bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Evaluation of the m6A Regulator Prognostic Risk Score in the Prediction of Immunotherapy Response in Clear Cell Renal Cell Carcinoma
Authors: Yu Mingke , Liu Xuefei , Xu Han , Shen Sangyu , Wang Fajiu , Chen Dajin , Li Guorong , Wang Zongping , Zuo Zhixiang , Zhao An 
Published: June 2022

BackgroundClear cell renal cell carcinoma (ccRCC) is known for its high drug resistance. The tumor-immune crosstalk mediated by the epigenetic regulation of N6-methyladenosine (m6A) modification has been demonstrated in recent studies. Therefore, m6A modification-mediated immune cell infiltration characteristics may be helpful to guide immunotherapy for ccRCC.MethodsThis study comprehensively analyzed m6A modifications using the clinical parameters, single-cell RNA sequencing data, and bulk RNA sequencing data from the TCGA-ccRC cohort and 13 external validation cohorts. A series of bioinformatic approaches were applied to construct an m6A regulator prognostic risk score (MRPRS) to predict survival and immunotherapy response in ccRCC patients. Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low-MRPRS groups.ResultsThe expressional alteration landscape of m6A regulators was profiled in ccRCC cell clusters and tissue. The 8 regulator genes with minimal lambda were integrated to build an MRPRS, and it was positively correlated with immunotherapeutic response in extent validation cohorts. The clinicopathological features and immune infiltration characteristics could be distinguished by the high- and low-MRPRS. Moreover, the MRPRS-mediated mutation pattern has an enhanced response to immune checkpoint blockade in the ccRCC and pan-cancer cohorts.ConclusionsThe proposed MRPRS is a promising biomarker to predict clinical outcomes and therapeutic responses in ccRCC patients.
Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort
Authors: Mauro Daniele , Ciancio Antonio , Di Vico Claudio , Passariello Luana , Rozza Gelsomina , Pasquale Maria Dora , Pantano Ilenia , Cannistrà Carlo , Bucci Laura , Scriffignano Silvia , Riccio Flavia , Patrone Martina , Scalise Giuseppe , Ruscitti Piero , Montemurro Maria Vittoria , Giordano Antonio , Vietri Maria Teresa , Ciccia Francesco 
Published: June 2022

ObjectiveIn the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination.MethodsVolunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers.ResultsSamples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p&lt;0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p&lt;0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age.ConclusionThe response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients.
Clinical Characteristics and Risk Factors for Evisceration in Trauma-Dominant Orbital Cellulitis: A 10-Year Review
Authors: Jiang Zhaoxin , Zhongliu Xueying , Ding Xiaohu , Yang Yao , Duan Fang , Lin Xiaofeng 
Published: June 2022

PurposeTo analyze the clinical characteristics of trauma-dominant orbital cellulitis (OC) and evaluate the risk factors associated with evisceration.MethodsThis retrospective study included inpatients diagnosed with orbital cellulitis at the Zhongshan Ophthalmic Center between January 2010 and December 2020. The demographic features, etiology, clinical characteristics, microbiological isolates, and risk factors associated with evisceration were analyzed.ResultsAmong 148 consecutive subjects (n = 148, 148 eyes), the mean age was 42.07 ± 20.35 years and 70.27% were male. Penetrating globe injuries were the most common (52.03%). No light perception (NLP) was recorded in 50% of patients on admission. Endophthalmitis was observed in 103 cases (69.59%), intraocular foreign bodies (IOFB) were detected in 43 cases (29.05%), and total corneal melting was observed in 31 cases (20.95%). Sixty patients (40.54%) underwent evisceration. Logistic regression analysis showed that total corneal dissolution [odds ratio (OR) = 83.019, P = 0.000], IOFB (OR = 3.402, P = 0.016), and NLP (OR = 0.185, P = 0.001) were risk factors for evisceration. Microorganism detection showed that Pseudomonas aeruginosa and Bacillus cereus were the leading pathogens.ConclusionAmong hospitalized trauma-dominant OC patients, middle-aged men were the major subjects and penetrating globe injury was the major cause. Significant complications such as complete visual loss and evisceration were unavoidable in many patients with OC in the current study. NLP, IOFB, and total corneal melting were the risk factors for evisceration.
Comparison of Conventional Logistic Regression and Machine Learning Methods for Predicting Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Multicentric Observational Cohort Study
Authors: Hu Ping , Li Yuntao , Liu Yangfan , Guo Geng , Gao Xu , Su Zhongzhou , Wang Long , Deng Gang , Yang Shuang , Qi Yangzhi , Xu Yang , Ye Liguo , Sun Qian , Nie Xiaohu , Sun Yanqi , Li Mingchang , Zhang Hongbo , Chen Qianxue 
Published: June 2022

