bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of romosozumab combined with routine therapy on pain relief, disease progression and adverse reactions in patients with postmenopausal osteoporosis: a systematic review and meta-analysis
Authors: Gao Ge , Cui Jian , Xie Yuanyuan , Dong Jing 
Published: August 2024

BackgroundPostmenopausal osteoporosis (PMOP) increases fracture risk in women. Though traditional treatments are slow to act, combining romosozumab with conventional therapy shows promise. Despite its growing use, studies on effectiveness are limited. This study aims to systematically evaluate the combined therapy’s impact on pain relief, disease progression, and adverse reactions in PMOP patients.MethodsDatabases including PubMed, EMBASE, ScienceDirect, and the Cochrane Library were searched from their inception to September 2023 to identify randomized controlled trials (RCTs) evaluating the role of romosozumab in PMOP. Random or fixed effect models were employed for statistical analysis. Two reviewers independently assessed the quality of the included studies and extracted the data. The meta-analysis was conducted using RevMan 5.4 software.ResultsSix RCTs with a total sample size of 17,985 cases were included. The incidence of vertebral fractures was compared and analyzed after 12 and 24 months of treatment. Romosozumab significantly reduced the incidence of vertebral fractures at 24 months (OR = 0.36; 95% CI: 0.35–0.52) but not at 12 months (OR = 0.39; 95% CI: 0.14–1.05). It was also associated with a decreased incidence of nonvertebral fractures (OR = 0.79; 95% CI: 0.66–0.94) and clinical fractures at 24 months (OR = 0.70; 95% CI: 0.59–0.82) compared to standard therapy. Romosozumab demonstrated a significant improvement in percentage change in bone mineral density (BMD) [mean difference (MD) = 10.38; 95% CI: 4.62–16.14] and in hip joint BMD (MD = 4.24; 95% CI: 2.92–5.56). There was no notable difference in adverse reactions compared to standard care (p &gt; 0.05). Funnel plots displayed a predominantly symmetrical pattern, suggesting no evidence of publication bias in the selected literature.ConclusionCombining romosozumab with conventional therapy effectively treats PMOP, significantly reducing vertebral, non-vertebral, and clinical fractures while increasing BMD in the hip, femoral neck, and lumbar spine. However, further high-quality studies are needed for validation.
Case report: Solitary fibrous tumor of the paracervical uterus combined with vaginal wall adenocarcinoma
Authors: Zhang Xiaowei , Chen Jun , Du Junqiang , Ying Jiajia 
Published: August 2024

BackgroundSolitary fibrous tumors are rare mesenchymal tumors that typically occur in the pleura. Solitary fibrous tumors of the uterine cervix are uncommon. We report the first case of a patient who underwent total hysterectomy for vaginal wall adenocarcinoma and was found to have a concurrent solitary fibrous tumor in the paracervical-uterus.Case presentationA 51-year-old woman was admitted to our hospital due to contact bleeding. A gynecological examination revealed nodules of 3.0 × 1.0 cm on the vaginal wall, and a colposcopy with biopsy revealed adenocarcinoma of the vaginal wall. After the recommended staging examinations, the patient underwent total hysterectomy, double adnexectomy, pelvic lymph node dissection, and vaginal wall resection. During surgery, a nodule measuring approximately 2 × 2 cm was found in the middle of the mass in the left paracervical region. Subsequent postoperative histopathological examination confirmed an solitary fibrous tumor of the uterine cervix with adenocarcinoma of the vaginal wall. The patient was followed up for 46 months after hospitalization, and no recurrence or distant metastases were observed.ConclusionIn rare cases, solitary fibrous tumors may form large masses in the cervical or vaginal wall. They can easily be misdiagnosed as benign or malignant cervical tumors before and during surgery. Postoperative pathology and immunohistochemistry are helpful for diagnosis. Most solitary fibrous cervical tumors are benign, occasionally with low malignant potential, and surgical treatment is feasible and effective.
Regulatory T cells administration reduces anxiety-like behavior in mice submitted to chronic restraint stress
Authors: Cepeda Yamila , Elizondo-Vega Roberto , Garrido Camila , Tobar Catalina , Araneda Matías , Oliveros Patricia , Ordenes Patricio , Carril Claudio , Vidal Pía M. , Luz-Crawford Patricia , García-Robles María. A. , Oyarce Karina 
Published: August 2024

