bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 2 Study of TAS-117 in Advanced Solid Tumors Harboring Phosphatidylinositol 3-Kinase/v-akt Murine Thymoma Viral Oncogene Homolog Gene Aberrations
Authors: Lee Jii Bum , Jung Minkyu , Beom Seung Hoon , Kim Gun Min , Kim Hye Ryun , Choi Hye Jin , Sohn Joo Hyuk , Ahn Joong Bae , Rha Sun Young , Chung Hyun Cheol
Published: December 2020

Background: TAS-117 is a highly potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor. We conducted a single-arm, single-center, phase 2 study of TAS-117 in heavily treated patients with multiple tumors refractory to systemic chemotherapy harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations using a basket trial design.Methods: Patients with gastrointestinal (GI) cancers were orally administered 16 mg of TAS-117 daily and those with non-GI tumors were administered 24 mg of TAS-117, 4 days on/3-days off. The study was conducted over 21-day treatment cycles. Tumors were assessed by imaging every 6 weeks until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was the overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, and safety and tolerability of TAS-117. Results: Thirteen patients were enrolled; eight with non-GI cancer (breast cancer (31%), ovarian cancer (15%), endometrial cancer (8%), and non-small cell lung cancer (8%)) and five with GI cancer (colon cancer (15%), rectal cancer (8%), gastric cancer (8%), and gallbladder cancer (8%)). The median age was 53 years. The Eastern Cooperative Oncology Group performance status was 0 in eight patients; ten patients were treated with TAS-117 after >4 lines of therapy. Twelve patients showed mutations in PIK3 catalytic subunit alpha (PIK3CA): E542K (15%), E545A (8%), E545K (31%), H1047R (31%), and Q546K (8%). One patient harbored an Akt1E17K mutation. The median treatment duration was 1.4 months; the median number of treatment cycles was 2. The ORR was 8%, and the DCR was 23%. The median PFS and OS were 1.4 and 4.8 months, respectively. Nine patients had disease progression, two experienced adverse events, one withdrew, and one discontinued treatment on the physician’s recommendation. Treatment-related adverse events (AEs) occurred in 85% of patients, and 27% experienced grade 3–4 AEs (grade 3 anorexia, 9%) and hyperglycemia (grade 3, 9%; grade 4, 9%). Conclusions: TAS-117 showed limited antitumor activity and manageable toxicity in patients with advanced solid tumors. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations and in those with breast cancer harboring PIK3CA H1047R and Akt1E17K mutations. Trial registration: This study was registered with ClinicalTrial.gov (NCT03017521 in January 11, 2017.).
The Role of EORTC QLQ-C15-PAL Scores and Inflammatory Biomarkers in Predicting Survival in Terminally Ill Patients with Cancer
Authors: Koyama Nanako , Matsumura Chikako , Shitashimizu Yoshihiro , Sako Morito , Kurosawa Hideo , Nomura Takehisa , Eguchi Yuki , Ohba Kazuki , Yano Yoshitaka
Published: December 2020

Background The clinical use of patient-reported outcomes as compared to inflammatory biomarkers for predicting cancer survival remains a challenge in palliative care settings. We evaluated the accuracy of survival prediction in both indicators of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative scores (EORTC QLQ-C15-PAL) and the inflammatory biomarkers C-reactive protein (CRP), albumin (Alb), and neutrophil-lymphocyte ratio (NLR) in patients with advanced cancer. Methods This was an observational study in terminally ill patients with cancer hospitalized in a palliative care unit between June 2018 and December 2019. Patients’ data collected at the time of hospitalization were analyzed. Cox regression was performed to examine significant factors influencing survival. A receiver operating characteristic (ROC) analysis was performed to estimate cut-off values for predicting survival within 3 weeks, and a log-rank test was performed to compare survival curves between groups divided by the cut-off values. Results Totally, 130 patients participated in the study. Cox regression suggested that the QLQ-C15-PAL dyspnea and fatigue scores and levels of CRP, Alb, and NLR were significantly associated with survival time, and cut-off values were 66.67, 66.67, 3.0 mg/dL, 2.5 g/dL, and 8.2, respectively. The areas under ROC curves of these variables were 0.6–0.7. There were statistically significant differences in the survival curves between groups categorized using each of these cut-off values (p < .05 for all cases). Conclusion Our findings suggest that the assessment of not only objective indicators for the systemic inflammatory response but also patient-reported outcomes using EORTC QLQ-C15-PAL is beneficial for the prediction of short-term survival in terminally ill patients with cancer.
Abnormal TACC3 Expression is an Independent Prognostic Biomarker in Lung Carcinoma
Authors: He Dongwei , Fan Xiaoyan , Zhang Yulong , Li You
Published: December 2020

