bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of diabetes itself and glycemic control status on tuberculosis
Authors: Meng Fanqi , Lan Lijuan , Wu Guihui , Ren Xiaoxia , Yuan Xiaoyan , Yang Ming , Chen Qing , Peng Xiaoli , Liu Dafeng 
Published: November 2023

ObjectivesTo explore the impact of diabetes itself and glycemic control status on tuberculosis (TB).MethodsA total of 3393 patients with TB and diabetes mellitus (DM) who were hospitalized in the Public Health Clinical Center of Chengdu from January 1, 2019, to December 31, 2021, were retrospectively included and divided into three groups according to baseline glycemic control status: two groups according to glycemic status at discharge, two groups according to cavity occurrence, three groups according to sputum results, and three groups according to lesion location. The influencing factors and the differences in cavity occurrence, sputum positivity and lesion location among different glycemic control groups or between different glycemic status groups were analyzed.ResultsIn this TB with DM cohort, most of the subjects were male, with a male to female ratio of 4.54:1, most of them were 45-59 years old, with an average age of 57.44 ± 13.22 years old. Among them, 16.8% (569/3393) had cavities, 52.2% (1770/3393) were sputum positive, 30.4% (1030/3393) had simple intrapulmonary lesions, 68.1% (2311/3393) had both intra and extrapulmonary lesions, only 15.8% (537/3393) had good glycemic control,16.0% (542/3393) and 68.2% (2314/3393) had fair and poor glycemic control, respectively. Compared with the non-cavity group, the sputum-negative group and the extrapulmonary lesion group, the cavity group, sputum-positive group, intrapulmonary lesion group and the intra and extrapulmonary lesion group all had higher fasting plasma glucose (FPG) and glycosylated hemoglobin A 1c (HbA1c) and lower good glycemic control rates at admission (all P&lt;0.001). Another aspect, compared with the good glycemic control group, the poor glycemic control group had a higher cavity occurrence rate, sputum positive rate, and greater proportion of intrapulmonary lesions. Moreover, FPG and HbA1c levels and poor glycemic control were significantly positively correlated with cavity occurrence, sputum positivity, and intrapulmonary lesions and were the main risk factors for TB disease progression. On the other hand, cavity occurrence, sputum positivity, and intrapulmonary lesions were also main risk factors for hyperglycemia and poor glycemic control.ConclusionDiabetes itself and glycemic control status could impact TB disease. Good glycemic control throughout the whole process is necessary for patients with TB and DM to reduce cavity occurrence and promote sputum negative conversion and lesion absorption.
Fecal short chain fatty acids modify therapeutic effects of sleeve gastrectomy
Authors: Shen Chongrong , Chen Yanru , Wang Qiaoling , Sun Yingkai , Lin Huibin , Ni Mengshan , Chen Yufei , Zhang Ling , Jin Jiabin , Ying Xiayang , Zou Yuyao , Wang Xiaolin , Ye Yaorui , Yuan Miaomiao , Yin Nan , Cao Zhiwen , Zhang Yifei , Gu Weiqiong , Wang Weiqing , Ning Guang , Wang Jiqiu , Zhao Shaoqian , Hong Jie , Liu Ruixin 
Published: November 2023

AimsWe aimed to investigate changes of fecal short chain fatty acids (SCFAs) and their association with metabolic benefits after sleeve gastrectomy (SG). Specifically, whether pre-surgery SCFAs modify surgical therapeutic effects was determined.Methods62 participants with measurements of fecal SCFAs and metabolic indices before and 1, 3, 6 months after SG were included. Changes of fecal SCFAs and their association with post-surgery metabolic benefits were calculated. Then, participants were stratified by medians of pre-surgery fecal SCFAs and modification effects of pre-surgery fecal SCFAs on surgical therapeutic effects were investigated, through calculating interaction of group by surgery.ResultsFecal SCFAs were markedly changed by SG. Changes of propionate and acetate were positively correlated with serum triglycerides and total cholesterol, respectively. Notably, high pre-surgery fecal hexanoate group showed a better effect of SG treatment on lowering body weight (P=0.01), BMI (P=0.041) and serum triglycerides (P=0.031), and low pre-surgery fecal butyrate had a better effect of SG on lowering ALT (P=0.003) and AST (P=0.019).ConclusionFecal SCFAs were changed and correlated with lipid profiles improvement after SG. Pre-surgery fecal hexanoate and butyrate were potential modifiers impacting metabolic benefits of SG.
The causal relationship between sarcopenic obesity factors and benign prostate hyperplasia
Authors: Rao Xuezhi , Xu Zhijie , Zhang Jingchun , Zhou Jiaxiang , Huang Jian , Toh Zhanhao , Zheng Ruwen , Zhou Zhiyu 
Published: November 2023

