bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a nomogram for predicting rapid relapse in triple-negative breast cancer patients treated with neoadjuvant chemotherapy
Authors: Ma Tao , Liu Xin-Yu , Cai Shuang-Long , Zhang Jin 
Published: September 2024

BackgroundTriple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. This study aimed to develop and validate a nomogram based on clinicopathological characteristics to predict rapid relapse in TNBC patients treated with neoadjuvant chemotherapy (NAC) first.MethodsThe clinicopathological data of 504 TNBC patients treated with NAC first in Tianjin Medical University Cancer Hospital were analyzed retrospectively, with 109 rapid relapsed patients, and 395 non-rapid relapsed patients, respectively. Based on clinicopathologic characteristics, and follow-up data were analyzed. The independent predictors of clinicopathological characteristics were identified by logistic regression analysis and then used to build a nomogram. The concordance index (C-index), the area under the curve (AUC) of receiver operating characteristic (ROC), and calibration plots were used to evaluate the performance of the model.ResultsUnivariate and multivariate logistic regression analyses showed that age at diagnosis (age≥50 years, OR = 0.325,95% CI:0.137–0.771), Nodal staging (N3 staging, OR = 13.669,95% CI:3.693–50.592),sTIL expression levels (sTIL intermediate expression, OR = 0.272,95% CI:0.109–0.678; sTIL high expression, OR = 0.169,95% CI:0.048–0.594), and NAC response (ORR, OR = 0.059,95% CI:0.024–0.143) were independent predictors of rapid relapse in TNBC patients treated with NAC firstly. Among these independent predictors, age ≥ 50 years, sTIL intermediate expression, sTIL high expression, and ORR in NAC were independent protective factors for rapid relapse in TNBC NAC patients. N3 staging was an independent risk factor for rapid relapse in TNBC NAC patients. The ROC curve, calibration curve, and decision curve analysis were used to validate the model. The C-Index of the training sets and validation sets were 0.938 and 0.910, respectively. The Brier scores of the training sets and validation sets were 0.076 and 0.097, respectively.ConclusionThis study developed and verified a nomogram for predicting rapid relapse in TNBC NAC patients, and the predictive model had high discrimination and accuracy.
Additive engineering for efficient wide-bandgap perovskite solar cells with low open-circuit voltage losses
Authors: Yu Xixi , He Huxue , Hui Yunuo , Wang Hua , Zhu Xing , Li Shaoyuan , Zhu Tao 
Published: September 2024

High-performance wide-bandgap (WBG) perovskite solar cells are used as top cells in perovskite/silicon or perovskite/perovskite tandem solar cells, which possess the potential to overcome the Shockley-Queisser limitation of single-junction perovskite solar cells (PSCs). However, WBG perovskites still suffer from severe nonradiative recombination and large open-circuit voltage (Voc) losses, which restrict the improvement of PSC performance. Herein, we introduce 3,3′-diethyl-oxacarbo-cyanine iodide (DiOC2(3)) and multifunctional groups (C=N, C=C, C-O-C, C-N) into perovskite precursor solutions to simultaneously passivate deep level defects and reduce recombination centers. The multifunctional groups in DiOC2(3) coordinate with free Pb2+ at symmetric sites, passivating Pb vacancy defects, effectively suppressing nonradiative recombination, and maintaining considerable stability. The results reveal that the power conversion efficiency (PCE) of the 1.68 eV WBG perovskite solar cell with an inverted structure increases from 18.51% to 21.50%, and the Voc loss is only 0.487 V. The unpackaged device maintains 95% of its initial PCE after 500 h, in an N2 environment at 25°C.
AI-based cluster analysis enables outcomes prediction among patients with increased LVM
Authors: Loutati Ranel , Kolben Yotam , Luria David , Amir Offer , Biton Yitschak 
Published: September 2024

