bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Chromosome Microarray Analysis and Karyotype Analysis in Diagnostic Assessment of Abnormal Down's Syndrome Screening Results
Authors: Kang Han , Wang Lingxi , Li Xingyu , Gao Chonglan , Xie Yamei , Hu Yu
Published: September 2021

Background: Although screening for fetal aneuploidy with the use of cell-free DNA obtained from maternal plasma is highly effective, biomarkers screening is in extensive use in economically underdeveloped areas and poor population. This study aims to explore the application value of chromosomal microarray analysis (CMA) and karyotype analysis in prenatal diagnosis for pregnant women with abnormal Down’s syndrome (DS) screening results.Methods: The study recruited 813 pregnant women with abnormal DS screening results from Chengdu Women’s and Children’s Central Hospital. They underwent amniocentesis to obtain fetal amniotic fluid for CMA and G-band karyotype analysis. An Affymetrix CytoScan 750 K Array chip was used for CMA analysis according to the manufacturer’s instructions.Results: In total, CMA identified 21/813 abnormal results, which was more efficient than karyotype analysis(10/813, P<0.001.) CMA is equivalent to traditional karyotype analysis for the prenatal diagnosis of aneuploidies. However, CMA identified 1.60% more copy number variants(CNVs) than karyotype analysis. These pathogenic/likely pathogenic(P/LP) CNVs ranged from 159Kb deletion to 3616Kb deletion. 53.8% of them were recurrent pathogenic CNVs associated with risk of neurodevelopmental disorders. CMA identified 7 variants of uncertain significance (VUS) results, including 6 microduplication and 1 microdeletion, with the size ranged from 840kb-1484kb. Karyotype analysis identified 2 mosaic sex chromosome aneuploidy, 2 balanced translocation and 1 mosaic balanced translocation, which could not be identified by CMA. Conclusions: Performing both CMA and karyotype analysis simultaneously is more beneficial to pregnant women with abnormal DS screening results.
Initial Evaluation of Uroplakins UPIIIa and UPII in Selected Benign Urological Diseases
Authors: Szymańska Beata , Matuszewski Michał , Dembowski Janusz , Piwowar Agnieszka
Published: September 2021

BackgroundUroplakins (UPs) are glycoproteins that play a specific role in the structure and function of the urothelium. Disorders of normal expression of uroplakins are associated with the pathogenesis of infections and neoplasms of the urinary tract, primary vesicoureteral reflux, hydronephrosis and renal dysfunction. The appearance of uroplakins in the urine and/or plasma may be of potential importance in the detection of urinary tract dysfunction. The aim of the study was to investigate uroplakin IIIa (UPIIIa) and uroplakin II (UPII) expression in patients with selected urological diseases. Plasma and urine from patients with benign prostatic hyperplasia (BPH), urethral stricture (US), urinary tract infection (UTI) and urolithiasis, were compared to healthy people without urological disorders. MethodsA total 152 of human urine and plasma samples from normal and patients with selected benign urological diseases were analyzed. UPs concentration was measured by immunoenzymatic method. All calculations were done using the STATISTICA 13.3 (TIBCO software Inc.).ResultsIn patients with BPH and UTI, UPIIIa in urine and plasma also UPII in urine concentrations were statistically significantly higher than in the control groups. In the US group, only the plasma UPIIIa concentration differed significantly from the control. There were no significant differences between the concentrations of UPs compared to the controls in both the urine and plasma of patients with urolithiasis. ConclusionThe conducted research shows that benign urological diseases may affect the state of the urothelium, as manifested by an increased concentration of both UPs in patients’ urine and plasma, especially in BPH and UTI.
Yifei Sanjie Formula Treats Chronic Obstructive Pulmonary Disease by Regulating Lung Microbiota Dysbiosis
Authors: Wu Yue-Ying , Qiao Bo , Zhang Qiang , Jia Wen-Qing , Meng Hui , Xing Hai-Jing , Li Yu-Qing , Yang Zhong-Shan , Yuan Jia-Li
Published: September 2021

BackgroundChronic obstructive pulmonary disease (COPD) is one of the most common pulmonary diseases. There is evidence to suggest that dysbiosis of pulmonary microbiota participates in COPD development. Yifei Sanjie Formula (YS) is widely used to treat diseases in respiratory systems, yet its mechanisms are little known. MethodsIn the present study, the efficacy of YS was evaluated by analyzing its effects on the severity of pulmonary pathological damage, pulmonary function, pro-inflammation cytokines, the activation of NLRP3/caspase-1/IL-1β signaling pathway, and changes of lung microbiota. ResultsYS improved animal behaviors, prevented declines in pulmonary ventilatory function and lung injury in a rat model of COPD. Administration of YS significantly suppressed the release of proinflammatory cytokines and collagen deposition and downregulated NLRP3/caspase-1/IL-1β signaling in vivo. YS changed the relative abundance of specific pulmonary microbiota and modulated bacterial flora in the rat model. Conclusions﻿These results suggest that the effects of YS involved lung microbes and anti-inflammatory mechanisms.
A Simple Nomogram Developed for Predicting HCC Metastasis Based on microRNAs
Authors: Zhu Yong , Jie Yusheng , Wu Yuankai , Tang Wenting , Cao Jing , Su Zhongzhen , Zhuo ZhenJian , Gong Jiao , Chong Yutian
Published: September 2021

