bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health related Quality of Life over time in German sarcoma patients. An analysis of associated factors - results of the PROSa study
Authors: Eichler Martin , Hentschel Leopold , Singer Susanne , Hornemann Beate , Richter Stephan , Hofbauer Christine , Hohenberger Peter , Kasper Bernd , Andreou Dimosthenis , Pink Daniel , Jakob Jens , Grützmann Robert , Fung Stephen , Wardelmann Eva , Arndt Karin , Hermes-Moll Kerstin , Schoffer Olaf , Fried Marius , Jambor Helena K. , Weitz Jürgen , Schaser Klaus-Dieter , Bornhäuser Martin , Schmitt Jochen , Schuler Markus K. 
Published: August 2023

IntroductionSarcomas are rare cancers and very heterogeneous in their location, histological subtype, and treatment. Health-Related Quality of Life (HRQoL) of sarcoma patients has rarely been investigated in longitudinal studies.MethodsHere, we assessed adult sarcoma patients and survivors between September 2017 and February 2020, and followed-up for one year in 39 study centers in Germany. Follow-up time points were 6 (t1) and 12 months (t2) after inclusion. We used a standardized, validated questionnaire (the European Organisation for Research and Treatment of Cancer Quality of Life Core Instrument (EORTC QLQ-C30) and explored predictors of HRQoL in two populations (all patients (Analysis 1), patients in ongoing complete remission (Analysis 2)) using generalized linear mixed models.ResultsIn total we included up to 1111 patients at baseline (915 at t1, and 847 at t2), thereof 387 participants were in complete remission at baseline (334 at t1, and 200 at t2). When analyzing all patients, HRQoL differed with regard to tumor locations: patients with sarcoma in lower extremities reported lower HRQoL values than patients with sarcomas in the upper extremities. Treatment which included radiotherapy and/or systemic therapy was associated with lower HRQoL. For patients in complete remission, smoking was associated with worse HRQoL-outcomes. In both analyses, bone sarcomas were associated with the worst HRQoL values. Being female, in the age group 55-&lt;65 years, having lower socioeconomic status, and comorbidities were all associated with a lower HRQoL, in both analyses.DiscussionHRQoL increased partially over time since treatment and with sporting activities. HRQoL improved with time since treatment, although not in all domains, and was associated with lifestyle and socioeconomic factors. Bone sarcomas were the most affected subgroup. Methods to preserve and improve HRQoL should be developed for sarcoma patients.
A possible genetic association between obesity and colon cancer in females
Authors: Zhang Xiao-li , Zhang Xin-feng , Fang Yuan , Li Meng-li , Shu Ruo , Gong Yi , Luo Hua-you , Tian Yan 
Published: August 2023

ObjectThere is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms.MethodsGSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions.ResultsBetween the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software’s MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p.ConclusionOur research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.
Association between female circulating heavy metal concentration and abortion: a systematic review and meta-analysis
Authors: Ren Meiqi , Wang Liantong , Wen Liqin , Chen Jinghua , Quan Song , Shi Xiao 
Published: August 2023

ObjectiveThis study aimed to evaluate the association between blood heavy metal (zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd)) concentrations and spontaneous abortion (SA) and recurrent pregnancy loss (RPL) and explore the possible endocrine dysfunction associated with it.MethodsA literature search was performed in the PubMed, Embase, Cochrane Library, and Web of Science databases up to April 2023. The overall effects were expressed as the standard mean difference (SMD). Subgroup analysis was performed according to the type of abortion (SA or RPL). Stata 16.0 was utilized for data analysis.ResultsBased on the integrated findings, abortion women showed significantly lower Zn (SMD = −1.05, 95% CI: −1.74 to −0.36, p = 0.003) and Cu concentrations (SMD = −1.42, 95% CI: −1.97 to −0.87, p &lt;0.001) and higher Pb (SMD = 1.47, 95% CI: 0.89–2.05, p &lt;0.001) and Cd concentrations (SMD = 1.15, 95% CI: 0.45–1.85, p = 0.001) than normal pregnant women. Subgroup analysis showed that Zn and Cu deficiency and Cd and Pb exposure were significantly (p &lt;0.05) associated with RPL, whereas Cu deficiency and Cd and Pb exposure were significantly (p &lt;0.05) associated with SA.ConclusionZn and Cu deficiencies and Pb and Cd exposure were associated with abortion. Endocrine dysfunction, such as insulin resistance, vitamin D insufficiency, and abnormal thyroid and sex hormone concentrations, is thought to be involved in heavy metal-related abortion.
Identification and precision therapy for three maturity-onset diabetes of the young (MODY) families caused by mutations in the HNF4A gene
Authors: Zhang Juan , Jiang Yanyan , Li Jianhua , Zou Haiyin , Yin Li , Yang Yang , Yang Lei 
Published: August 2023

