bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
Authors: Yuan Lin , Wang Leyuan , Du Xizi , Qin Ling , Yang Ming , Zhou Kai , Wu Mengping , Yang Yu , Zheng Zhiyuan , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Liu Chi 
Published: December 2020

AbstractBackgroundLate-onset asthma (LOA) is beginning to account for an increasing proportion of asthma patients, which is often underdiagnosed in the elderly. Studies on the possible relations between aging-related genes and LOA contribute to the diagnosis and treatment of LOA. Forkhead Box O3 (FOXO3) and TP53 are two classic aging-related genes. DNA methylation varies greatly with age which may play an important role in the pathogenesis of LOA. We supposed that the differentially methylated sites of FOXO3 and TP53 associated with clinical phenotypes of LOA may be useful biomarkers for the early screening of LOA.MethodsThe mRNA expression and DNA methylation of FOXO3 and TP53 in peripheral blood of 43 LOA patients (15 mild LOA, 15 moderate LOA and 13 severe LOA) and 60 healthy controls (HCs) were determined. The association of methylated sites with age was assessed by Cox regression to control the potential confounders. Then, the correlation between differentially methylated sites (DMSs;p-value < 0.05) and clinical lung function in LOA patients was evaluated. Next, candidate DMSs combining with age were evaluated to predict LOA by receiver operating characteristic (ROC) analysis and principal components analysis (PCA). Finally, HDM-stressed asthma model was constructed, and DNA methylation inhibitor 5-Aza-2′-deoxycytidine (5-AZA) were used to determine the regulation of DNA methylation on the expression of FOXO3 and TP53.ResultsCompared with HCs, the mRNA expression and DNA methylation of FOXO3 and TP53 vary significantly in LOA patients. Besides, 8 DMSs from LOA patients were identified. Two of the DMSs, chr6:108882977 (FOXO3) and chr17:7591672 (TP53), were associated with the severity of LOA. The combination of the two DMSs and age could predict LOA with high accuracy (AUC values = 0.924). In HDM-stressed asthma model, DNA demethylation increased the expression of FOXO3 and P53.ConclusionsThe mRNA expression of FOXO3 and TP53 varies significantly in peripheral blood of LOA patients, which may be due to the regulation of DNA methylation. FOXO3 and TP53 methylation is a suitable blood biomarker to predict LOA, which may be useful targets for the risk diagnosis and clinical management of LOA.
Different expression pattern of human cytomegalovirus-encoded microRNAs in circulation from virus latency to reactivation
Authors: Zhou Wanqing , Wang Cheng , Ding Meng , Bian Yuying , Zhong Yujie , Shen Han , Wang Junjun , Zhang Chen-Yu , Zhang Chunni 
Published: December 2020