BackgroundBoth benign prostatic hyperplasia (BPH) and sarcopenic obesity (SO) are common conditions among older adult/adults males. The prevalent lifestyle associated with SO is a significant risk factor for the development of BPH. Therefore, we investigated the causal relationship between SO factors and BPH.MethodThe instrumental variables for SO factors were selected using the inverse variance-weighted method, which served as the primary approach for Mendelian randomization analysis to assess the causal effect based on summary data derived from genome-wide association studies of BPH.ResultThe increase in BMR (OR = 1.248; 95% CI = (1.087, 1.432); P = 0.002) and ALM (OR = 1.126; 95% CI = (1.032, 1.228); P = 0.008) was found to be associated with an elevated risk of BPH. However, no genetic causality between fat-free mass distribution, muscle mass distribution, and BPH was observed.ConclusionOur findings indicate that a genetic causal association between BMR, ALM and BPH. BMR and ALM are risk factors for BPH. The decrease in BMR and ALM signified the onset and progression of SO, thus SO is a protective factor for BPH.
Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway
Authors: Kijima Ken , Ono Gentaro , Kobayakawa Kazu , Saiwai Hirokazu , Hara Masamitsu , Yoshizaki Shingo , Yokota Kazuya , Saito Takeyuki , Tamaru Tetsuya , Iura Hirotaka , Haruta Yohei , Kitade Kazuki , Utsunomiya Takeshi , Konno Daijiro , Edgerton V. Reggie , Liu Charles Y. , Sakai Hiroaki , Maeda Takeshi , Kawaguchi Kenichi , Matsumoto Yoshihiro , Okada Seiji , Nakashima Yasuharu 
Published: November 2023

BackgroundSpinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target.MethodsWe created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test.ResultsIn macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function.ConclusionWe demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.
Development and characterization of narsoplimab, a selective MASP-2 inhibitor, for the treatment of lectin-pathway–mediated disorders
Authors: Dudler Thomas , Yaseen Sadam , Cummings W. Jason 
Published: November 2023

IntroductionOveractivation of the lectin pathway of complement plays a pathogenic role in a broad range of immune-mediated and inflammatory disorders; mannan-binding lectin-associated serine protease-2 (MASP-2) is the key effector enzyme of the lectin pathway. We developed a fully human monoclonal antibody, narsoplimab, to bind to MASP-2 and specifically inhibit lectin pathway activation. Herein, we describe the preclinical characterization of narsoplimab that supports its evaluation in clinical trials.Methods and resultsELISA binding studies demonstrated that narsoplimab interacted with both zymogen and enzymatically active forms of human MASP-2 with high affinity (KD 0.062 and 0.089 nM, respectively) and a selectivity ratio of &gt;5,000-fold relative to closely related serine proteases C1r, C1s, MASP-1, and MASP-3. Interaction studies using surface plasmon resonance and ELISA demonstrated approximately 100-fold greater binding affinity for intact narsoplimab compared to a monovalent antigen binding fragment, suggesting an important contribution of functional bivalency to high-affinity binding. In functional assays conducted in dilute serum under pathway-specific assay conditions, narsoplimab selectively inhibited lectin pathway-dependent activation of C5b-9 with high potency (IC50 ~ 1 nM) but had no observable effect on classical pathway or alternative pathway activity at concentrations up to 500 nM. In functional assays conducted in 90% serum, narsoplimab inhibited lectin pathway activation in human serum with high potency (IC50 ~ 3.4 nM) whereas its potency in cynomolgus monkey serum was approximately 10-fold lower (IC50 ~ 33 nM). Following single dose intravenous administration to cynomolgus monkeys, narsoplimab exposure increased in an approximately dose-proportional manner. Clear dose-dependent pharmacodynamic responses were observed at doses &gt;1.5 mg/kg, as evidenced by a reduction in lectin pathway activity assessed ex vivo that increased in magnitude and duration with increasing dose. Analysis of pharmacokinetic and pharmacodynamic data revealed a well-defined concentration-effect relationship with an ex vivo EC50 value of approximately 6.1 μg/mL, which was comparable to the in vitro functional potency (IC50 33 nM; ~ 5 μg/mL).DiscussionBased on these results, narsoplimab has been evaluated in clinical trials for the treatment of conditions associated with inappropriate lectin pathway activation, such as hematopoietic stem cell transplantation-associated thrombotic microangiopathy.
Factors determining antenatal care utilization among mothers of deceased perinates in Ethiopia
Authors: Tesfay Neamin , Kebede Mandefro , Asamene Negga , Tadesse Muse , Begna Dumesa , Woldeyohannes Fitsum 
Published: November 2023

