bluuebunny/crossref_metadata_2025_split huggingface dataset:
Older veterans associated with reduced risk of cancer: Retrospective nationwide matched cohort study in Taiwan
Authors: Pan Li-Fei , Chang Renin , Hsu Chung Y. , Tsui Kuan-Hao 
Published: January 2023

ImportanceIt remains unknown whether Taiwanese veterans have a lower risk of subsequent cancer compared with non-veterans.ObjectiveTo examine whether veterans are associated with reduced cancer risk.MethodsFrom January 2004 to December 2017, this study included 957 veterans and 957 civilians who were propensity score (PS) matched by years of birth, sex, residence, index year, days in the hospital, frequency of outpatient visits, and relevant comorbidities at baseline. Multivariate Cox proportional hazards regression analysis was applied to compare the risks of cancer, overall and by subgroup, and mortality. All the participants were cancer free at the baseline.ExposuresVeterans retrieved from Taiwan National Health Insurance Research Database (NHIRD).Main outcomeCancer extracted from the Registry for Catastrophic Illness Patients Database (RCIPD).ResultsOverall, 1,914 participants were included, and 957 veterans with a mean (SD) age of 75.9 (6.79) years and 946 men (98.9%). The mean follow-up was about 10.5 (±4.51) years. Cancer was recorded in 6.68% (N = 64) and 12.12% (N = 116) of veterans and non-veterans, respectively. Veterans were associated with decreased risk [adjusted hazard ratio (aHR), 0.57; 95% CI: 0.41–0.78; P &lt; 0.001] of cancer compared with civilians after controlling for age, sex, urbanization, hypertension, diabetes, hyperlipidemia, cardiovascular event, COPD, asthma, chronic liver disease, alcohol-related illness, and Parkinson’s disease. Cancer subgroup analyses verified this finding (HRs &lt;1.0). The decreased incidence rate was predominantly for liver cancer (aHR, 0.18; 95% CI: 0.05–0.72; P &lt; 0.05).ConclusionTaiwanese older veterans are associated with reduced overall cancer risk than individuals without veteran status.
Severe hypoglycemia in patients with liver cirrhosis and type 2 diabetes
Authors: Yen Fu-Shun , Hou Ming-Chih , Liu Jia-Sin , Hsu Chih-Cheng , Hwu Chii-Min 
Published: January 2023

IntroductionAdvanced liver disease with massive liver damage may affect the metabolism of hypoglycemic agents and increase the risk of hypoglycemia. We conduct this research to compare the risk of severe hypoglycemia between patients with type 2 diabetes, with and without compensated liver cirrhosis.MethodsFrom Taiwan’s National Health Insurance Research Database, we identified persons with type 2 diabetes with cirrhosis (n = 18,209) and without cirrhosis (n = 538,510) from January 1, 2000, to December 31, 2010. Cox proportional hazards models were adopted to assess risks of all-cause mortality and severe hypoglycemia.ResultsThe mean follow-up period of this study was 3.7 years. The incidence rates of death during follow-up were 26.54 and 2.75 per 1,000 patient-years [aHR 7.63 (6.70–8.70)] for patients with cirrhosis and without cirrhosis, respectively. The incidence rates of severe hypoglycemia during follow-up were 0.53 and 0.14 per 1,000 patient-years [aHR 2.74 (1.52–4.92)] for patients with and without cirrhosis, respectively. The subgroup analysis of hypoglycemia risks in patients with and without cirrhosis disclosed no significant interaction for variables such as age, sex, chronic kidney disease, sulfonylurea use, number of oral antidiabetic drugs, insulin, b-blocker, and fibrate.ConclusionThis cohort study demonstrated that patients with type 2 diabetes and compensated cirrhosis showed a higher risk of mortality and severe hypoglycemia than those without liver cirrhosis.
Spread of the mcr-1 colistin-resistance gene in Escherichia coli through plasmid transmission and chromosomal transposition in French goats
Authors: Treilles Michaël , Châtre Pierre , Drapeau Antoine , Madec Jean-Yves , Haenni Marisa 
Published: January 2023