BackgroundTimely and accurate prediction of delayed cerebral ischemia is critical for improving the prognosis of patients with aneurysmal subarachnoid hemorrhage. Machine learning (ML) algorithms are increasingly regarded as having a higher prediction power than conventional logistic regression (LR). This study aims to construct LR and ML models and compare their prediction power on delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH).MethodsThis was a multicenter, retrospective, observational cohort study that enrolled patients with aneurysmal subarachnoid hemorrhage from five hospitals in China. A total of 404 aSAH patients were prospectively enrolled. We randomly divided the patients into training (N = 303) and validation cohorts (N = 101) according to a ratio of 75–25%. One LR and six popular ML algorithms were used to construct models. The area under the receiver operating characteristic curve (AUC), accuracy, balanced accuracy, confusion matrix, sensitivity, specificity, calibration curve, and Hosmer–Lemeshow test were used to assess and compare the model performance. Finally, we calculated each feature of importance.ResultsA total of 112 (27.7%) patients developed DCI. Our results showed that conventional LR with an AUC value of 0.824 (95%CI: 0.73–0.91) in the validation cohort outperformed k-nearest neighbor, decision tree, support vector machine, and extreme gradient boosting model with the AUCs of 0.792 (95%CI: 0.68–0.9, P = 0.46), 0.675 (95%CI: 0.56–0.79, P &lt; 0.01), 0.677 (95%CI: 0.57–0.77, P &lt; 0.01), and 0.78 (95%CI: 0.68–0.87, P = 0.50). However, random forest (RF) and artificial neural network model with the same AUC (0.858, 95%CI: 0.78–0.93, P = 0.26) were better than the LR. The accuracy and the balanced accuracy of the RF were 20.8% and 11% higher than the latter, and the RF also showed good calibration in the validation cohort (Hosmer-Lemeshow: P = 0.203). We found that the CT value of subarachnoid hemorrhage, WBC count, neutrophil count, CT value of cerebral edema, and monocyte count were the five most important features for DCI prediction in the RF model. We then developed an online prediction tool (https://dynamic-nomogram.shinyapps.io/DynNomapp-DCI/) based on important features to calculate DCI risk precisely.ConclusionsIn this multicenter study, we found that several ML methods, particularly RF, outperformed conventional LR. Furthermore, an online prediction tool based on the RF model was developed to identify patients at high risk for DCI after SAH and facilitate timely interventions.Clinical Trial Registrationhttp://www.chictr.org.cn, Unique identifier: ChiCTR2100044448.
The Impact of COVID-19 Confinement on Tinnitus and Hearing Loss in Older Adults: Data From the LOST in Lombardia Study
Authors: Jarach Carlotta Micaela , Lugo Alessandra , Stival Chiara , Bosetti Cristina , Amerio Andrea , Cavalieri d'Oro Luca , Iacoviello Licia , Odone Anna , Stuckler David , Zucchi Alberto , van den Brandt Piet , Garavello Werner , Cederroth Christopher R. , Schlee Winfried , Gallus Silvano ,   The LOST in Lombardia Study Investigators
Published: June 2022

