bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in disease severity and prognosis of exercise-induced right-to-left shunt between idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients
Authors: Wang Shang , Guo Zi-Yan , Sun Xing-Xing , Yuan Ping , Zhao Qin-Hua , Wu Wen-Hui , Qiu Hong-Ling , Luo Ci-Jun , Gong Su-Gang , Li Hui-Ting , Zhang Rui , He Jing , Wang Lan , Liu Jin-Ming , Guo Jian , Jiang Rong 
Published: December 2022

ObjectiveWhether exercise-induced venous-to-systemic shunt (EIS) during cardiopulmonary exercise testing (CPET) has different manifestations or characteristics in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients remains unknown. We explored the differences in hemodynamics, echocardiography, and prognosis between IPAH and CTEPH patients with and without EIS.MethodsWe conducted a retrospective cross-sectional cohort study and included 161 PH patients at Shanghai Pulmonary Hospital. Demographic, echocardiography, pulmonary hemodynamic, and CPET variables were compared between patients with and without EIS stratified by IPAH and CTEPH. EIS was determined by CPET. Binary logistic regression analyses were performed to explore independent influencing factors of EIS. Cox survival analysis was used to quantify the impact of EIS on the prognosis of patients.ResultsExercise-induced venous-to-systemic shunt was found in approximately 17.4% of 86 IPAH patients and 20% of 75 CTEPH patients. All-cause mortality occurred in 43 (26.7%) patients during a median follow-up of 6.5 years. Compared with those without EIS, patients with EIS had higher peak end-tidal O2 and lower VO2/VE and tricuspid annular plane systolic excursion (TAPSE). Among the IPAH patients, EIS was associated with lower cardiac output, cardiac index, mixed venous oxygen saturation, VO2/VE, and TAPSE and higher VE/VCO2 and right ventricular end-diastolic transverse diameter. Logistic regression analysis indicated that VO2/VE was an independent factor influencing whether IPAH patients developed EIS during CPET. Cox logistic regression indicated that female IPAH patients or IPAH patients with higher VO2/VE and EIS had a better prognosis. Female IPAH patients had better 10-year survival. In IPAH patients without EIS, patients with higher VO2/VE had better 10-year survival. However, compared with CTEPH patients without EIS, those with EIS had similar echocardiographic, hemodynamic, CPET parameter results and 10-year survival.ConclusionExercise-induced venous-to-systemic shunt exhibits different profiles among IPAH and CTEPH patients. Among IPAH patients, those with EIS had worse peak end-tidal O2, VO2/VE, and TAPSE than those without EIS. VO2/VE was an independent factor of EIS among IPAH patients. IPAH patients with EIS, female sex or higher VO2/VE had better survival. However, the association between EIS and PAH severity or prognosis in CTEPH patients needs to be further explored.
Causal associations of hand grip strength with bone mineral density and fracture risk: A mendelian randomization study
Authors: Song Jidong , Liu Tun , Zhao Jiaxin , Wang Siyuan , Dang Xiaoqian , Wang Wei 
Published: December 2022

BackgroundMuscle strength has been shown to exert positive effects on bone health. The causal relationship between hand grip strength and osteoporosis is an important public health issue but is not fully revealed. The goal of this study was to investigate whether and to what extent hand grip strength affects bone mineral density (BMD) and fracture risk.MethodsWe conducted a state-of-the-art two-sample Mendelian randomization analysis. Genomewide significant (P&lt;5×10-8) single nucleotide polymorphisms associated with hand grip strength were obtained. Summary level data of BMD and fractures at different body sites (lumbar spine, heel, forearm and femoral neck) was obtained from a large-scale osteoporosis database. The inverse variance weighted method was the primary method used for analysis, and the weighted-median, MR-Egger were utilized for sensitivity analyses.ResultsThe results provided strong evidence that hand grip strength trait was causally and positively associated with lumbar spine BMD (β: 0.288, 95% CI: 0.079 to 0.497; P=0.007), while no causal relationship was found between hand grip strength and BMD at heel (β: -0.081, 95% CI: -0.232 to 0.070; P=0.295), forearm (β: 0.-0.101, 95% CI: -0.451 to 0.248; P=0.571) or femoral neck (β: 0.054, 95% CI: -0.171 to 0.278; P=0.639). In addition, no statistically significant effects were observed for hand grip strength on fracture risks (β: -0.004, 95% CI: -0.019 to 0.012; P=0.662).ConclusionsThis study showed a positive causal relationship between hand grip strength and lumbar BMD, which is the most common site of osteoporotic fracture, but did not find a causal relationship between hand grip strength and BMD of heel, forearm, or femoral neck. No statistically significant effect of hand grip strength on fracture risk was observed. This study indicates variations in the abilities of hand grip strength trait to causally influence BMD at different skeleton sites. These results should be considered in further studies and public health measures on osteoporosis prevention strategies.
Derivation and external validation of dendritic cell-related gene signatures for predicting prognosis and immunotherapy efficacy in bladder urothelial carcinoma
Authors: An Bingzheng , Guo Zhaoxin , Wang Junyan , Zhang Chen , Zhang Guanghao , Yan Lei 
Published: December 2022