IntroductionReceiving adequate antenatal care (ANC) had an integral role in improving maternal and child health outcomes. However, several factors influence the utilization of ANC from the individual level up to the community level factors. Thus, this study aims to investigate factors that determine ANC service utilization among mothers of deceased perinate using the proper count regression model.MethodSecondary data analysis was performed on perinatal death surveillance data. A total of 3,814 mothers of deceased perinates were included in this study. Hurdle Poisson regression with a random intercept at both count-and zero-part (MHPR.ERE) model was selected as a best-fitted model. The result of the model was presented in two ways, the first part of the count segment of the model was presented using the incidence rate ratio (IRR), while the zero parts of the model utilized the adjusted odds ratio (AOR).ResultThis study revealed that 33.0% of mothers of deceased perinates had four ANC visits. Being in advanced maternal age [IRR = 1.03; 95CI: (1.01–1.09)], attending primary level education [IRR = 1.08; 95 CI: (1.02–1.15)], having an advanced education (secondary and above) [IRR = 1.14; 95 CI: (1.07–1.21)] and being resident of a city administration [IRR = 1.17; 95 CI: (1.05–1.31)] were associated with a significantly higher frequency of ANC visits. On the other hand, women with secondary and above education [AOR = 0.37; 95CI: (0.26–0.53)] and women who live in urban areas [AOR = 0.42; 95 CI: (0.33–0.54)] were less likely to have unbooked ANC visit, while women who resided in pastoralist regions [AOR = 2.63; 95 CI: (1.02–6.81)] were more likely to have no ANC visit.ConclusionThe uptake of ANC service among mothers having a deceased perinate was determined by both individual (maternal age and educational status) and community (residence and type of region) level factors. Thus, a concerted effort is needed to improve community awareness through various means of communication by targeting younger women. Furthermore, efforts should be intensified to narrow down inequalities observed in ANC service provision due to the residence of the mothers by availing necessary personnel and improving the accessibility of service in rural areas.
Identification of five novel SCN1A variants
Authors: Zeng Baitao , Zhang Haoyi , Lu Qing , Fu Qingzi , Yan Yang , Lu Wan , Ma Pengpeng , Feng Chuanxin , Qin Jiawei , Luo Laipeng , Yang Bicheng , Zou Yongyi , Liu Yanqiu 
Published: November 2023

