bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Fiberoptic Bronchoscopy in the Diagnosis of Pulmonary Disease: Experience in a Tertiary Care Hospital
Authors: Islam Md Rezaul , Sani Ahmad Zainuddin , Majumdar Samir C 
Published: January 2021

Introduction: Fiberoptic bronchoscopy is a very important tool in the modern era in the field of pulmonary medicine in arriving to a definite diagnosis. Since the introduction of the first flexible fiberoptic bronchoscope (FOB) has been a valuable tool in the diagnosis of pulmonary diseases.
Material & methods: This study was conducted in Rajshahi Medical College Hospital (RMCH), Rajshahi. It was undertaken to study the role of fiberoptic bronchoscopy (FOB) in diagnosis of pulmonary disease. The study period was between 1st June 2017 to 30th June 2019. A total number of 300 patients (48 females and 252 males) who underwent elective fiberoptic bronchoscopy were included in this study. Data was collected from hospital record regarding age, clinical presentation, diagnostic procedure and outcome.
Results: A total number of 300 patients had fiberoptic bronchoscopy during the study period. 252(84.00%) patients were male and 48(16.00%) were female. As per age distribution 8(2.67%) were of age group 20-32 years and majority 111(37.00%) of patients were in age group 60-72 years. Min age group was 20 and max 85 and the mean±SD age was (58.70±13.11). Occupation of the study participants most of them are farmer 134(44.67%). Bronchoscopy findings: most of the patients had malignant lesion 228(76.00) and a few had foreign body 6(2.00%), mean±SD (2.03±0.68). Majority of the patients had problems in their upper lobe 167(55.67%) and some of the patients had problems in lower lobe 22(7.33%), mean±SD (0.97±0.15). Regarding location, left principal bronchus were involved in 115(38.33%), upper lobe 95(31.67%), lower lobe 36(12.00%) and lingular lobe 36(12.00%), mean±SD (2.01±1.02). Trachea was found normal 261(87.00%) and growth 29(13.00%), mean±SD (1.13±0.33). Vocal cord found normal 246(82.00%) and palsy was found in 54(18.00%), mean±SD (1.18±0.38). carina findings were normal 54(18.00%), blunt 230(76.67%) and sharp 13(4.33%), mean±SD (1.26±0.50).
Conclusion: FOB can be successfully employed for the diagnosis of lung diseases, including malignancies and granulomatous lesions. Routine bronchoscopy technique continues to have a good diagnostic yield in current clinical practice in various lung diseases.
TAJ 2020; 33(2): 46-55
Increased Expression of TICRR Predicts Poor Clinical Outcomes: A Potential Therapeutic Target for Papillary Renal Cell Carcinoma
Authors: Xia Shuang , Lin Yan , Lin Jiaqiong , Li Xiaoyong , Tan Xuexian , Huang Zena 
Published: January 2021

Background: Papillary renal cell carcinoma (PRCC), although the second-most common type of renal cell carcinoma, still lacks specific biomarkers for diagnosis, treatment, and prognosis. TopBP1-interacting checkpoint and replication regulator (TICRR) is a DNA replication initiation regulator upregulated in various cancers. We aimed to evaluate the role of TICRR in PRCC tumorigenesis and prognosis.Methods: Based on the Kidney Renal Papillary cell carcinoma Project (KIRP) on The Cancer Genome Atlas (TCGA) database, we determined the expression of TICRR using the Wilcoxon rank sum test. The biological functions of TICRR were evaluated using the Metascape database and Gene Set Enrichment Analysis (GSEA). The association between TICRR and immune cell infiltration was investigated by single sample GSEA. Logistic analysis was applied to study the correlation between TICRR expression and clinicopathological characteristics. Finally, Cox regression analysis, Kaplan–Meier analysis, and nomograms were used to determine the predictive value of TICRR on clinical outcomes in PRCC patients.Results:TICRR expression was significantly elevated in PRCC tumors (P &lt; 0.001). Functional annotation indicated enrichment with negative regulation of cell division, cell cycle, and corresponding pathways in the high TICRR expression phenotype. High TICRR expression in PRCC was associated with female sex, younger age, and worse clinical stages. Cox regression analysis revealed that TICRR was a risk factor for overall survival [hazard ratio (HR): 2.80, P = 0.002], progression-free interval (HR: 2.86, P &lt; 0.001), and disease-specific survival (HR: 7.03, P &lt; 0.001), especially in patients with male sex, age below 60 years, clinical stages II–IV and clinical T stage T1–T2.Conclusion: Increased TICRR expression in PRCC might play a role in tumorigenesis by regulating the cell cycle and has prognostic value for clinical outcomes.
The Association Between Handgrip Strength and Predialysis Serum Sodium Level in Patients With Chronic Kidney Disease Stage 5D
Authors: Markaki Anastasia , Kyriazis Periklis , Dermitzaki Eleftheria-Kleio , Maragou Sevasti , Psylinakis Emmanuel , Spyridaki Aspasia , Drosataki Helen , Lygerou Dimitra , Grammatikopoulou Maria G. , Petrakis Ioannis , Stylianou Kostas 
Published: January 2021