IntroductionColistin-resistance widely disseminated in food-producing animals due to decades of colistin use to treat diarrhea. The plasmid-borne mcr-1 gene has been extensively reported from bovine, swine and chicken worldwide, but smaller productions such as the goat farming sector were much less surveyed.MethodsWe looked for colistin-resistant isolates presenting plasmid-borne genes of the mcr family in both breeding (n=80) and fattening farms (n=5). Localization of the mcr-1 gene was performed using Southern blot analysis coupled to short-read and long-read sequencing.ResultsOnly the mcr-1 gene was identified in 10% (8/80) of the breeding farms and four over the five fattening farms. In total, 4.2% (65/1561) of the animals tested in breeding farms and 60.0% (84/140) of those tested in fattening farms presented a mcr-1-positive E. coli. The mcr-1 gene was located either on the chromosome (32.2%) or on IncX4 (38.9%) and IncHI2 (26.8%) plasmids. As expected, both clonal expansion and plasmidic transfers were observed in farms where the mcr-1 gene was carried by plasmids. Tn6330 transposition was observed in the chromosome of diverse E. coli sequence types within the same farm.DiscussionOur results show that the mcr-1 gene is circulating in goat production and is located either on plasmids or on the chromosome. Evidence of Tn6330 transposition highlighted the fact that chromosomal insertion does not impair the transmission capability of the mcr-1 gene. Only strict hygiene and biosecurity procedures in breeding farms, as well as a prudent use of antibiotics in fattening farms, can avoid such complex contamination pathways.
High rates of antibodies against Toscana and Sicilian phleboviruses in common quail Coturnix coturnix birds
Authors: Ayhan Nazli , Rodríguez-Teijeiro José Domingo , López-Roig Marc , Vinyoles Dolors , Ferreres Josep Anton , Monastiri Abir , Charrel Remi , Serra-Cobo Jordi 
Published: January 2023

IntroductionBirds are involved natural cycle of a number of vector-borne viruses in both rural and urban areas. Toscana (TOSV) and Sicilian (SFSV) phleboviruses are sandfly-borne viruses in the genus Phlebovirus that can cause diseases in human. However, there is limited information on the role of the birds in sandfly-borne phleboviruses natural cycle and reservoirs ofthese viruses remain unknown.MethodsIn this study, we analyzed Common Quail (Coturnix coturnix) sera from Spain to identify the seroprevalence of these two phleboviruses. We tested respectively, 106 and 110 quail serum against TOSV and SFSV from 2018, 2019, and 2021 from two locations in northern Spain with using virus neutralization test.ResultsWe identified high neutralizing antibody rates for SFSV (45.45%) and TOSV (42.45%) with yearly fluctuation.DiscussionThis is the first identification of SFSV and TOSV neutralizing antibodies in wild birds. High seroprevalence rates of TOSV and SFSV in quail birds raises the question whether birds have a role as amplifying hosts in the natural cycle of phleboviruses.
The role of cell membrane-coated nanoparticles as a novel treatment approach in glioblastoma
Authors: Allami Pantea , Heidari Arash , Rezaei Nima 
Published: January 2023

Glioblastoma multiform (GBM) is the most prevalent and deadliest primary brain malignancy in adults, whose median survival rate does not exceed 15 months after diagnosis. The conventional treatment of GBM, including maximal safe surgery followed by chemotherapy and radiotherapy, usually cannot lead to notable improvements in the disease prognosis and the tumor always recurs. Many GBM characteristics make its treatment challenging. The most important ones are the impermeability of the blood-brain barrier (BBB), preventing chemotherapeutic drugs from reaching in adequate amounts to the tumor site, intratumoral heterogeneity, and roles of glioblastoma stem cells (GSCs). To overcome these barriers, the recently-developed drug-carrying approach using nanoparticles (NPs) may play a significant role. NPs are tiny particles, usually less than 100 nm showing various diagnostic and therapeutic medical applications. In this regard, cell membrane (CM)-coated NPs demonstrated several promising effects in GBM in pre-clinical studies. They benefit from fewer adverse effects due to their specific targeting of tumor cells, biocompatibility because of their CM surfaces, prolonged half-life, easy penetrating of the BBB, and escaping from the immune reaction, making them an attractive option for GBM treatment. To date, CM-coated NPs have been applied to enhance the effectiveness of major therapeutic approaches in GBM treatment, including chemotherapy, immunotherapy, gene therapy, and photo-based therapies. Despite the promising results in pre-clinical studies regarding the effectiveness of CM-coated NPs in GBM, significant barriers like high expenses, complex preparation processes, and unknown long-term effects still hinder its mass production for the clinic. In this regard, the current study aims to provide an overview of different characteristics of CM-coated NPs and comprehensively investigate their application as a novel treatment approach in GBM.
Effects of medication intake on the risk of hemorrhage in patients with sporadic cerebral cavernous malformations
Authors: Chen Bixia , Lahl Kirstin , Saban Dino , Lenkeit Annika , Rauschenbach Laurèl , Santos Alejandro N. , Li Yan , Schmidt Boerge , Zhu Yuan , Jabbarli Ramazan , Wrede Karsten H. , Kleinschnitz Christoph , Sure Ulrich , Dammann Philipp 
Published: January 2023