Background: Abnormal expression of transforming acidic coiled-coil protein 3 (TACC3) correlates with tumorigenesis of many human malignancies. However, the expression pattern of TACC3 and its clinical significance have not been well characterized in lung carcinoma (LUAD) so far. Objective: To investigate the association of TACC3 expression level with the clinicopathological characteristics and prognosis of LUAD patients.Methods: In the study, based on Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and The Cancer Genome Atlas (TCGA) databases, the expression of TACC3 was determined in LUAD patients. Further, the expression of TACC3 was established using qRT-PCR in LUAD patients. Results: Our results showed that TACC3 was significantly overexpressed in LUAD tumors compared with non-tumors in the above public databases (all p<0.01). A receiver operating characteristic (ROC) curve analysis suggested that TACC3 may have diagnostic value in LUAD patients (normal vs tumor: AUC = 0.940). Kaplan-Meier analysis further demonstrated that high TACC3 expression in tumors was significantly associated with worse overall survival (OS) in LUAD patients (all p<0.01). In addition, Univariate and multivariate Cox regression analyses showed that TACC3 was an independent risk factor for OS among LUAD patients (HR = 1.02, 95% CI: 1.01-1.04, p = 0.00823; HR=1.43, 95% CI: 1.17-1.70, p <0.001). Finally, using gene set enrichment analysis (GSEA 3.0), we found that a series of potential pathways related to TACC3 were highly enriched with the high TACC3 expression phenotype (p = 0.024, p = 0.003, respectively). Conclusions: The present study provides evidence that TACC3 expression is upregulated in tumors and may be an independent risk factor for prognosis in LUAD patients.
Retrospective Analysis of Prognostic Factors of Localised or Locally Advanced Prostate Cancer and Their Influence on Treatment Choice
Authors: Liutkauskiene Sigita , Martinaityte Karolina , Malonyte Rasa , Jureniene Kristina , Grizas Saulius , Juozaityte Elona
Published: December 2020

Background: According to the majority of retrospective analyses and meta-analyses published in recent years, radical prostatectomy is a more effective treatment method than radical radiotherapy. The objective of this study was to assess whether the treatment method influences the survival of patients with early prostate cancer and to evaluate the impact of patient-dependent and prostate cancer-dependent prognostic factors on the choice of radical treatment method of prostate cancer.Methods: Medical records of selected patients were reviewed. Inclusion criteria involved histologically confirmed prostate adenocarcinoma; localised or locally advanced prostate cancer diagnosed in 2008-2012; no distant metastases at the time of initial diagnosis; medical records maintain comprehensive data on treatment and follow-up. The influence of prognostic factors on the choice of treatment method was assessed by making comparisons between groups using the Chi-square test.Results: More favorable prognostic factors were found in the RP treatment group compared to the RT treatment group: patients aged 60 years and younger accounted for 35% in the RP group, and 18% - in the RT group, with increasing age the number of RP decreased and the number of RT increased (p < 0.001); score of 3-4 points of CCI was set in 36% patients in the RP group, and 6% - in the RT group, with increasing CCI score, the number of RP decreased and the number of RT increased (p < 0.001); baseline PSA level of 10 ng/ml and less was found in 67% patients in the RP group, and 52% - in the RT group, with increasing PSA level, the number of RP decreased and the number of RT increased (p < 0.001). Gleason score did not influence the choice of treatment method (p = 0.24).Conclusions: Prognostic factors of localised or locally advanced prostate cancer influenced the choice of treatment method. In case of more favorable prognostic factors, radical prostatectomy was more often chosen.
Postmastectomy Radiotherapy in T1–2 Women Breast Cancer Patients with 1–3 Positive Axillary Lymph Nodes: A Propensity Score Matched SEER Analysis
Authors: Xu Gang , Bu Shanshan , Wang Xiushen , Ge Hong
Published: December 2020

Purpose: The application of postmastectomy radiotherapy (PMRT) in T1–2 women breast cancer patients with 1–3 positive lymph nodes has been controversial. We sought to determine the survival benefits of PMRT in the patients with T1–2 and 1–3 positive nodes.Methods: A retrospective study using the Surveillance, Epidemiology, and End Results (SEER) Regs Custom Data (with additional treatment fields) from 2001 to 2011 was performed. Patients who received PMRT were matched by the propensity score with patients who did not receive PMRT. The Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed. Results: We identified 56,725 women breast cancer patients with T1–2 and 1–3 positive nodes, and 18,646 patients were included in the analysis. After propensity score matching (1:1), with a median follow-up of 116 months, PMRT showed an increase in the OS (P = 0.018) but had no effect on the BCSS. The 10-year OS rates were 76.8% and 74.4%, and the 10-year BCSS rates were 82.8% and 82.2% for the patients who received and who did not receive PMRT, respectively. Only patients with 3 positive nodes could gain the benefit of PMRT for BCSS.Conclusion: PMRT for patients with T1–2 and 1–3 positive lymph nodes could increase the 10-year OS, and had no effect on the 10-year BCSS. Subgroup analysis indicated that only patients with 3 positive lymph nodes could benefit from PMRT for both the OS and BCSS.
Immunological effect of irreversible electroporation on solid tumors
Authors: Guo Xiaoxia , Du Fang , Liu Qin , Guo Yan , Wang Qingbing , Huang Wei , Wang Zhongmin , Ding Xiaoyi , wu zhiyuan
Published: December 2020