BackgroundThe traditional classification of left ventricular hypertrophy (LVH), which relies on left ventricular geometry, fails to correlate with outcomes among patients with increased LV mass (LVM).ObjectivesTo identify unique clinical phenotypes of increased LVM patients using unsupervised cluster analysis, and to explore their association with clinical outcomes.MethodsAmong the UK Biobank participants, increased LVM was defined as LVM index ≥72 g/m2 for men, and LVM index ≥55 g/m2 for women. Baseline demographic, clinical, and laboratory data were collected from the database. Using Ward's minimum variance method, patients were clustered based on 27 variables. The primary outcome was a composite of all-cause mortality with heart failure (HF) admissions, ventricular arrhythmia, and atrial fibrillation (AF). Cox proportional hazard model and Kaplan-Meier survival analysis were applied.ResultsIncreased LVM was found in 4,255 individuals, with an average age of 64 ± 7 years. Of these patients, 2,447 (58%) were women. Through cluster analysis, four distinct subgroups were identified. Over a median follow-up period of 5 years (IQR: 4-6), 100 patients (2%) died, 118 (2.8%) were admissioned due to HF, 29 (0.7%) were admissioned due to VA, and 208 (5%) were admissioned due to AF. Univariate Cox analysis demonstrated significantly elevated risks of major events for patients in the 2nd (HR = 1.6; 95% CI 1.2–2.16; p &lt; .001), 3rd (HR = 2.04; 95% CI 1.49–2.78; p &lt; .001), and 4th (HR = 2.64; 95% CI 1.92–3.62; p &lt; .001) clusters compared to the 1st cluster. Further exploration of each cluster revealed unique clinical phenotypes: Cluster 2 comprised mostly overweight women with a high prevalence of chronic lung disease; Cluster 3 consisted mostly of men with a heightened burden of comorbidities; and Cluster 4, mostly men, exhibited the most abnormal cardiac measures.ConclusionsUnsupervised cluster analysis identified four outcomes-correlated clusters among patients with increased LVM. This phenotypic classification holds promise in offering valuable insights regarding clinical course and outcomes of patients with increased LVM.
The causal effects of inflammatory and autoimmune skin diseases on thyroid diseases: evidence from Mendelian randomization study
Authors: You Ruixuan , Duan Jiayue , Zhou Yong , Yu Jiangfan , Zou Puyu , Wei Yi , Chai Ke , Zeng Zhuotong , Xiao Yangfan , Yuan Lingqing , Xiao Rong 
Published: September 2024

BackgroundTo clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses.ParticipantsGenetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry.Main measuresThe inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO).Key resultsAD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p &lt; 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p &lt; 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism.ConclusionThe findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships.
Case report: Second report of neuromuscular syndrome caused by biallelic variants in ASCC3
Authors: Li Wang , Li Zhongliang , Fu Junhui , Xu Kaili , Mei Daoqi , Wang Xiaona , Li Taisong , Du Xilong 
Published: September 2024

IntroductionActivating Signal Cointegrator 1 Complex, Subunit 3 (ASCC3) has been implicated in the pathogenesis of neurodevelopmental disorders and neuromuscular diseases (MIM: 620700). This paper analyzes the clinical manifestations of three patients with developmental delay caused by ASCC3 genetic variation. Additionally, we discuss the previously reported clinical features of these patients along with our own findings, thereby enhancing our understanding of these genetic disorders and providing valuable insights into diagnosis, treatment, and potential interventions for affected individuals.MethodsIn this study, we utilized trio-whole-exome sequencing (Trio-WES) and trio-copy number variations sequencing (Trio-CNV-seq) to analyze three unique families diagnosed with developmental delay caused by variation in ASCC3. Additionally, we retrospectively examined eleven previously reported ASCC3 genetic variations exhibiting similar clinical features.ResultsProband I (family 1) and Proband III (family 3) exhibited global developmental delays, characterized by intellectual disability, motor impairment, language retardation, lower muscle strength, and reduced muscle tone in their extremities. Proband II (family 2) presented poor response and dysphagia during feeding within 7 days after birth, clinical examination displayed short limbs, long trunk proportions, and clenched fists frequently observed alongside high muscle tone in his limbs -all indicative signs of developmental delay. Trio-WES revealed compound heterozygous variants in ASCC3 inherited from their parents. Proband I carried c. [489 dup]; [1897C&gt;T], proband II carried c. [2314C&gt;T]; [5002T&gt;A], and proband III carried c. [5113G&gt;T]; [718delG] variations, respectively.ConclusionThis study present the first report of Chinese children carrying compound heterozygous genetic variants in ASCC3 with LOF variants, elucidating the relationship between these variants and various aspects of intellectual disability. This novel finding expands the existing spectrum of ASCC3 variations.
Multi-omics landscape of Interferon-stimulated gene OASL reveals a potential biomarker in pan-cancer: from prognosis to tumor microenvironment
Authors: Liu Yi , Yang Runyu , Zhang Mengyao , Yang Bingyu , Du Yue , Feng Hui , Wang Wenjuan , Xue Busheng , Niu Fan , He Pengcheng 
Published: September 2024