BackgroundEpilepsy is characterized by recurrent unprovoked seizures. Mutations in the voltage-gated sodium channel alpha subunit 1 (SCN1A) gene are the main monogenic cause of epilepsy. Type and location of variants make a huge difference in the severity of SCN1A disorder, ranging from the mild phenotype (genetic epilepsy with febrile seizures plus, GEFS+) to the severe phenotype (developmental and epileptic encephalopathies, DEEs). Dravet Syndrome (DS) is an infantile-onset DEE, characterized by drug-resistant epilepsy and temperature sensitivity or febrile seizures. Genetic test results reveal SCN1A variants are positive in 80% DS patients and DS is mainly caused by de novo variants.MethodsTrio-whole exome sequencing (WES) was used to detect variants which were associated with clinical phenotype of five probands with epilepsy or twitching. Then, Sanger sequencing was performed to validate the five novel SCN1A variants and segregation analysis. After analyzing the location of five SCN1A variants, the pathogenic potential was assessed.ResultsIn this study, we identified five novel SCN1A variants (c.4224G &gt; C, c.3744_3752del, c.209del, c.5727_5734delTTTAAAACinsCTTAAAAAG and c.5776delT) as the causative variants. In the five novel SCN1A variants, four were de novo and the remaining one was inherited. All novel variants would be classified as “pathogenic” or “likely pathogenic.”ConclusionThe five novel SCN1A variants will enrich the SCN1A mutations database and provide the corresponding reference data for the further genetic counseling.
Mechanical thrombectomy for symptomatic stent thrombosis after carotid artery stenting
Authors: Fan You-Min , Liu Han-Yang , Xue Yu-Yang 
Published: November 2023

BackgroundAs there is still no consensus on the treatment of carotid stent thrombosis (CST), we would like to describe our experience with the revascularization of CST by mechanical thrombectomy.MethodsWe retrospectively studied patients who underwent mechanical thrombectomy after CST at Xuzhou Municipal First People’s Hospital and Xuzhou Central Hospital between January 2020 and November 2022. The results of the procedures, complications, and clinical and imaging follow-up were recorded.ResultsA total of six patients were included in this study. The stenosis grade before stent implantation was ≥85% in all patients, and the stenosis length ranged from 7 to 20 mm. Patients experienced CST within 6 days to 45 months after carotid artery stenting (CAS); the median admission on the National Institutes of Health Stroke Scale (NIHSS) at CST was 12 (range 8–25). Mechanical thrombectomy was successfully performed in all patients. There was no periprocedural death, and the modified Rankin Scale (mRS) at the 3-month follow-up was 0–2. All patients showed recovery from their neurological deficits.ConclusionThe treatment of symptomatic CST with mechanical thrombectomy resulted in satisfactory clinical outcomes. This regimen could be effective and safe, and future prospective and randomized studies are warranted.
Lowered oxidative capacity in spinal muscular atrophy, Jokela type; comparison with mitochondrial muscle disease
Authors: Ratia Nadja , Palu Edouard , Lantto Hanna , Ylikallio Emil , Luukkonen Ritva , Suomalainen Anu , Auranen Mari , Piirilä Päivi 
Published: November 2023

IntroductionSpinal muscular atrophy, Jokela type (SMAJ) is a rare autosomal dominantly hereditary form of spinal muscular atrophy caused by a point mutation c.197G&gt;T in CHCHD10. CHCHD10 is known to be involved in the regulation of mitochondrial function even though patients with SMAJ do not present with multiorgan symptoms of mitochondrial disease. We aimed to characterize the cardiopulmonary oxidative capacity of subjects with SMAJ compared to healthy controls and patients with mitochondrial myopathy.MethodsEleven patients with genetically verified SMAJ, 26 subjects with mitochondrial myopathy (MM), and 28 healthy volunteers underwent a cardiopulmonary exercise test with lactate and ammonia sampling. The effect of the diagnosis group on the test results was analysed using a linear model.ResultsAdjusted for sex, age, and BMI, the SMAJ group had lower power output (p &lt; 0.001), maximal oxygen consumption (VO2 max) (p &lt; 0.001), and mechanical efficiency (p &lt; 0.001) compared to the healthy controls but like that in MM. In the SMAJ group and healthy controls, plasma lactate was lower than in MM measured at rest, light exercise, and 30 min after exercise (p ≤ 0.001–0.030) and otherwise lactate in SMAJ was lower than controls and MM, in longitudinal analysis p = 0.018. In MM, the ventilatory equivalent for oxygen was higher (p = 0.040), and the fraction of end-tidal CO2 lower in maximal exercise compared to healthy controls (p = 0.023) and subjects with SMAJ.ConclusionIn cardiopulmonary exercise test, subjects with SMAJ showed a similar decrease in power output and oxidative capacity as subjects with mitochondrial myopathy but did not exhibit findings typical of mitochondrial disease.
Tumor cell cytoplasmic metallothionein expression associates with differential tumor immunogenicity and prognostic outcome in high-grade serous ovarian carcinoma
Authors: Mairinger Elena , Wessolly Michael , Buderath Paul , Borchert Sabrina , Henrich Larissa , Mach Pawel , Steinborn Julia , Kimming Rainer , Jasani Bharat , Schmid Kurt Werner , Bankfalvi Agnes , Mairinger Fabian Dominik 
Published: November 2023