Background
This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE).
Methods
We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice.
Results
We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4+ T cell subsets, but not CD8+, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8+ T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group.
Conclusions
Our study demonstrated that IRE not only induced immediate innate immune response dominated by the increase of neutrophils, monocytes and NK cells, but also upregulated activated T cells and downregulated Treg. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by cytotoxic CD8+ T cells.
Clinical Characteristics and Prognostic Nomogram in Patients With Pineoblastoma
Authors: JING YaJun , DENG WenShuai , JIANG YunXia , BI MingXia , FAN MingChao , GAO YiJun , Sun Peng
Published: December 2020

Background: Pineoblastoma (PB) is an infrequent entity of the central nervous system. The data about clinical outcomes of PB is exceedingly limited due to its rarity. Notably, the optimal treatment approaches and prognostic factors on PB is still unclear. Thus the aims of this study are to identify prognosis-associated factors and develop a predictive nomogram of PB.Method: Data of 243 patients with PB (≤29 years), collected by the Surveillance, Epidemiology, and End Results database, were randomly carved up the primary (n=172) and validation cohort (n=71) two groups. A prognostic nomogram was developed based on primary cohorts and optimized via the Akaike Information Criterion. Calibration curves were applied to show the results of validation (internal, external, and cross-validation). Additionally, its predictive performance was evaluated by the concordance index and receiver operating characteristic curve. Finally, decision curve analyses were employed to assess its clinical utility. Results: Age, year of diagnosis, treatment, tumor size, and tumor extension were identified as independent predictors of PB based on multivariate Cox regression analysis. The model presented an excellent discriminating ability (concordance index of the nomogram: 0.805; 95% confidence interval: 0.78–0.83; area under the receiver operating characteristic curve with a range from 0.7 to 0.9). The calibration plots (probability of survival) is consistent with the results predicted by the nomogram. The results of the decision curve analysis showed that the nomogram has potential clinical applicability.Conclusion: The nomogram can be used to assess prognosis and determine appropriate treatment options.
LncRNA AWPPH as a Prognostic Predictor in Human Cancers: Evidence From Meta-analysis
Authors: Li Yongfeng , Rui Xinmiao , Chen Daobao , Xuan Haojun , Yang Hongjian , Meng Xuli
Published: December 2020

Background: Long noncoding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is a novel oncogene and dysregulated in a variety of human cancers. It has been revealed to be associated with the clinicopathological features and prognosis. However, the prognostic value of AWPPH in various cancers remains unclear. Therefore, we perform this meta-analysis to evaluate the relationship between AWPPH expression and clinical outcomes in human cancers.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR=1.79, 95%CI: 1.44-2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR=2.67, 95%CI: 1.86-3.83, P<0.001) , bigger tumor size (OR=2.64, 95%CI:1.47-4.73, P=0.001), macro-vascular invasion (OR=2.08, 95%CI: 1.04-4.16, P=0.04) and lymph node metastasis (OR=2.68, 95%CI: 1.82-3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding. Conclusions: Upregulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion, and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers.
Evaluation of prosthetic complications and tumor recurrence with the single energy metal artifact reduction algorithm in patients with hip tumor prostheses
Authors: Zhang Fangling , Zhang Xiaoling , Ma Ling , Li Ruocheng , Zhang Zhaohui , Zeng Donglin , Ding Lei
Published: December 2020

Background: To evaluate the effectiveness of the single energy metal artifact reduction (SEMAR) algorithm with a second-generation 320-row multi-detector computed tomography (MDCT) on complications and tumor recurrence detection in patients with hip tumor prostheses.Methods: From February 2016 to June 2019, 31consecutive patients with tumor prostheses of the hip joint underwent CT scans. Lesions were confirmed by histology or clinical and imaging follow-up. Images were reconstructed using 2 methods: iterative (IR) algorithm alone and SEMAR algorithm (IR+ SEMAR). Two radiologists graded the image quality visually by a 6-point (from 0 to 5) ordinal scale. Standard deviations (SD) of CT attenuation value defined as the artifact index (AI) were compared between the two reconstructed methods. Paired sample t-test was adopted to compare the AI values on IR and SEMAR images. Wilcoxon matched-pairs signed rank test was performed to compare the visual scores on IR and SEMAR images. A p- value less than 0.05 was considered statistically significant. Results: The artifacts of the SEMAR images were reduced compared to the Non-SEMAR images (113.94 ±128.54 vs 35.98 ± 53.75HU，t=2.867, P < 0.05). 20 and 16 more lesions were detected by observer 1 and observer 2 with SEMAR algorithm respectively. The mean scores of lesions without SEMAR were 1.39 ± 1.45 (observer 1) and 1.55± 1.34 (observer 2); with SEMAR, the scores were significantly higher, 4.42±0.56 (z=-4.752, p < 0.001) and 4.54± 0.72 (z=-4.837, p < 0.001) respectively. Conclusion: The SEMAR algorithm can effectively reduce metal artifacts in patients with hip tumor prostheses and increase the diagnostic accuracy of prosthetic complications and tumor recurrence.
HINT3 suppresses AKT/mTOR signaling activity during breast cancer tumorigenesis through transcriptionally activation of PTEN
Authors: Ju Qi , Liu Yaobang , Lian Bing , Li Hong , Chai Dahai , Gao Yali , Wang Yanbai , Li Jinping
Published: December 2020