ObjectiveRecurrent intracerebral hemorrhage (ICH) poses a high risk for patients with cerebral cavernous malformations (CCMs). This study aimed to assess the influence of medication intake on hemorrhage risk in sporadic CCMs.MethodsFrom a database of 1,409 consecutive patients with CCM (2003–2021), subjects with sporadic CCMs and complete magnetic resonance imaging data were included. We evaluated the presence of ICH as a mode of presentation, the occurrence of ICH during follow-up, and medication intake, including beta blockers, statins, antithrombotic therapy, and thyroid hormones. The impact of medication intake on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. The longitudinal cumulative 5-year risk for (re-)hemorrhage was analyzed using the Kaplan–Meier curves and the Cox regression analysis.ResultsA total of 1116 patients with CCM were included. Logistic regression analysis showed a significant correlation (OR: 0.520, 95% CI: 0.284–0.951, p = 0.034) between antithrombotic therapy and ICH as a mode of presentation. Cox regression analysis revealed no significant correlation between medication intake and occurrence of (re-)hemorrhage (hazard ratios: betablockers 1.270 [95% CI: 0.703–2.293], statins 0.543 [95% CI: 0.194–1.526], antithrombotic therapy 0.507 [95% CI: 0.182–1.410], and thyroid hormones 0.834 [95% CI: 0.378–1.839]).ConclusionIn this observational study, antithrombotic treatment was associated with the tendency to a lower rate of ICH as a mode of presentation in a large cohort of patients with sporadic CCM. Intake of beta blockers, statins, and thyroid hormones had no effect on hemorrhage as a mode of presentation. During the 5-year follow-up period, none of the drugs affected the further risk of (re-)hemorrhage.
Case Report: Abnormalities of sperm motility and morphology in a patient with Leber hereditary optic neuropathy: Improvement after idebenone therapy
Authors: Orssaud Christophe , Barraud Lange Virginie , Wolf Jean Philippe , LeFoll Nathalie , Soufir Jean Claude 
Published: January 2023

CaseWe report the sperm characteristics of a male patient who developed, when he was 18 years old, a Leber hereditary optic neuropathy, a hereditary optic neuropathy due to mtDNA mutation as well as variants in the nuclear DNA. At the age of 30 years-old, he complained of infertility lasting for 2 years. Semen analyses showed low motility spermatozoa and a high percentage of morphological or ultrastructural abnormalities. Levels of epididymal markers were strongly atypical. Idebenone was prescribed as treatment of his Leber hereditary optic neuropathy in order to improve his visual acuity. After 5 months of this treatment, motility of spermatozoa increased, and their vitality improved. A natural conception occurred.OutcomeThis case is the first description of an anomaly of spermatozoas and of the epididymis epithelium in a patient with Leber hereditary optic neuropathy. It draws attention to sperm pathologies in patients with mitochondrial disorders. The role of the mtDNA mutations must be suspected since it plays an important role in the development and motility of spermatozoa. In addition, idebenone can by-pass the complex I and transfer electrons to complex III. It has been suspected to have a favorable effect on spermatogenesis.ConclusionThis case confirms the possibility of sperm dysfunction in Leber hereditary optic neuropathy and the interest of idebenone as a treatment for infertility due to mtDNA mutations in human.
Large mismatch profile predicts rapidly progressing brain edema in acute anterior circulation large vessel occlusion patients undergoing endovascular thrombectomy
Authors: Shao Yanqi , Chen Xinyi , Wang Huiyuan , Shang Yafei , Xu Jie , Zhang Jinshi , Wang Peng , Geng Yu 
Published: January 2023