AbstractBackgroundHuman cytomegalovirus (HCMV) is a beta-hersvirinae that has a high latent infection rate worldwide and can cause serious consequences in immunocompromised patients when reactivation; however, the mechanism of how HCMV convert from latent to reactivation has rarely been investigated. In the present study, we aimed to perform a comprehensive analysis of the HCMV-encoded microRNA (miRNA) profile in serum of patients upon HCMV reactivation from latency and to further evaluate its clinical significance for the disease monitoring and preventing usefulness.MethodsSerum samples from 59 viremia patients and 60 age-gender matched controls were enrolled in this study for screening and validation of different expression of HCMV miRNAs. Serum concentrations of 22 known HCMV miRNAs were determined by a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. HCMV DNA was measured by quantitative real-time PCR (qPCR) with the whole blood sample. Serum HCMV IgG and IgM were assessed using enzyme linked immunosorbent assay (ELISA). Another 47 samples from 5 patients at different time points were collected to evaluate the monitoring effectiveness and disease prediction ability of differential expression HCMV-miRNAs during the antiviral treatment.ResultsThe RT-qPCR analysis revealed that the serum levels of 16 of the 22 examined HCMV miRNAs were elevated in HCMV viremia patients compared with controls, and a profile of 8 HCMV miRNAs including hcmv-miR-US25-2-3p, hcmv-miR-US4-5p, hcmv-miR-US25-2-5p, hcmv-miR-US25-1-3p, hcmv-miR-US25-1, hcmv-miR-UL36, hcmv-miR-UL148D, hcmv-miR-US29-3p were markedly elevated (fold change > 2, P < 0.01). Receiver operating characteristic curve (ROC) analysis were performed on the selected HCMV-miRNAs in all of the patients and controls that enrolled in this study, and which ranged from 0.72 to 0.80 in the autoimmune patients. In addition, hcmv-miR-US25-1-3p levels were significantly correlated with HCMV DNA load (r = 0.349, P = 0.007), and were obviously higher in the reactivation set than the latency set in the autoimmune patients, which could be a predictor for the monitoring of the antiviral treatment.ConclusionsHCMV miRNAs profile showed markedly shift-switch from latency to reactivation in circulation from HCMV infected patients and hcmv-miR-US25-1-3p may be served as a predictor for the switch upon reactivation from latency in patients suffered with autoimmune diseases.
Non-invasive biomarkers for monitoring the immunotherapeutic response to cancer
Authors: Nisar Sabah , Bhat Ajaz A. , Hashem Sheema , Yadav Santosh K. , Rizwan Arshi , Singh Mayank , Bagga Puneet , Macha Muzafar A. , Frenneaux Michael P. , Reddy Ravinder , Haris Mohammad 
Published: December 2020

AbstractImmunotherapy is an efficient way to cure cancer by modulating the patient’s immune response. However, the immunotherapy response is heterogeneous and varies between individual patients and cancer subtypes, reinforcing the need for early benefit predictors. Evaluating the infiltration of immune cells in the tumor and changes in cell-intrinsic tumor characteristics provide potential response markers to treatment. However, this approach requires invasive sampling and may not be suitable for real-time monitoring of treatment response. The recent emergence of quantitative imaging biomarkers provides promising opportunities. In vivo imaging technologies that interrogate T cell responses, metabolic activities, and immune microenvironment could offer a powerful tool to monitor the cancer response to immunotherapy. Advances in imaging techniques to identify tumors' immunological characteristics can help stratify patients who are more likely to respond to immunotherapy. This review discusses the metabolic events that occur during T cell activation and differentiation, anti-cancer immunotherapy-induced T cell responses, focusing on non-invasive imaging techniques to monitor T cell metabolism in the search for novel biomarkers of response to cancer immunotherapy.
Effect of duloxetine premedication for postherpetic neuralgia within 72 h of herpes zoster reactivation [PROCESS]: a study protocol for a randomized controlled trial
Authors: Chen Zheng , Shrestha Niti , Zhao Chunmei , Fan Bifa , Luo Fang 
Published: December 2020

Abstract
Background
Postherpetic neuralgia (PHN) is the most common complication attributed to herpes zoster, which involves the reactivation of residual varicella zoster virus. It has been reported previously that pre-emptive amitriptyline following acute herpes zoster has shown latent positive effects in the prevention of PHN. In this study, by interfering with the same targets, norepinephrine and serotonin, we aim to evaluate whether pre-emptive duloxetine may proactively prevent PHN development.