BackgroundOASL (Oligoadenylate Synthetase-Like), an interferon-induced protein in the OAS family, plays a significant role in anti-viral response. Studies have demonstrated its association with prognosis of certain tumors. However, the mechanism through which OASL affects tumors is unclear. A systemic pan-cancer study of OASL needs to be illustrated.MethodsAnalysis of OASL expression across 33 tumors was conducted utilizing TCGA, GTEx and CPTAC databases. COX and Log-Rank regressions were employed to calculate the prognosis. We validated the impact of OASL on apoptosis, migration, and invasion in pancreatic cancer cell lines. Moreover, we employed seven algorithms in bulk data to investigate the association of OASL expression and immune cell infiltration within tumor immune microenvironment (TIME) and ultimately validated at single-cell transcriptome level.ResultsWe discovered elevated expression of OASL and its genetic heterogeneity in certain tumors, which link closely to prognosis. Validation experiments were conducted in PAAD and confirmed these findings. Additionally, OASL regulates immune checkpoint ligand such as programmed death ligand 1 (PD-L1), through IFN-γ/STAT1 and IL-6/JAK/STAT3 pathways in tumor cells. Meanwhile, OASL affects macrophages infiltration in TIME. By these mechanisms OASL could cause dysfunction of cytotoxic T lymphocytes (CTLs) in tumors.DiscussionMulti-omics analysis reveals OASL as a prognostic and immunological biomarker in pan-cancer.
Exploiting branched-chain amino acid metabolism and NOTCH3 expression to predict and target colorectal cancer progression
Authors: Shen Kuan , Zhu Chuming , Wu Jianjun , Yan Jiang , Li Pengyu , Cao Shuqing , Zhou Xinyi , Yao Guozhong 
Published: September 2024

BackgroundThe interplay between colon adenocarcinoma (COAD) and branched-chain amino acid (BCAA) metabolism is not fully understood, presenting a crucial area for investigation.MethodsWe developed a prognostic model based on BCAA metabolism using the least absolute shrinkage and selection operator (LASSO) regression algorithm. We employed qRT-PCR and Western blot analyses to examine NOTCH3 expression in COAD tissues versus adjacent non-cancerous tissues and various cell lines. We also investigated the impact of NOTCH3 on COAD cell proliferation, invasion, and migration through in vitro and in vivo experiments.ResultsOur BCAA metabolism-related signature (BRS) distinguished between different immune features, tumor mutation burdens, responses to immunotherapy, and drug sensitivity among COAD patients. NOTCH3 was found to be overexpressed in COAD, promoting tumor growth as verified through various assays. The model effectively predicted COAD prognosis and patient responses to treatments, underscoring the potential of BCAA pathways as therapeutic targets.ConclusionThe BRS is instrumental in predicting the prognosis and therapeutic response in COAD, with NOTCH3 playing a significant role in the proliferation, invasion and migration of COAD. These findings suggest that targeting BCAA metabolism and NOTCH3 could advance COAD treatment strategies.
Causal associations between gut microbiota and premature rupture of membranes: a two-sample Mendelian randomization study
Authors: Zhang Lei , Li Qian , Huang Jiafeng , Zou Qin , Zou Hua , Zhang Xinyuan , Su Yan , Li Chunli 
Published: September 2024