BackgroundIn the regulation of tumor-related immunity, dendritic cells (DCs) are crucial sentinel cells; they are powerful to present antigens and initiate immune responses. Therefore, we concentrated on investigating the DC-related gene profile, prognosis, and gene mutations in bladder urothelial carcinoma (BLCA) patients to identify sensitivity to immunotherapy of patients.MethodsAccording to DC infiltration, BLCA patients were divided into two subgroups, and differentially expressed genes (DEGs) were obtained. Patients were classified by unsupervised clustering into new subgroups. The least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression were used to develop a DC-related risk model. CIBERSORT, xCell, and GSEA were used to infer immune cells’ relative abundance separately and enriched immune pathways.ResultsA total of 29 prognosis-related DEGs were identified from the unsupervised cluster. Among them, 22 genes were selected for constructing the DC-related risk model. The dendritic cell-related risk score (DCRS) can accurately distinguish patients with different sensitive responses to immunotherapy and overall survival outcomes. Furthermore, patients with ryanodine receptor 2 (RYR2) mutation had a better prognosis.ConclusionsThe DCRS played an essential part in immunity pathway and formation of TME diversity. Our study indicated that RYR2 mutation combined with DCRS is useful for predicting the prognosis and discovering appropriate patients for immunotherapy.
From linoleic acid to hexanal and hexanol by whole cell catalysis with a lipoxygenase, hydroperoxide lyase and reductase cascade in Komagataella phaffii
Authors: Hashem Chiam , Hochrinner Julius , Bürgler Moritz B. , Rinnofner Claudia , Pichler Harald , Winkler Margit 
Published: December 2022

Green leaf volatiles (GLVs) cover a group of mainly C6-and C9-aldehydes, -alcohols and -esters. Their name refers to their characteristic herbal and fruity scent, which is similar to that of freshly cut grass or vegetables. Lipoxygenases (LOXs) catalyze the peroxidation of unsaturated fatty acids. The resulting hydroperoxy fatty acids are then cleaved into aldehydes and oxo acids by fatty acid hydroperoxide lyases (HPLs). Herein, we equipped the yeast Komagataella phaffii with recombinant genes coding for LOX and HPL, to serve as a biocatalyst for GLV production. We expressed the well-known 13S-specific LOX gene from Pleurotus sapidus and a compatible HPL gene from Medicago truncatula. In bioconversions, glycerol induced strains formed 12.9 mM hexanal using whole cells, and 8 mM hexanol was produced with whole cells induced by methanol. We applied various inducible and constitutive promoters in bidirectional systems to influence the final ratio of LOX and HPL proteins. By implementing these recombinant enzymes in Komagataella phaffii, challenges such as biocatalyst supply and lack of product specificity can finally be overcome.
CMTM6 as a candidate risk gene for cervical cancer: Comprehensive bioinformatics study
Authors: Huang Xiaoting , Liu Wei , Liu Chunshan , Hu Jijie , Wang Baiyao , Ren Anbang , Huang Xiaona , Yuan Yawei , Liu Jinquan , Li Mingyi 
Published: December 2022