BackgroundBrain edema is a severe complication in patients with large vessel occlusion (LVO) that can reduce the effectiveness of endovascular therapy (EVT). This study aimed to investigate the association of the perfusion profile at baseline computed tomography (CT) perfusion with rapidly progressing brain edema (RPBE) after EVT in patients with acute anterior LVO.MethodsWe retrospectively reviewed consecutive data collected from 149 patients with anterior LVO who underwent EVT at our center. Brain edema was measured by the swelling score (0–6 score), and RPBE was defined as the swelling score increased by more than 2 scores within 24 h after EVT. We investigated the effect of RPBE on poor outcomes [National Institute of Health Stroke Scale (NIHSS) score and modified Rankin scale (mRS) score at discharge, the occurrence of hemorrhagic transformation, and mortality rate in the hospital] using the Mann–Whitney U-test and chi-square test. A multivariate logistic regression model was used to assess the relationship between perfusion imaging parameters and RPBE occurrence.ResultsOverall, 39 patients (26.2%) experienced RPBE after EVT. At discharge, RPBE was associated with higher NIHSS scores (Z = 3.52, 95% CI 2.0–12.0, P &lt; 0.001) and higher mRS scores (Z = 3.67, 95% CI 0.0–1.0, P &lt; 0.001) including the more frequent occurrence of hemorrhagic transformation (χ2 = 22.17, 95% CI 0.29–0.59, P &lt; 0.001) and higher mortality rates in hospital (χ2 = 9.54, 95% CI 0.06–0.36, P = 0.002). Univariate analysis showed that intravenous thrombolysis, baseline ischemic core volume, and baseline mismatch ratio correlated with RPBE (all P &lt; 0.05). After dividing the mismatch ratio into quartiles and performing a chi-square test between quartiles, we found that the occurrence of RPBE in Q4 (mismatch ratio &gt; 11.3) was significantly lower than that in Q1 (mismatch ratio ≤ 3.0) (P &lt; 0.05). The result of multivariate logistic regression analysis showed that compared with baseline mismatch ratio &lt;5.1, baseline mismatch ratio between 5.1 and 11.3 (OR:3.85, 95% CI 1.06–14.29, P = 0.040), and mismatch ratio &gt;11.3 (OR:5.26, 95% CI 1.28–20.00, P = 0.021) were independent protective factors for RPBE.ConclusionIn patients with anterior circulation LVO stroke undergoing successful EVT, a large mismatch ratio at baseline is a protective factor for RPBE, which is associated with poor outcomes.
Chronology of auditory processing and related co-activation in the orbitofrontal cortex depends on musical expertise
Authors: Bücher Steffen , Bernhofs Valdis , Thieme Andrea , Christiner Markus , Schneider Peter 
Published: January 2023

IntroductionThe present study aims to explore the extent to which auditory processing is reflected in the prefrontal cortex.MethodsUsing magnetoencephalography (MEG), we investigated the chronology of primary and secondary auditory responses and associated co-activation in the orbitofrontal cortex in a large cohort of 162 participants of various ages. The sample consisted of 38 primary school children, 39 adolescents, 43 younger, and 42 middle-aged adults and was further divided into musically experienced participants and non-musicians by quantifying musical training and aptitude parameters.ResultsWe observed that the co-activation in the orbitofrontal cortex [Brodmann-Area 10 (BA10)] strongly depended on musical expertise but not on age. In the musically experienced groups, a systematic coincidence of peak latencies of the primary auditory P1 response and the co-activated response in the orbitofrontal cortex was observed in childhood at the onset of musical education. In marked contrast, in all non-musicians, the orbitofrontal co-activation occurred 25–40 ms later when compared with the P1 response. Musical practice and musical aptitude contributed equally to the observed activation and co-activation patterns in the auditory and orbitofrontal cortex, confirming the reciprocal, interrelated influence of nature, and nurture in the musical brain.DiscussionBased on the observed ageindependent differences in the chronology and lateralization of neurological responses, we suggest that orbitofrontal functions may contribute to musical learning at an early age.
New natural compound inhibitors of PDGFRA (platelet-derived growth factor receptor α) based on computational study for high−grade glioma therapy
Authors: Yang Wenzhuo , Wang Shengnan , Zhang Xiangmao , Sun Hu , Zhang Menghan , Chen Hongyu , Cui Junxiang , Li Jinyang , Peng Fei , Zhu Mingqin , Yu Bingcheng , Li Yifan , Yang Liu , Min Wanwan , Xue Mengru , Pan Lin , Zhu Hao , Wu Bo , Gu Yinghao 
Published: January 2023