Purpose: Handgrip strength (HGS) is a useful tool for the systematic assessment of muscle function related to nutritional status. Reduced HGS has been associated with adverse clinical outcomes in chronic kidney disease (CKD) stage 5D patients. In the same patients, predialysis low serum sodium (sNa) has been associated with malnutrition and mortality. Here, we investigated the role of predialysis sNa on muscle function in CKD-5D patients.Methods: We evaluated 45 patients on hemodialysis (HD) and 28 patients on peritoneal dialysis (PD) with HGS measurement, bioimpedance analysis, anthropometric measures, and malnutrition inflammation score (MIS). According to established diagnostic criteria, reduced HGS was defined as strength below 30 and 20 Kg in men and women, respectively. Predialysis sNa values were defined as the mean of all predialysis measurements during the preceding 6 months. Data analysis was performed separately for each of the HD and PD groups.Results: The proportions of reduced HGS did not differ between the HD (66%) and PD (54%) groups, respectively. Patients in the HD group as compared to those in the PD group had higher serum albumin and potassium and mid-arm muscle circumference and lower residual renal function (RRF) and residual urine volume. Multivariate logistic analysis, after controlling for muscle mass, nutritional biomarkers, MIS, fluid overload and RRF, showed that for every 1 mmol/l increase of sNa the odds of reduced HGS was decreased by 60% (OR = 0.40, 95% CI: 0.16–0.99) and 42% (OR = 0.58, 95% CI: 0.36–0.93) in HD and PD patients, respectively. However, stratified analysis indicated that lower sNa levels predicted reduced HGS in individuals with a background of malnutrition, inflammation, overhydration and less preserved RRF, representing unfavorable conditions strongly related to muscle wasting in the dialysis setting.Conclusions: Predialysis sNa is a strong and independent determinant of HGS, a reliable nutritional marker in CKD-5D stage patients. However, according to our findings, lower sNa levels appear to be a marker of underlying unfavorable conditions that are heavily associated with reduced HGS, rather than a causal determinant of reduced HGS. Whether optimizing sNa levels improves patient muscle performance requires further investigations.
Extracorporeal Membrane Oxygenation for SARS-CoV-2 Acute Respiratory Distress Syndrome: A Retrospective Study From Hubei, China
Authors: Yang Xiaobo , Hu Ming , Yu Yuan , Zhang Xijing , Fang Minghao , Lian Yingtao , Peng Yong , Wu Lingling , Wu Yongran , Yi Jun , Zhang Lu , Wang Bing , Xu Zhengqin , Liu Boyi , Yang Yadong , Xiang Xiaowei , Qu Xingguang , Xu Wenhao , Li Hunian , Shen Zubo , Yang Changming , Cao Fengsheng , Liu Jie , Zhang Zhaohui , Li Lianghai , Liu Xiaoyun , Li Ruiting , Zou Xiaojing , Shu Huaqing , Ouyang Yaqi , Xu Dan , Xu Jiqian , Zhang Jiancheng , Liu Hong , Qi Hong , Fan Xuepeng , Huang Chaolin , Yu Zhui , Yuan Shiying , Zhang Dingyu , Shang You 
Published: January 2021