BackgroundAlthough a direct relationship between tinnitus or hearing difficulties and COVID-19 has been suggested, current literature provides inconsistent results, and no research has been undertaken in older adults.MethodsIn November 2020, we conducted the LOST in Lombardia survey, a telephone-based cross-sectional study on a sample of 4,400 individuals representative of the general population aged ≥65 years from Lombardy region, Northern Italy. Individuals with diagnosed tinnitus and/or hearing loss were asked whether their conditions had improved or deteriorated in 2020 compared to 2019.ResultsOverall, 8.1% of older adults reported a diagnosis of tinnitus and 10.5% of hearing loss. In 2020 compared to 2019, among individuals with tinnitus, those with increasing severity (5.0%) were similar to those decreasing it (5.3%). Among individuals with hearing loss, more people reported an increase (13.6%) than a decrease (3.2%) in their disease severity. No individual with a diagnosis in 2020 of tinnitus (n = 6) or hearing loss (n = 13) had COVID-19. The incidence of tinnitus was lower in 2020 (rate: 14.8 per 10,000 person-years) than in previous years (rate in 1990–2019: 36.0 per 10,000 person-years; p = 0.026). There was no change in the incidence of hearing loss (p = 0.134).ConclusionsIn this large representative sample of older adults, on average neither COVID-19 confinement nor SARS-CoV-2 infection appeared to increase the severity or incidence of tinnitus. The increased severity of hearing difficulties may totally or partially be explained by physiologic deterioration of the condition, or by a misperception due to the use of face-masks.
Multi-Omic Analyses Reveal Bifidogenic Effect and Metabolomic Shifts in Healthy Human Cohort Supplemented With a Prebiotic Dietary Fiber Blend
Authors: Kang Jea Woo , Tang Xinyu , Walton Charles J. , Brown Mark J. , Brewer Rachel A. , Maddela Rolando L. , Zheng Jack Jingyuan , Agus Joanne K. , Zivkovic Angela M. 
Published: June 2022

Dietary fiber, a nutrient derived mainly from whole grains, vegetables, fruits, and legumes, is known to confer a number of health benefits, yet most Americans consume less than half of the daily recommended amount. Convenience and affordability are key factors determining the ability of individuals to incorporate fiber-rich foods into their diet, and many Americans struggle to access, afford, and prepare foods rich in fiber. The objective of this clinical study was to test the changes in microbial community composition, human metabolomics, and general health markers of a convenient, easy to use prebiotic supplement in generally healthy young participants consuming a diet low in fiber. Twenty healthy adults participated in this randomized, placebo-controlled, double-blind, crossover study which was registered at clinicaltrials.gov as NCT03785860. During the study participants consumed 12 g of a prebiotic fiber supplement and 12 g of placebo daily as a powder mixed with water as part of their habitual diet in randomized order for 4 weeks, with a 4-week washout between treatment arms. Fecal microbial DNA was extracted and sequenced by shallow shotgun sequencing on an Illumina NovaSeq. Plasma metabolites were detected using liquid chromatography–mass spectrometry with untargeted analysis. The phylum Actinobacteria, genusBifidobacterium, and severalBifidobacteriumspecies (B. bifidum, B. adolescentis, B. breve, B. catenulatum, andB. longum)significantly increased after prebiotic supplementation when compared to the placebo. The abundance of genes associated with the utilization of the prebiotic fiber ingredients (sacA, xfp, xpk) and the production of acetate (poxB, ackA) significantly changed with prebiotic supplementation. Additionally, the abundance of genes associated with the prebiotic utilization (xfp, xpk), acetate production (ackA), and choline to betaine oxidation (gbsB) were significantly correlated with changes in the abundance of the genusBifidobacteriumin the prebiotic group. Plasma concentrations of the bacterially produced metabolite indolepropionate significantly increased. The results of this study demonstrate that an easy to consume, low dose (12 g) of a prebiotic powder taken daily increases the abundance of beneficial bifidobacteria and the production of health-promoting bacteria-derived metabolites in healthy individuals with a habitual low-fiber diet.Clinical Trial Registrationwww.clinicaltrials.gov/, identifier: NCT03785860
NTF2 Upregulation in HNSCC: a Predictive Marker and Potential Therapeutic Target Associated With Immune Infiltration
Authors: Xuan Guangxu , Zhang Xin , Zhang Min , Yu Minghang , Zhou Yujie , He Xiaosong , Hu Xiaopeng , Wang Xi , Liu Liangfa 
Published: June 2022

