bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRcaller: a novel tool for precise and ultrafast tandem repeat variant genotyping in massively parallel sequencing reads
Authors: Wang Xuewen , Huang Meng , Budowle Bruce , Ge Jianye 
Published: July 2023

Calling tandem repeat (TR) variants from DNA sequences is of both theoretical and practical significance. Some bioinformatics tools have been developed for detecting or genotyping TRs. However, little study has been done to genotyping TR alleles from long-read sequencing data, and the accuracy of genotyping TR alleles from next-generation sequencing data still needs to be improved. Herein, a novel algorithm is described to retrieve TR regions from sequence alignment, and a software program TRcaller has been developed and integrated into a web portal to call TR alleles from both short- and long-read sequences, both whole genome and targeted sequences generated from multiple sequencing platforms. All TR alleles are genotyped as haplotypes and the robust alleles will be reported, even multiple alleles in a DNA mixture. TRcaller could provide substantially higher accuracy (&gt;99% in 289 human individuals) in detecting TR alleles with magnitudes faster (e.g., ∼2 s for 300x human sequence data) than the mainstream software tools. The web portal preselected 119 TR loci from forensics, genealogy, and disease related TR loci. TRcaller is validated to be scalable in various applications, such as DNA forensics and disease diagnosis, which can be expanded into other fields like breeding programs. Availability: TRcaller is available at https://www.trcaller.com/SignIn.aspx.
CD73 regulates zoledronate-induced lymphocyte infiltration in triple-negative breast cancer tumors and lung metastases
Authors: Petruk Nataliia , Siddiqui Arafat , Tadayon Sina , Määttä Jorma , Mattila Pieta K. , Jukkola Arja , Sandholm Jouko , Selander Katri S. 
Published: July 2023

IntroductionBisphosphonates (BPs) are bone-protecting osteoclast inhibitors, typically used in the treatment of osteoporosis and skeletal complications of malignancies. When given in the adjuvant setting, these drugs may also prevent relapses and prolong overall survival in early breast cancer (EBC), specifically among postmenopausal patients. Because of these findings, adjuvant nitrogen-containing BPs (N-BPs), such as zoledronate (ZOL), are now the standard of care for high-risk EBC patients, but there are no benefit-associated biomarkers, and the efficacy remains low. BPs have been demonstrated to possess anti-tumor activities, but the mechanisms by which they provide the beneficial effects in EBC are not known. MethodsWe used stably transfected 4T1 breast cancer cells together with suppression of CD73 (sh-CD73) or control cells (sh-NT). We compared ZOL effects on tumor growth and infiltrating lymphocytes (TILs) into tumors and lung metastases using two mouse models. B cell depletion was performed using anti-CD20 antibody.ResultsSh-CD73 4T1 cells were significantly more sensitive to the growth inhibitory effects of n-BPs in vitro. However, while ZOL-induced growth inhibition was similar between the tumor groups in vivo, ZOL enhanced B and T lymphocyte infiltration into the orthotopic tumors with down-regulated CD73. A similar trend was detected in lung metastases. ZOL-induced tumor growth inhibition was found to be augmented with B cell depletion in sh-NT tumors, but not in sh-CD73 tumors. As an internal control, ZOL effects on bone were similar in mice bearing both tumor groups.DiscussionTaken together, these results indicate that ZOL modifies TILs in breast cancer, both in primary tumors and metastases. Our results further demonstrate that B cells may counteract the growth inhibitory effects of ZOL. However, all ZOL-induced TIL effects may be influenced by immunomodulatory characteristics of the tumor.
Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza
Authors: Novak Tanya , Crawford Jeremy Chase , Hahn Georg , Hall Mark W. , Thair Simone A. , Newhams Margaret M. , Chou Janet , Mourani Peter M. , Tarquinio Keiko M. , Markovitz Barry , Loftis Laura L. , Weiss Scott L. , Higgerson Renee , Schwarz Adam J. , Pinto Neethi P. , Thomas Neal J. , Gedeit Rainer G. , Sanders Ronald C. , Mahapatra Sidharth , Coates Bria M. , Cvijanovich Natalie Z. , Ackerman Kate G. , Tellez David W. , McQuillen Patrick , Kurachek Stephen C. , Shein Steven L. , Lange Christoph , Thomas Paul G. , Randolph Adrienne G. 
Published: July 2023

BackgroundInfluenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.MethodsWe measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q&lt;0.05).ResultsComparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week.ConclusionThus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
Probiotics treatment ameliorated mycophenolic acid-induced colitis by enhancing intestinal barrier function and improving intestinal microbiota dysbiosis in mice
Authors: Zhang Pengpeng , Chen Jinwen , Ming Yingzi , Niu Ying 
Published: July 2023

BackgroundMycophenolic acid (MPA)-induced colitis was still a severe side effect and challenge faced by solid transplant recipients. We aimed to explore the function and mechanism of probiotics in the treatment of MPA-induced colitis.MethodsIn this study, 15 mice (C57BL/6) were randomly assigned into three groups: control (CNTL) group (n = 5), MPA group (n = 5) and the MPA + Probiotic group (n = 5). Bifid Triple Viable capsules, which were drugs for clinical use and consisted of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis, were used in Probiotic group. Body weight change, stool scores, colon histopathology and morphology were used to evaluate the disease severity. The intestinal mucosal barrier function was assessed by measuring the expression level of secretory immunoglobulin A (sIgA), Zonula occludens-1 (ZO-1) and Occludin. Finally, 16S rDNA sequencing and bioinformatics analysis were performed on mice feces to compare the different intestinal microbial composition and diversity among three groups.ResultsCompared with the CNTL group, the mice in MPA group showed a significantly decreased body weight, increased stool scores, shortened colon length and severe colon inflammation. However, probiotics treated MPA mice reversed the disease severity, indicating that probiotics ameliorated MPA-induced colitis in mice. Mechanistically, probiotics improved the intestinal barrier function by up-regulating the expression of sIgA, ZO-1 and Occludin. Moreover, MPA-induced colitis led to intestinal microbiota dysbiosis, including the change of Firmicutes/Bacteroidetes ratio, α- and β-diversity. But probiotic treated group showed mild change in these microbial features. Additionally, we found that Clostridiales was the most significantly different microbiota flora in MPA group.ConclusionProbiotics treatment ameliorated MPA-induced colitis by enhancing intestinal barrier function and improving intestinal microbiota dysbiosis. Clostridiales might be the dominant functional intestinal microflora and serve as the potential therapy target in MPA-induced colitis.
Investigating associations between social determinants, self-efficacy measurement of sleep apnea and CPAP adherence: the SEMSA study
Authors: Gentina Thibaut , Gentina Elodie , Douay Bernard , Micoulaud-Franchi Jean-Arthur , Pépin Jean-Louis , Bailly Sébastien 
Published: July 2023

