bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Dose Hydroxychloroquine is Associated with Lower Mortality in COVID-19: A Meta-Analysis of 27 Studies and 44,684 Patients
Authors: Castelnuovo Augusto Di , Costanzo Simona , Cassone Antonio , Cauda Roberto , Gaetano Giovanni de , Iacoviello Licia 
Published: December 2020

Abstract
Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is not well characterized. We conducted two meta-analyses to evaluate the association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.Methods: Articles were retrieved until November 10th, 2020 by searching in seven databases. Data were combined using the general variance-based method.Results: A total of 27 articles were found (N=44,684 patients, including N=7,803 from 5 randomized clinical trials (RCTs)). Overall, the use of HCQ was associated with 22% lower mortality risk (pooled risk ratio: 0.78, 95%CI: 0.67 to 0.91; I2=80%, random effects). This association was found reversed when pooling only RCTs (16.7% of the overall weight; pooled risk ratio: 1.11, 0.99 to 1.24) or studies in which daily dose >400 mg or total dose >4,400 mg were used (pooled risk ratio: 1.10, 95%CI: 0.99 to 1.23 in both cases). Overall, HCQ+AZM (10 studies) was also associated with 28% lower mortality risk, but uncertainty was large (95%CI: 0.48 to 1.08; P=0.11). Use of HCQ was not associated with severe adverse events.Conclusions: HCQ use was not associated with mortality reduction in COVID-19 patients when 5 RCTs only were evaluated, while a 9% to 33% reduced mortality was observed when observational studies were also included. The association was mainly apparent in studies that used lower doses of HCQ. These findings can help disentangling the debate on HCQ use in COVID-19.
Family Caregivers' Experiences of Caring for Patients with COVID-19: A Phenomenological Study
Authors: Rahimi Tahereh , Dastyar Neda , Rafati Foozieh 
Published: December 2020

Abstract
Background: Family caregivers of patients with COVID-19 face many challenges that affect their physical and mental health. Aim: The aim of the present study was to explore the family caregivers' experiences of caring for patients with COVID-19. Methods: This qualitative phenomenological study was performed based on 13 family caregivers who had experience in home caring for patients with COVID-19. Data were collected through purposive sampling with in-depth semi-structured interviews. The Colaizzi's 7-step method was used to determine themes. The MAXQDA10 software was used to manage qualitative data analysis.Results: Five themes of (a) “nature of the disease” with 2 subcategories, including “fluctuating symptoms” and “emergent and unpredictable disease;” (b) “unmet needs” with 3 subcategories, including “lack of knowledge,” “lack of health facilities,” and” financial problems;” (c) “unpleasant physical, psychological, and social experiences” with 3 subcategories, including “unpleasant physical experiences,” “unpleasant psychological experiences,” and “unpleasant social experiences;” (d) “care facilitators” with 3 subcategories, including “social support,” “adaptive mechanisms,” and “intrinsic motivations;” and (e) “positive experiences” with 3 subcategories, including “promoting spirituality,” “improving relationships,” and “growth” were extracted.Conclusion: Information and financial support for COVID-19 should be provided to family caregivers. Also, community members should embrace patients and family caregivers and reinforce the positive experiences of caregivers.
Maternal health care utilization and the obstetric outcomes of undocumented women in Finland – a retrospective register-based study
Authors: Tasa Janita , Holmberg Ville , Sainio Susanna , Kankkunen Päivi , Vehviläinen-Julkunen Katri 
Published: December 2020