Background: Owing to lack of predictive models for Hepatocellular carcinoma (HCC) metastasis based on the expression of miRNAs, we aimed to develop a simple model for identification of HCC patients at high risk of metastasis. Results: HCC datasets with metastasis information were acquired from the Gene Expression Omnibus (GEO), and samples were randomly divided into training group (n=169) and testing group (n=72). Based on expression of miRNAs in the training group, we developed a predictive nomogram for HCC metastasis and evaluated its performance using area under the receiver operating characteristic curve (AUC), calibration curve, decision curve and clinical impact curve analysis. We found that the expression of miR-30c, miR-185 and miR-323 in HCC correlated with metastasis by the least absolute shrinkage and selection operator regression (LASSO) method and multivariate logistic regression. Based on these three miRNAs, we generated the nomogram for predicting metastasis in the training group (AUC 0.869 [95% CI .813-0.925], sensitivity 80.5%, specificity 78.9%); in testing group (0.821 [0.770-0.872], 48.5%, 92.3%). The calibration curve showed a good agreement between actual observation and prediction by nomogram. The nomogram represented high clinical net benefits using decision curve. Moreover, total scores calculated by nomogram were higher in dead patients than that in alive patients. In addition, the predicted target genes of these 3 miRNAs correlated with tumor metastasis by functional enrichment analysis, such as filopodium and we identified their related hub genes. Conclusions: Our easy-to-use nomogram could assist in identifying HCC patients at high risk of metastasis, which offer valuable information for clinical treatment.
Sensitivity Assessment of Chemotherapeutic Agents for Ovarian Tumors Based on Test in Vitro Culture: A Blind Study
Authors: RAO Qunxian , WEI Yuan , CHEN Qing , GUAN Meimei , ZHOU Hui , HAN Xue , XING Xiaohui , SHEN Tianran , SHU Yu , LU Huaiwu , HE Yuanqiao , chen qingsong
Published: September 2021

Background: Ovarian cancer is common malignant tumors but the survival rate has not been improved well for a long time. One of the important reasons is that the current clinical guidelines for treatment still do not solve the problem of patient heterogeneity and drug resistance, which are exactly the key factors affecting the efficacy of chemotherapy. In addition, there are limited research data that can help accurately identify patients' preferred drugs and combination regimen, which fails to meet the needs of individualized treatment. Methods：The objective was used the Hydrogel Embedded Histoculture Drug Sensitivity Test (HDST), to verified its accuracy in predicting the response to chemotherapy in ovarian tumors and evaluate the sensitivity of chemotherapy drugs. Tissue samples of 82 ovarian tumor patients were tested for HDST drug sensitivity and follow-up who were included in randomized study. The consistency of drug sensitivity results and clinical outcomes were analyzed through preliminary study to determine the feasibility of this technology, and then a comprehensive blind study was conducted to evaluate Drug sensitivity.Result: HDST in determining the efficacy of chemotherapy drugs were consistent with the actual clinical efficacy of patients (Kappa=0.535), and the sensitivity, specificity, AUC were 82.14%, 100.00%, 0.911. Single-drug resistance rates of TXL, DOC, CDDP, CBP, Lobaplatin, and VP-16 were 21.95%, 74.39%, 62.20% , 52.44%, 39.02%, 60.98%, respectively. Highest Secondary drug resistance rate of CBP was 44.44%, followed by CDDP and VP-16 (22.22%). TXL’s IR was significantly higher than DOC wherever the location, and Loplatin’s was higher than CDDP (P<0.05). TXL’s IR was higher than VP-16 in primary foci, but VP-16’s was not only higher than DOC, but also CDDP, and similar to the CBP and Lobaplatin in abdominal metastases(P<0.05).Conclusion: HDST can effectively predict the response to existing chemotherapy regimens as new tool to screen individualized treatment for patients. Paclitaxel combined with Lobaplatin regimen may have more advantages in chemotherapy and Etoposide should not be ignored in ovarian tumors.
Prevalence of Asthma-COPD Overlap in COPD and Severe Asthma Cohorts
Authors: Joo Hyonsoo , Park So-Young , Park So Young , Park Seo Young , Kim Sang-Heon , Cho You Sook , Yoo Kwang Ha , Jung Ki Suck , Rhee Chin Kook
Published: September 2021

Background: Asthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.Methods: Patients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and blood eosinophil count (threshold: 300 cells/μL).Results: The prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1839] vs. 12.5% [104/832], respectively, P < 0.001). The numbers of patients in each group were as follows: Group A (smoking 10–20 pack-years and blood eosinophil count ≥ 300 cells/μL), 42 (9.1%); Group B (smoking 10–20 pack-years and eosinophil count < 300 cells/μL), 17 (3.7%); Group C (smoking ≥ 20 pack-years and eosinophil count ≥ 300 cells/μL), 341 (73.8%); and Group D (smoking ≥ 20 pack-years and eosinophil count < 300 cells/μL), 62 (13.4%). Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.Conclusion: The prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.
Serum Lactate Dehydrogenase to Phosphate Ratio as an Independent Predictor for Adverse Outcome of Microsurgical Clipping for Ruptured Intracranial Aneurysm: A Retrospective Study
Authors: Zheng Shufa , Xie Xueling , Wang Haojie , Yao Peisen , Chen Guorong , Shangguan Huangcheng , Yu Lianghong , Lin Yuanxiang , Lin Zhangya , Kang Dezhi
Published: September 2021