Study objectivesThe prospective Self-Efficacy Measure for Sleep Apnea study (SEMSAS) is investigating thresholds for health literacy, self-efficacy and precariousness at obstructive sleep apnea (OSA) diagnosis to predict CPAP adherence. This paper describes the study protocol and presents baseline data from the ongoing study.MethodsEligible individuals had confirmed OSA and were referred to a homecare provider for continuous positive airway pressure (CPAP) therapy initiation. Data on patient characteristics and comorbidities were collected, along with baseline evaluations of self-efficacy [15-item Self-Efficacy Measure for Sleep Apnea tool (SEMSA-15)], precariousness [Deprivation in Primary Care Questionnaire (DipCareQ)], and health literacy (Health Literacy Questionnaire). CPAP adherence over 12 months of follow-up will be determined using remote monitoring of CPAP device data. The primary objective is to define an optimal SEMSA-15 score threshold to predict CPAP adherence at 3- and 12-month follow-up.ResultsEnrollment of 302 participants (71% male, median age 55 years, median body mass index 31.6 kg/m2) is complete. Low self-efficacy (SEMSA-15 score ≤ 2.78) was found in 93/302 participants (31%), and 38 (12.6%) reported precariousness (DipCareQ score &gt; 1); precariousness did not differ significantly between individuals with a SEMSA-15 score ≤ 2.78 versus &gt;2.78. Health literacy was generally good, but was significantly lower in individuals with versus without precariousness, and with low versus high self-efficacy.ConclusionSEMSAS is the first study using multidimensional baseline assessment of self-efficacy, health literacy and precariousness, plus other characteristics, to determine future adherence to CPAP, including CPAP adherence trajectories. Collection of follow-up data is underway.
The safety of colorectal cancer surgery during the COVID-19: a systematic review and meta-analysis
Authors: Wang Qiuxiang , Wu Ruike , Wang Juan , Li Yilin , Xiong Qin , Xie Fengjiao , Feng Peimin 
Published: July 2023

BackgroundThe ongoing coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented pressure on the healthcare systems. This study evaluated the safety of colorectal cancer (CRC) surgery during the COVID-19 pandemic.MethodsA systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO ID: CRD 42022327968). Relevant articles were systematically searched in the PubMed, Embase, Web of Science, and Cochrane databases. The postoperative complications, anastomotic leakage, postoperative mortality, 30-day readmission, tumor stage, total hospitalization, postoperative hospitalization, preoperative waiting, operation time, and hospitalization in the intensive care unit (ICU) were compared between the pre-pandemic and during the COVID-19 pandemic periods.ResultsAmong the identified 561 articles, 12 met the inclusion criteria. The data indicated that preoperative waiting time related to CRC surgery was higher during the COVID-19 pandemic (MD, 0.99; 95%CI, 0.71–1.28; p &lt; 0.00001). A similar trend was observed for the total operative time (MD, 25.07; 95%CI, 11.14–39.00; p =0.0004), and on T4 tumor stage during the pandemic (OR, 1.77; 95%CI, 1.22–2.59; p=0.003). However, there was no difference in the postoperative complications, postoperative 90-day mortality, anastomotic leakage, and 30-day readmission times between pre-COVID-19 pandemic and during the COVID-19 pandemic periods. Furthermore, there was no difference in the total hospitalization time, postoperative hospitalization time, and hospitalization time in ICU related to CRC surgery before and during the COVID-19 pandemic.ConclusionThe COVID-19 pandemic did not affect the safety of CRC surgery. The operation of CRC during the COVID-19 pandemic did not increase postoperative complications, postoperative 90-day mortality, anastomotic leakage, 30-day readmission, the total hospitalization time, postoperative hospitalization time, and postoperative ICU hospitalization time. However, the operation of CRC during COVID-19 pandemic increased T4 of tumor stage during the COVID-19 pandemic. Additionally, the preoperative waiting and operation times were longer during the COVID-19 pandemic. This provides a reference for making CRC surgical strategy in the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022327968.
Effect of four fluoroquinolones on the viability of bladder cancer cells in 2D and 3D cultures
Authors: Kloskowski Tomasz , Fekner Zuzanna , Szeliski Kamil , Paradowska Michelle , Balcerczyk Daria , Rasmus Marta , Dąbrowski Paweł , Kaźmierski Łukasz , Drewa Tomasz , Pokrywczyńska Marta 
Published: July 2023