BackgroundPrevious study has indicated a potential link between gut microbiota and maternal pregnancy outcomes. However, the causal relationship between gut microbiota and premature rupture of membranes (PROM) remains a topic of ongoing debate.MethodsA two-sample Mendelian Randomization (MR) study was used to investigate the relationship between gut microbiota and PROM. Genetic data on gut microbiota was obtained from the MiBioGen consortium’s largest genome-wide association study (GWAS) (n=14,306). Genetic data on PROM (3011 cases and 104247 controls) were sourced from publicly available GWAS data from the Finnish National Biobank FinnGen consortium. Various methods including Inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were utilized to assess the causal relationship by calculating the odd ratio (OR) value and confidence interval (CI). Sensitivity analyses for quality control were performed using MR-Egger intercept tests, Cochran’s Q tests, and leave-one-out analyses.ResultsThe IVW method revealed that class Mollicutes (IVW, OR=0.773, 95%CI: 0.61-0.981, pval = 0.034), genus Marvinbryantia (IVW, OR=00.736, 95%CI: 0.555-0.977, pval = 0.034), genus Ruminooccaceae UCG003 (IVW, OR=0.734, 95%CI: 0.568-0.947, pval = 0.017) and phylum Tenericutes (IVW, OR=0.773, 95%CI: 0.566-1.067, pval = 0.034) were associated with a reduced risk of PROM, while genus Collinsella (IVW, OR=1.444, 95%CI: 1.028-2.026, pval = 0.034), genus Intestinibacter (IVW, OR=1.304, 95%CI: 1.047-1.623, pval = 0.018) and genus Turicibacter (IVW, OR=1.282, 95%CI: 1.02-1.611, pval = 0.033) increased the risk of PROM. Based on the other four supplementary methods, six gut microbiota may have a potential effect on PROM. Due to the presence of pleiotropy (pval=0.045), genus Lachnoclostridium should be ruled out. No evidence of horizontal pleiotropy or heterogeneity was found in other microbiota (pval &gt;0.05).ConclusionsIn this study, we have discovered a causal relationship between the presence of specific probiotics and pathogens in the host and the risk of PROM. The identification of specific gut microbiota associated with PROM through MR studies offers a novel approach to diagnosing and treating this condition, thereby providing a new strategy for clinically preventing PROM.
Identification of ribosome biogenesis genes and subgroups in ischaemic stroke
Authors: Wang Xi , Zhang Xiao-Yu , Liao Nan-Qing , He Ze-Hua , Chen Qing-Feng 
Published: September 2024

BackgroundIschaemic stroke is a leading cause of death and severe disability worldwide. Given the importance of protein synthesis in the inflammatory response and neuronal repair and regeneration after stroke, and that proteins are acquired by ribosomal translation of mRNA, it has been theorised that ribosome biogenesis may have an impact on promoting and facilitating recovery after stroke. However, the relationship between stroke and ribosome biogenesis has not been investigated.MethodsIn the present study, a ribosome biogenesis gene signature (RSG) was developed using Cox and least absolute shrinkage and selection operator (LASSO) analysis. We classified ischaemic stroke patients into high-risk and low-risk groups using the obtained relevant genes, and further elucidated the immune infiltration of the disease using ssGSEA, which clarified the close relationship between ischaemic stroke and immune subgroups. The concentration of related proteins in the serum of stroke patients was determined by ELISA, and the patients were divided into groups to evaluate the effect of the ribosome biogenesis gene on patients. Through bioinformatics analysis, we identified potential IS-RSGs and explored future therapeutic targets, thereby facilitating the development of more effective therapeutic strategies and novel drugs against potential therapeutic targets in ischaemic stroke.ResultsWe obtained a set of 12 ribosome biogenesis-related genes (EXOSC5, MRPS11, MRPS7, RNASEL, RPF1, RPS28, C1QBP, GAR1, GRWD1, PELP1, UTP, ERI3), which play a key role in assessing the prognostic risk of ischaemic stroke. Importantly, risk grouping using ribosome biogenesis-related genes was also closely associated with important signaling pathways in stroke. ELISA detected the expression of C1QBP, RPS28 and RNASEL proteins in stroke patients, and the proportion of neutrophils was significantly increased in the high-risk group.ConclusionsThe present study demonstrates the involvement of ribosomal biogenesis genes in the pathogenesis of ischaemic stroke, providing novel insights into the underlying pathogenic mechanisms and potential therapeutic strategies for ischaemic stroke.
Construction of tissue engineered cornea with skin-derived corneal endothelial-like cell and mechanism research for the cell differentiation
Authors: Shen Lin , Han Fang , Pan Lijie , Du Liqun , Sun Peng , Zhang Kai , Wu Xinyi , Pang Kunpeng , Zhu Jing 
Published: September 2024