Objective: We assessed the correlation between lactate dehydrogenase(LDH) to phosphate ratio and the prognosis of microsurgically clipping for ruptured intracranial aneurysm (rIA) in this study, to test the hypothesis that serum LDH to phosphate ratio could be a predictor for the outcome of microsurgically clipping for rIA. Methods: The rIA patients between 2012 and 2018 were retrospectively collected. Age, sex, Hunt-Hess(H-H) grade, Fisher grade, smoking, drink, medical history, aneurysm location, hydrocephalus, laboratory data including serum LDH, phosphate and LDH to phosphate ratio, related complication and the outcomes in 3 months were recorded. Results: A total of 1608 rIA patients in our institution were collected, and 856 patients treated by microsurgical clipping were enrolled. A significantly higher LDH- phosphate ratio on admission was observed in patients with poor outcome at 3 months (median±SD, 200.175±107.290 for mRS 0–2 vs 323.826±219.075 for mRS score 3–6; P <0.001). A LDH to phosphate ratio of 226.25 in the receiver operating characteristic (ROC) curve was identified as optimal cutoff value to discriminate between good and poor outcome at 3 months. LDH to phosphate ratio≥226.25 on admission was independently correlated with poor outcome in rIA patients. In addition, H-H grade, Fisher grade, pneumonia and DIND were also independently correlated with poor outcome. After removing the bias in basic clinical variables between patients with LDH to phosphate ratio≥226.25 versus <226.25 by PSM, the number of patients with poor outcome at 3 months was obviously increased in patients with LDH to phosphate ratio≥226.25 ( P =0.005). Conclusions: LDH to phosphate ratio was a potential biomarker and could predict the unfavorable outcome of microsurgically clipping for rIA in 3 months. However, the detailed mechanism remain unclear and the conclusion needs be further confirmed by large-scale randomized clinical trials.
After Habitat Changed, Evaluation For Genetic Diversity And Secondary Metabolic Changes of Cultivated And Wild Populations of Medicinal Plants
Authors: Li Yulong , Zhao Wei , Zuo Xianghua , Ni Biao , You Jian , Xing Ming , Du Yingda , Liu Chen , Chen Xia
Published: September 2021

Background: With the increasing use of traditional herbal medicine, the issue of the genetic diversity of medicinal plants has received considerable critical attention. A high degree of genetic diversity is the basis for maintaining the stability and long-term survival of the population, so the changes in genetic diversity and genetic structure of cultivated medicinal plants caused by habitat changes can not be ignored; Meanwhile, the difference of secondary metabolism of medicinal plants caused by habitat change is also deserving of attention simultaneously. And It is also worth pondering whether the changes between them are consistent. Results: In this study, the wild and cultivated populations of Polygonatum odoratum, Dioscorea nipponica and Acanthopanax sessiliflorus were selected as the research objects. and the genetic structure and HPLC fingerprint between wild and cultivated populations were compared and analyzed by using Simple Sequence Repeats (SSR) marker and HPLC . The results demonstrated that the wild and cultivated populations of the three medicinal plants maintained higher genetic diversity, however, the genetic structure of wild populations of P.odoratum and D.nipponica is more similar. In addition, there was a great genetic differentiation between P.odoratum and D.nipponica populations. There were significant differences in HPLC fingerprints among different populations, in which the secondary metabolites of wild populations were more complex, nevertheless, there was less difference in HPLC fingerprints between wild and cultivated populations of P.odoratum and D.nipponica. Spearman correlation analysis implied that environmental factors (including soil environmental factors, rainfall, temperature) had significant effects on the secondary metabolites of the three medicinal plants, whereas, soil environmental factors had less effect on the genetic structure of the three medicinal plants. Conclusion: In conclusion, during the cultivation years, environmental factors only have a significant effect on the secondary metabolism of the three medicinal plants, their populations still maintain higher genetic diversity and stable genetic structure, what’s more, the secondary metabolites of the same medicinal plants with stable and similar genetic structure may still be different from each other when the habitat is changed. It indicated that there is no obvious consistency between them during the cultivation years.
Implementation and Scale Up of Tobacco Cessation Within TB Programmes: Findings from a Multi-Country, Mixed-Methods Implementation Study
Authors: Elsey Helen , Azdi Zunayed Al , Regmi Shophika , Baral Sushil , Fatima Razia , Feroze Fariza , Huque Rumana , Karki Jiban , Khan Dost Mohammad , Khan Amina , Khan Zohaib , Li Jinshuo , Noor Maryam , Arjyal Abriti , Shrestha Prabin , Ullah Safat , Siddiqi Kamran
Published: September 2021

