functional assays were used to analyze the pathogenicity of a novel CFTR mutation. We identified a novel compound heterozygous mutation of CFTR comprising the known disease-causing variant c.1210-11T > G (also known as IVS9‐5T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring. Our study revealed that this novel compound heterozygous mutation is involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.
Identification of the shared gene signatures and biological mechanism in Atrial Fibrillation and Ischemic cardiomyopathy
Authors: Naman Tuersunjiang , Mahemuti Ailiman , Abudouwayiti Aihaidan , Sun Juan , Abuduhalike Refukaiti 
Published: May 2023

Abstract
Objective the relationship between Atrial fibrillation(AF) and Ischemic cardiomyopathy(ICM) has long been widely recognized, but no previous study explore the interaction mechanisms and method to confirm the casual relation ship of them. this study was aimed to investigate the shared gene signatures and molecular process between AF and ICM.Methods The Gene expression Omnibus(GEO) database was used to retrieve the data of AF and ICM used in this syudy. Weighted gene co-expression network analysis(WGCNA) was performed to discover associated genes with AF and ICM. Than intersecting the correlated genes by venn and filtered out the co-expression gene both AF and ICM, than performed GO enrichmen analysis and PPI network analysis, than usig the cytoscape software screened out the most significant hub genes correlated with AF and ICM, finally validated by other dataset.Result using WGCNA the most correlated module with AF and ICM respectively were identified. By venn the most correlated genes with AF and ICM filtered out 188 genes as the co-expressed genes with AF and ICM. than performed GO enrichmen analysis and PPI network analysis, than usig the cytoscape software screened out the three most significant hub genes(CHD1,MSH2, NIBPL) correlated with AF and ICM, finally validated using other dataset by ROC, all of thre genes has the good discrimination ability both in AF and ICM.Conclusion This work firstly revealed the three co-expression genes correlated with AF and ICM, maybe the expression level of these genes have diagnostic value of AF and ICM and have diagnostic value to confirm the cause of AF is ICM.