BackgroundMajor depression disorder (MDD) and anxiety are common mental disorders that significantly affect the quality of life of those who suffer from them, altering the person’s normal functioning. From the biological perspective, the most classical hypothesis explaining their occurrence relies on neurotransmission and hippocampal excitability alterations. However, around 30% of MDD patients do not respond to medication targeting these processes. Over the last decade, the involvement of inflammatory responses in depression and anxiety pathogenesis has been strongly acknowledged, opening the possibility of tackling these disorders from an immunological point of view. In this context, regulatory T cells (Treg cells), which naturally maintain immune homeostasis by suppressing inflammation could be promising candidates for their therapeutic use in mental disorders.MethodsTo test this hypothesis, C57BL/6 adult male mice were submitted to classical stress protocols to induce depressive and anxiety-like behavior; chronic restriction stress (CRS), and chronic unpredictable stress (CUS). Some of the stressed mice received a single adoptive transfer of Treg cells during stress protocols. Mouse behavior was analyzed through the open field (OFT) and forced swim test (FST). Blood and spleen samples were collected for T cell analysis using cell cytometry, while brains were collected to study changes in microglia by immunohistochemistry.ResultsMice submitted to CRS and CUS develop anxiety and depressive-like behavior, and only CRS mice exhibit lower frequencies of circulating Treg cells. Adoptive transfer of Treg cells decreased anxiety-like behavior in the OFT only in CRS model, but not depressive behavior in FST in neither of the two models. In CRS mice, Treg cells administration lowered the number of microglia in the hippocampus, which increased due this stress paradigm, and restored its arborization. However, in CUS mice, Treg cells administration increased microglia number with no significant effect on their arborization.ConclusionOur results for effector CD4+ T cells in the spleen and microglia number and morphology in the hippocampus add new evidence in favor of the participation of inflammatory responses in the development of depressive and anxiety-like behavior and suggest that the modulation of key immune cells such as Treg cells, could have beneficial effects on these disorders.
Genetic information supports a causal relationship between trace elements, inflammatory proteins, and COPD: evidence from a Mendelian randomization analysis
Authors: Cao Zhenghua , Zhao Shengkun , Wu Tong , Sun Feng , Ding Huan , Hu Shaodan , Shi Li 
Published: August 2024

ObjectiveDietary factors and nutritional status may be among the risk factors for Chronic Obstructive Pulmonary Disease (COPD). There exists a certain correlation between trace elements and COPD. Through Mendelian Randomization (MR) analysis, we investigated the causal relationships between trace elements, inflammatory proteins, and COPD.MethodsWe employed MR, multivariable MR (MVMR), and two-step MR (TSMR) approaches to assess the causal links between 15 trace elements and COPD, with 91 inflammatory proteins serving as mediators to further elucidate the tripartite causal relationships.ResultsTrace elements such as Folate (OR = 1.293, 95%CI 1.027–1.628; p = 0.029), Vitamin D (OR = 1.331, 95%CI 1.071–1.654; p = 0.010), Vitamin B12 (OR = 1.424, 95%CI 1.108–1.828; p = 0.006), and Iron (OR = 0.741, 95%CI 0.580–0.946; p = 0.016) demonstrated causal relationships with COPD. No causal relationship was observed in reverse MR. After adjusting for BMI, Folate (OR = 1.633, 95%CI 1.098–2.429; p = 0.015), Iron (OR = 0.507, 95%CI 0.31–0.778; p = 0.001), and Vitamin D (OR = 1.511, 95%CI 1.029–2.217; p = 0.034) were identified as independent risk factors for COPD, whereas Vitamin B12 (OR = 1.118, 95%CI 0.751–1.666; p = 0.581) was not. Mediation analysis indicated that CDCP1 (5.76%) may play a mediating role between Iron and COPD.ConclusionTrace elements such as Folate, Vitamin D, Vitamin B12, and Iron have causal relationships with COPD. After BMI adjustment, Folate, Vitamin D, and Iron emerge as independent risk factors. Furthermore, the inflammatory protein CDCP1 may partially mediate the causal relationship between Iron and COPD, offering a scientific basis for dietary recommendations that could benefit COPD patients. The supplementation of trace elements may be advantageous for individuals suffering from COPD.
Causal effect of lifestyle and metabolic indicator with herpes zoster: a two-sample Mendelian randomization study
Authors: Huang Mingsheng , Liu Yiheng , Chen Cheng , Dai Weiran 
Published: August 2024