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available.Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected.Results: The 73 ECMO-treated patients had a median age of 62 (range 33–78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6–87.0] mmHg and a median PCO2 of 62 [IQR, 43–84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15–25] days, and 23 [IQR, 19–31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12–30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively.Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.
Effects of Rare Microbiome Taxa Filtering on Statistical Analysis
Authors: Cao Quy , Sun Xinxin , Rajesh Karun , Chalasani Naga , Gelow Kayla , Katz Barry , Shah Vijay H. , Sanyal Arun J. , Smirnova Ekaterina 
Published: January 2021

Background: The accuracy of microbial community detection in 16S rRNA marker-gene and metagenomic studies suffers from contamination and sequencing errors that lead to either falsely identifying microbial taxa that were not in the sample or misclassifying the taxa of DNA fragment reads. Removing contaminants and filtering rare features are two common approaches to deal with this problem. While contaminant detection methods use auxiliary sequencing process information to identify known contaminants, filtering methods remove taxa that are present in a small number of samples and have small counts in the samples where they are observed. The latter approach reduces the extreme sparsity of microbiome data and has been shown to correctly remove contaminant taxa in cultured “mock” datasets, where the true taxa compositions are known. Although filtering is frequently used, careful evaluation of its effect on the data analysis and scientific conclusions remains unreported. Here, we assess the effect of filtering on the alpha and beta diversity estimation as well as its impact on identifying taxa that discriminate between disease states.Results: The effect of filtering on microbiome data analysis is illustrated on four datasets: two mock quality control datasets where the same cultured samples with known microbial composition are processed at different labs and two disease study datasets. Results show that in microbiome quality control datasets, filtering reduces the magnitude of differences in alpha diversity and alleviates technical variability between labs while preserving the between samples similarity (beta diversity). In the disease study datasets, DESeq2 and linear discriminant analysis Effect Size (LEfSe) methods were used to identify taxa that are differentially abundant across groups of samples, and random forest models were used to rank features with the largest contribution toward disease classification. Results reveal that filtering retains significant taxa and preserves the model classification ability measured by the area under the receiver operating characteristic curve (AUC). The comparison between the filtering and the contaminant removal method shows that they have complementary effects and are advised to be used in conjunction.Conclusions: Filtering reduces the complexity of microbiome data while preserving their integrity in downstream analysis. This leads to mitigation of the classification methods' sensitivity and reduction of technical variability, allowing researchers to generate more reproducible and comparable results in microbiome data analysis.
E2F1 Induces KIF26A Transcription and Promotes Cell Cycle Progression via CDK–RB–E2Fs Feedback Loop in Breast Cancer
Authors: Xu Jing , Liu Lei , Ma Ranran , Wang Yawen , Chen Xu , Liu Haiting , Ji Youxin , Liu Tiantian , Gao Peng 
Published: January 2021

ObjectiveThe aim of this study was to investigate the role of KIF26A in breast cancer.MethodqRT-PCR and immunohistochemistry were conducted to explore KIF26A expression and functional contribution to breast cancer development. MTS, EDU, colony formation assays, and flow cytometry analysis were conducted to assess cell proliferation characteristics and cell cycle progression. A series of 5′-flanking region deletion plasmids and mutating the binding site, with the luciferase reporter assay, were used to identify the core promotor region of KIF26A. The prediction by software and construction of the transcriptional factor plasmids were used to identify the transcriptional factor. Chromatin immunoprecipitation assay could demonstrate transcriptional factor directly binding to the KIF26A promoter. Human Genome Oligo Microarray Assay and gene ontology (GO) and pathway analyses were used to predict the downstream pathway.ResultsOur results showed that in breast cancer tissues, elevated KIF26A expression was significantly correlated with lymph node metastasis. KIF26A could promote proliferation and G0/G1 phase cell cycle progression in breast cancer cells. The core promoter region of the human KIF26A gene was located upstream of the transcription start site at position −395 to −385. The transcriptional factor E2F1 was shown to activate KIF26A expression. Furthermore, KIF26A was shown to inhibit the expression of p21, then activate CDK–RB–E2Fs pathway. The elevated E2F1 can activate the cell cycle progression and the KIF26A expression, forming feedback loop.ConclusionsThe present study demonstrated that KIF26A, directly upregulated by E2F1, promoted cell proliferation and cell cycle progression via CDK–RB–E2Fs feedback loop in breast cancer.
Development and Validation of a Nomogram for Predicting Survival in Gallbladder Cancer Patients With Recurrence After Surgery
Authors: Chen Mingyu , Li Shijie , Topatana Win , Lv Xiaozhong , Cao Jiasheng , Hu Jiahao , Lin Jian , Juengpanich Sarun , Shen Jiliang , Cai Xiujun 
Published: January 2021

