bluuebunny/crossref_metadata_2025_split huggingface dataset:
A broad cuproptosis landscape in inflammatory bowel disease
Authors: Chen Yuan , Li Xinfang , Sun Ran , Ji Jiamin , Yang Fan , Tian Weiliang , Ji Wu , Huang Qian 
Published: November 2022

BackgroundCuproptosis, a genetic process of copper-dependent cell death linked to mitochondria respiration, demonstrates its correlation with inhibiting tumoral angiogenesis and motility. Recent studies have developed systematic bioinformatics frameworks to identify the association of cuproptosis with tumors but any non-neoplastic diseases. Therefore, against the background of an increased incidence of inflammatory bowel disease (IBD), the landscape of cuproptosis regulation in IBD is a critical need to be investigated.MethodsThe differentially expressed cuproptosis-related genes (DECRGs) were identified with human sequencing profiles for four inflammatory digestive disorders. Another four independent IBD datasets from GEO were used as a validation cohort. And experimental mice model provides another validation method. Using single sample gene set enrichment analysis (ssGSEA), receiver operating characteristic (ROC) curve, CIBERSORT, and consensus clustering algorithms, we explored the association between immune score and cuproptosis-related genes, as well as the diagnostic value of these genes. Molecular docking screened potential interaction of IBD drugs with the structural regulator by Autodock Vina.ResultsCuproptosis-related regulators exhibited extensive differential expression in Crohn’s Disease (CD), Ulcerative Colitis (UC), Celiac Disease (CEL), and IBD-induced cancer (IBD-CA) that share common differential genes (PDHA1, DBT, DLAT, LIAS). The differential expression of DECRGs was reverified in the validated cohort and immunohistochemistry assay. Moreover, the cell signaling pathways and ontology mainly focused on the mitochondrial respiratory function, which was highly enriched in Gene set enrichment analysis (GSEA). According to ssGSEA and ROC, when considering the four regulators, which showed robust association with immune infiltration in IBD, the area under the ROC (AUC) was 0.743. In addition, two clusters of consensus clustering based on the four regulators exhibit different immune phenotypes. According to molecular docking results, methotrexate gained the highest binding affinity to the main chain of key cuproptosis-related regulators compared with the remaining ten drugs.ConclusionCuproptosis-related regulators were widely linked to risk variants, immune cells, immune function, and drug efficacy in IBD. Regulation of cuproptosis may deeply influence the occurrence and development of patients with IBD.
SMO mutation predicts the effect of immune checkpoint inhibitor: From NSCLC to multiple cancers
Authors: Ji Wenxiang , Niu Xiaomin , Yu Yongfeng , Li Ziming , Gu LinPing , Lu Shun 
Published: November 2022

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) is one of the most promising breakthroughs for the treatment of multiple cancer types, but responses vary. Growing evidence points to a link between developmental signaling pathway-related genes and antitumor immunity, but the association between the genomic alterations in these genes and the response to ICIs still needs to be elucidated.MethodsClinical data and sequencing data from published studies and our cohort were collected to analyze the association of the mutation status of SMO with the efficacy of ICI therapy in the non-small cell lung cancer (NSCLC) cohort and the pan-cancer cohort. Furthermore, the correlation between SMO mutation and immunotherapeutic biomarkers such as immune cell infiltration, immune-related genes, and underlying signaling pathways was analyzed. Three SMO mutant plasmids were transfected into cells to explore the SMO mutation status in the context of its expression and cell growth.ResultIn the NSCLC discovery cohort, the median progression-free survival in the SMO mutant (SMO_MUT) was longer than that in the wild type (SMO_WT) (23.0 vs. 3.8 months, adjusted p = 0.041). This finding was further confirmed in the NSCLC validation cohort (8.7 vs. 5.1 months, adjusted p = 0.013). In the pan-cancer cohort (n = 1,347), a significant overall survival advantage was observed in patients with SMO mutations [not reached (NR) vs. 18 months, adjusted p = 0.024]. In the subgroup analysis, the survival advantage of SMO_MUT against SMO_WT was prominent and consistent across genders, ages, treatment types, cancer types, and the tumor mutation burden (TMB) status (all pinteraction &gt; 0.05). In an in vitro experiment, we found that both the mutant and wild-type plasmids can promote the expression of SMO, but the mutant plasmid had lower SMO mRNA and protein levels than the wild type. In CCK-8 experiments, we found that SMO_MUT plasmids can improve the growth of Calu-1 and PC-9 cells, but this capability varied between different mutations and cells. Upon further exploration, the SMO mutation status was found to be related to a higher TMB, more neoantigen load, more DNA damage repair (DDR) mutations, higher microsatellite instability (MSI) score, and higher CD8+ T-cell infiltration.ConclusionsThe SMO mutation status is an independent prognostic factor that can be used to predict better clinical outcomes of ICI treatment across multiple cancer types.
Single cell analysis of docosahexaenoic acid suppression of sequential LPS-induced proinflammatory and interferon-regulated gene expression in the macrophage
Authors: Wierenga Kathryn A. , Riemers Frank M. , Westendorp Bart , Harkema Jack R. , Pestka James J. 
Published: November 2022