Abstract
Background: Undocumented pregnant women constitute a vulnerable group of people who lack equal access to pregnancy care. Previous research has shown that undocumented migrants encounter difficulties in accessing health services, the onset of prenatal care is delayed, and women have an increased risk for infectious diseases. The aim of this study was to describe the use of maternal health care services and the obstetric outcomes of undocumented women in Helsinki, in addition to comparing the results with all pregnant women in Finland.Methods: The study was a retrospective register-based study consisting of data collected between 2014 to 2018 from the electronic medical records of the public maternity clinic and maternity hospital in Helsinki, Finland. The study population consists of 62 individual pregnancies of undocumented women. The results of the study were compared with national data on parturients and deliveries (N=47,274 women) and with prenatal screening tests for infectious diseases (N=51,447 [HIV, HBV], N=51,446 [syphilis]) (relative risk, RR with 95 % CI).Results: The majority (91 %) of the undocumented women attended public prenatal care. However, four women received no prenatal care and three women were denied access to care. Undocumented women entered prenatal care later and had fewer visits compared with all pregnant women. The majority (71 %) of the undocumented women received inadequate prenatal care as the number of visits was less than eight. Of the study population, 5 % (3/61) tested positive for HIV, 3 % (2/61) for HBV, and 2 % (1/62) for syphilis. The prevalence of HIV (RR 62, 95 % CI 20­–195), HBV (RR 16, 95 % CI 4–63), and syphilis (RR 20, 95 % CI 3–145) were higher amongst undocumented women compared with all pregnant women.Conclusions: Undocumented women entered prenatal care later than recommended. Most women received inadequate prenatal care and some of them did not receive prenatal care at all. The prevalence of infectious diseases was higher and the coverage of prenatal screenings deficient amongst undocumented pregnant women.
Factors affecting pre-hospital and in-hospital delays at time-to-treatment and complications in stroke: A prospective cohort study
Authors: Hanifi Nasrin , Dinmohammadi Mohammadreza , Ghadimi Neda 
Published: December 2020

Abstract
Background: Time-to-treatment affects the outcomes of acute ischemic stroke (AIS). The aim of this study was to determine the factors affecting pre-hospital and in-hospital delays in the time-to-treatment and complication in AIS. Methods: This prospective study was performed on 204 AIS patients referred to the stroke care unit in Iran (Zanjan) in 2019. Data were completed by interviewing the patients, their families, records, and observations. The mortality and complication rates were recorded for 30 post-stroke days through call follow-up. Results: The results showed that the highest delay was related to the onset-to-arrival time (288.19 ±339.02 minutes). Results of logistic regression showed that treatment delay declined significantly by consulting followed by symptoms onset, patient transfer through emergency medical service to the hospital, and patients’ understanding of AIS symptoms. The results also showed that increasing the onset-to-treatment time (P< .001) and high National Institutes of Health Stroke Scale (NIHSS) score (P< .000) were the most important factors associated with post-stroke complications. High age (P< .044) and high NIHSS scores (P< .001) were significantly associated with mortality in patients with AIS. Conclusion: Informing people about AIS symptoms and referring to AIS treatment units are essential in reducing the treatment time.
Imputing Partial Status and Estimating Incidence Rate in an Illness-death Model with Application to a Phase IV Cancer Trial
Authors: Srivast Deo , Pan Jianmin , Qian Chen , Hudson Melissa , Rai Shesh 
Published: December 2020

Abstract
BackgroundPhase IV clinical trials are designed to monitor the long-term toxic effects of drugs in cancer survivors. Evaluations to study the long-term effects of the cancer treatment are often made with cross-sectional surveys. This leads to interval censored data since the exact time of the onset of toxicity is not known. In addition to finding prognostic factors for log-term survival outcome, estimating and comparing the cumulative incidence rates for adverse outcomes of interest for interval censored data is also desired. However, the analysis of such data is further complicated by many issues, such as incomplete data, competing risks and selection bias. For example, one such study was designed by Hudson et al. to study the effect of anthracyclines exposure, received as part of treatment for childhood cancer, to cardiotoxicity. Rai et al. had utilized a parametric approach for assessing the effect of anthracycline on the cumulative incidence of cardiotoxicity but excluded the patients with missing information on the parameters used for assessing cardiotoxicity.MethodsIn this paper our focus is on imputing the missing data and then using the current status regression methods, previously described in Rai et al. for estimating and comparing cumulative incidence rates in an illness-death/failure model.ResultsWe undertook a comprehensive simulation study to evaluate the performance of our imputation approach and applied it to a Phase IV clinical trial to evaluate the effect of anthracycline exposure on long-term cardiotoxicity in childhood cancer survivors, which had missing cardiotoxicity information. ConclusionsOur simulations suggest that the results obtained by imputing the missing values using regression methods are significantly more efficient than those obtained without imputation. The proposed approach is easy to implement, and we demonstrate its usefulness by applying it to the data reported in Rai et al. and compare the results reported there to our approach that utilizes imputation.
Comparison of Neuromuscular Blockade Recovery Co-Administered With Neostigmine and Different Doses of Calcium Gluconate: A Randomized Control Trial
Authors: Choi So Ron , Park Sang Yoong , Kim Jeong Ho , Lee Kyung Hyun 
Published: December 2020