Background
Histidine triad nucleotide-binding (HINT) protein belongs to the histidine triad proteins family. Recent studies have shown that HINT1 and HINT2 play pivotal roles in cancer growth. However, the function of HINT3 in cancers, including breast cancer (BRCA) remains to be determined. In the present study, we investigated the role of HINT3 in BRCA.
Methods
The clinical relevance of HINT3 in BRCA was analyzed using the datasets from The Cancer Genome Atlas. HINT3 was over-expressed and knocked down using lentivirus system. qRT-PCR and Western blot assays were performed to detect mRNA and protein expression. CCK-8 and colony formation assays were used to assess cell proliferation. Migration was analyzed using Transwell assay. Luciferase reporter activity assay was performed using pGL3.Basic/TK system. Xenogrfted tumorigenesis was performed to evaluate the effect of HINT3 on tumor development.
Results
HINT3 was down-regulated in BRCA tissues based on TCGA analysis and our qPCR analysis. TCGA database also showed that HINT3 transcript was much lower in BRCA tissues with higher stage. In vitro, HINT3 knockdown promoted the cell proliferation, colony growth and EDU cooperation in MCF7 and MDA-MB-231 cells. Oppositely, HINT3 overexpression suppressed the DNA synthesis and proliferation in both cells. In vivo, HINT3 ectopic expression blunted the xenografted tumorigenesis of MDA-MB-231 cells. Furthermore, HINT3 silencing or overexpression enhanced and inhibited the migration capacity of MCF7 and MDA-MB-231 cells, respectively. Lastly, HINT3 upregulated PTEN at transcription level, which resulted in inactivation of AKT/mTOR signaling in vitro and in vivo.
Conclusions
Taken together, HINT3 inhibits PTEN/AKT/mTOR signaling pathway and suppresses the proliferation, growth, migration and tumor development of BRCA cells.
The gut microbial composition in polycystic ovary syndrome with insulin resistance: Findings from a normal-weight Population
Authors: He Fangfang , Li Yu-mei
Published: December 2020

Background
A few studies have reported on the relationship between intestinal flora dysbiosis and clinical characteristics in polycystic ovary syndrome (PCOS). But the structure and characteristics of gut microbiota in PCOS have not been fully elucidated.
Objective
To analyze the composition of the Intestinal flora population in normal-weight women with PCOS and insulin resistance(IR) compared to PCOS alone and healthy women.
Methods
The study included 14 PCOS patients with insulin resistant(PCOS-IR) and 12 PCOS alone༈PCOS-NIR༉,and 10 age- and body mass index-matched healthy control women. BMI: 18.5–23.9 kg/m2. The bacterial 16S rDNA V3-V4 fragment was amplified and sequenced. The sequencing data were analyzed for species annotation, community diversity, inter-group differences, to explore the composition characteristics of gut microbial of the subjects and their correlation with clinical parameters.
Results
No significant difference in diversity was observed between PCOA and sample cluster analysis among the three groups (Beta-diversity) and Alpha-diversity. The relative abundance of Rothia, Ruminococcus, and Enterococcus were significantly higher in the PCOS-IR group than in the other two groups (P < 0.05), whereas the abundance of the Prevotella was dramatically decreased (P < 0.05). The abundance of Enterococcus was positively correlated with waist circumference, hip circumference, diastolic blood pressure, and insulin resistance index. Meanwhile, Rothia abundance was positively associated with waist circumference and free fatty acids.
Conclusion
The gut microbial composition of PCOS patients with insulin resistance is different from that of PCOS alone and healthy women. The difference is correlated with the clinical characteristics of PCOS, with regards to insulin resistance, abdominal obesity, free fatty acids, and other indicators. PCOS-IR patients have an increased abundance of Enterococcus. It may affect the intestinal environment of the host by enriching the metabolic pathways related to insulin resistance, leading to the occurrence and development of PCOS.
Low expression of circular RNA hsa_circ_0078607 predicts poor prognosis in high-grade serous ovarian cancer
Authors: Zhang Nan , Yang Zhiyou , Jin Yue , Cheng Shanshan , Yang Jiani , Wang Yu
Published: December 2020

Background

Ovarian cancer remains one of the most lethal malignancies in women which is typically diagnosed at a late stage and has no effective screening strategy. It is essential to explore novel biomarkers for the diagnosis and prognosis of ovarian cancer, as well as therapeutic targets. Recent studies have shown that circRNAs participate in ovarian cancer progression by regulating various processes and being able to act as potential biomarkers for ovarian cancer diagnosis and prognosis. In the present study we aimed to explore the prognostic role of circ_0078607 in high-grade serous ovarian cancer.
Results

The expression of circ_0078607 in 49 high-grade serous ovarian cancer and adjacent non-cancerous tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We noticed that circ_0078607 expression was significantly downregulated in ovarian cancer tissues compared with adjacent non-cancerous tissues. Besides, patients with low circ_0078607 expression exhibited parameters associated with poor prognosis, including advanced FIGO stage and higher serum CA125 level. Kaplan-Meier survival curve analysis showed that both progression-free survival and overall survival were significantly shortened in patients with low circ_0078607 expression. Cox regression model analysis showed that low expression of circ_0078607 was an adverse prognostic indicator for high-grade serous ovarian cancer patients.
Conclusions