BackgroundHigh-grade glioma (HGG) is a malignant brain tumor that is common and aggressive in children and adults. In the current medical paradigm, surgery and radiotherapy are the standard treatments for HGG patients. Despite this, the overall prognosis is still very bleak. Studies have shown that platelet-derived growth factor receptor α (PDGFRA) is an essential target to treat tumors and inhibiting the activity of PDGFRA can improve the prognosis of HGG. Thus, PDGFRA inhibitors are critical to developing drugs and cancer treatment.ObjectiveThe purpose of this study was to screen lead compounds and candidate drugs with potential inhibitors against platelet-derived growth factor receptor α (PDGFRA) from the drug library (ZINC database) in order to improve the prognosis of patients with high-grade glioma (HGG).Materials and methodsIn our study, we selected Imatinib as the reference drug. A series of computer-aided technologies, such as Discovery Studio 2019 and Schrodinger, were used to screen and assess potential inhibitors of PDGFRA. The first step was to calculate the LibDock scores and then analyze the pharmacological and toxicological properties. Following this, we docked the small molecules selected in the previous steps with PDGFRA to study their docking mechanism and affinity. In addition, molecular dynamics simulation was used to determine whether the ligand-PDGFRA complex was stable in nature.ResultsTwo novel natural compounds 1 and 2 (ZINC000008829785 and ZINC000013377891) from the ZINC database were found binding to PDGFRA with more favorable interaction energy. Also, they were predicted with less Ames mutagenicity, rodent carcinogenicity, non-developmental toxic potential, and tolerant with cytochrome P450 2D6 (CYP2D6). The dynamic simulation analysis demonstrated that ZINC000008829785-PDGFRA and ZINC000013377891-PDGFRA dimer complex had more favorable potential energy compared with Imatinib, and they can exist in natural environments stably.ConclusionZINC000008829785 and ZINC000013377891 might provide a solid foundation for drugs that inhibit PDGFRA in HGG. In addition to being safe drug candidates, these compounds had important implications for improving drugs targeting PDGFRA.
High levels of Bifidobacteriaceae are associated with the pathogenesis of Parkinson’s disease
Authors: Zuo ShuJia , Wang HaiJing , Zhao Qiang , Tang Jie , Wang Min , Zhang Yu , Sang Ming , Tian Jing , Wang Puqing 
Published: January 2023

BackgroundThe diagnosis of Parkinson’s disease (PD) is complex and there are no biomarkers for early identification. Many studies have reported altered gut microbiota in patients with PD compared with healthy individuals. However, results from previous studies vary across countries.AimsThe aim of this study was to identify gut microbiota biomarkers that could be used as a marker for the diagnosis of PD.MethodsFirstly, the differential gut microbiota was obtained by meta-analysis, and then the results of meta-analysis were validated through metagenomic cohort. Finally, the ROC curve was drawn based on the metagenomic validation results.ResultsThe meta-analysis showed a lower relative abundance of Prevotellaceae (p &lt; 0.00001) and Lachnospiraceae (p = 0.002), and a higher of Ruminococcaceae (p &lt; 0.00001), Christensenellaceae (p = 0.03), Bifidobacteriaceae (p &lt; 0.00001), and Verrucomicrobiaceae (p = 0.23) in patients with PD. Only Bifidobacteriaceae was also at high levels in the validation cohort of the metagenome. Meanwhile, three species from the Bifidobacteriaceae, including Scardovia_inopinata (p = 0.022), Bifidobacterium_dentium (p = 0.005), and Scardovia_wiggsiae (p = 0.024) were also high. The ROC curve showed that the three species (71.2%) from Bifidobacteriaceae had good predictive efficiency for PD.ConclusionElevated Bifidobacteriaceae may be associated with PD. Elevated three species from the Bifidobacteriaceae, including Scardovia_inopinata, Bifidobacterium_dentium and Scardovia_wiggsiae may provide new potential biomarkers for the diagnosis of PD.
Technetium (Tc)/Rhenium (Re) solubility and leaching behavior from waste forms: An overview
Authors: Singh Bhupendra Kumar , Kim Jueun , Pak Donghun , Kim Kyungwon , Um Wooyong 
Published: January 2023

Technetium-99 (99Tc), a radionuclide generated from nuclear industry is a great environmental concern because of its long half-life (2.13 × 105 years) and high mobility in environment. Therefore, apposite management of 99Tc is imperative to control its hazardous radiological impact on humans and other livings. So far, the major strategy implementation has been the solidification and immobilization of 99Tc radioactive waste in various matrices as waste forms and disposal in deep geological repository. However, by passing the time, 99Tc may leach out/solubilize from the waste forms under different geochemical/environmental conditions. In this minireview, we discuss some key contributions towards the solubility of 99Tc and rhenium (Re; a well-known surrogate of 99Tc) from different waste forms. Specifically, we review the solubility of 99Tc from glass, cement, ceramic, and geopolymer waste forms. The final section (conclusion) presents a short summary and future challenges need be addressed to impede the solubility of 99Tc from the designed waste forms. We believe this minireview will be beneficial to provide a significant insight on the solubility of 99Tc from aforementioned waste forms and in the design of robust matrices to minimize/prevent 99Tc migration in various environments.