Background: Brief behavioural support can effectively help TB patients to quit smoking and improve their outcomes. In collaboration with TB programmes in Bangladesh, Nepal and Pakistan, we evaluated implementation and scale-up of cessation support using four strategies: i) brief tobacco cessation intervention ii) integration of tobacco cessation within routine training iii) inclusion of tobacco indicators in routine records and iv) embedding research within TB programmes.Methods: We used mixed methods of observation, interviews and routine data within WHO’s ExpandNet framework for scale-up. We aimed to understand the extent of, and strategies which facilitated vertical scale-up (institutionalisation) within 59 health facility learning sites in Pakistan, 18 in Nepal and 15 in Bangladesh and horizontal scale-up (increased coverage beyond learning sites). We observed training and surveyed 169 TB health workers to measure changes in their confidence to deliver cessation. Routine TB data from the learning sites was analysed to assess delivery of the intervention and use of TB forms revised to report smoking status and cessation support provided. A purposive sample of TB health workers, managers and policymakers were interviewed (Bangladesh: n=12; Nepal n=13; Pakistan n=19;). Costs of scale-up were estimated using activity-based cost-analysis. Results: Routine data indicated health workers in learning sites asked all TB patients about tobacco use and offered them cessation support. Qualitative data showed use of intervention materials, often with adaptation and partial implementation in busy clinics. Short (1-2 hours) training integrated within existing programmes increased mean confidence to deliver cessation by 17% (95% CI: 14% to 20%). A focus on health system changes (reporting, training, supervision) facilitated vertical scale-up. Dissemination of materials beyond learning sites and changes to national reporting forms and training indicated horizontal scale-up. Embedding research within TB health systems was crucial for horizontal scale-up and required dynamic use of tactics e.g. alliance-building, engagement in wider policy process, use of insider-researchers, and deep understanding of health system actors and processes. Conclusions: System-level changes within TB programmes may enable routine delivery of cessation support to TB patients. These strategies are inexpensive and, with concerted efforts from TB programmes and donors, tobacco cessation can be institutionalised at-scale.
Effects of ACE2 and Co-factors on the Mechanism of SARS-CoV-2 Infection Among Colorectal Cancer Patients
Authors: Li Shuwei , Chen Silu , Zhu Qiuyuan , Ben Shuai , Gao Fang , Xin Junyi , Du Mulong , Chu Haiyan , Gu Dongying , Zhang Zhengdong , Wang Meilin
Published: September 2021

Background: The infection of host cells by SARS-CoV-2 is mediated by ACE2 and its co-factors, including TMPRSS2 and FURIN. Patients with cancer are highly susceptible to COVID-19 and exhibit a higher risk of severe progression. However, the mechanism of SARS-CoV-2 infection on colorectal cancer prognosis is largely unknown. Here, we investigated the role of key genes related to SARS-CoV-2 in colorectal cancer.Methods: RNA sequencing (RNA-Seq), proteomics and single-cell RNA-Seq were used to profile the expression of ACE2, TMPRSS2, and FURIN in colorectal cancer. A pseudovirus was used to transfect colon cells to compare the infection rate of SARS-CoV-2 between different cell types. The TIMER database was used to analyze the association of candidate genes with immune infiltration in colorectal cancer. Cox regression model was performed to evaluate genetic effects of ACE2 on colorectal cancer prognosis.Results: ACE2 was upregulated in colorectal cancer tissues, while TMPRSS2 and FURIN were downregulated. Increased ACE2 expression was significantly associated with a decreased tumor mutational burden. Furthermore, ACE2 promoted the SARS-CoV-2 infection in colon cancer cells than that in normal colon epithelial cells, as well as that ACE2 could affected the immune infiltration level and prognosis in colorectal cancer patients. Moreover, individuals with genetic variants in ACE2 exhibited poor overall survival of colorectal cancer.Conclusions: These results are the first time to identify that ACE2 and its co-factors are associated with the infection and survival of colorectal cancer patients with SARS-CoV-2. Our findings would be helpful for extending the mechanisms in SARS-CoV-2 infection among colorectal cancer.
Role of Plasma Proteomics in Predicting the Prognosis of Older Adult Patients with Chronic Coronary Syndrome
Authors: Cai Yulun , Hao Benchuan , Chen Jianqiao , Li Yuerui , Liu Hongbin
Published: September 2021

Background: Chronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification.Methods: Data-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay (ELISA) in an independent prospective cohort (n = 352).Results: Fifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. A correlation analysis showed that CETP was positively related to high-density lipoprotein cholesterol and triglyceride, and EPCR was positively related to fibrinogen. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. The cumulative risk duration of patients with high EPCR and CETP levels was significantly shorter than that of patients with low EPCR and CETP levels. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone (AUC 0.732 vs. 0.684, p<0.05).Conclusions: Plasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS. The Framingham CHD risk model combined with EPCR and CETP levels was shown to be a high-performance prognostic model for CCS.
Evaluating Implementation Contexts, Mechanisms, and Outcomes: A Normalization Process Theory Coding Manual for Qualitative Research and Instrument Development
Authors: May Carl , Albers Bianca , Bracher Mike , Finch Tracy L , Gilbert Anthony , Girling Melissa , Greenwood Kathryn , MacFarlane Anne , Mair Frances , May Christine M , Murray Elizabeth , Potthoff Sebastian , Rapley Tim
Published: September 2021