Methods
This is a nationwide multicentric, randomized, open-label, blinded-endpoint study that will recruit 750 participants from 18 primary centres in China. Patients aged more than 50 years who are diagnosed with uncomplicated HZ, present with vesicles within 72 h of their emergence, and have an average pain score of at least 40/100 mm on a visual analogue scale (VAS, 0 mm = no pain, 100 mm = worst possible pain, at opposite ends of a 100-mm line) will be recruited for this study. Participants will be randomized into a duloxetine arm and a control arm. Participants allocated to the duloxetine arm will be given antivirals, analgesics and duloxetine, while those allocated to the control arm will receive antivirals and analgesics but no duloxetine. The primary outcome of this study is preventive efficacy against PHN, which will be evaluated based on a 100 mm VAS. Any pain scores other than 0 mm on the VAS 12 weeks after HZ onset will be defined as PHN. The secondary outcomes will consist of the average weekly VAS score, the average weekly consumption of each analgesic, weekly feature of the pain, patients’ quality of life based on the 12-item Short-Form Health Survey, Patient Global Impression of Change Scale, sleep quality as evaluated by the Pittsburgh Sleep Quality Index and adverse events during the study period.

Discussion
This study will investigate a prophylactic approach for reducing the prevalence of postherpetic neuralgia with duloxetine and will add significant new knowledge on the preventive effects of duloxetine on PHN.

Trial registration
Clinicaltrials.gov NCT04313335. Registered on 18 March 2020.
A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
Authors: Heiden Stefan E. , Hübner Nils-Olaf , Bohnert Jürgen A. , Heidecke Claus-Dieter , Kramer Axel , Balau Veronika , Gierer Wolfgang , Schaefer Stephan , Eckmanns Tim , Gatermann Sören , Eger Elias , Guenther Sebastian , Becker Karsten , Schaufler Katharina 
Published: December 2020

AbstractBackgroundAntibiotic-resistantKlebsiella pneumoniaeare a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. TheK. pneumoniaesequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany.MethodsHere, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone.ResultsPhylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, whichK. pneumoniaeST307 likely donated to otherK. pneumoniaeisolates of different STs and even other bacterial species (e.g.,Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulentK. pneumoniaestrain (hvKP1).ConclusionsThe combination of extensive drug resistance and virulence, partly conferred through a “mosaic” plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.
Data of risk analysis management in university campuses
Authors: Dehdashti Alireza , Fatemi Farin , Janati Muhammadreza , Asadi Fatemeh , Kangarloo Marzieh Belji 
Published: December 2020

Abstract
Objectives
This data paper aims to provide the data set of a practical method to health, safety, and environmental risk assessment to assess and rank potential threats/hazards and to prevent and decrease the accidents and harmful consequences at an academic setting. Descriptive data on type of hazards, places, and persons at risk were collected. Quantitative data on risk probability and severity of identified hazards were determined. Additionally, the descriptive statistics and analytical tests were applied to create a concise perspective on health, safety and environmental hazards/threats situation in research location under study. The dataset further provides information on the prioritization of determined risks according to the relevant scores and levels for doing the relevant control measures to remove and mitigate the related risks.

Data description
This paper provides data of comprehensive risk assessment of health, safety and, environmental hazards of academic setting. For each identified hazard, the descriptive and numeric data are available. The information about the risk level and prevention or mitigation measure related to each hazard is provided. Additionally, the statistical tests are applied for determining the relations among the variables under study. The data and methodology on risk assessment in this article may be used to manage variety of risks in higher education institutions.
Factors affecting hospital mortality rate in Iran: a panel data analysis
Authors: Bayati Mohsen , Emadi Mehrnoosh 
Published: December 2020

Abstract
Objective
Hospital deaths account for a large number of community deaths. Moreover, one of the main indicators of inpatient services quality is the hospital death. This study was performed to investigate the factors affecting hospital death rate in Iran using panel data analysis.