BackgroundThe management of gallbladder cancer (GBC) patients with recurrence who need additional therapy or intensive follow-up remains controversial. Therefore, we aim to develop a nomogram to predict survival in GBC patients with recurrence after surgery.MethodsA total of 313 GBC patients with recurrence from our center was identified as a primary cohort, which were randomly divided into a training cohort (N = 209) and an internal validation cohort (N = 104). In addition, 105 patients from other centers were selected as an external validation cohort. Independent prognostic factors, identified by univariate and multivariable analysis, were used to construct a nomogram. The performance of this nomogram was measured using Harrell’s concordance index (C-index) and calibration curves.ResultsOur nomogram was established by four factors, including time-to-recurrence, site of recurrence, CA19-9 at recurrence, and treatment of recurrence. The C-index of this nomogram in the training, internal and external validation cohort was 0.871, 0.812, and 0.754, respectively. The calibration curves showed an optimal agreement between nomogram prediction and actual observation. Notably, this nomogram could accurately stratify patients into different risk subgroups, which allowed more significant distinction of Kaplan-Meier curves than that of using T category. The 3-year post-recurrence survival (PRS) rates in the low-, medium-, and high-risk subgroups from the external validation cohort were 53.3, 26.2, and 4.1%, respectively.ConclusionThis nomogram provides a tool to predict 1- and 3-year PRS rates in GBC patients with recurrence after surgery.
Insights Into the Impacts of BRCA Mutations on Clinicopathology and Management of Early-Onset Triple-Negative Breast Cancer
Authors: Ye Fugui , He Min , Huang Liang , Lang Guantian , Hu Xin , Shao Zhimin , Di Genhong , Cao Ayong 
Published: January 2021

BackgroundLittle is known regarding the clinicopathologic characteristics, oncologic outcomes, and treatment strategies that could be ascribed to BRCA mutation in early-onset triple-negative breast cancer (eTNBC).MethodseTNBC patients who underwent BRCA genetic testing were derived from our clinical database between 2012 and 2018. Differences in clinical features and pathologic characteristics were examined in groups divided by BRCA mutation status, and the contribution of germline mutations in conjunction with treatment modalities to survival outcomes was determined.ResultsOf the 355 qualifying eTNBC patients, 67 (18.87%) were BRCA mutated and 288 (81.13%) were BRCA wild. Overall, median age at diagnosis was 34 years (range, 24–40 years) in the BRCA mutated subgroup and 35 years (range, 21–40 years) in BRCA wild. The majority of clinicopathologic parameters were parallel; however, tumor size (P = 0.07) and nuclear grade (P =0.08) tend to be more aggressive in the BRCA mutated subgroup. Compared with BRCA wild patients, BRCA mutated patients had a higher likelihood of receiving anthracyclines and taxane-based combination chemotherapy (P = 0.04) and tend to be lower tumor burden (P =0.01). After approximately 5-year median follow-up, the overall survival (OS) (P = 0.021) and breast cancer-specific survival (BCSS) (P = 0.004) in BRCA mutated patients were superior to those in their BRCA wild counterparts. Intriguingly, the clinical outcomes were comparable in patients with breast conserving surgery (BCS) regardless of BRCA mutations and in patients with BRCA mutations in spite of surgical schedules.ConclusionsThese results suggest that eTNBC patients with BRCA mutations are prone to better OS and BCSS, which might be largely attributed to more benefit from anthracyclines and taxane-based chemotherapy. The BCS procedure could be a safe alternative surgical option for eTNBC patients with BRCA mutations. Future studies with substantial numbers of participants are urgently needed to validate whether BRCA mutation eTNBC patients are more sensitive to chemotherapy.
Vitamin C Administration by Intravenous Infusion Increases Tumor Ascorbate Content in Patients With Colon Cancer: A Clinical Intervention Study
Authors: Dachs Gabi U. , Gandhi Jamish , Wohlrab Christina , Carr Anitra C. , Morrin Helen R. , Pullar Juliet M. , Bayer Simone B. , Eglinton Tim W. , Robinson Bridget A. , Vissers Margreet C. M. 
Published: January 2021

