bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling Blautia at high taxonomic resolution reveals correlations with cognitive dysfunction in Chinese children with Down syndrome
Authors: Hou Xueyu , Wu Na , Ren Shimeng , Wang Xinjuan , Mu Qing , Zhang Yang , Wang Shan , Yu Weidong , Guo Jingzhu 
Published: February 2023

IntroductionDown syndrome (DS), the presence of a supernumerary chromosome 21, is associated with cognitive dysfunction caused by early neurodegenerative processes. Alterations in the gut microbiota were observed in Chinese children with DS, and the genus Blautia was associated with cognitive function in these children. Therefore, it is crucial to understand the detailed composition of this group at the species level and to explore the effect of specific species on cognitive function.MethodsIn this study, Blautia-specific amplicon sequencing was conducted to identify the specific Blautia species in 15 children with DS and 15 matched healthy children.ResultsThe taxonomic analyses suggested that the Blautia taxa were clustered by disease status. The diversity of Blautia at the species level differed between DS patients and healthy controls, with the abundances of Blautia massiliensis and Blautia argi decreasing in DS children, while Blautia faecis was increased. Acetic acid, one of the metabolites of Blautia, was significantly reduced in the DS group. Of particular interest, Kyoto Encyclopaedia of Genes and Genomes analysis revealed decreased modules related to starch and sucrose metabolism and glycolysis. In addition, B. argi was positively related to DS cognitive scores, and B. faecis was negatively related to cognitive function, implying its role on the DS cognitive impairments. DiscussionOur study has important implications for understanding the important effects of specific species of Blautia on cognitive function and thus possibly provides a new strategy for future studies of cognitive improvement in individuals with DS.
The efficacy and adverse events of conventional and second-generation androgen receptor inhibitors for castration-resistant prostate cancer: A network meta-analysis
Authors: Zhang Xianlu , Zhang Gejun , Wang Jianfeng , Bi Jianbin 
Published: February 2023

BackgroundSecond-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of direct comparison of the therapeutic effects and adverse events between the conventional ARI (bicalutamide) and three second-generation ARIs (enzalutamide, apalutamide and darolutamide).MethodsOur network meta-analysis evaluated therapeutic effects and adverse events of the conventional ARI (bicalutamide) and the second-generation ARIs in treating CRPC. We systematically searched the Pubmed, Cochrane library and Embase databases for studies published until October 2022 and only randomized clinical trials (RCTs) were included. The progression-free survival, prostate-specific antigen (PSA) progression-free survival, overall survival (PFS/PSA-PFS/OS), PSA response rate and relative adverse events (AEs) of CRPC patients were collected and synthesized. We then performed subgroup analysis. The non-metastatic and metastatic CRPC (nm/mCRPC) observations were analyzed separately. Data analyses were performed using R software (4.2.1) based on Bayesian framework.Results6,993 subjects from seven eligible RCTs were analyzed. Enzalutamide, apalutamide and darolutamide were more effective than bicalutamide in treating CRPC, and the performance of darolutamide was slightly worse than the other two second-generation ARIs. Similar adverse events rate were observed among the second-generation ARIs and bicalutamide. Apalutamide showed a slightly higher rate of Grade 3+ AEs, percentages of AE-related drug withdrawals and AE-related mortality. Patients receiving enzalutamide had significantly higher rate of hypertension and fatigue. In subgroup analysis, enzalutamide showed better therapeutic effects compared with bicalutamide in both nmCRPC and mCRPC groups. In nmCRPC group, enzalutamide and apalutamide had more benefits on PFS and PSA-PFS compared with darolutamide. We displayed the probability ranking map of PFS, PSA-PFS, OS, time to cytotoxic chemotherapy, PSA response rate and relative AE outcomes.ConclusionThe current network meta-analysis indicated that the second-generation ARIs were superior to the conventional ARI, bicalutamide. The three second-generation ARIs showed incomplete equivalence on CRPC treatment. The darolutamide was slightly less effective compared with enzalutamide and apalutamide. The adverse events of apalutamide were worse than the others, but no statistical significance was observed among these vital AEs. All ARIs were generally well-tolerated. These results may provide reference to clinical decision and further direct comparison trials.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022370842.
The clinical characteristics and gene mutations associated with thyroid hormone resistance syndrome coexisting with pituitary tumors
Authors: Zhao Junyu , Xu Lusi , Li Chunyu , Wang Fei , Liao Lin , Dong Jianjun 
Published: February 2023