IntroductionThe anticancer properties of fluoroquinolones and the high concentrations they achieve in urine may help in bladder cancer therapy. This study aimed to analyze the properties of 4 fluoroquinolones as potential candidates for supportive treatment of bladder cancer. MethodsComparative analyses were performed on the cytotoxic effects of norfloxacin, enrofloxacin, moxifloxacin, and ofloxacin on normal and cancer urothelial cell lines. In 2D culture, the cytotoxic properties of fluoroquinolones were evaluated using MTT assay, real-time cell growth analysis, fluorescence and light microscopy, flow cytometry, and molecular analysis. In 3D culture, the properties of fluoroquinolones were tested using luminescence assays and confocal microscopy.Results and DiscussionAll tested fluoroquinolones in 2D culture decreased the viability of both tested cell lines in a dose- and timedependent manner. Lower concentrations did not influence cell morphology and cytoskeletal organization. In higher concentrations, destruction of the actin cytoskeleton and shrinkage of the nucleus was visible. Flow cytometry analysis showed cell cycle inhibition of bladder cancer cell lines in the G2/M phase. This influence was minimal in the case of normal urothelium cells. In both tested cell lines, increases in the number of late apoptotic cells were observed. Molecular analysis showed variable expression of studied genes depending on the drug and concentration. In 3D culture, tested drugs were effective only in the highest tested concentrations which was accompanied by caspase 3/7 activation and cytoskeleton degradation. This effect was hardly visible in non-cancer cell lines. According to the data, norfloxacin and enrofloxacin had the most promising properties. These two fluoroquinolones exhibited the highest cytotoxic properties against both tested cell lines. In the case of norfloxacin, almost all calculated LC values for bladder cancer cell lines were achievable in the urine. Enrofloxacin and norfloxacin can be used to support chemotherapy in bladder cancer patients.
Heterogeneous temporal representation for diabetic blood glucose prediction
Authors: Huang Yaohui , Ni Zhikai , Lu Zhenkun , He Xinqi , Hu Jinbo , Li Boxuan , Ya Houguan , Shi Yunxian 
Published: July 2023

Background and aims: Blood glucose prediction (BGP) has increasingly been adopted for personalized monitoring of blood glucose levels in diabetic patients, providing valuable support for physicians in diagnosis and treatment planning. Despite the remarkable success achieved, applying BGP in multi-patient scenarios remains problematic, largely due to the inherent heterogeneity and uncertain nature of continuous glucose monitoring (CGM) data obtained from diverse patient profiles.Methodology: This study proposes the first graph-based Heterogeneous Temporal Representation (HETER) network for multi-patient Blood Glucose Prediction (BGP). Specifically, HETER employs a flexible subsequence repetition method (SSR) to align the heterogeneous input samples, in contrast to the traditional padding or truncation methods. Then, the relationships between multiple samples are constructed as a graph and learned by HETER to capture global temporal characteristics. Moreover, to address the limitations of conventional graph neural networks in capturing local temporal dependencies and providing linear representations, HETER incorporates both a temporally-enhanced mechanism and a linear residual fusion into its architecture.Results: Comprehensive experiments were conducted to validate the proposed method using real-world data from 112 patients in two hospitals, comparing it with five well-known baseline methods. The experimental results verify the robustness and accuracy of the proposed HETER, which achieves the maximal improvement of 31.42%, 27.18%, and 34.85% in terms of MAE, MAPE, and RMSE, respectively, over the second-best comparable method.Discussions: HETER integrates global and local temporal information from multi-patient samples to alleviate the impact of heterogeneity and uncertainty. This method can also be extended to other clinical tasks, thereby facilitating efficient and accurate capture of crucial pattern information in structured medical data.
Biopsychosocial factors of gaming disorder: a systematic review employing screening tools with well-defined psychometric properties
Authors: Chang Rose Seoyoung , Lee Minju , Im Jooyeon Jamie , Choi Kee-Hong , Kim Jueun , Chey Jeanyung , Shin Suk-Ho , Ahn Woo-Young 
Published: July 2023