BackgroundHeterozygous pathogenic variants in HNF4A gene cause maturity-onset diabetes of the young type 1 (MODY1). The mutation carriers for MODY1 have been reported to be relatively rare, in contrast to the most frequently reported forms of MODY2 and MODY3.MethodsWhole exome sequencing (WES) and Sanger sequencing were performed for genetic analysis of MODY pedigrees. Tertiary structures of the mutated proteins were predicted using PyMOL software.ResultsThree heterozygous missense mutations in the HNF4A gene, I159T, W179C, and D260N, were identified in the probands of three unrelated MODY families using WES, one of which (W179C) was novel. Cascade genetic screening revealed that the mutations co-segregated with hyperglycemic phenotypes in their families. The molecular diagnosis of MODY1 has partly transformed its management in clinical practice and improved glycemic control. The proband in family A successfully converted to sulfonylureas and achieved good glycemic control. Proband B responded well to metformin combined with diet therapy because of his higher body mass index (BMI). The proband in family C, with paternal-derived mutations, had markedly defective pancreatic β-cell function due to the superposition effect of T2DM susceptibility genes from the maternal grandfather, and he is currently treated with insulin. In silico analysis using PyMOL showed that the I159T and D260N mutations altered polar interactions with the surrounding residues, and W179C resulted in a smaller side chain.DiscussionWe identified three heterozygous missense mutations of HNF4A from Chinese MODY families. Structural alterations in these mutations may lead to defects in protein function, further contributing to the hyperglycemic phenotype of mutation carriers.
Flow field analysis and noise characteristics of an automotive cooling fan at different speeds
Authors: Ren Kai , Zhang Shuguang , Zhang Huanping , Deng Changming , Sun Haiyang 
Published: August 2023

As the core component of the automotive air conditioning cooling system, the automotive cooling fan directly affects the cooling performance of the entire system. Therefore, it is necessary to study the flow field and noise of the automotive cooling fan. This study focuses on the analysis off low field characteristics and noise generation in an automotive air conditioning systems, specifically related to an automobile cooling fan at different speeds. The flow field properties of the fan are examined through the distribution off low line trajectory, pressure distribution on the blade surface, and velocity distribution characteristics at various speeds. The analysis reveals that the maximum air velocity occurs at the point where the fan blade meets the wind guard, while the maximum pressure is observed at this point and at the edge where the fan blade cuts through the cavity. Furthermore, a monitoring point located 1 m in front of the fan is selected to study the average value of fan pneumatic noise pulsation and generate a noise cloud map, aiming to identify the main noise source of the fan. To better understand the noise distribution and variation at different speeds, various noise metrics are utilized, including noise Sound Pressure Level (SPL) spectrum, 1/3-octave SPL spectrum, and 1/3-octave A-weighted SPL spectrum. The noise characterization results indicate that the primary areas of fan noise generation are located at the tip of the leaf margin of the forward swept wing. This research provides valuable insights for the improvement and optimization of the cooling fan design, as well as subsequent noise reduction efforts.
Interference effect of configuration parameters of vertical sand-obstacles on near-surface sand transport
Authors: Luo Xiangying , Li Jinrong , Tang Guodong , Li Yingkun , Wang Ru , Han Zhaoen , Feng Jiaxin , Ren Tingjie 
Published: August 2023