AimsResistance to thyroid hormone (RTH) and pituitary tumors are both rare diseases, and the differential diagnosis of these two diseases is difficult in some cases. There are also patients who have both conditions, making diagnosis more difficult. To better understand this aspect, we analyzed the clinical characteristics and gene mutations of RTH coexisting with pituitary tumors.MethodsDatabase retrieval was conducted in the PubMed, Cochrane Library, and SinoMed databases, and the search contents were case reports or case series of patients with RTH coexisting with pituitary tumors. The demographic, clinical manifestations, and imaging characteristics of pituitary tumors and gene mutations were summarized.ResultsThirteen articles involving 16 patients with RTH coexistent with pituitary tumors, consisting of 13 female patients, one male patient, and two patients with unknown sex, were included. The patients were 10 to 79 years old and most patients were 41-55 years old (43.75%). The 16 patients were from seven different countries and three continents (Asia, the Americas, and Europe). All the patients showed an abnormal secretion of TSH, and five patients underwent transsphenoidal surgery. Finally, four patients were pathologically confirmed to have TSHoma. A total of 11 different mutations occurred at nine amino acid sequence sites (251, 310, 344, 347, 383, 429, 435, 438, and 453). Two different mutations occurred in both the no. 435 and no. 453 amino acid sequences. Fourteen patients provided their treatment histories, and all had undergone different treatment regimens.ConclusionsPatients with both RTH and pituitary tumors had multiple clinical manifestations and different thyroid functions, imaging characteristics of pituitary tumors, genetic mutations of THRβ, and treatments. However, due to the limited number of cases, the patients were mainly women. Further studies with more cases that focus on the mechanism are still needed.
Integrating single-cell RNA-seq and bulk RNA-seq to construct prognostic signatures to explore the role of glutamine metabolism in breast cancer
Authors: Pei Shengbin , Zhang Pengpeng , Chen Huilin , Zhao Shuhan , Dai Yuhan , Yang Lili , Kang Yakun , Zheng Mingjie , Xia Yiqin , Xie Hui 
Published: February 2023

BackgroundAlthough breast cancer (BC) treatment has entered the era of precision therapy, the prognosis is good in the case of comprehensive multimodal treatment such as neoadjuvant, endocrine, and targeted therapy. However, due to its high heterogeneity, some patients still cannot benefit from conventional treatment and have poor survival prognoses. Amino acids and their metabolites affect tumor development, alter the tumor microenvironment, play an increasingly obvious role in immune response and regulation of immune cell function, and are involved in acquired and innate immune regulation; therefore, amino acid metabolism is receiving increasing attention.MethodsBased on public datasets, we carried out a comprehensive transcriptome and single-cell sequencing investigation. Then we used 2.5 Weighted Co-Expression Network Analysis (WGCNA) and Cox to evaluate glutamine metabolism-related genes (GRGs) in BC and constructed a prognostic model for BC patients. Finally, the expression and function of the signature key gene SNX3 were examined by in vitro experiments.ResultsIn this study, we constituted a risk signature to predict overall survival (OS) in BC patients by glutamine-related genes. According to our risk signature, BC patients can obtain a Prognostic Risk Signature (PRS), and the response to immunotherapy can be further stratified according to PRS. Compared with traditional clinicopathological features, PRS demonstrated robust prognostic power and accurate survival prediction. In addition, altered pathways and mutational patterns were analyzed in PRS subgroups. Our study sheds some light on the immune status of BC. In in vitro experiments, the knockdown of SNX3, an essential gene in the signature, resulted in a dramatic reduction in proliferation, invasion, and migration of MDA-MB-231 and MCF-7 cell lines.ConclusionWe established a brand-new PRS consisting of genes associated with glutamine metabolism. It expands unique ideas for the diagnosis, treatment, and prognosis of BC.
Valuing changes in the portfolio of service flows from climate-induced extremes on a linked food, energy, water system (C-FEWS)
Authors: Chang Joseph W. , Ando Amy W. , Chen Mengye 
Published: February 2023