Background. Qualitative studies, especially those conducted by teams of researchers, may benefit from clearly structured, parsimonious, coding manuals. The process of creating rigorous and robust coding manuals for individual studies is rarely described, and generalizable coding manuals are rare. Normalization Process Theory (NPT) provides conceptual tools to facilitate understanding of the dynamics of adoption, implementation, and sustainment of socio-technical and organizational innovations. As a widely used theory, a generalizable coding manual would be of utility to implementation researchersObjectives. To make the application of NPT simple for the user, to describe the development of a coding manual for qualitative content analytic studies using NPT, and present this for wider use.Method. Concept Selection and Structuring. Qualitative Content Analysis of selected published papers and interview transcripts. Results. All identifiable theoretical concepts (n=149) embedded in papers and chapters that developed NPT between 2006 and 2020 were identified and extracted from their texts. Overlapping, ambiguous, and duplicate versions of concepts were eliminated, as were concepts derived from other theories. This left 38 core concept definitions. These were piloted in coding of qualitative transcripts collected in two implementation studies, and by collaboratively coding papers collected for a systematic review of implementation studies. At the end of this process, a further process of elimination of overlapping or ambiguous concepts was undertaken leaving 12 primary NPT concepts. Conclusion. The process of coding manual resulted in the presentation of NPT concepts according to the Context-Mechanism-Outcomes configuration of realist evaluation research. A coding manual for NPT that is in accordance with realistic evaluation research was successfully produced and is now freely available to researchers who wish to use NPT in primary and secondary research that employs qualitative methods.
Establishment and Evaluation of Immune Checkpoint Inhibitor Treatment Response Model Based on Gene Expression Value
Authors: Li Xiaoyan , Li Guoyin , Tang Xiyang , Zhou Yongsheng , Zheng Kaifu , Luo Zhonglin , Zhang Xiao , Xiong Yanlu , Feng Yangbo
Published: September 2021

Background: In the past 10 years, the identification of new mutant genes involved in the pathogenesis of melanoma and the discovery of key immune checkpoints have promoted the development of targeted therapy and immunotherapy. There is no doubt that an important breakthrough has been made in the treatment of advanced or metastatic melanoma. However, the treatment of melanoma also faces many challenges. In addition to resistance to existing targeted therapies or immunotherapy, most patients do not respond to immunotherapy or have serious adverse reactions. At present, the value of existing biomarkers to predict treatment response and toxicity is still limited. Therefore, there is an urgent need to establish a convenient and reliable immunotherapy response prediction model in order to preliminarily clarify the population benefiting from immunotherapy.Results: We established a predictive model based on the expression values of five genes for patients with melanoma with an anti-PD1 immunotherapy response score. This model showed better predictive ability compared with other common immunotherapy predictors. Differences were found in the number of immune cells and the expression of common immune checkpoint genes between the high- and low-score groups. The model played a pivotal role in predicting renal cell carcinoma anti-PD1 immunotherapy response. Conclusions: The anti-PD1 immunotherapy response score prediction model for patients with melanoma showed good predictive power, thus having far-reaching significance for identifying people who benefited from anti-PD1 immunotherapy and reducing the potential toxicity of insensitive patients.
Isolated Donor site Tumour Recurrence at Pectoralis Major Myocutaneous Flap in Oral Cavity Squamous Cell Carcinoma – A Rare Case Report and Review of Literature
Authors: Chandrapattan Prathamesh , Panda Sangram Keshari , Sahoo Pradyumna Kumar , Khadanga Chira , Agrawala Sunil
Published: September 2021

Background: Pectoralis Major MyoCutaneous (PMMC) flap has been commonly used since decades for plastic reconstruction in oral cavity cancer surgery. However, rarely the PMMC donor site develops tumor recurrence. Management includes surgical resection in unifocal lesion or salvage radical chemoradiotherapy in clinico-radiologically nonmetastatic unresectable disease which results in satisfactory tumor related outcomes.Case presentation: A 46 year gentleman known case of Squamous Cell Carcinoma left Retromolar Trigone after surgery and adjuvant radiotherapy presented with isolated recurrence at PMMC flap donor vascular pedicle site which was abutting left subclavian vein and so was managed with concurrent chemo-radiotherapy with curative intent and is on follow up since 2 years with no evidence of recurrence.Conclusions: Isolated PMMC flap donor site recurrence in oral cavity squamous cell carcinoma management is complex, with surgical intervention with excision of such lesions in absence of any other deposits is preferable approach. Concurrent CTRT is an alternative option in curative intent when the lesion is not surgically resectable or the patient refuses surgery.
Genes Associated with Prognosis of Hepatocellular Carcinoma
Authors: Gu Wang , Zhang Chao
Published: September 2021