IntroductionCorneal endothelial transplantation accounts for most of corneal transplantation for treating corneal diseases, however severe shortage of corneal donors is the biggest obstacle. In our previous study, we differentiated human skin-derived precursors (SKPs) into corneal endothelial cell (CEC)-like cells with a co-culture system. In this study, we aimed to investigate cell differentiation molecular mechanism and evaluate the function of CEC-like cells by developing tissue-engineered corneas in order to improve cell production efficiency and provide basic research for clinical transformation.MethodsWe performed transcriptome sequencing of SKPs and CEC-like cells. Further, we focused on the possible enriching pathways, including PI3K/Akt, MAPK/Erk, WNT/β-catenin, and important transcription factors Pitx2 and Foxc1. The PI3K and β-catenin inhibitors were also added to the culture system to observe the differentiation alteration. We developed a graft for a tissue-engineered cornea (TEC) using CEC-like cells and acellular porcine cornea matrix scaffold. The tissue-engineered corneas were transplanted into rabbits via penetrating keratoplasty.ResultsThe PI3K/Akt, MAPK/Erk, and WNT/β-catenin pathways play important roles during the differentiation of SKPs into CEC-like cells. Crosstalk existed between the PI3K/Akt and MAPK/Erk pathways. The PI3K/Akt and WNT/β-catenin pathways were connected. Pitx2 and Foxc1 were subject to temporal and spatial controls of the WNT/β-catenin pathway. The inhibition of the PI3K/Akt and WNT/β-catenin pathways both prevented cell differentiation. CEC-like cells grew well on the acellular porcine cornea matrix scaffold, and the tissue-engineered corneal graft performed well after transplantation into rabbits.ConclusionWe provide experimental basis for CEC-like cell industrial production and drive the cells to be clinically applied in cellular replacement therapy or alternative graft substitution for treating corneal diseases in the future.
Mendelian randomization identifies causal associations between GWAS-associated bacteria and their metabolites and rheumatoid arthritis
Authors: Zhou Donghai , Jiao Wenyue , Shi Weiman , Wang Qiao , Chen Muzhi 
Published: September 2024

BackgroundAccumulating evidence suggests that an imbalance of gut microbiota is commonly observed in patients with rheumatoid arthritis (RA). However, it remains unclear whether gut microbiota dysbiosis is a cause or consequence of RA, and the mechanisms by which gut dysbiosis contributes to RA have not been fully understood. This study aimed to investigate the causal relationship between gut microbiota and metabolites with RA.MethodsA two-sample Mendelian randomization analysis was performed to estimate the causality of gut microbiota and metabolites on RA. A genome-wide association study (GWAS) of 211 gut microbiota and 217 metabolites was used as the exposure, whereas RA was treated as the outcome. Inverse variance weighted (IVW) was regarded as the primary approach for calculating causal estimates. MR Egger method, Weighted median method, Simple mode method, and weighted mode method were used for sensitive analysis. Metabolic pathway analysis was performed via the web-based Metaconflict 5.0. Additionally, an animal study was undertaken to evaluate the results inferred by Mendelian randomization.ResultThis study indicated that six gut microbiota taxa (RuminococcaceaeUCG013, Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, Clostridia, and Veillonellaceae) were estimated to exert a positive impact on RA. Conversely, seven gut microbiota taxa (Oxalobacter, Cyanobacteria, RuminococcaceaeUCG002, LachnospiraceaeUCG010, Christensenellaceae, Oxalobacteraceae, Anaerostipes) were estimated to exert a negative impact on RA. Three metabolites, namely indole-3-propionate (IPA), glycine and sphingomyelin (SM 16:1), were found to be linked to lower RA risk, while five metabolites (argininosuccinate, CE 20_4, TAG 58_8, PC 40_6, and LPC 20_4) were linked to higher RA risk. Additionally, four metabolic pathways were identified by metabolic pathway analysis. The collagen-induced arthritis (CIA) rats exhibited a higher relative abundance of Class_Clostridia and a lower abundance of Genus_Lachnospiraceae (p &lt; 0.05) than the healthy controls.ConclusionThis study identified causal associations between specific gut microbiota, metabolites, and RA. These findings support the significant role of gut microbiota and metabolites in RA pathogenesis.