Results
The net death rates in teaching and not-teaching hospitals were 6.24 and 5.58 per 1000 patients, respectively. Models' estimates showed, in teaching hospitals the number of surgeries (P < 0.05) and special beds (P < 0.01) had a significant positive relationship with death rate. In non-teaching hospitals, outpatient admissions (P < 0.01), number of surgeries (P < 0.05), number of special beds (P < 0.01), and length of stay (P < 0.01) had a positive and the number of inpatient admissions (P < 0.05) and active beds (P < 0.01) had a negative relationship with death rate.
Policy-making towards optimization of hospital service size and volume, standardization of length of stay, interventions to control nosocomial infections, and planning to control the complications of surgeries and anesthesia could effectively reduce hospital death rate.
Relationship between tumor mutational burden and maximum standardized uptake value in 2-[18F]FDG PET (positron emission tomography) scan in cancer patients
Authors: Haghighat Jahromi Amin , Barkauskas Donald A. , Zabel Matthew , Goodman Aaron M. , Frampton Garret , Nikanjam Mina , Hoh Carl K. , Kurzrock Razelle 
Published: December 2020

Abstract
Purpose
Deriving links between imaging and genomic markers is an evolving field. 2-[18F]FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography–computed tomography) is commonly used for cancer imaging, with maximum standardized uptake value (SUVmax) as the main quantitative parameter. Tumor mutational burden (TMB), the quantitative variable obtained using next-generation sequencing on a tissue biopsy sample, is a putative immunotherapy response predictor. We report the relationship between TMB and SUVmax, linking these two important parameters.

Methods
In this pilot study, we analyzed 1923 patients with diverse cancers and available TMB values. Overall, 273 patients met our eligibility criteria in that they had no systemic treatment prior to imaging/biopsy, and also had 2-[18F]FDG PET/CT within 6 months prior to the tissue biopsy, to ensure acceptable temporal correlation between imaging and genomic evaluation.

Results
We found a linear correlation between TMB and SUVmax (p < 0.001). In the multivariate analysis, only TMB independently correlated with SUVmax, whereas age, gender, and tumor organ did not.

Conclusion
Our observations link SUVmax in readily available, routinely used, and noninvasive 2-[18F]FDG PET/CT imaging to the TMB, which requires a tissue biopsy and time to process. Since higher TMB has been implicated as a prognostic biomarker for better outcomes after immunotherapy, further investigation will be needed to determine if SUVmax can stratify patient response to immunotherapy.
A novel ELISA method to determine human MrgX2 in chronic urticaria
Authors: Ding Yuanyuan , Zhang Tao , Liu Rui , Che Delu , Wang Nan , He Langchong 
Published: December 2020

Abstract
Background
Mas-related G-protein coupled receptor member X2 (MrgX2) directly mediates drug-induced pseudo allergic reactions. Skin mast cell MrgX2 is upregulated in severe chronic urticaria (CU). Mast cells and leukocytes are key effector cells in allergic reactions and undergo degranulation upon stimulation. It is unknown whether circulating MrgX2 expression can be detected occurs in the whole blood of CU patients and reflects pseudo-allergic reaction. There is no effective method for its detection. Therefore, an enzyme-linked immuno-sorbent assay (ELISA) for MrgX2 was developed.

Methods
Monoclonal and polyclonal MrgX2 specific antibodies were obtained from rabbits and mice immunized by MrgX2 peptides prepared. Indirect ELISA and Dot blot were used to determine antibody titers before a sandwich ELISA for MrgX2 was established. The whole blood from healthy subjects and CU patients was used to detect MrgX2 concentrations. The use of feasibility of this MrgX2-ELISA as a clinical detection tool was explored and diagnostic purposes was assessed.

Results
The sandwich antibody ELISA method for MrgX2 was established with good linearity regression (R2 = 0.9910). The lowest detection limit was 3.125 ng/mL. The quantification limit was 6.25 ng/mL. The sandwich ELISA for MrgX2 have good stability and high specificity. The initial truncation value of MrgX2 was 60.91 ng/mL (95% confidence interval). The whole blood MrgX2 concentrations in CU patients (median 98.01 ± 4.317 ng/mL, n = 75) was significantly increased compared to healthy subjects (58.09 ± 1.418 ng/mL, n = 75), with significant difference (p < 0.0001) and higher accuracy of (AUC = 0.8795). Comprehensive the frequency analysis of MrgX2 expression in 75 CU patients reference frequency distribution and ROC curve analysis, determined the threshold for CU patients as 71.23 ng/mL, with 81.33% sensitivity and 90.67% specificity.