BackgroundPrevious observational studies have reported certain causal relationships between factors such as smoking, alcohol consumption, obesity, physical activity, metabolic disorders, and the incidence of herpes zoster (HZ). However, there is controversy regarding the observed results across different studies. Our objective was to investigate the causal effects of these risk factors on the risk of herpes zoster through a Mendelian randomization analysis using two-sample bidirectional approaches.MethodsWe conducted two-sample bidirectional Mendelian randomization analyses to explore the causal relationships between different lifestyles, obesity assessment indices, metabolic indicators, and the risk of herpes zoster. All exposure and outcome data were sourced from publicly available data from genome-wide association studies.ResultsIn the inverse-variance weighted (IVW) analysis, body mass index (BMI) (OR: 1.160, 95% CI: 1.030–1.307, p = 0.014), Body fat percentage (BFP) (OR: 1.241, 95% CI: 1.050–1.467, p = 0.011), and whole body fat mass (WBFM) (OR: 1.199, 95% CI: 1.057–1.362, p = 0.005) exhibited positive associations with the risk of HZ. However, usual walking pace (UWP) (OR: 0.498, 95% CI: 0.254–0.976, p = 0.042) demonstrated a significant negative correlation with HZ risk. Other factors including alcohol intake frequency, smoking initiation, smoking status, insomnia, and sleep duration did not show significant causal relationships with HZ.ConclusionMendelian randomization studies revealed that BMI, BFP, and WBFM are risk factors for HZ. UWP showed a protective effect against HZ. These findings provide a straightforward method for evaluating future clinical practices aiming to develop personalized management strategies and assess high-risk populations for HZ.
An A2 β-casein infant formula with high sn-2 palmitate and casein phosphopeptides supports adequate growth, improved stool consistency, and bone strength in healthy, term Chinese infants: a randomized, double-blind, controlled clinical trial
Authors: Sheng Xiao-Yang , Mi Wiola , Yuan Qing Bin , Liu Bryan Yanwen , Carnielli Virgilio , Ning Yi Bing , Einerhand Alexandra W. C. 
Published: August 2024

The aim of this randomized, double-blind, controlled trial was to examine the effects of infant formula on the growth, stool consistency, and bone strength of infants (n = 120) over a period of 4 months. The investigational group was fed an A2 β-casein cow’s milk infant formula containing casein phosphopeptides (CPP) and high sn-2 palmitate (54% of total palmitate at sn-2). The control group was fed a standard cow’s milk formula without CPP and with low sn-2 palmitate (29% of total palmitate at sn-2). The third group was fed human milk (HM) (n = 60). All three groups had similar baseline characteristics, and maintained similar BMI, sleep habits, and growth rates in body weight and length throughout the study. However, compared to the control group, infants in the investigational and human milk groups had significantly: (i) greater body length at 90, 120, and 150 days of age; (ii) greater growth rate in head circumference from 30 to 60 days of age, with larger head circumference at 60 days of age; (iii) larger daily stool frequency at 60, 90, and 120 days of age; (iv) softer stool at 60, 90, and 120 days of age; (v) higher bone quality index and bone speed of sound at 150 days of age; (vi) fewer hours of crying at 60 and 90 days of age; (vii) less abdominal distention, burp, and flatus at 60, 90, and 120 days of age; and (viii) less constipation at 90 days of age. At other time points, no significant differences were observed between the three groups. No serious adverse events (AEs) related to the study products were reported, and significantly fewer infants in the investigational and HM groups experienced at least one AE compared to the control group. The study suggests that the A2 β-casein formula with high sn-2 palmitate and CPP supports adequate growth, is well tolerated, and may have beneficial effects on stool consistency, gastrointestinal comfort, crying duration, and bone density, comparable to HM.Clinical trial registration:https://clinicaltrials.gov/, NCT04749290.
A dual-radiomics model for overall survival prediction in early-stage NSCLC patient using pre-treatment CT images
Authors: Zhang Rihui , Zhu Haiming , Chen Minbin , Sang Weiwei , Lu Ke , Li Zhen , Wang Chunhao , Zhang Lei , Yin Fang-Fang , Yang Zhenyu 
Published: August 2024