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a type of malignant tumor with an increasing incidence worldwide and a meager 5-year survival rate. It is known that nuclear transporter factor 2 (NTF2) transports related proteins into the nucleus physiologically. However, the role of NTF2 in HNSCC remains unclear.MethodsIn this study, RNA-Seq data of HNSCC samples with corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) database. In addition, other expression profiling data were downloaded from the Gene Expression Omnibus (GEO) database. The differential expressions of NTF2, along with the overall survival (OS) rates were identified and analyzed. Then, the clinical features and expression levels of NTF2 were utilized to develop a prognostic model. The study also utilized the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods to determine the related pathways of NTF2. Furthermore, the Tumor Immune Estimation Resource (TIMER) database was referenced to discover the immune correlation of NTF2. In this research investigation, RT-qPCR, western blotting, Cell Counting Kit-8 (CCK-8) assay, wound-healing assay, and immunohistochemical (IHC) staining methods were adopted to perform experimental verifications.ResultsThis study’s results confirmed that the NTF2 expressions were significantly increased in HNSCC tissue when compared with normal tissue. In addition, the high expression levels of NTF2 were found to be associated with poor prognoses, which was confirmed via the IHC validations of HNSCC samples with survival data. The results of functional enrichment analysis showed that the NTF2 was associated with epithelial cell growth, skin differentiation, keratosis, and estrogen metabolism. Furthermore, the expressions of NTF2 were determined to be negatively involved with immune infiltrations and correlated with immune checkpoint blockade (ICB) responses following various ICB therapy strategies. The results of the CCK-8 assay and wound-healing assay confirmed the NTF2’s promoting effects on the proliferation and migration of tumor cells.ConclusionsThis study defined a novel prognostic model associated with the expressions of NTF2, which was shown to be independently related to the OS of HNSCC. It was concluded in this study that NTF2 might be a potential diagnostic and prognostic biomarker for HNSCC.
The Histopathological Types and Distribution Characteristics of Gastric Mixed Tumors
Authors: Zhu Fang-Heng , Wang Yang-Kun , Zhou Jun-Ling , Meng Nian-Long , Wang Yue , Jiang Bo , Wang Su-Nan 
Published: June 2022

ObjectiveThe present study aimed to investigate the histopathological types and distribution characteristics of gastric mixed tumors.MethodsDetailed histological observations, together with related immunohistochemical and genetic tests, were analyzed on 960 surgically resected samples in 6 hospitals with gastric mixed tumors from May 2017 to May 2021 in this retrospective study.ResultsEpithelial-derived tumors accounted for 80.10% (769/960) of the gastric mixed tumor samples studied, and tumors of different tissue origins accounting for 10.83% (104/960), mesenchymal-derived tumors accounting for 6.25% (60/960), neuroendocrine tumors accounting for 2.40% (23/960), and lymphoma accounting for 0.42% (4/960). The histological types of gastric mixed tumors identified as most commonly were epithelial originated, followed by mixed tumors of different tissue originated, then mixed neuroendocrine, lymphoma, and mesenchymal originated in sequence. The histological number of gastric mixed tumors was ≤ 3 in 83.23% (799/960) of cases and &gt; 4 in 16.77% (161/960) of cases. The mixed histological patterns of gastric mixed tumors were divided into three types: those with tumor cells interspersed with each other, those with incomplete fibrous tissue separation, and those without fibrous tissue separation. The gene target characteristics of gastric mixed tumors were the existence of multi-gene mutation, including human epidermalgrowth factor receptor-2 (HER2) gene amplification, key result areas (K-ras) and platelet-derived growth factor receptor alpha (PDGFRA).ConclusionGastric mixed tumors should be adequately sampled, each piece of tissue should be involved in the morphological proportional division of the tumor, and any independent histological component should be written into the pathological examination report.
Treatment Patterns for Patients With Unresected Stage III NSCLC: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database
Authors: Shang Shijie , Wang Ruiyang , Wang Fei , Wu Meng , Chen Dawei , Yu Jinming 
Published: June 2022