This study investigates the impacts of height (H) and porosity (P) on the structural properties of wind-driven sand flux in vertical sunflower straw sand-obstacles. We conducted an experiment on sand transport within barriers of various configurations within a 1 m proximity to the surface. In tandem, we monitored wind velocity and direction within the barriers, analyzed total sand transport rate, sand-blocking effects, and cumulative sediment transport rate heights for various parameter configurations, and devised a best sand transport flux model for use within the sand-obstacle. The efficacy of vertical sunflower stalk sand-obstacles in mitigating sand movement has been demonstrated to fall within the range of 37.26%–92.31%. This study reveals a significant correlation between barrier height and porosity in achieving this effect (p &lt; 0.05). High and densely configured sand-obstacles lead to an accumulation of intercepted sand material in front of the front row of the sand-obstacle. In contrast, low and sparsely arranged sand-obstacles exhibit a delayed state of sand material accumulation. Furthermore, with an increase in the height of the obstacle and a decrease in porosity, there is a diminishing trend in the sand transport rate within the obstacle. Concurrently, the height of sand transport within the barrier exhibits an upward trend. A three-parameter exponential function has been employed to more precisely simulate the wind-sand flow structure characteristics within a 1-m height range of the barrier. These research findings contribute to an enhanced understanding of the impact of different vertical sand-obstacle configurations on near-surface wind-driven sand transport patterns in active desert areas. Moreover, they furnish both theoretical underpinnings and practical guidance for the scientific configuration of vertical sand-obstacles.
Optimal fertilizer rates towards the improvement of nitrogen use efficiency and reduction of nitrogen export in paddy rice-wheat intensive farming
Authors: Legesse Nebiyou , Sheng Wu , Yao Wang , Manqin Gan , Peishi Liu , Yu Huang , Hongjun Xu , HongXiang Hu , Youhua Ma 
Published: August 2023

Introduction: Fertilizer application above plant nitrogen (N) requirements, leading to N use inefficiency, has become the primary source of N surplus, posing nonpoint pollution threats. Chao Lake has received N loadings, primarily from the agroecosystem that surrounds it. Based on 10 years of field monitoring and experiment, this study used optimum fertilizer rates (30% N reduction) to evaluate nitrogen use efficiency (NUE) and N export in the Chao Lake watershed of paddy rice-wheat rotational farming.Methods: Five treatments were tested, namely, the Blank Treatment (CK), Conventional Fertilization Treatment (CFT), High Fertilization Treatment (HFT), Reduced Fertilization Treatment (CFT), Reduced Fertilization Treatment plus Straw addition (RFTS). The parameters employed to measure NUE were 1) by calculating NUE indicators; Agronomic efficiency (kg kg-1), recovery efficiency (%), and partial factor productivity (kg kg-1) 2) using the European Union NUE framework as a comparison tool. N export was measured using N export parameters, namely, nitrogen loading (kg ha-1yr-1), nitrogen runoff loss ratio (%), and net nitrogen runoff loss ratio (%).Results and discussion: Results revealed that optimum N fertilizer input levels maintained high crop and biomass yields. The empirical model of y = y0 + a * exp (−0.5 * (x-x0)/b2) explains the relationships between input N fertilizer and corresponding yield returns. Low yield responses to increased N input beyond certain limits were observed, which may lead to N accumulations. N export was much lower from the reduced fertilization treatments than other treatments. N export increased in 10 years for both paddy rice and wheat seasons. Runoff volume influenced N export more than any other environmental factor studied.Conclusion: Overall, optimal fertilizer levels produced high NUE, maintained high economic yield, and produced lesser N exports; NUE was in the order of reduced &gt; high &gt; conventional fertilization treatments, while it decreased in 10 years (2008–2018) across all treatments. Such strategies that further reduce fertilizer levels by accounting for excess supplies are vital for consolidating effective N control measures.
A meta-analysis of microarray datasets to identify biological regulatory networks in Alzheimer’s disease
Authors: Hashemi Kimia Sadat , Aliabadi Mohadese Koohi , Mehrara Arian , Talebi Elham , Hemmati Ali Akbar , Rezaeiye Radin Dabbagh , Ghanbary Mohammad Javad , Motealleh Maryam , Dayeri Behnaz , Alashti Shayan Khalili 
Published: August 2023