IntroductionRadiation therapy (RT) is one of the primary treatment options for early-stage non-small cell lung cancer (ES-NSCLC). Therefore, accurately predicting the overall survival (OS) rate following radiotherapy is crucial for implementing personalized treatment strategies. This work aims to develop a dual-radiomics (DR) model to (1) predict 3-year OS in ES-NSCLC patients receiving RT using pre-treatment CT images, and (2) provide explanations between feature importanceand model prediction performance.MethodsThe publicly available TCIA Lung1 dataset with 132 ES-NSCLC patients received RT were studied: 89/43 patients in the under/over 3-year OS group. For each patient, two types of radiomic features were examined: 56 handcrafted radiomic features (HRFs) extracted within gross tumor volume, and 512 image deep features (IDFs) extracted using a pre-trained U-Net encoder. They were combined as inputs to an explainable boosting machine (EBM) model for OS prediction. The EBM’s mean absolute scores for HRFs and IDFs were used as feature importance explanations. To evaluate identified feature importance, the DR model was compared with EBM using either (1) key or (2) non-key feature type only. Comparison studies with other models, including supporting vector machine (SVM) and random forest (RF), were also included. The performance was evaluated by the area under the receiver operating characteristic curve (AUCROC), accuracy, sensitivity, and specificity with a 100-fold Monte Carlo cross-validation.ResultsThe DR model showed highestperformance in predicting 3-year OS (AUCROC=0.81 ± 0.04), and EBM scores suggested that IDFs showed significantly greater importance (normalized mean score=0.0019) than HRFs (score=0.0008). The comparison studies showed that EBM with key feature type (IDFs-only demonstrated comparable AUCROC results (0.81 ± 0.04), while EBM with non-key feature type (HRFs-only) showed limited AUCROC (0.64 ± 0.10). The results suggested that feature importance score identified by EBM is highly correlated with OS prediction performance. Both SVM and RF models were unable to explain key feature type while showing limited overall AUCROC=0.66 ± 0.07 and 0.77 ± 0.06, respectively. Accuracy, sensitivity, and specificity showed a similar trend.DiscussionIn conclusion, a DR model was successfully developed to predict ES-NSCLC OS based on pre-treatment CT images. The results suggested that the feature importance from DR model is highly correlated to the model prediction power.
Contrast-enhanced computed tomography-based radiomics nomogram for predicting HER2 status in urothelial bladder carcinoma
Authors: Peng Jiao , Tang Zhen , Li Tao , Pan Xiaoyu , Feng Lijuan , Long Liling 
Published: August 2024

ObjectiveTo evaluate the performance of a clinical-radiomics model based on contrast-enhanced computed tomography (CE-CT) in assessing human epidermal growth factor receptor 2 (HER2) status in urothelial bladder carcinoma (UBC).MethodsFrom January 2022 to December 2023, 124 patients with UBC were classified into the training (n=100) and test (n=24) sets. CE-CT scans were performed on the patients. Univariate and multivariate analyses were conducted to identify independent predictors of HER2 status in patients with UBC. We employed eight machine learning algorithms to establish radiomic models. A clinical-radiomics model was developed by integrating radiomic signatures and clinical features. Receiver operating characteristic curves and decision curve analysis (DCA) were generated to evaluate and validate the predictive capabilities of the models.ResultsAmong the eight classifiers, the random forest radiomics model based on CE-CT demonstrated the highest efficacy in predicting HER2 status, with area under the curve (AUC) values of 0.880 (95% CI: 0.813–0.946) and 0.814 (95% CI: 0.642–0.986) in the training and test sets, respectively. In the training set, the clinical-radiomics model achieved an AUC of 0.935, an accuracy of 0.870, a sensitivity of 0.881, and a specificity of 0.854. In the test set, the clinical-radiomics model achieved an AUC of 0.857, an accuracy of 0.760, a sensitivity of 0.643, and a specificity of 0.900. DCA analysis indicated that the clinical-radiomics model provided good clinical benefit.ConclusionThe radiomics nomogram demonstrates good diagnostic performance in predicting HER2 expression in patients with UBC.
Analysis of the causes of neonatal death and genetic variations in congenital anomalies: a multi-center study
Authors: Yang Xue , Bai Ruimiao , Zhang Juan , Yang Yunfan , Zhang JuanJuan , Wang Baozhu , Li Zhankui , Yu Xiping 
Published: August 2024

BackgroundNeonatal deaths often result from preventable conditions that can be addressed with appropriate interventions. This study aims to analyze the distribution of the causes of neonatal death and explore genetic variations that lead to congenital anomalies in Northwest China.MethodsThis multi-center observational study was conducted across six medical centers in Shaanxi province, Northwest China. Clinical data were retrospectively collected from neonates admitted between 2016 and 2020. Kaplan-Meier analysis was utilized to estimate survival rates, while high-throughput sequencing platforms were employed to detect mutations causing congenital anomalies.ResultsAmong 73,967 neonates requiring hospital care, 424 neonatal deaths were recorded, leading to a neonatal mortality rate of 0.57%. The primary causes of death included neonatal respiratory distress syndrome (23.8%), birth asphyxia (19.8%), neonatal septicemia (19.3%), and congenital anomalies (13.6%). The leading causes of neonatal deaths due to congenital anomalies were congenital heart defects (38.6%), bronchopulmonary dysplasia (14.0%), and inherited metabolic disorders (10.5%). Genetic analysis identified 83 pathogenic or likely pathogenic variants in 23 genes among the neonates with congenital anomalies, including four novel mutations (c.4198+1G&gt;T, c.1075delG, c.610-1G&gt;A, c.7769C&gt;T) in the ABCC8, CDKL5, PLA2G6, and NIPBL genes.ConclusionCongenital anomalies represent a significant and preventable cause of neonatal deaths in Northwest China. Early detection of congenital anomalies through genetic testing and comprehensive prenatal care are crucial for reducing neonatal mortality rates and improving pregnancy outcomes.
Ling-gui-zhu-gan promotes adipocytes browning via targeting the miR-27b/PRDM16 pathway in 3T3-L1 cells
Authors: Ye Zimengwei , Zhao Yi , Cui Yanjing , Xu Bingrui , Wang Fan , Zhao Dandan , Dong Guangtong , Wang Zhufeng , Wu Rui 
Published: August 2024