Conclusion
MrgX2-ELISA provides a useful and convenient method for detecting MrgX2 in whole blood samples. The MrgX2-ELISA will help improve the understanding of the role of MrgX2 in regulating chronic urticaria.
Disability-adjusted life years and mortality rate attributed to unsafe sex and drug use for AIDS in the Middle East and North Africa countries
Authors: Najafi Farid , Shadmani Fatemeh Khosravi , Ghalandari Mojtaba , Darbandi Mitra 
Published: December 2020

Abstract
Background
The Middle East and North Africa, is one of few regions where the number of new human immunodeficiency virus infections is increasing. The present study aimed to estimate the attributable burden of unsafe sex and drug use in Acquired immunodeficiency syndrome in the Middle East and North Africa countries.

Methods
We used the Global Burden of Disease data 2017 to estimate the attributable mortality and disability-adjusted life-years to unsafe sex and drug use in Acquired immunodeficiency syndrome in the Middle East and North Africa countries (21 countries) from 1990 to 2017 by region, sex and age. The percent change was calculated at three time points by country and sex.

Results
The rate of Disability-adjusted life years/100,000 attributed to drug use for Acquired immunodeficiency syndrome increased 1.10 (95% CI: 0.75–1.71) to 13.39 (95% CI: 9.98–18.17) in women of Middle East and North Africa countries from 1990 to 2017, and there is an increasing trend in Disability-adjusted life years attributable to drug use for Acquired immunodeficiency syndrome in men. The rate of Disability-adjusted life years/100,000 attributed to unsafe sex for Acquired immunodeficiency syndrome increased in women of Middle East and North Africa countries, 5.15 (95% CI: 3.34–8.07) to 53.44 (95% CI: 38.79–75.89); and 10.06 (95% CI: 6.61–16.18) to 46.16 (95% CI: 31.30–72.66) in men. Age-standardized mortality rate attributed to drug use and unsafe sex for Acquired immunodeficiency syndrome increased from 1990 to 2017 in both sex in Middle East and North Africa countries.

Conclusion
The rate of Disability-adjusted life years /100,000 and age-standardized mortality rate attributed to unsafe sex and drug use increased in Middle East and North Africa from 1990 to 2017. While most of such countries have traditional cultures with religious believes, such increase need to be addressed in more depth by all policy makers.
KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors
Authors: Zhang Rui , Wu Hao-Xiang , Xu Ming , Xie Xiaoyan 
Published: December 2020

AbstractEpigenetic factors play important roles in tumor immunology. Histone-lysine N-methyltransferase 2 (KMT2) family genes exert histone H3 methylation, but its role in immunotherapy remains unclear. Our study is the first to investigate the correlation between KMT2 gene mutations and the clinical benefit of immune checkpoint inhibitors (ICI) treatment. We firstly collected a primary ICI-treated cohort (n = 546) and found that patients with KMT2A/C mutations yielded better prognosis in terms of progression-free survival (PFS, Hazard ratio [HR] = 0.66, P = 0.002), objective response rate (ORR, 40.9% vs 20.3%, P < 0.001), durable clinical benefit (DCB, 48.3% vs 29.8%, P = 0.001) and overall survival (OS, HR = 0.70, P = 0.033). Furthermore, we validated the predictive potential of KMT2A/C mutations in an expanded ICI-treated cohort (n = 1395). KMT2A/C-mutant patients achieved better OS compared with KMT2A/C-wildtype patients (HR = 0.68, P = 0.003); and the survival advantages appeared in the majority of cancer subtypes. Our study suggests that KMT2A/C mutations function as a novel and potential predictive biomarker for ICI treatment in multiple solid tumors and the underlying mechanism is worth investigating.