Introduction:Recent work examining the impact of climate-change induced extremes on food-energy-water systems (FEWS) estimates the potential changes in physical flows of multiple elements of the systems. Climate adaptation decisions can involve tradeoffs between different system outcomes. Thus, it is important for decision makers to consider the potential changes in monetary value attributed to the observed changes in physical flows from these events, since the value to society of a unit change in an outcome varies widely between thing like food and energy production, water quality, and carbon sequestration.Methods:We develop a valuation tool (FEWSVT) that applies theoretically sound valuation techniques to estimates changes in value for four parameters within the food-energy-water nexus. We demonstrate the utility of the tool through the application of a case study that analyzes the monetary changes in value of a modelled heat wave scenario relative to historic (baseline) conditions in two study regions in the United States.Results:We find that food (corn and soybeans) comprises the majority (89%) of total changes in value, as heatwaves trigger physical changes in corn and soybeans yields. We also find that specifying overly simplified and incorrect valuation methods lead to monetary values that largely differ from FEWSVT results that use accepted valuation methods.Discussion:These results demonstrate the value in considering changes in monetary value instead of just physical flows when making decisions on how to distribute investments and address the many potential impacts of climate change-induced extremes.
BMP-6 promotes type 2 immune response during enhancement of rat mandibular bone defect healing
Authors: McColl Logan F. , Chen Xizhao , Solga Michael D. , Schlegel Kailo , Haughey Sean P. , Lobo Peter I. , Fread Kristen , Zunder Eli , Cha Ryan , Park Stephen , Christophel J. Jared , Cui Quanjun , Dighe Abhijit S. 
Published: February 2023

IntroductionBone morphogenetic proteins (BMPs) are used as key therapeutic agents for the treatment of difficult fractures. While their effects on osteoprogenitors are known, little is known about their effects on the immune system.MethodsWe used permutations of BMP-6 (B), vascular endothelial growth factor (V), and Hedgehog signaling pathway activator smoothened agonist (S), to treat a rat mandibular defect and investigated healing outcomes at week 8, in correlation with the cellular landscape of the immune cells in the fracture callus at week 2.ResultsMaximum recruitment of immune cells to the fracture callus is known to occur at week 2. While the control, S, V, and VS groups remained as nonunions at week 8; all BMP-6 containing groups - B, BV, BS and BVS, showed near-complete to complete healing. This healing pattern was strongly associated with significantly higher ratios of CD4 T (CD45+CD3+CD4+) to putative CD8 T cells (CD45+CD3+CD4-), in groups treated with any permutation of BMP-6. Although, the numbers of putative M1 macrophages (CD45+CD3-CD11b/c+CD38high) were significantly lower in BMP-6 containing groups in comparison with S and VS groups, percentages of putative - Th1 cells or M1 macrophages (CD45+CD4+IFN-γ+) and putative – NK, NKT or cytotoxic CD8T cells (CD45+CD4-IFN-γ+) were similar in control and all treatment groups. Further interrogation revealed that the BMP-6 treatment promoted type 2 immune response by significantly increasing the numbers of CD45+CD3-CD11b/c+CD38low putative M2 macrophages, putative - Th2 cells or M2 macrophages (CD45+CD4+IL-4+) cells and putative – mast cells, eosinophils or basophils (CD45+CD4-IL-4+ cells). CD45- non-haematopoietic fractions of cells which encompass all known osteoprogenitor stem cells populations, were similar in control and treatment groups.DiscussionThis study uncovers previously unidentified regulatory functions of BMP-6 and shows that BMP-6 enhances fracture healing by not only acting on osteoprogenitor stem cells but also by promoting type 2 immune response.
Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy
Authors: Mastelic-Gavillet Beatris , Sarivalasis Apostolos , Lozano Leyder Elena , Lofek Sebastien , Wyss Tania , Melero Ignacio , de Vries I. Jolanda M. , Harari Alexandre , Romero Pedro , Kandalaft Lana Elias , Viganó Selena 
Published: February 2023