Background: Alzheimer’s Disease (AD) is an age-related progressive neurodegenerative disorder characterized by mental deterioration, memory deficit, and multiple cognitive abnormalities, with an overall prevalence of ∼2% among industrialized countries. Although a proper diagnosis is not yet available, identification of miRNAs and mRNAs could offer valuable insights into the molecular pathways underlying AD’s prognosis.Method: This study aims to utilize microarray bioinformatic analysis to identify potential biomarkers of AD, by analyzing six microarray datasets (GSE4757, GSE5281, GSE16759, GSE28146, GSE12685, and GSE1297) of AD patients, and control groups. Furthermore, this study conducted gene ontology, pathways analysis, and protein-protein interaction network to reveal major pathways linked to probable biological events. The datasets were meta-analyzed using bioinformatics tools, to identify significant differentially expressed genes (DEGs) and hub genes and their targeted miRNAs’.Results: According to the findings, CXCR4, TGFB1, ITGB1, MYH11, and SELE genes were identified as hub genes in this study. The analysis of DEGs using GO (gene ontology) revealed that these genes were significantly enriched in actin cytoskeleton regulation, ECM-receptor interaction, and hypertrophic cardiomyopathy. Eventually, hsa-mir-122-5p, hsa-mir-106a-5p, hsa-mir-27a-3p, hsa-mir16-5p, hsa-mir-145-5p, hsa-mir-12-5p, hsa-mir-128-3p, hsa-mir 3200-3p, hsa-mir-103a-3p, and hsa-mir-9-3p exhibited significant interactions with most of the hub genes.Conclusion: Overall, these genes can be considered as pivotal biomarkers for diagnosing the pathogenesis and molecular functions of AD.
Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin
Authors: Jung Young Hoon , Kwak Jay Jiyong , Joo Kwangsic , Lee Hyuk Jun , Park Kyu Hyung , Kim Min Seok , Lee Eun Kyoung , Byeon Suk Ho , Lee Christopher Seungkyu , Han Jinu , Lee Junwon , Yoon Chang Ki , Woo Se Joon 
Published: August 2023

Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP).Design: We conducted a retrospective, multicenter, observational cohort study.Participants: We reviewed the medical records of 42 patients with RHO-associated RP of 36 families who visited 4 hospitals in Korea.Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of &lt;10° or a best-corrected visual acuity of the better-seeing eye &lt;20/40 indicated the progression to late-stage RP.Results: The mean age at which symptoms first appeared was 26.3 ± 17.9 years (range: 8–78 years), and the mean follow-up period was 80.9 ± 68.7 months (range: 6–268 months). At the last follow-up visit, the generalized RP group showed a significantly higher rate of visual field impairment progression to late-stage RP than that of the sector RP group (22 of 35 [62.9%] vs. 0 of 7 [0.0%], p = 0.003). No cases in the sector RP group progressed to generalized RP. Best-corrected visual acuity deterioration to late-stage RP was observed only in the generalized RP group (13 of 35 patients; 37.1%), whereas no deterioration was observed in the sector RP group. We identified 16 known and three novel RHO mutations, including two missense mutations (p.T108P and p.G121R) and one deletion mutation (p.P347_A348del). The pathogenic variants were most frequently detected in exon 1 (14 of 36 [38.9%]). The most common pathogenic variants were p.P347L and T17M (5 of 36 [13.9%] families). Among 42 patients of 36 families, 35 patients of 29 families (80.6%) presented with the generalized RP phenotype, and seven patients of seven families (19.4%) presented with the sector RP phenotype. Three variants (p.T17M, p.G101E, and p.E181K) presented with both the generalized and sector RP phenotypes.Conclusion: This multicenter cohort study provided information on the clinical and genetic features of RHO-associated RP in Koreans. It is clinically important to expand the genetic spectrum and understand genotype-phenotype correlations to ultimately facilitate the development of gene therapy.
Identification of human genetic variants modulating the course of COVID-19 infection with importance in other viral infections
Authors: Salihefendić Lana , Čeko Ivana , Bešić Larisa , Mulahuseinović Naida , Durgut Selma , Pećar Dino , Prnjavorac Lejla , Kandić Enis , Meseldžić Neven , Bego Tamer , Prnjavorac Besim , Marjanović Damir , Konjhodžić Rijad , Ašić Adna 
Published: August 2023