Background: Hepatocellular carcinoma (HCC) is the foremost common malignant liver malady within the world. In any case, the unthinking relationship between each quality and the signaling pathway remains vague. In this think about, we pointed to explain the potential center candidate genes and pathways for HCC. Methods: The GSE41804, GSE62232 and GSE65372 expression profiles cover 139 tumors and 46 non tumors and can be downloaded from the Gene Expression Integrated Database (GEO). Furthermore, we also downloaded the RNA arrangement information set of liver cancer from the cancer genome map (TCGA) database. Then use the online database David 6.8 The Kyoto Encyclopedia of Genes and Genomic Pathways. The protein-protein interaction organized complexes of these Differentially expressed genes (DEGs) were developed by utilizing cytokeratin program, atomic complex discovery plug-in and online database STRING. Results: To begin with, we identified 84 abnormally expressed genes (39 upregulation genes and 45 downregulation genes) that were abnormally expressed in both the Earth synthetic orbit and the TCGA dataset. In expansion, 10 center qualities were recognized: CCNB1, CCNA2, NCAPG, AURKA, ASPM, TOP2A, DLGAP5, NUSAP1, NUF2 and RACGAP1. At long last, the by and large survival examination and relationship examination were performed for these qualities. Conclusions: These discoveries recommend that center qualities and pathways recognized through bioinformatics examination can incredibly enhance our understanding of HCC improvement and repeat. In expansion, these candidate qualities and pathways may be restorative targets for HCC treatment.
Comparing The Clinical Sequels of Trans-Photorefractive Keratectomy And Photorefractive Keratectomy In Correction of Moderate Myopia: A Randomized Clinical Trial
Authors: Nassiri Nader , Shahriari Mansoor , Azemati Mansoor , rezaeyeh Arvin Porkar , Azemati Ali , Alam Zahra Rezaee
Published: September 2021

Purpose: Trans- photorefractive keratectomy (tPRK) technique using the Amaris laser is an alternative and modified method for PRK in correction of mild to moderate myopia. We assessed and compare the clinical sequels of the two techniques. Methods: This randomized clinical trial was conducted on 60 consecutive suffering moderate grades of myopia patients referred to Vanak Ophthalmology Clinic in 2020. The patients were randomly assigned to operate as both eyes of one patient by tPRK method (using Wong baker scale) and both eyes of another patient were by PRK method. Results: The change in patients' vision (UCVA, BCVA) in one and three months of follow-up in both groups was significant compared to preoperative values, but the rate of vision improvement was significantly better than before surgery in the tPRK group. There was no statistically significant difference between the two groups in terms of average refraction score, except for the sphere difference in one month follow-up. The mean Spherical Equivalent change in the PRK group in the one-month follow-up was 1.68 ± 1.00 and in the opposite group was 4.12 ± 0.92, indicating a better improvement in the tPRK group. There was less haziness in patients in the tPRK group than those in the PRK group. The patients undergoing tPRK experienced significantly less pain than another group. There is no difference between the two groups after surgery regarding intraocular pressure. Conclusion: The results of our study showed the superiority of the tPRK method over the PRK in correcting mild to moderate myopia
Oral delivery of Lactobacillus paracasei via microcapsule modulates gut health and intestinal microbiota
Authors: Gyawali Ishwari , Zhou Guilian , Xu Guli , Zeng Yuxian , Li Jincheng , Zhou Jingjing , Jiang Qingyan , Shu Gang , Zhu Canjun
Published: September 2021

Background:

The beneficial impact of probiotics on host health is impaired due to the significant loss of survivability during gastric transit, small intestinal enzymes, and bile acids. Encapsulation helps to preserve the probiotics species from severe environmental factors. This study investigated the effects of oral delivery of probiotics via microcapsule on different parameters of gut health.
Methods:

Lactobacillus paracasei, highly sensitive probiotic species to gastric acid, was encapsulated with novel encapsulating material, polyacrylate resin, to get a microcapsule. C57BL/6 male mice were equally divided into three groups; supplementing basal feed, a mixture of encapsulating material and Lactobacillus paracasei, and encapsulated Lactobacillus paracasei (microcapsule) for four weeks. Fecal moisture percentage was measured regularly, which was elevated in the encapsulated group, but not in the mixed group. Based on this data, mice from control and encapsulated groups were sacrificed to study the different parameters of gut health.
Results:

Compared to control, encapsulated probiotics increased villi height, the ratio of villi height to crypt depth, and decreased crypt depth. Simultaneously, the tight junction proteins were upregulated on encapsulated group showing enhancement of intestinal barrier functions. The level of SigA and mucin increased along with gene expression of MUC-2 but, albumin level was decreased. In addition, we found a rise in the relative gene expression of anti-inflammatory factor (IL-10) and decreased pro-inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α). Meanwhile, microbiota metabolites, fecal LPS and TMAO were downregulated while SCFA and lactate were upraised compared to control. Furthermore, GSH-Px and TAOC level were increased and MDA was decreased. Microbiota analysis revealed the proportion of firmicutes was higher at the phylum level on an encapsulated group, while Lactobacillus was elevated at the genus level. We also found a remarkable increase in the population of Lactobacillus murinus at the species level. In summary, the oral delivery of probiotics via microcapsule effectively improves the animals' gut health by improving morphology, barrier function, anti-inflammatory action, antioxidant ability and modulating gut microbiota.
Seropositivity of anti-SARS-CoV-2 IgG antibodies among asymptomatic and pauci-symptomatic students and staff at the Arab International University, Syria: a snapshot after a year of pandemic
Authors: Zarzour Wafika , Habbal Wafa , Oraige Alaa , Ganama Ahmad , Serri Raghad
Published: September 2021