BackgroundThe use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced.MethodsWe recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry.ResultsWe show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141+ DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased.ConclusionsOur study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets.
Associations between trajectories of cardiovascular risk factor change and cognitive impairment in Chinese elderly: A nationwide cohort study
Authors: Duan Xinyu , Dang Yusong , Kang Chenxi , Rong Peixi , Yan Mingxin , Zhang Shutong , Cui Jing , Zhao Yaling , Chen Fangyao , Zhou Jing , Wang Duolao , Pei Leilei 
Published: February 2023

ObjectivesThis study aimed to investigate the relationship between long-term trajectories of changes in cardiovascular risk factors (CVRFs) and the risk of cognitive impairment among Chinese adults over 60 years old.MethodsData were obtained from the Chinese Longitudinal Healthy Longevity Survey 2005–2018. Cognitive function was evaluated longitudinally through the Chinese version of the Mini-Mental State Examination (C-MMSE), and cognitive impairment (C-MMSE ≤23) was used as the main outcome variable. The cardiovascular risk factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and body mass index (BMI), were continuously measured in the follow-up duration. The patterns of trajectories of changes in CVRFs were derived from the latent growth mixture model (LGMM). The Cox regression model was used to evaluate the cognitive impairment hazard ratio (HR) across different CVRF trajectories.ResultsA total of 5,164 participants aged ≥60 years with normal cognitive function at baseline were included in the study. After a median follow-up of 8 years, 2,071 participants (40.1%) developed cognitive impairment (C-MMSE ≤ 23). The four-class trajectories of SBP and BMI were obtained by means of LGMM, and the trajectories of DBP, MAP, and PP were grouped into a three-class subgroup. In the final adjusted Cox model, the lowered SBP [adjusted HR (aHR): 1.59; 95% CI: 1.17–2.16], lowered PP (aHR: 2.64; 95% CI: 1.66–4.19), and progressively obese (aHR: 1.28; 95% CI: 1.02–1.62) and stable slim (aHR: 1.13; 95% CI: 1.02–1.25) were associated with the higher risk of cognitive impairment. Low stable DBP (aHR: 0.80; 95% CI: 0.66–0.96) and elevated PP (aHR: 0.76; 95% CI: 0.63–0.92) decreased the risk for cognitive impairment among participants.ConclusionLowered SBP, lowered PP, progressive obesity, and stable slim increased the risk for cognitive impairment in the Chinese elderly. Low stable DBP and elevated PP were protective against cognitive impairment, but more DBP lowering and ≥25 mmHg growth in PP contributed to a higher risk of cognitive impairment. The findings have important implications for preventing cognitive impairment in elder adults based on the long-term trajectories of changes in CVRFs.
Signature of miRNAs derived from the circulating exosomes of patients with amyotrophic lateral sclerosis
Authors: Cheng Yang-Fan , Gu Xiao-Jing , Yang Tian-Mi , Wei Qian-Qian , Cao Bei , Zhang Yang , Shang Hui-Fang , Chen Yong-Ping 
Published: February 2023