Low expression of circ_0078607 might be an adverse prognostic indicator for high-grade serous ovarian cancer patients.
Mycobacterium tuberculosis latency-associated antigen Rv1733c SLP improves the accuracy of differential diagnosis of active tuberculosis and latent tuberculosis infection
Authors: Zhang Lifan , Ma Huimin , Wan Shijun , Zhang Yueqiu , Gao Mengqiu , Liu Xiaoqing
Published: December 2020

Background
The differential diagnosis of active tuberculosis(ATB) and latent tuberculosis infection(LTBI) is still challenging. The objective of the study was to evaluate the accuracy of the novel M. tuberculosis latency-associated antigens Rv1733c and Rv1733c SLP for differentiating ATB from LTBI.
Methods
A case-control study was designed to enroll pathogen-confirmed ATB cases admitted to the Peking Union Medical College Hospital and Beijing Chest Hospital, whereas those with LTBI were denoted as the control group. The Fluorescence-Immunospot (FluoroSpot) assay was used to detect the frequencies of IL-2-, IFN-γ-secreting T cells stimulated by the M. tuberculosis latency-associated antigens Rv1733c and Rv1733c SLP. The combination of the ESAT-6/CFP-10-Fluorospot test was evaluated with regard to the sensitivity, specificity, predictive value and likelihood ratio for the differential diagnosis of ATB and LTBI.
Results
A total of 20 pathogens-confirmed TB and 28 LTBI cases were included. The sensitivity and specificity of ESAT-6/CFP-10-FluoroSpot for the differential diagnosis of ATB and LTBI were 95% (95% CI, 75.13–99.87%) and 82.14% (95% CI, 63.11–93.94%), respectively. Following stimulation with Rv1733c and Rv1733c SLP, the maximum AUROC was 0.711 (95% CI, 0.566–0.856) as determined by the ROC curve, which was used to assess the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP. The cutoff value of 0 SFCs/2.5 × 105 PBMCs was used for the analysis. The frequency, sensitivity and specificity of Rv1733c SLP for differentiating ATB and LTBI were 75% (95% CI, 50.90–91.34%) and 60.71% (95% CI, 40.58–78.50%), respectively. The ESAT-6/cfp-10-fluorospot was combined with the frequency of single IL-2-secreting T cells, which were stimulated by Rv1733c SLP for the differential diagnosis of ATB and LTBI. This resulted in an increased sensitivity and specificity to 100% (95% CI, 83.16–100.00%), as determined by the parallel test and to 92.86% (95% CI, 71.77–97.73%) as determined by the serial test, respectively.
Conclusions
Rv1733c SLP has the potential to be used as a candidate antigen for T cell-based tuberculosis diagnostic tests, in combination with ESAT-6 and CFP-10, to differentiate between ATB and LTBI diagnosis.
Bio-lipid production from crude glycerol and lignocellulosic hydrolysate with oleaginous yeasts
Authors: Chmielarz Mikolaj , Blomqvist Johanna , Sampels Sabine , Sandgren Mats , Passoth Volkmar
Published: December 2020

Background: Crude glycerol (CG) and hemicellulose hydrolysate (HH) are low- value side-products of biodiesel transesterification and pulp- and paper industry, respectively, which can be converted to microbial lipids by oleaginous yeasts. This study aimed to test the ability of oleaginous yeasts to utilise CG and HH and mixtures of them as carbon source. Results: Eleven out of 27 tested strains of oleaginous yeast species were able to grow in plate tests on CG as sole carbon source. Among them, only one ascomycetous strain, belonging to Lipomyces starkeyi , was identified, the other 10 strains were Rhodotorula spec. When yeasts were cultivated in mixed CG/ HH medium, we observed an activation of glycerol conversion in the Rhodotorula strains, but not in L. starkeyi . Two strains - Rhodotorula toruloides CBS 14 and Rhodotorula glutinis CBS 3044 were further tested in controlled fermentations in bioreactors in different mixtures of CG and HH. The highest measured average biomass and lipid concentration were achieved with R. toruloides in 40% HH medium mixed with 60 g/L CG - 19.4 g/L and 10.6 g/L, respectively, with a lipid yield of 0.22 g lipids per consumed g of carbon source. Fatty acid composition was similar to other R. toruloides strains and comparable to that of vegetable oils. Conclusions: There were big strain differences in the ability to convert CG to lipids, as only few of the tested strains were able to grow. Lipid production rates and yields showed that mixing GC and HH have a stimulating effect on lipid accumulation resulting in shortened fermentation time to reach maximum lipid concentration, which provides a new perspective on converting these low- value compounds to biolipids.
Racial and Ethnic Disparities in Viral Acute Respiratory Infections in the United States: Protocol of a Systematic Review
Authors: Menezes Neia Prata , Malone Jowanna , Lyons Carrie , Cadet Kechna , Dean Lorraine , Millett Gregorio , Baral Stefan
Published: December 2020