Background: After a year of pandemic in Syria, how prevalent the seropositivity is, and how far we are from herd immunity is a raised question. Our study aimed to estimate the overall exposure to SARS-COV-2 among students and staff at the Arab International University (AIU) in Syria. Methods: All AIU students and staff were invited to voluntarily participate in the study by filling out and submitting an anonymous web-based survey. Responses were evaluated and asymptomatic and pauci-symptomatic respondents were notified of a phlebotomy appointment. Anti-SARS-CoV-2 IgG antibodies were analyzed by ELISA and a group of sera showing various IgG titers were chosen for retesting using the COVID-19 IgG Rapid Test. Results: One third (122 of 381; 32%) of respondents were asymptomatic. The remaining respondents reported COVID-19-specific symptoms (177 of 381; 46.5%), mainly anosmia and/or ageusia (132 of 381; 34.6%), or nonspecific symptoms (82 of 381; 21.5%). Frequencies of symptoms onset showed a strong, positive correlation (τb=0.53, P<0.01) with the incidence of confirmed SARS-CoV-2 RNA-positive cases reported by the Ministry of Health in Syria. The majority of symptomatic respondents (243 of 259; 94%) were considered ‘mild cases’ where neither oxygen therapy nor pulmonary infiltrates were reported. Anti-SARS-CoV-2 IgG antibodies were similarly detected in both symptomatic (21 of 33; 63.6%) and asymptomatic (39 of 61; 63.9%) individuals. The concordance rate between Rapid and ELISA IgG tests was 75% and discrepancy was confined to low antibody titers. Conclusions: Approaching herd immunity, a 69% exposure to SARS-CoV-2 is roughly estimated. Absence of COVID-19-specific symptoms does not guarantee that an individual is uninfected thus noninfectious. Preventive measures are highly recommended even when no symptomatic COVID-19 patients exist around.
Yiqi Dingxuan Yin improves cerebral ischaemic injury in rats by inhibiting apoptosis and promoting angiogenesis
Authors: Liu Fei , Xie Liuyang , Liu Chunhua , He Guilian , Yuan Chunyun , Hou Fan , He Hongwei , Peng Juan
Published: September 2021

Background

Clinically, Yiqi Dingxuan Yin promotes nerve function recovery and improves nerve function defect symptoms; however, the underlying molecular pathways remain unknown. In this study, we established a rat model of cerebral ischaemia induced by middle cerebral artery occlusion (MCAO). The effects of Yiqi Dingxuan Yin on the neurological function and local neuron morphology were compared with those of butylphthalide, which is used to treat ischemic stroke, and the possible mechanisms of action were explored.
Methods

Of 97 healthy adult male Sprague‒Dawley rats, 20 were randomly assigned to the sham operation group. The remaining rats underwent MCAO. Model generation was successful in 60 rats, which were randomly divided into a model group, butylphthalide group, and Yiqi Dingxuan Yin group (n = 20/group) administered distilled water, butylphthalide capsule, and Yiqi Dingxuan Yin, respectively. Zea-Longa scores were used to assess the neurological function of the rats at 1, 3, 7, and 14 days. Haematoxylin and eosin staining of brain sections was used to observe morphological changes in the rat hippocampus. Apoptosis of nerve cells was detected using TUNEL staining. The expression levels of erythropoietin/erythropoietin receptor (EPO/EPOR), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor/tyrosine receptor kinase B (BDNF/TrkB) protein in the ischaemic brain tissue were detected using immunohistochemistry.
Results

The apoptosis rate, and EPO/EPOR, VEGF, and BDNF/TrkB expression levels were higher in the model group than in the sham operation group (P < 0.05). Among MCAO groups, the nerve function deficit score and cell apoptosis rate were lower (P < 0.05), whereas the EPO/EPOR, VEGF, and BDNF/TrkB protein expression levels were higher (P < 0.05) in both the butylphthalide and Yiqi Dingxuan Yin groups than in the model group.
Conclusions

Yiqi Dingxuan Yin can improve the neural function and morphology of neurons after cerebral ischaemia injury in rats, with a more significant effect at 14 days. This may be related to the upregulation of EPO/EPOR, VEGF, and BDNF/TrkB protein expression, which may promote angiogenesis to improve cerebral blood flow and oxygen supply, thereby protecting the form and function of neurons and promoting the restoration of impaired neural function.
Preeclampsia prediction model using the dipstick test for proteinuria during early gestation
Authors: Ohseto Hisashi , Ishikuro Mami , Obara Taku , Murakami Keiko , Onuma Tomomi , Noda Aoi , Ueno Fumihiko , Iwama Noriyuki , Kikuya Masahiro , Metoki Hirohito , Sugawara Junichi , Kuriyama Shinichi
Published: September 2021