Background: CKLF like MARVEL transmembrane domain containing 6 (CMTM6) is an important programmed cell death 1 ligand 1 regulator (PD-L1). CMTM6 was reported as an important regulator of PD-L1 by promoting PD-L1 expression in tumor cells against T cells. However, the function of CMTM6 in cervical cancer is not well characterized. In addition, the role of CMTM6 in the induction of epithelial-mesenchymal transition (EMT) in the context of cervical cancer is unknown.Methods: In this study, we evaluated the role of CMTM6, including gene expression analysis, miRNA target regulation, and methylation characteristic, using multiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database. The expression of CMTM6 in cervical cancer tissues and non-cancerous adjacent tissues was assessed using immunohistochemistry. In vitro and in vivo function experiments were performed to explore the effects of CMTM6 on growth and metastasis of cervical cancer.Results: Human cervical cancer tissues showed higher expression of CMTM6 than the adjacent non-cancerous tissues. In vitro assays showed that CMTM6 promoted cervical cancer cell invasion, migration, proliferation, and epithelial-mesenchymal transition via activation of mitogen-activated protein kinase (MAPK) c-jun N-terminal kinase (JNK)/p38 signaling pathway. We identified transcription factors (TFs), miRNAs, and immune cells that may interact with CMTM6.Conclusion: These results indicate that CMTM6 is a potential therapeutic target in the context of cervical cancer.
Impact of daily vitamin D3 supplementation on the risk of vitamin D deficiency with the interaction of rs2282679 in vitamin D binding protein gene (GC) among overweight and obese children and adolescents: A one-year randomized controlled trial
Authors: Asghari Golaleh , Yuzbashian Emad , Nikparast Ali , Najd Hassan Bonab Leila , Mahdavi Maryam , Daneshpour Maryam S. , Hosseinpanah Farhad , Mirmiran Parvin 
Published: December 2022

BackgroundThe rs2282679 polymorphism in the vitamin D binding protein (DBP) gene may influence the response to vitamin D supplementation. Therefore, we examine the effect of 1-year vitamin D supplementation on vitamin D deficiency (VDD) with the interaction of rs2282679 polymorphism in overweight and obese children and adolescents.Materials and methodsThe participants (n = 300) were part of a randomized controlled trial who received a daily supplement of either 1,000 or 2,000 IU or four supplements of 1,000 IU weekly (equal to 600 IU daily) of vitamin D3 for 12 months. Genotyping was performed using amplification refractory mutation system polymerase chain reaction (ARMS-PCR).ResultsThe mean of 25(OH)D values at baseline for participants with the TT, TG, and GG genotypes were 15.4, 14.4, and 10.8 ng/mL, respectively, and were not different between the three genotype groups (P = 0.062). A significant reduction in VDD was observed after vitamin D supplementation with dosages of 1,000 or 2,000 IU compared to 600 IU. No significant association of genotypes with risk of VDD was observed in each intervention group after vitamin D supplementation, except, that individuals with TG genotype showed a higher risk of VDD compared to those with TT genotype in the 2,000 IU group after 6 months of supplementation [odds ratio (95% CI): 6.94; 1.30–37.02]. We observed no interaction between time duration, three genotypes, and dosages with serum 25(OH)D, calcium, phosphorus, alkaline phosphatase, and parathyroid hormone levels.ConclusionResponse to vitamin D supplementation by three doses of 600, 1,000, and 2,000 IU could not be affected by rs2282679 polymorphism during 12 months in overweight and obese children and adolescents.
HER-2-positive primary neuroendocrine neoplasms of the breast with signet ring feature: A case report and review of literature
Authors: Li Yunjin , Cao Yi , Wu Xiaoying , Liu Ruijie , Wang Kuansong 
Published: December 2022