Background: The COVID-19 pandemic caused by SARS-CoV-2 has highlighted consistent inequities in the risk of infection, severity of disease, or mortality across racial and ethnic minority populations in the United States and beyond. Although novel, SARS-CoV-2 shares commonalities in transmission dynamics with other viral respiratory pathogens where similar disparities in morbidity and mortality have been documented. However, to date, there has not been a systematic review of disparities in viral respiratory pathogens. In response, this review aims to synthesize data on racial and ethnic disparities in morbidity and mortality due to viral acute respiratory infections (ARI) other than SARS-CoV-2. In particular, this review will focus on understanding structural health and social factors outside of race and ethnicity driving these disparities in the United States.Methods: We will conduct a systematic review of studies published between January 1, 2002 and September 30, 2020 that capture data on racial and ethnic disparities associated with increased incidence, disease severity, risk of hospitalization and/or death in viral ARI in the United States. Data characterizing individual-, community-, and structural-level factors associated with these disparities will be abstracted to better understand the underlying structural inequities contributing to racial disparities in ARI. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be used with reviewers employing COVIDENCE to conduct two independent rounds of title/abstract and full text reviews for all articles. A built-in tool in COVIDENCE will be used for data abstraction.Discussion: Findings from this systematic review will shed light on patterns of racial and ethnic disparities in viral ARI in the United States. Leveraging these data can support predictive studies of the differential impacts of COVID-19 across the United States as well as adaptive intervention strategies mitigating structural inequities, including structural racism, driving both incidence and disparities in marginalized communities. Moreover, data emerging from this review may reignite pandemic preparedness focused on vulnerable communities given structural inequities, facilitating improved future pandemic responses to novel or endemic viral respiratory pathogens in the United States.Systematic review registration: PROSPERO CRD42020219771
Novel mutations identified in the Chinese Han population with keratoconus by next-generation sequencing
Authors: Chen Binbin , Yu Xiaoning , Zhang Xin , Yang Hao , Cui Yilei , Shentu Xingchao
Published: December 2020

BACKGROUND
Keratoconus (KC) is characterized by bilateral progressive corneal thinning and ectasia. The prevalence of KC is approximately 8.8 to 54.4 per 100,000 individuals across the globe. Genetic factors have been shown to contribute to the pathogenesis of KC. This study will identify new mutations in the susceptibility gene of keratoconus (KC) in the Chinese Han population.
METHODS
A total of fifty-two patients with primary KC were recruited. Blood samples were collected, and genomic DNA was isolated from peripheral blood leukocytes. The entire coding region, intron–exon junctions, and promoter regions of sixteen known KC susceptibility genes were screened with next-generation sequencing technology, and all identified variants were further confirmed using the Sanger sequencing technology. The Sorting Intolerant from Tolerant (SIFT), Mutation Taster and PolyPhen 2 programs were used to predict the effect of amino acid substitution on protein.
RESULTS
After removing twelve known SNPs (single nucleotide polymorphisms) and three variants predicted to be harmless, nine novel mutations were identified in eight of the fifty-two patients, including c.455C > T:p.P152L in FNDC3B, c.3636_3637del:p.R1212fs in COL4A4, c.5015G > T:p.R1672L, c.3798dupA:p.P1267fs and c.28G > A:p.A10T in MPDZ, c.1940C > T:p.P647L in DOCK9, c.127_128insGGC:p.Q43delinsRQ in POLG, c.3019G > A:p.V1007I in IPO5, and c.624 + 7->A in TGFBI. All nine mutations in the patients with KC were heterozygote.
CONCLUSION
This study enlarged the gene profile of KC and should be further confirmed by well-powered, genome-wide association studies (GWAS) of Han Chinese patients.
Comparison of ocular biometric parameters between concomitant exotropic and orthotropic eyes
Authors: Gong Weifen , Yang Fan , Lin Shibin , Wang Geng
Published: December 2020

PurposeTo compare the biometric characteristics between concomitant exotropia (XT) and orthotropia (OT) with OA2000.MethodThis cross-sectional study collected 4–18 years old children. All subjects underwent a comprehensive ophthalmic examination and prism alternate cover test for ocular alignment measurement. Included subjects had no any eye surgery, structural ocular anomalies, amblyopia of either eyes, ptosis, cataract and nystagmus. OA-2000 was used for the measurement of ocular biological parameters. Spherical equivalent (SE, spherical power + (cylindrical power)/2), keratometry, central corneal thickness (CCT), white to white distance (WTW), pupil diameter (PD), anterior chamber depth (ACD), lens thickness (LT), axial lengths (AL) and intereye differences in SE, keratometry, CCT, WTW, PD, ACD, LT and AL were analyzed by independent sample t-tests. Pearson correlation was used for correlations assessment. Partial correlation was used to control for intereye differences in SE.ResultsA total of 156 subjects (79 XT and 77 OT) were collected. Intereye differences in spherical equivalent (SE) (t 2.369, P 0.019), AL (t 3.423, P 0.001), ACD (t 3.782, P < 0.001), LT (t 3.136, P 0.002) and PD (t 3.229, P 0.002) were significantly larger in XT patients than OT patients. The correlation coefficient of XT with SE asymmetry was 0.187 (P 0.020), 0.265 with AL asymmetry (P 0.001), 0.289 with ACD asymmetry (P < 0.001), 0.251 with PD asymmetry (P 0.002) and 0.243 with LT asymmetry (P 0.002). Strong correlation (r 0.875) was found between anisometropia and AL asymmetry. After controlling the effect of anisometropia, the correlation coefficients slightly reduced between XT patients and intereye differences in AL (reduced to 0.213), ACD (reduced to 0.266), PD (reduced to 0.230) and LT (reduced to 0.230). Strong correlation (r 0.855) was found between intereye differences in ACD and LT.ConclusionCompared with OT subjects, intereye differences in SE, AL, ACD, LT and PD were significantly larger in XT patients and had positive correlation with XT and may be associated with the pathogenesis of XT.
Comparative Analysis of Super-enhancers Across Mammals Reveals Their High Function Conservation
Authors: Peng Yanling , Zhang Yubo
Published: December 2020