ObjectiveThe aim of our study was to develop prediction model for preeclampsia (PE) using routinely examined items in early pregnancy especially dipstick test for proteinuria.MethodThe Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study recruited pregnant women and we included 9,086 of them in analysis. Maternal basic characteristics were obtained by self-report, and blood pressure and dipstick test of proteinuria were obtained by medical record at regular antenatal care. The outcome was defined as PE including superimposed preeclampsia. We developed prediction model without dipstick test of proteinuria (model 1) and model with it (model 2), and we compared them by the mean of area under the receiver operating characteristic curve (mAUROC) using five-fold cross validation.ResultsmAUROC of model 1 was 0.769 (95% CI; 0.741 to 0.797) and that of model 2 was 0.785 (95% CI; 0.758 to 0.812). The difference of two mAUROCs was 0.016 (95% CI; 0.004 to 0.028). In model 2, detection rates at false-positive rate of 5%, 10% and 20% were 40%, 49% and 64%, respectively.ConclusionsWe could develop prediction model for PE using routine antenatal care items and it was improved by including dipstick test for proteinuria.
Video Capsule endoscopy in patients with Iron Deficiency Anaemia: Experience at a Regional Australian Service
Authors: Furner Maddison , Nagel Robyn , Pinidiyapathirage Janani
Published: September 2021

Background

Few studies have examined the diagnostic yield of video capsule endoscopy (VCE) in patients with iron deficiency anaemia (IDA). This retrospective study aims to identify the yield of VCE, distribution of VCE findings in IDA and factors predictive of positive findings among patients presenting to a gasteroendoscopy practice in regional Australia.
Methods

Findings of consecutive VCE studies between March 2017 and April 2020 performed in patients with unexplained IDA and negative conventional endoscopy were included in this retrospective analysis. All endoscopies were performed and reported by a single specialist physician. Relevant clinical data including demographics, medication use, haemoglobin and ferritin levels were extracted into a standardised spreadsheet with procedural findings. A positive diagnostic yield was considered when VCE diagnosed one or more lesions that could explain the IDA. Statistical analysis was used to determine variables correlated with definite VCE findings.
Results

In total 123 procedures were included. Mean age of the patients was 67.9 years. Mean haemoglobin and ferritin levels were 93.3 g/L and 11.9ug/L, respectively. Positive findings were present in 54.5% of patients with the most frequent finding being angiodysplasia (52.2%). Haemoglobin level was the only variable associated with a positive finding. A significant number of studies had significant findings outside the small bowel (41.8%), overwhelmingly within reach of conventional upper endoscopy (89.3%).
Conclusions

VCE is a valuable diagnostic modality in patients with IDA. Low haemoglobin was associated with a positive finding on VCE in this group of patients.
Child Maltreatment and Risk of Developing Panic Symptoms among Adolescent Aged 11-17-Year-old in Karachi, Pakistan: A Prospective Cohort Study
Authors: Lakhdir Maryam Pyar Ali , Nathwani Apsara Ali , Ali Naureen Akber , Farooq Salima , Peerwani Ghazal , Khaliq Asif , Azam Syed Iqbal , Kadir Muhammad Masood
Published: September 2021

Background

The effect of childhood maltreatment in the developmental pathway of panic symptoms was not well documented specifically in Pakistan. Therefore, this study aimed to examine the association between child maltreatment and the risk of developing Panic symptoms among adolescents aged 11–17 years in Karachi, Pakistan.
Methods

The sample of this study comprised of 800 adolescents aged 11–17 years from 32 systematically selected urban and peri-urban clusters of Karachi. The symptoms of panic (significant somatic symptoms) were assessed using a validated tool “SCARED” and the association between childhood maltreatment and panic symptoms was measured using a cox-proportional algorithm.
Results

Sixty-three percent of severely maltreated children developed Panic symptoms compared to nineteen percent of non-maltreated children. Severely maltreated Female children had approximately four times (95% CI: 2.11–6.35) the risk of panic symptoms and severely maltreated male children were three times (95% CI: 2.27–5.99) more likely to develop panic symptoms.
Conclusion

The current study provided evidence that maltreated children are at increased risk of developing panic symptoms later in adolescence. Interventions and policies to reduce childhood maltreatment and professional support and counseling to the victims may be an effective strategy to reduce the burden of panic symptoms to some extent.
Complete genome sequence of a novel mitovirus isolated from Paris polyphylla var. yunnanensis
Authors: Chen Zeli , Chen Lu , Anane Rex Frimpong , Wang Zhe , Gao Like , Li Shangyun , Wen Guosong , Yu Daihong , Zhao Mingfu
Published: September 2021

Paris mitovirus 1 (ParMV1) is a positive-sense RNA virus isolated from diseased Paris polyphylla var. yunnanensis plants in Wenshan, Yunnan. The complete genome sequence of ParMV1 consists of 2,751 nucleotides with a genome structure typical of the mitoviruses. ParMV1 genome has a single open reading frame (ORF: 358-2,637 nt) that encodes RNA-dependent RNA polymerase (RdRp) with a molecular mass of 86.42 kDa. ParMV1 contains six conserved motifs (Ι-VΙ) that are unique to mitoviruses. In addition, the 5′and 3′ terminals of the genome have a stable secondary structure, and the reverse complementary sequence forms a panhandle structure. Comparative genome analysis revealed that ParMV1 shares 23.1–40.6% amino acid (aa) and 32.3–45.7% nucleotide (nt) sequence identities with the RdRp of other mitoviruses. The phylogenetic tree inferred from RdRp aa sequence showed that ParMV1 clusters with mitoviruses, and hence should be considered as a new member of the genus Mitovirus in the family Motiviridae. This is the first report of a novel mitovirus infecting Paris polyphylla var. yunnanensis.