The use of high dose ascorbate infusions in cancer patients is widespread, but without evidence of efficacy. Several mechanisms whereby ascorbate could affect tumor progression have been proposed, including: (i) the localized generation of cytotoxic quantities of H2O2; (ii) ascorbate-dependent activation of the 2-oxoglutarate-dependent dioxygenases that control the hypoxia-inducible factors (HIFs) and that are responsible for the demethylation of DNA and histones; (iii) increased oxidative stress induced by dehydroascorbic acid. We hypothesize that the dysfunctional vasculature of solid tumors results in compromised delivery of ascorbate to poorly perfused regions of the tumor and that this ascorbate deficit acts as an additional driver of the hypoxic response via upregulation of HIFs. Using a randomized “therapeutic window of opportunity” clinical study design we aimed to determine whether ascorbate infusions affected tumor ascorbate content and tumor biology. Patients with colon cancer were randomized to receive infusions of up to 1 g/kg ascorbate for 4 days before surgical resection (n = 9) or to not receive infusions (n = 6). Ascorbate was measured in plasma, erythrocytes, tumor and histologically normal mucosa at diagnostic colonoscopy and at surgery. Protein markers of tumor hypoxia or DNA damage were monitored in resected tissue. Plasma ascorbate reached millimolar levels following infusion and returned to micromolar levels over 24 h. Pre-infusion plasma ascorbate increased from 38 ± 10 µM to 241 ± 33 µM (p &lt; 0.0001) over 4 days and erythrocyte ascorbate from 18 ± 20 µM to 2509 ± 1016 µM (p &lt; 0.005). Tumor ascorbate increased from 15 ± 6 to 28 ± 6 mg/100 g tissue (p &lt; 0.0001) and normal tissue from 14 ± 6 to 21 ± 4 mg/100 g (p &lt; 0.001). A gradient of lower ascorbate was evident towards the tumor centre in both control and infusion samples. Lower expression of hypoxia-associated proteins was seen in post-infusion tumors compared with controls. There were no significant adverse events and quality of life was unaffected by ascorbate infusion. This is the first clinical study to demonstrate that tumor ascorbate levels increase following infusion, even in regions of poor diffusion, and that this could modify tumor biology.Clinical Trial RegistrationANZCTR Trial ID ACTRN12615001277538 (https://www.anzctr.org.au/).
Physical Activity Level Influences MTHFR Gene Methylation Profile in Diabetic Patients
Authors: Diniz Tainá Gomes , Silva Alexandre Sérgio , dos Santos Nunes Mayara Karla , Ribeiro Mateus Duarte , Filho João Modesto , do Nascimento Rayner Anderson Ferreira , Gomes Cecília Neta Alves Pegado , Evangelista Isabella Wanderley de Queiroga , de Oliveira Naila Francis Paulo , Persuhn Darlene Camati 
Published: January 2021

IntroductionMTHFR methylation status is associated with microvascular complications in diabetes, but the factors influencing this profile remain unknown.ObjectiveThe aim of this study was to evaluate the influence of physical activity level and nutritional status on the methylation profile of the MTHFR gene in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 111 patients, 43 men and 68 women diagnosed with DM (7.0 ± 2.3 years), answered the International Physical Activity Questionnaire (IPAQ) and underwent blood collection for biochemical analysis, DNA extraction, and MTHFR gene methylation profile determination.ResultThe comparison of the methylation pattern showed that the partially methylated profile predominates in the insufficiently active group (85%), which does not occur in the sufficiently active group (54%) (p = 0.012). No differences were found in the nutritional status comparison. Logistic regression including overweight, waist circumference, gender, age, time of DM, hypertension, dyslipidemia, smoking, alcoholism, and family DM revealed that the association of the level of physical activity with methylation profile proved to be independent of these confounding variables. Considering the partially methylated profile as a result, being physically inactive favors the partially methylated MTHFR pattern in patients with DM.ConclusionWe concluded that insufficient physical activity is associated with partially methylated pattern of MTHFR promoter.