BackgroundSuper-enhancers (SEs) are key positive regulatory elements in defining cells/tissues identity in mammals, yet their similarities and differences of sequence and function across mammals have been poor studied. To allow sequence and function comparison across mammalian SEs, we employ H3K27ac ChIP-seq data to six cell types/tissues across human, pig, and mouse, which represent different lineages of mammals in the evolutionary tree.ResultsOverall, a median of 848 human SEs, 888 pig SEs and 503 mouse SEs are identified across cells/tissues. These SEs are largely distributed in promoter regions for human (91.9% in median) and mouse (63.4% in median), while mostly in distal intergenic regions for pig (66.1% in median). Extremely higher unique orthologous SEs frequency (91.6%~92.1%) has been detected for the same cell/tissue across species. Consistently, their overlapping rates are very low for the same cell/tissue across species (0.1%~0.5%). For the SE-associated orthologous genes, they also show high unique frequency for species (63.3%~83.9%) and low overlapping rates (0.8%~1.3%) at inter-species comparison. However, orthologous SEs function comparisons across species have shown similar biological processes related to cells/tissues identity in the top 15 significant enriched terms for the same cell/tissue. Meanwhile, common core transcription factors that determine cells/tissues identity are determined for the same cell/tissue across mammals.ConclusionsThis study highlights the differences of SEs genomic distribution across mammals. It reveals low orthologous sequence overlapping but high function conservation of SEs across mammals. It would improve our understanding of regulation function cis-regulatory elements in mammals.
Driving After Total Knee and Hip Arthroplasty - an Observational Study From the Perspective of Rehabilitative Orthopaedic Therapy
Authors: Lazar Tiberiu-Adrian , Edelmann Martin , Lohmann Christoph , Awiszus Friedemann
Published: December 2020

Background: For a large proportion of the population, especially those residing in the countryside, the use of a car for daily activities is indispensable. Following a total knee – (TKA) or hip arthroplasty (THA) the overseeing doctor or physical therapist will usually recommend refraining from driving for several weeks. The aim of this study is to find out when patients with TKA or THA actually take up driving again, and how the replaced joint, side, gender and place of residence influences this decision. Methods: 92 eligible participants, contained within the frame of a prospective experimental observational study, were contacted via telephone 12 weeks after surgery and interviewed using a structured questionnaire. The answers were statistically analysed using SPSS®.Discussion: There were statistically significant differences regarding operated side, gender and place of residence. Male patients drove in the 6th and 7th postoperative week, while female patients drove in the 8th and 9th postoperative week. For 58.6% of patients the reasoning for the first post-operative drive was medical: the journey to physiotherapy or to a doctor’s appointment. TKA impaired patients the most. Patients recovering from a TKA drive considerably later. Patients recovering from a right sided TKA have an increased risk by a factor of nine, not to become an “early driver”. Female patients who underwent TKA had an increased risk by a factor of 21, of becoming a “late driver”. Conclusions: The rehabilitation following a right sided TKA proved a challenge with regard to the reuptake of driving. This should be taken into account when planning the course of therapy for patients who are regular drivers. Female patients could benefit from special training. Trial registration: DRKS00018693. Registered 20 September 2019 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018693
“The Underground Water Sources were Contaminated” A Qualitative Assessment of the Spread of Typhoid Fever in Kampala City, Uganda
Authors: Atuyambe Lynn , Atusingwize Edwinah , Kayemba Christine Nalwadda
Published: December 2020