BackgroundRecently, immunotherapy (IO) has shown striking survival improvement in unresectable stage III non-small cell lung cancer (NSCLC). However, the role of chemo-radiotherapy (CRT) for improvement in outcomes should not be disregarded. This study aimed to compare the treatment patterns and illustrate the impact of radiotherapy on the cancer-specific survival (CSS) and overall survival (OS) of patients with unresected locally advanced stage III NSCLC.MethodsWe retrospectively analyzed the data of patients with stage III NSCLC patients who did not undergo surgery from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 2001 and 2016, and three continuous years were regarded as one unit. Using the Kaplan-Meier method, we identified the CSS and OS. Then, a linear regression model was graphed to analyze the correlation between median survival of CSS or OS and calendar years in the radiotherapy alone, chemotherapy alone, and CRT groups.ResultsA total of 20986 patients were included in this study. In the overall cohort, CSS and OS improved consistently. To explore the reason for the improved survival, patients were divided into three different cohorts: radiotherapy alone, chemotherapy alone, and CRT. From 2001 to 2015, the median CSS improved persistently, 7, 8, 8, 9, and 11 months in the radiotherapy alone group and 12, 13, 15, 17, 19 months in the CRT group, but improvement in outcomes was less consistent in the chemotherapy alone group (10, 9, 11, 12, 12 months). To better visualize the correlation between CSS and calendar year, linear regression was performed, yielding r2 = 0.8032, P = 0.0395 for the radiotherapy alone group; r2 = 0.7206, P = 0.0689 for the chemotherapy alone group; and r2 = 0.9878, P = 0.0006 for the CRT group. Similar findings were observed in the OS data. In addition to this, we also analyzed different pathological types and also obtained the same results.ConclusionsThe survival of patients with unresectable stage III NSCLC has improved substantially, and the most pronounced and consistent improvements were observed in the CRT group. In addition to IO, radiotherapy played an essential role in the treatment of unresectable stage III NSCLC in the past years and should be considered in the design of clinical trials.
Trends in Incidence, Mortality, and Survival of Penile Cancer in the United States: A Population-Based Study
Authors: Deng Xinxi , Liu Yang , Zhan Xiangpeng , Chen Tao , Jiang Ming , Jiang Xinhao , Chen Luyao , Fu Bin 
Published: June 2022

PurposeThe aim of this study is to investigate the trends in incidence and mortality, and explore any change in survival of penile cancer in the United States.MethodsWe obtained data from the Surveillance, Epidemiology, and End Results (SEER) database (2000–2018) utilizing the SEER Stat software. The joinpoint regression was used to analyze the secular trend of incidence and incidence-based mortality (IBM) stratified by age, race, and summary stage. The 5-year relative survival rate was also calculated.ResultThe age-adjusted rates of penile cancer patients were 0.38 (0.37–0.39) and 0.21 (0.2–0.21) for overall incidence and IBM, respectively. The 5-year relative survival rates were 67.7%, 66.99%, and 65.67% for the calendar periods of 2000–2004, 2005–2009, and 2010–2014, respectively. No significant changes in incidence by era were observed from 2000 to 2018 [annual percentage change (APC) = 0.5%, p = 0.064]. The IBM rate of penile cancer showed an initial significant increase from 2000 to 2002 (APC = 78.6%, 95% CI, −1.7–224.6) followed by a deceleration rate of 4.6% (95% CI, 3.9–5.3) during 2002 to 2018. No significant improvement in 5-year relative survival was observed. The trends by age, race, and summary stage in incidence and IBM were significantly different.ConclusionThis study, using population-level data from the SEER database, showed an increasing trend in IBM and no significant improvement in the 5-year relative survival rate. Meanwhile, the incidence of penile cancer exhibited a relatively stable trend during the study period. These results might be due to the lack of significant progress in the treatment and management of penile cancer patients in the United States in recent decades. More efforts, like increasing awareness among the general population and doctors, and centralized management, might be needed in the future to improve the survival of this rare disease.