Preclinical and clinical studies suggest that consumption of long chain omega-3 polyunsaturated fatty acids (PUFAs) reduces severity of chronic inflammatory and autoimmune diseases. While these ameliorative effects are conventionally associated with downregulated expression of proinflammatory cytokine and chemokine genes, our laboratory has recently identified Type 1 interferon (IFN1)-regulated gene expression to be another key target of omega-3 PUFAs. Here we used single cell RNA sequencing (scRNAseq) to gain new mechanistic perspectives on how the omega-3 PUFA docosahexaenoic acid (DHA) influences TLR4-driven proinflammatory and IFN1-regulated gene expression in a novel self-renewing murine fetal liver-derived macrophage (FLM) model. FLMs were cultured with 25 µM DHA or vehicle for 24 h, treated with modest concentration of LPS (20 ng/ml) for 1 and 4 h, and then subjected to scRNAseq using the 10X Chromium System. At 0 h (i.e., in the absence of LPS), DHA increased expression of genes associated with the NRF2 antioxidant response (e.g. Sqstm1, Hmox1, Chchd10) and metal homeostasis (e.g.Mt1, Mt2, Ftl1, Fth1), both of which are consistent with DHA-induced polarization of FLMs to a more anti-inflammatory phenotype. At 1 h post-LPS treatment, DHA inhibited LPS-induced cholesterol synthesis genes (e.g. Scd1, Scd2, Pmvk, Cyp51, Hmgcs1, and Fdps) which potentially could contribute to interference with TLR4-mediated inflammatory signaling. At 4 h post-LPS treatment, LPS-treated FLMs reflected a more robust inflammatory response including upregulation of proinflammatory cytokine (e.g. Il1a, Il1b, Tnf) and chemokine (e.g.Ccl2, Ccl3, Ccl4, Ccl7) genes as well as IFN1-regulated genes (e.g. Irf7, Mx1, Oasl1, Ifit1), many of which were suppressed by DHA. Using single-cell regulatory network inference and clustering (SCENIC) to identify gene expression networks, we found DHA modestly downregulated LPS-induced expression of NF-κB-target genes. Importantly, LPS induced a subset of FLMs simultaneously expressing NF-κB- and IRF7/STAT1/STAT2-target genes that were conspicuously absent in DHA-pretreated FLMs. Thus, DHA potently targeted both the NF-κB and the IFN1 responses. Altogether, scRNAseq generated a valuable dataset that provides new insights into multiple overlapping mechanisms by which DHA may transcriptionally or post-transcriptionally regulate LPS-induced proinflammatory and IFN1-driven responses in macrophages.
Temperature denpendent microwave absorption properties of SrFe12O19 in X-band
Authors: Li Xiling , Qiao Liang , Shi Huigang , Chai Guozhi , Wang Tao , Wang Jianbo 
Published: November 2022