Introduction: COVID-19 has been a major focus of scientific research since early 2020. Due to its societal, economic, and clinical impact worldwide, research efforts aimed, among other questions, to address the effect of host genetics in susceptibility and severity of COVID-19.Methods: We, therefore, performed next-generation sequencing of coding and regulatory regions of 16 human genes, involved in maintenance of the immune system or encoding receptors for viral entry into the host cells, in a subset of 60 COVID-19 patients from the General Hospital Tešanj, Bosnia and Herzegovina, classified into three groups of clinical conditions of different severity (“mild,” “moderate,” and “severe”).Results: We confirmed that the male sex and older age are risk factors for severe clinical picture and identified 13 variants on seven genes (CD55, IL1B, IL4, IRF7, DDX58, TMPRSS2, and ACE2) with potential functional significance, either as genetic markers of modulated susceptibility to SARS-CoV-2 infection or modifiers of the infection severity. Our results include variants reported for the first time as potentially associated with COVID-19, but further research and larger patient cohorts are required to confirm their effect.Discussion: Such studies, focused on candidate genes and/or variants, have a potential to answer the questions regarding the effect of human genetic makeup on the expected infection outcome. In addition, loci we identified here were previously reported to have clinical significance in other diseases and viral infections, thus confirming a general, broader significance of COVID-19-related research results following the end of the pandemic period.
Construction and validation of a signature for T cell-positive regulators related to tumor microenvironment and heterogeneity of gastric cancer
Authors: Guo Yangyang , Zhang Yingjue , Cen Kenan , Dai Ying , Mai Yifeng , Hong Kai 
Published: August 2023

BackgroundPositive regulators of T cell function play a vital role in the proliferation and differentiation of T cells. However, their functions in gastric cancer have not been explored so far.MethodsThe TCGA-STAD dataset was utilized to perform consensus clustering in order to identify subtypes related to T cell-positive regulators. The prognostic differentially expressed genes of these subtypes were identified using the least absolute shrinkage and selection operator (LASSO) regression analysis. To validate the robustness of the identified signature, verification analyses were conducted across the TCGA-train, TCGA-test, and GEO datasets. Additionally, a nomogram was constructed to enhance the clinical efficacy of this predictive tool. Transwell migration, colony formation, and T cell co-culture assays were used to confirm the function of the signature gene in gastric cancer and its influence on T cell activation.ResultsTwo distinct clusters of gastric cancer, related to T cell-positive regulation, were discovered through the analysis of gene expression. These clusters exhibited notable disparities in terms of survival rates (P = 0.028), immune cell infiltration (P&lt; 0.05), and response to immunotherapy (P&lt; 0.05). Furthermore, a 14-gene signature was developed to classify gastric cancer into low- and high-risk groups, revealing significant differences in survival rates, tumor microenvironment, tumor mutation burden, and drug sensitivity (P&lt; 0.05). Lastly, a comprehensive nomogram model was constructed, incorporating risk factors and various clinical characteristics, to provide an optimal predictive tool. Additionally, an assessment was conducted on the purported molecular functionalities of low- and high-risk gastric cancers. Suppression of DNAAF3 has been observed to diminish the migratory and proliferative capabilities of gastric cancer, as well as attenuate the activation of T cells induced by gastric cancer within the tumor microenvironment.ConclusionWe identified an ideal prognostic signature based on the positive regulators of T cell function in this study.