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder (NDS) with unclear pathophysiology and few therapeutic options. Mutations in SOD1 and C9orf72 are the most common in Asian and Caucasian patients with ALS, respectively. Aberrant (microRNAs) miRNAs found in patients with gene-mutated ALS may be involved in the pathogenesis of gene-specific ALS and sporadic ALS (SALS). The aim of this study was to screen for differentially expressed miRNAs from exosomes in patients with ALS and healthy controls (HCs) and to construct a miRNA-based diagnostic model to classify patients and HCs.MethodsWe compared circulating exosome-derived miRNAs of patients with ALS and HCs using the following two cohorts: a discovery cohort (three patients with SOD1-mutated ALS, three patients with C9orf72-mutated ALS, and three HCs) analyzed by microarray and a validation cohort (16 patients with gene-mutated ALS, 65 patients with SALS, and 61 HCs) confirmed by RT-qPCR. The support vector machine (SVM) model was used to help diagnose ALS using five differentially expressed miRNAs between SALS and HCs.ResultsA total of 64 differentially expressed miRNAs in patients with SOD1-mutated ALS and 128 differentially expressed miRNAs in patients with C9orf72-mutated ALS were obtained by microarray compared to HCs. Of these, 11 overlapping dysregulated miRNAs were identified in both groups. Among the 14 top-hit candidate miRNAs validated by RT-qPCR, hsa-miR-34a-3p was specifically downregulated in patients with SOD1-mutated ALS, while hsa-miR-1306-3p was downregulated in ALS patients with both SOD1 and C9orf72 mutations. In addition, hsa-miR-199a-3p and hsa-miR-30b-5p were upregulated significantly in patients with SALS, while hsa-miR-501-3p, hsa-miR-103a-2-5p, and hsa-miR-181d-5p had a trend to be upregulated. The SVM diagnostic model used five miRNAs as features to distinguish ALS from HCs in our cohort with an area under receiver operating characteristic curve (AUC) of 0.80.ConclusionOur study identified aberrant miRNAs from exosomes of SALS and ALS patients with SOD1/C9orf72 mutations and provided additional evidence that aberrant miRNAs were involved in the pathogenesis of ALS regardless of the presence or absence of the gene mutation. The machine learning algorithm had high accuracy in predicting the diagnosis of ALS, shedding light on the foundation for the clinical application of blood tests in the diagnosis of ALS, and revealing the pathological mechanisms of the disease.
Spiral drawing analysis with a smart ink pen to identify Parkinson's disease fine motor deficits
Authors: Toffoli Simone , Lunardini Francesca , Parati Monica , Gallotta Matteo , De Maria Beatrice , Longoni Luca , Dell'Anna Maria Elisabetta , Ferrante Simona 
Published: February 2023

IntroductionSince the uptake of digitizers, quantitative spiral drawing assessment allowed gaining insight into motor impairments related to Parkinson's disease. However, the reduced naturalness of the gesture and the poor user-friendliness of the data acquisition hamper the adoption of such technologies in the clinical practice. To overcome such limitations, we present a novel smart ink pen for spiral drawing assessment, intending to better characterize Parkinson's disease motor symptoms. The device, used on paper as a normal pen, is enriched with motion and force sensors.MethodsForty-five indicators were computed from spirals acquired from 29 Parkinsonian patients and 29 age-matched controls. We investigated between-group differences and correlations with clinical scores. We applied machine learning classification models to test the indicators ability to discriminate between groups, with a focus on model interpretability.ResultsCompared to control, patients' drawings were characterized by reduced fluency and lower but more variable applied force, while tremor occurrence was reflected in kinematic spectral peaks selectively concentrated in the 4–7 Hz band. The indicators revealed aspects of the disease not captured by simple trace inspection, nor by the clinical scales, which, indeed, correlate moderately. The classification achieved 94.38% accuracy, with indicators related to fluency and power distribution emerging as the most important.ConclusionIndicators were able to significantly identify Parkinson's disease motor symptoms. Our findings support the introduction of the smart ink pen as a time-efficient tool to juxtapose the clinical assessment with quantitative information, without changing the way the classical examination is performed.