Researchers are currently focusing on the electromagnetic and microwave absorption properties of SrFe12O19 hexaferrites. The high-temperature absorption (more than 573 K) is highly demanded in various including the military, national defense, aviation, and other fields. SrFe12O19 has good thermal stability at high temperature, and it has large coercivity, which also determines that it has good stability in magnetic properties and is not easy to be affected by the environment. Thus, it is necessary to explore the magnetic characteristics of SrFe12O19 hexaferrites at high temperatures. SrFe12O19 hexaferrites were fabricated by the molten salt method and their microstructure, high-temperature electromagnetic properties, and microwave properties were investigated in detail. The complex permeability and permittivity of SrFe12O19 were measured at varying temperatures (293–673 K) in the X band. While the real parts of permittivity and permeability increased with the increasing temperature, the imaginary parts of permittivity and permeability did not change significantly with increasing temperature. The calculated absorption properties displayed that as temperature increased from 293K to 623K, the frequency of the RL peaks moved to a low-frequency direction, and the sample’s minimum value of RL could be smaller than -10dB across the whole X band. The results indicate that SrFe12O19 particles have better absorption properties and can be used in high-temperature environments. These particles can be possibly used in many particular fields.
A deep learning-based approach toward differentiating scalp psoriasis and seborrheic dermatitis from dermoscopic images
Authors: Yu Zhang , Kaizhi Shen , Jianwen Han , Guanyu Yu , Yonggang Wang 
Published: November 2022

ObjectivesThis study aims to develop a new diagnostic method for discriminating scalp psoriasis and seborrheic dermatitis based on a deep learning (DL) model, which uses the dermatoscopic image as input and achieved higher accuracy than dermatologists trained with dermoscopy.MethodsA total of 1,358 pictures (obtained from 617 patients) with pathological and diagnostic confirmed skin diseases (508 psoriases, 850 seborrheic dermatitides) were randomly allocated into the training, validation, and testing datasets (1,088/134/136) in this study. A DL model concerning dermatoscopic images was established using the transfer learning technique and trained for diagnosing two diseases.ResultsThe developed DL model exhibits good sensitivity, specificity, and Area Under Curve (AUC) (96.1, 88.2, and 0.922%, respectively), it outperformed all dermatologists in the diagnosis of scalp psoriasis and seborrheic dermatitis when compared to five dermatologists with various levels of experience. Furthermore, non-proficient doctors with the assistance of the DL model can achieve comparable diagnostic performance to dermatologists proficient in dermoscopy. One dermatology graduate student and two general practitioners significantly improved their diagnostic performance, where their AUC values increased from 0.600, 0.537, and 0.575 to 0.849, 0.778, and 0.788, respectively, and their diagnosis consistency was also improved as the kappa values went from 0.191, 0.071, and 0.143 to 0.679, 0.550, and 0.568, respectively. DL enjoys favorable computational efficiency and requires few computational resources, making it easy to deploy in hospitals.ConclusionsThe developed DL model has favorable performance in discriminating two skin diseases and can improve the diagnosis, clinical decision-making, and treatment of dermatologists in primary hospitals.
Impact of antibiotic treatment for chronic endometritis on pregnancy outcomes in women with reproductive failures (RIF and RPL): A systematic review and meta-analysis
Authors: Liu Jingjing , Liu Zheng Ai , Liu Yichun , Cheng Lei , Yan Lei 
Published: November 2022

ObjectiveThe aim of this study was to investigate the effect of antibiotic treatment for chronic endometritis (CE) on reproductive outcomes.DesignSystematic review and meta-analysis.PatientsWomen with reproductive failures, including recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL).InterventionsLiterature searches were performed using three electronic databases (PubMed, Embase, and Web of Science) until 1 December 2021 (without date restriction). The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with normal endometrial histology (negative for CE); and women with cured CE vs. women with persistent CE (PCE). The summary measures were indicated as odds ratio (OR) with a 95% confidence interval (CI).Main outcome measuresThese include on-going pregnancy rate/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), and miscarriage rate/pregnancy loss rate (MR/PLR).ResultsA total of 2,154 women (from twelve studies) were enrolled. Compared with the control group, women with CE receiving antibiotics did not show a statistically significant difference in OPR/LBR (P = 0.09) and CPR (P = 0.36), although there was a lower MR (P = 0.03). Women with cured CE have higher OPR/LBR (OR 1.57) and CPR (OR 1.56) in comparison with those with non-CE. There was a statistically significantly higher OPR/LBR (OR 6.82, P &lt; 0.00001) and CPR (OR 9.75, P &lt; 0.00001) in women with cured CE vs. those with persistent CE.ConclusionWhile antibiotic treatment is a sensible option to cure CE, more well-designed prospective studies are needed to evaluate the reproductive impact of antibiotic treatment. Cured CE provides high-quality maternal conditions for subsequent embryo transfer and successful pregnancy.
Risk factors of severe fever with thrombocytopenia syndrome combined with central neurological complications: A five-year retrospective case–control study
Authors: Wang Min , Huang Peng , Liu Wei , Tan Weilong , Chen Tianyan , Zeng Tian , Zhu Chuanlong , Shao Jianguo , Xue Hong , Li Jun , Yue Ming 
Published: November 2022

ObjectiveSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality rate, especially SFTS combined with central neurological complications. The purpose of this study was to explore risk factors of central neurological complications in SFTS patients.MethodsIn this retrospective study, SFTS patients admitted to the First Affiliated Hospital of Nanjing Medical University between January 2017 and December 2021 were enrolled. Based on the presence or absence of central neurological complications, SFTS patients were divided into case group and control group. The patients’ laboratory parameters and clinical data were collected for statistical analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of independent risk factors in identifying SFTS patients with central neurological complications.ResultsIn total, 198 hospitalized SFTS patients with complete medical records, clear etiological diagnosis and clinical outcomes were enrolled in this study. Of these, 74 (37.4%) cases were diagnosed with SFTS with central neurological complications, 29 (39.2%) cases died, and no death occurred in the control group. Multivariate logistic regression analysis revealed pulmonary rales, atrial fibrillation, and high serum SFTSV RNA, lactate dehydrogenase level during the fever stage as independent risk factors for the development of central neurological complications in SFTS patients. ROC curve analysis showed that the area under the ROC curve (AUC) of serum SFTSV RNA and lactate dehydrogenase levels were 0.748 (95%CI: 0.673–0.823, p &lt; 0.001) and 0.864 (95%CI: 0.815–0.914, p &lt; 0.001), respectively, in central neurological complications predicted in SFTS patients.ConclusionSevere fever with thrombocytopenia syndrome (SFTS) combined with central neurological complications has high morbidity and mortality and diverse clinical manifestations. Early monitoring of lung signs, electrocardiogram, blood SFTSV RNA, and lactate dehydrogenase levels in SFTS patients may be useful in predicting the occurrence of central neurological complications.
Association of cognitive function with Neurofilament light chain in the aqueous humor of human eye
Authors: Bai Jianhao , Wan Zhongqi , Wang Minli , Wu Xue , Wang Tianyu , Zhang Yuanyuan , Xue Yawen , Xu Hong , Peng Qing 
Published: November 2022

ObjectivesTo evaluate the predictive clinical role of neurofilament light chain (NfL), amyloid-β (Aβ), glial fibrillary acidic protein (GFAP), and phosphorylated tau at threonine 181 (p-tau181) proteins in human aqueous humor (AH) and quantify the retinal macular microvascular parameters by optical coherence tomography angiography (OCTA) as early diagnostic markers of Alzheimer’s disease (AD).MethodsThis prospective, single-site, cross-sectional, cohort study enrolled 55 participants, including 38 patients with neovascular age-related macular degeneration (nAMD) and 17 individuals with senile cataracts. The single-molecule array platform was used to quantitatively measure the levels of AH NfL, Aβ40, Aβ42, GFAP, and p-tau181 proteins in AH. The mini-mental state examination (MMSE) score was used to assess the global cognitive function. OCTA scan with 6 × 6 mm macular area was used to quantify the retinal thickness and microvascular densities of superficial retinal capillary plexuses and deep retinal capillary plexuses.ResultsNfL, Aβ40, Aβ42, GFAP, and p-tau181 were detected in all AH samples by Simoa platform. Individuals with cataract had higher concentrations of NfL and p-tau181 but lower Aβ40 and Aβ42 and similar GFAP compared to those with nAMD. Lower MMSE scores showed a negative correlation with NfL concentration of AH not only in the nAMD group (p = 0.043), but also in the cataract group (p = 0.032). However, the MMSE scores were not associated with the levels of Aβ40, Aβ42, GFAP, or p-Tau181. Further analysis found that the Aβ40 and Aβ42 concentrations showed a strong positive correlation (p &lt; 0.0001). In addition, the NfL concentration showed a mild positive correlation with that of GFAP in the cataract group (p = 0.021). Although it has not reached statistical significance, there was a correlation between the levels of NfL and Aβ42 in the nAMD group (p = 0.051). Moreover, the macular superficial vessel density values had a negative correlation with the concentration of NfL (p = 0.004) but a positive correlation with MMSE scores (p = 0.045). The macular deep vessel density values were negatively correlated with the concentration of p-tau181 (p = 0.031) and positively correlated with MMSE scores (p = 0.020).ConclusionThe examination of AD-related biomarkers in human AH and OCTA may improve the ocular-based AD detection methods and contribute to forestalling the progression of preclinical AD.
Sex and age differences in the Multiple Sclerosis prodrome
Authors: Yusuf Fardowsa L. A. , Wijnands José M. A. , Karim Mohammad Ehsanul , Kingwell Elaine , Zhu Feng , Evans Charity , Fisk John D. , Zhao Yinshan , Marrie Ruth Ann , Tremlett Helen 
Published: November 2022