Introduction: Obesity, a global epidemic, is caused by an imbalance between energy intake and expenditure. The induction of white adipose browning to increase heat production has emerged as a potential effective strategy to address obesity. Ling-gui-zhu-gan (LGZG), a traditional Chinese medicine formula, has been proved to achieve promising results to combat obesity and related metabolic diseases, yet the mechanisms remain largely unexplored. This study aimed to elucidate the anti-obesity properties and the mechanisms of LGZG by investigating its browning effect on 3T3-L1 adipocytes.Methods: LGZG-containing serum obtained by oral administration of LGZG to animals was added to 3T3-L1 adipocytes to simulate in vivo conditions.Results: The results showed that 49 compounds were identified in LGZG-containing serum by UHPLC-Q-Orbitrap HRMS, including compounds such as atractylenolides and polyporenic acid C, etc. LGZG-containing serum alleviated the lipid accumulation and decreased both intracellular and extracellular triglyceride contents in a dose-dependent manner. This reduction is accompanied by enhanced mitochondrial respiratory and heat production function. Mechanistically, LGZG-containing serum led to a decrease in miR-27b expression and an increase in the mRNA and protein levels of browning-related markers, including UCP1, PRDM16, PGC-1α, PPARγ, CTBP1, and CTBP2. Further investigation using miR-27b mimic transfection confirmed that miR-27b/PRDM16 pathway might be a potential mechanism by which LGZG-containing serum promotes browning of 3T3-L1 adipocytes.Discussion: These results underscore the therapeutic potential of LGZG in addressing obesity and its associated metabolic disorders through the promotion of adipose browning.
Cost-effectiveness of pembrolizumab plus chemotherapy vs. chemotherapy as first-line treatment for advanced biliary tract cancer in China and the US
Authors: Luo Xianmei , Cai Tingting , Wu Jinyan , Li Xingyu , Wang Xiaofan , Ma Haiying 
Published: August 2024

Background: Pembrolizumab is a potentially valuable treatment. However, patients, doctors, and healthcare decision-makers are uncertain about its cost-effectiveness and an appropriate pricing for this new therapy. This study aims to appraise the cost-effectiveness of pembrolizumab as a first-line treatment for advanced biliary tract cancer (BTC) patients in China and the United States (US).Methods: A Markov model was constructed from the perspectives of healthcare systems in both China and the US for pharmacoeconomic evaluation. Patient baseline characteristics and key clinical data were sourced from the KEYNOTE-966 trial (ClinicalTrials.gov, NCT04003636). Costs and utilities were collected from drug cost websites and published literature. Cumulative costs (in USD), life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. Price simulations were conducted under given willingness-to-pay (WTP) thresholds to provide pricing scheme references. The model’s robustness was analyzed through one-way sensitivity analysis and probabilistic sensitivity analysis.Results: Basic data analysis illustrates that pembrolizumab ($2662.41/100 mg) in combination with chemotherapy regimen was not cost-effective relative to chemotherapy regimens at the WTP threshold of $38,201.19 in China, and the additional cost relative to chemotherapy regimens was $77,114.94 (ICER $556,689.47/QALY) while increasing 0.14 QALYs. Pembrolizumab ($54.71/1 mg) also increased efficacy by 0.14 QALYs in the US, but remained also not cost-effective at the US WTP threshold of $229,044, and the total cost increased by $160,425.24 (ICER $1,109,462.92/QALY).Conclusion: Compared with chemotherapy, pembrolizumab plus chemotherapy reduces the disease of burden. However, at its current price, it may not be a cost-effective treatment for advanced BTC in both China and the US. This study can aid decision-makers in making optimal choices.