BackgroundThe underlying mechanism of high T-cell presence as a favorable prognostic factor in high-grade serous ovarian carcinoma (HGSOC) is not yet understood. In addition to immune cells, various cofactors are essential for immune processes. One of those are metallothioneins (MTs), metal-binding proteins comprising various isoforms. MTs play a role in tumor development and drug resistance. Moreover, MTs influence inflammatory processes by regulating zinc homeostasis. In particular, T-cell function and polarization are particularly susceptible to changes in zinc status. The aim of the present study was to investigate a possible role of MT-mediated immune response and its association with prognostic outcome in ovarian cancer.MethodsA retrospective study was conducted on a clinically well-characterized cohort of 24 patients with HGSOC treated at the University Hospital of Essen. Gene expression patterns for anti-cancer immunogenicity-related targets were performed using the NanoString nCounter platform for digital gene expression analysis with the appurtenant PanCancer Immune Profiling panel, consisting of 770 targets and 30 reference genes. Tumor-associated immunohistochemical MT protein expression was evaluated using a semi-quantitative four-tier Immunohistochemistry (IHC) scoring.ResultsMT immunoexpression was detected in 43% (10/23) of all HGSOC samples. MT immunoexpression levels showed a significant association to survival, leading to prolonged progression-free and overall survival in positively stained tumors. Furthermore, T-cell receptor signaling gene signature showed a strong activation in MT-positive tumors. Activated downstream signaling cascades resulting in elevated interferon-gamma expression with a shift in the balance between T helper cells (TH1 and TH2) could be observed in the MT-positive subgroup. In addition, a higher expression pattern of perforin and several granzymes could be detected, overall suggestive of acute, targeted anti-cancer immune response in MT-positive samples.ConclusionThis is the first study combining broad, digital mRNA screening of anti-tumor immune response–associated genes and their relation to MT-I/II in ovarian cancer. MT overexpression is associated with molecular characteristics of an anti-cancer immune response and is a strong prognostic marker in ovarian HGSOC. The observed immune cell activation associated with tumor MT expression comprises but is not limited to T cells and natural killer cells.
Cost-effectiveness analysis of atezolizumab plus bevacizumab versus sorafenib in first line treatment for Chinese subpopulation with unresectable hepatocellular carcinoma
Authors: Tseng Chien-Yu , Tsai Yi-Wen , Shiu Ming-Neng 
Published: November 2023

ObjectiveWe aimed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab (atezo-bev) versus sorafenib treatment in Taiwan.MethodsUsing sorafenib as the comparator, we developed a partitioned survival model to evaluate the costs and quality-adjusted life year (QALY) of the atezo-bev treatment. The time horizon of the study was 15 years, and the annual discount rate was 3%. We analyzed the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB) from the treatment effects (determined from the progression-free and overall survival outcomes of the IMbrave150 study), direct medical costs (collected and estimated from the National Health Insurance Research Database, Taiwan), and utility parameters (referred to the NICE technology appraisal guidance), as well as the deterministic sensitivity and probabilistic sensitivity.ResultsCompared with sorafenib, the incremental effectiveness of atezo-bev treatment was 1.7 QALY, with an incremental cost of USD 127,607. The ICER was USD 75,192 per QALY, which was less than the predefined willingness to pay in Taiwan.ConclusionThe combined treatment of atezo-bev is cost-effective when compared with sorafenib, which is currently the first-line treatment option for unresectable HCC in Taiwan.