Background and aimsConsidering the growing number of gamers worldwide and increasing public concerns regarding the negative consequences of problematic gaming, the aim of the present systematic review was to provide a comprehensive overview of gaming disorder (GD) by identifying empirical studies that investigate biological, psychological, and social factors of GD using screening tools with well-defined psychometric properties.Materials and methodsA systematic literature search was conducted through PsycINFO, PubMed, RISS, and KISS, and papers published up to January 2022 were included. Studies were screened based on the GD diagnostic tool usage, and only five scales with well-established psychometric properties were included. A total of 93 studies were included in the synthesis, and the results were classified into three groups based on biological, psychological, and social factors.ResultsBiological factors (n = 8) included reward, self-concept, brain structure, and functional connectivity. Psychological factors (n = 67) included psychiatric symptoms, psychological health, emotion regulation, personality traits, and other dimensions. Social factors (n = 29) included family, social interaction, culture, school, and social support.DiscussionWhen the excess amount of assessment tools with varying psychometric properties were controlled for, mixed results were observed with regards to impulsivity, social relations, and family-related factors, and some domains suffered from a lack of study results to confirm any relevant patterns.ConclusionMore longitudinal and neurobiological studies, consensus on a diagnostic tool with well-defined psychometric properties, and an in-depth understanding of gaming-related factors should be established to settle the debate regarding psychometric weaknesses of the current diagnostic system and for GD to gain greater legitimacy in the field of behavioral addiction.
Alleviatory Effects of Silicon and 24-Epibrassinolide in Modulation of Growth, Osmolytes, Metabolites, Antioxidant Defense System, and Gene Expression in Lead-Exposed Fenugreek (Trigonella foenum-graecum L.) Plants
Authors: Sharma Dhriti , Bhardwaj Savita , Raza Ali , Singh Rattandeep , Kapoor Dhriti , Sharma Neeta Raj , Prasad P. V. Vara 
Published: July 2023

Amplified concentrations of lead (Pb) in cultivable soils, being a major environmental concern, bring about malicious consequences for plant and human health. Trigonella foenum-graecum (fenugreek) is a multipurpose herb used as a spice, tonic, leafy vegetable, and therapeutic agent. Earlier works have revealed the inhibitory effects of Pb toxicity in Trigonella, affecting its growth and productivity. Therefore, the current experimental work was planned with the purpose of evaluating the effects of exogenously supplemented silicon (Si; 2 mM) and 24-epibrassinolide (24-EBL; 10−7 M) (in both individual and combined form) on growth attributes, osmolytes, metabolite measures, and antioxidant defense mechanisms of Trigonella foenum-graecum plants in response to three discrete concentrations of Pb stress (0.5, 0.7, and 0.9 mM). The results revealed that Pb stress affected morphological parameters of fenugreek plants via the genesis of reactive oxygen species (ROS), as indicated by higher measures of oxidative damage indicators like malondialdehyde (MDA) and hydrogen peroxide (H2O2). Spraying foliage with Si together with a pretreatment of 24-EBL alone as well as in a combined form yielded better outcomes in terms of growth parameters in the Pb-stressed plants. Pb toxicity decreased osmolytes, proteins, and metabolites. Components of the antioxidative defense system, i.e., enzymes [ascorbate peroxidase (APX), guaiacol peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), together with non-enzymes [ascorbic acid (AsA) and glutathione (GSH), were downregulated when subjected to Pb toxicity. Out of all, Pb III (0.9 mM) had a more adverse impact on various parameters in fenugreek compared to Pb I (0.5 mM) and Pb II (0.7 mM). However, external supplementation with Si and 24-EBL (individually and in combination) ameliorated the Pb-mediated oxidative stress in fenugreek plants by improving the content of different osmolytes and metabolites while upregulating the functioning of the antioxidative defense system. Downregulation in the expression of SOD and CAT genes was found in Pb-stressed plants, while their expression was upregulated by Si and 24-EBL both individually and in combination. The experimental study revealed that the combined application of Si and 24-EBL was significantly better at abating the Pb metal stress in fenugreek plants when compared with their individual applications.