BackgroundPrimary neuroendocrine neoplasm of the breast (BNEN) is an uncommon breast neoplasm, and in most cases, it presents as hormone receptors positive and HER-2 negative. Moreover, in neuroendocrine neoplasms (NENs), the signet ring feature is a rare morphological subtype, and only a few cases have been reported. Here, we report the case of a primary breast neuroendocrine neoplasm with an unusual signet ring cell appearance in this paper. The documentation of this case, combined with a review of the literature, may add to existing knowledge about the outcome and management of this rare tumor.MethodsIn the present review, we describe a unique case of HER-2-positive primary BNEN with a signet ring feature that has not been reported in English. Additionally, we performed a literature search of the PubMed and Web of Science databases and calculated statistics for clinical data and follow-up.ResultsOur literature search, excluding non-English literature, identified 15 articles with data from 24 cases, including ours. The mean age was 51.25 years (range, 30–79 years), and there were 13 male patients (54%) and 11 female patients (46%). Of the 24 cases, some cases (11/24) were associated with lymph node metastases, a few cases (6/24) had distant metastasis, and the vast majority of cases (23/24) occurred in the digestive system. Primary hepatic signet ring cell neuroendocrine tumor showed slow progression and good prognosis. Lymph node involvement was identified in one of eight (12.5%) documented cases, and one of eight (12.5%) reported cases presented with distant metastatic disease. However, the prognosis of neuroendocrine tumors with signet ring cells in the pancreas and stomach was poor. Lymph node involvement was identified in 9 of 15 (60%) documented cases, and 5 of 15 (33.3%) reported cases presented with distant metastatic disease.ConclusionNENs with a signet ring feature is uncommon, and this is the first case report of its occurrence in the breast. Current knowledge is limited to anecdotal experience based on case reports and small case series. We provide a literature review to summarize knowledge about this rare entity.
Nivolumab-induced capillary leak syndrome associated with chylothorax in a melanoma patient: A case report and review of the literature
Authors: Neuville Carole , Aubin François , Puzenat Eve , Popescu Dragos , Crepin Thomas , Nardin Charlée 
Published: December 2022

IntroductionAdverse events (AEs) of immune checkpoint inhibitors (ICIs) are frequent and mainly due to an overactivity of the immune system leading to excessive inflammatory responses (immune-related AE) that can affect any organ of the body. Beside the most frequent AEs, there are rare AEs whose diagnosis and treatment can be challenging. We report here a singular case of capillary leak syndrome (CLS) associated with chylothorax occurring in a patient who has been treated with adjuvant nivolumab (anti-PD1) for resected AJCC stage IIB primary melanoma.Case presentationA 43-year-old woman was diagnosed with a nodular stage IIB melanoma of her left thigh, according to the AJCC 8th edition (T3bN0M0). The woman was treated with adjuvant nivolumab. She stopped the treatment after 4 infusions due to thrombopenia. Three months later, she developed facial and leg edema and ascites due to capillary leak syndrome. The CLS was associated with chylothorax and elevated vascular endothelial growth factor. The patient was initially treated with several pleural puncturing and steroids. CLS and chylothorax progressively decreased with intravenous immunoglobulins and fat-free diet without recurrence of melanoma at one-year follow-up.ConclusionCLS is a rare and potentially life-threatening AE of ICIs such as anti-PD1. This AE may be associated with chylothorax probably related to lymphatic permeability induced by anti-PD1.
Tumor genomic profiling and personalized tracking of circulating tumor DNA in Vietnamese colorectal cancer patients
Authors: Nguyen Huu Thinh , Nguyen Trieu Vu , Nguyen Hoang Van-Anh , Tran Duc Huy , Le Trinh Ngoc An , Le Minh Triet , Nguyen Tran Tuan-Anh , Pham Thanh Huyen , Dinh Thi Cuc , Nguyen Tien Sy , Nguyen The Ky Cuong , Mai Hoa , Chu Minh Tuan , Pham Dinh Hoang , Nguyen Xuan Chi , Ngo Ha Thien My , Nguyen Duy Sinh , Nguyen Du Quyen , Lu Y-Thanh , Do Thi Thanh Thuy , Truong Dinh Kiet , Nguyen Quynh Tho , Nguyen Hoai-Nghia , Giang Hoa , Tu Lan N. 
Published: December 2022

BackgroundColorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients. During post-operative surveillance, clinical tools are limited to stratify risk of recurrence and detect residual disease.MethodIn this prospective multi-center study, 103 CRC patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived somatic mutations in 95 cancer-associated genes. Our bioinformatic algorithm identified top mutations unique for individual patient, which were then used to monitor the presence of circulating tumor DNA (ctDNA) in serial plasma samples.ResultsThe top mutated genes in our cohort were APC, TP53 and KRAS. 41.7% of the patients harbored KRAS and NRAS mutations predictive of resistance to Cetuximab and Panitumumab respectively; 41.7% had mutations targeted by either approved or experimental drugs. Using a personalized subset of top ranked mutations, we detected ctDNA in 90.5% of the pre-operative plasma samples, whereas carcinoembryonic antigen (CEA) was elevated in only 41.3% of them. Interim analysis after 16-month follow-up revealed post-operative detection of ctDNA in two patients that had recurrence, with the lead time of 4-10.5 months ahead of clinical diagnosis. CEA failed to predict recurrence in both cases.ConclusionOur assay showed promising dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies in CRC patients. This could lay foundation to empower precision cancer medicine in Vietnam and other developing countries.
De Novo transcriptome combined with physiological analyses revealed key genes for cadmium accumulation in Zhe-Maidong (Ophiopogon japonicus)
Authors: Zhao Qian , Li Qing , Lin Shuting , Hou Ruijun , Liu Jianying , Tao Yachen , Li Ye , Zhou Yifeng , Ye Zihong , Yu Xiaoping , Huang Jun 
Published: December 2022

IntroductionCadmium (Cd) is a toxic heavy metal that severely threatens safe food production. Zhe-Maidong, a well-known Chinese traditional herbal medicine, is susceptible to Cd stress. However, the characteristics of Cd transformation and migration, as well as the regulatory system for genes conferring Cd accumulation of Zhe-Maidong, remains an essential issue to be addressed.MethodsZhe-Maidong seedling growth in Cd-contaminated and uncontaminated soil was conducted for 90 days. The Cd concentration was determined by inductively coupled plasma-mass spectrometry, and the Cd2+ fluorescence probe detected Cd distributions. The root transcriptome of Zhe-Maidong was then evaluated using various Cd stress hydroponic treatments designated Cd-0, Cd-M, and Cd-H.Results and discussionThe enrichment factor (EF) value in the root was four times that of the leaves, indicating that the root has a high ability to absorb and accumulate Cd. The Cd2+ were mainly distributed in the root hair and the epidermis in both roots and leaves, revealing that the epidermal cells of roots may collect Cd2+ and also have an outstanding role in Cd2+ uptake. A total of 50 DEGs involved in Cd translocation and accumulation were identified. Among these DEGs, ANN, ABCC2/4, HMA1- 5, and CCX gene expression were positively correlated with EF-root, EF-leaf, EF-total, Cd-leaf, Cd-root, and Cd-plant, indicating their role in Cd transport and accumulation under Cd-stress. These data could be helpful in uncovering the Cd accumulation characteristics in Zhe-Maidong, as well as provide a bioinformatic foundation for investigations on finding gene functions and the screening of candidate genes related to Cd accumulation.
Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant
Authors: Khazaie Habibolah , Sadeghi Masoud , Khazaie Sepideh , Hirshkowitz Max , Sharafkhaneh Amir 
Published: December 2022

Study objectivesRecent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.MethodsWe conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval of each outcome.ResultsOur search showed eight articles (five for suvorexant and three for lemborexant). Results of diary measures, rating scales, polysomnography results, treatment discontinuation, and adverse events were measured. All efficacy outcome measures favorably and significantly differed in the suvorexant compared to placebo. Safety profile did not differ significantly except for somnolence, excessive daytime sleepiness/sedation, fatigue, back pain, dry mouth, and abnormal dreams. Important adverse events including hallucinations, suicidal ideation/behavior and motor vehicle accidents did not differ between suvorexant and placebo. All the efficacy outcomes significantly differed between lemborexant 5 and lemborexant 10 compared to placebo. Somnolence rate for lemborexant 5 and lemborexant 10 and nightmare for lemborexant 10 were significantly higher than placebo.ConclusionThe present meta-analysis reported that suvorexant and lemborexant are efficacious and safe agents for the patients with insomnia. Further data in patients with insomnia and various comorbid conditions are needed.