Background and objectivesLittle is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome.MethodsThis was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event (“administrative cohort;” n = 6,863) or MS symptom onset (“clinical cohort;” n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (&lt; 30, 30–49, ≥50 years).ResultsIn the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P &lt; 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries &lt; 30/30–49/≥50: aRR = 1.16/1.39/2.12, P &lt; 0.01; infections 30–49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30–49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular &lt; 30/30–49/≥50: aRR = 1.56/1.39/1.18, P &lt; 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P &lt; 0.01) and ≥50-year-olds (&lt; 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, &lt; 50-years-old (&lt; 30/30–49/≥50: aRR = 2.25/2.20/1.55, P &lt; 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05).DiscussionSex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.
Early diagnosis of intracranial atherosclerotic large vascular occlusion: A prediction model based on DIRECT-MT data
Authors: Li He , Ma Hong-Yu , Zhang Lei , Liu Pei , Zhang Yong-Xin , Zhang Xiao-Xi , Li Zi-Fu , Xing Peng-Fei , Zhang Yong-Wei , Li Qiang , Yang Peng-Fei , Liu Jian-Min 
Published: November 2022

AimsThis study aimed to build a prediction model to early diagnose intracranial atherosclerosis (ICAS)-related large vascular occlusion (LVO) in acute ischemic stroke patients before digital subtractive angiography.MethodsPatients enrolled in the DIRECT-MT trial (NCT03469206) were included in our secondary analysis and distributed into ICAS-LVO and non-ICAS-LVO groups. We also retrieved demographic data, medical histories, clinical characteristics, and pre-operative imaging data. Hypothesis testing was used to compare data of the two groups, and univariate logistic regression was used to identify the predictors of ICAS-LVO primarily. Then, we used multivariate logistic regression to determine the independent predictors and formulate the prediction model. Model efficacy was estimated by the area under the receiver operating characteristic (ROC) curve (AUC) and diagnostic parameters generated from internal and external validations.ResultsThe subgroup analysis included 45 cases in the ICAS-LVO group and 611 cases in the non-ICAS-LVO group. Variates with p &lt; 0.1 in the comparative analysis were used as inputs in the univariate logistic regression. Next, variates with p &lt; 0.1 in the univariate logistic regression were used as inputs in the multivariate logistic regression. The multivariate logistic regression indicated that the atrial fibrillation history, hypertension and smoking, occlusion located at the proximal M1 and M2, hyperdense artery sign, and clot burden score were related to the diagnosis of ICAS-LVO. Then, we constructed a prediction model based on multivariate logistics regression. The sensitivity and specificity of the model were 84.09 and 74.54% in internal validation and 73.11 and 71.53% in external validation.ConclusionOur current prediction model based on clinical data of patients from the DIRECT-MT trial might be a promising tool for predicting ICAS-LVO.