Background: Globally, approximately 11–21 million people get typhoid fever annually. The disease is characterized by prolonged fever, headache, nausea, loss of appetite, and constipation or diarrhoea and the transmission is oral-faecal. In early 2015, the Uganda Ministry of Health, confirmed typhoid fever outbreak in Kampala city which quickly spread to the neighbouring districts. Strategies including preventive and curative measures were put in place to control the disease although the outbreak persisted and spread quickly. In response, this study was commissioned to identify risk factors that propagated the outbreak in Kampala and the surrounding districts, and to establish innovative ways of communicating risk and behavioural change messages to the populations at risk. Methods: This was a qualitative study among residents working in major food markets of Kampala, Mukono and Wakiso districts. Data was collected using 14 focus group discussions (FGDs), 25 Key Informant Interviews (KIIs), 10 In-depth Interviews (IDIs), and environmental observations within communities including major markets. A total of 10 FGDs from Kampala district were stratified by sex while the 4 FGDs conducted in Mukono and Wakiso districts were mixed by sex. Data was analysed employing the thematic approach using open codding. Results: Behavioural practices, environmental, health system and policy related factors propagated the outbreak. We established that poor personal and food hygiene, contaminated water sources, consumption of unsafe beverages, the prolonged dry season, inadequate disease surveillance and delay in diagnosis and treatment of cases were main factors that led to the outbreak. Our study established that the behaviour change approaches were electronic, media, print and face to face communication. These strategies created an understanding of the presence of the outbreak but had some limitations. The study highlighted major recommendations for future control of typhoid outbreak included innovative use of technology and intersectoral collaborations. Conclusion: Typhoid outbreak was spread through individual behavioural, environmental and health system factors. Innovative communication strategies including use of mobile technologies, school children as messengers, strengthened face to face communication by community leaders and expressing messages in terms of economic losses and gains were recommended.
Migraine and Stress – An Explorative Cross-Country Study of External Stress Factors
Authors: Staveren Irene van
Published: December 2020

BackgroundAccording to the Global Burden of Disease 2016 project, migraine ranks first for 15-49 years and second for all ages. The project has reported no significant relation with socio-economic status of a country. To the contrary, migraine ranks first for all ages in low- and middle-income countries suffering from civic unrest and conflict. This raises the question whether external stress factors may be correlated with migraine years lived with disability (YLD).MethodsIn the absence of cross-country studies on migraine and stress, this is a unique exploratory study. The analysis uses two country groups: developed countries (including some middle-income countries) and developing (middle- and low-income) countries. For the first group, proxy variables for stress are included that relate to flexible and highly competitive labour markets (productivity and unemployment), whereas for the second group, proxy variables are used that relate to conflict and migration. The data were analysed with multiple ordinary least squares cross-section regressions.ResultsThe results show a positive relationship between the stress variables on the one hand and migraine YLD on the other hand for both country groups. Almost all results are statistically significant at p<0.01.ConclusionsThe findings from the exploratory cross-country analysis suggest that societal stress factors may be potential candidates for modifiable factors for the prevalence and severity of migraine at the country level.
Intralesional fenestration and corticosteroid injection for symptomatic Ledderhose disease of the foot: two case reports
Authors: Flanagan George , Burt Nicola , Reilly Ian
Published: December 2020

The description of corticosteroid injection as a treatment option for Ledderhose disease has received little attention in the literature and often merely receives a passing comment in scientific papers. We present a short case series of two patients that underwent corticosteroid injection in combination with fenestration to treat painful Ledderhose disease nodules. Both patients had their lesions injected on two occasions. Significant reduction in pain and lesion volume was seen at 12 months post treatment. Our protocol combines fenestration with the use of triamcinolone acetonide (mixed with local anaesthetic) which we believe conveys further advantage over corticosteroid infiltration alone.
Number of parity/live birth(s) and cardiovascular disease among Iranian women and men: Results of over 15 years of follow-up.
Authors: Moazzeni Seyyed Saeed , Toreyhi Hossein , Asgari Samaneh , Azizi Fereidoun , Tehrani Fahimeh Ramezani , Hadaegh Farzad
Published: December 2020

Background: Most previous studies conducted in non-Middle Eastern populations have suggested that an increase in the number of parity/live birth(s) leads to cardiovascular disease (CVD) development, although their findings were inconclusive on this issue for both sexes. Biologic and socioeconomic pathways were suggested to explain this association. We studied this issue among urban Iranian men and women.Methods: In this population-based cohort study, which included 3929 women and 2571 men aged ≥ 30 years, data for the number of parity/live birth(s) were obtained by a standard questionnaire. Participants were then annually followed for CVD events. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the number of parity/live birth(s) and other traditional CVD risk factors.Results: During more than 15 years of follow-up, 456 and 524 CVD events have occurred among women and men, respectively. Among women, a J-shaped association was found between the number of live births and incident CVD with the lowest risk for women with two live births. Among women in multivariate analyses, each unit increase in parity had a HR of 1.05 (CI: 1.01-1.10), and having ≥4 parity was associated with a HR of 1.86 (0.97-3.56, p-value=0.061). Among men, in comparison with participants who had 1 child, multivariate HRs of having 2, 3, and ≥4 children were 1.97 (1.24-3.12), 2.08 (1.31-3.31), and 2.08 (1.30-3.34), respectively.Conclusion: To the best of our knowledge, the current study is the first report on this issue in the Middle East and North Africa region, a region with a high burden of CVD. It can now be suggested that the number of parity/live birth(s) is linked to CVD among the Iranian population, with this issue being more prominent among men. Further research is needed to support our results and clarify the pathways between the number of parity/live birth(s) and CVD development among Iranian populations by considering potential risk factors, especially psycho-socio-economic risk factors.