Abstract
Background: Calcium increases the probability of transmitter release at the neuromuscular junction. However, it is not known whether there is a dose-dependent relationship between the dosage of calcium gluconate and the probability of transmitter release for non-depolarizing neuromuscular blockade (NMB) recovery by acetylcholinesterase inhibitors (AchEIs). This study compared the neuromuscular recovery time and the incidence of postoperative residual curarization (PORC) according to the dosage of calcium gluconate co-administered with neostigmine in three patient groups.Methods: Patients were randomly allocated to a control group, a 5 mg/kg calcium gluconate group (calcium 5 group), or a 10 mg/kg calcium gluconate group (calcium 10 group). The primary endpoint was neuromuscular recovery time. The secondary endpoints were the incidence of PORC at 5, 10, and 20 minutes after reversal administration and the train-of-four ratio (TOFr) at each time point.Results: The neuromuscular recovery time was 5.3 minutes in the control group, 3.9 minutes in the calcium 5 group, and 4.1 minutes in the calcium 10 group, respectively (P=0.012). Neuromuscular recovery time was significantly different between the control and calcium 10 groups (P=0.017). The incidence of PORC at 5 minutes after neostigmine administration was 12 (46.2%) in the control group, 4 (15.4%) in the calcium 5 group, and 4 (15.4%) in the calcium 10 group, respectively, with statistical significance (P=0.014). Conclusions: The co-administration of 10 mg/kg calcium gluconate with neostigmine achieved early NMB recovery and had the fewest variables.Trial Registration: https://cris.nih.go.kr/cris/index.jsp(KCT0004182). Date of registration:12 august 2019.
Labor Analgesia Reduces the Risk of Postpartum Depression in Women with Single-Term Pregnancy: A Prospective Cohort Clinical Study
Authors: Ren Li , Chen Qibin , Min Su , Peng Fangliang , Wang Bin , Yu Jian , Zhang Yuxi 
Published: December 2020

Abstract
Background: Postpartum depression (PPD) is a frequent mental disorder during the first year after delivery. Previous studies reported that patients with labor analgesia revealed lower incidence of PPD compared to those without. However, most pregnant women gave birth by labor analgesia or cesarean section in China, it is still unclear that whether there is a difference of the effects of labor analgesia and cesarean section on PPD.Methods: A single-centered, prospective cohort clinical study was designed. One hundred ninety-eight patients with single pregnancy at full term were allocated to receive epidural labor analgesia (group LA) or cesarean section with epidural anesthesia (group CS) according to the maternal preference of delivery and professional suggetions of obstetricians and anesthesiologists. PPD was assessed with Edinburgh Postnatal Depression Scale (EPDS) scores ≥10 at 6 weeks postpartum. Maternal and neonatal variables in the perinatal period were recorded. Multivariate logistical regression analysis was conducted to evaluate the associated factors of PPD. Results: 11 patients in group LA and 26 patients in group CS was diagnosed as PPD. The incidence of PPD in group LA was lower than group CS (P=0.011). Eight potential predictor factors (labor analgesia, family income, duration of labor, antenatal depression, perinatal classes attending, neonate of male, EPDS scores at 3 days postpartum and adverse event at 6 weeks postpartum) were correlated with PPD. And it was reported in the final model that labor analgesia was the protective factor of PPD, however, high family income and EPDS scores at 3 days postpartum were associated with an increased risk of PPD. Conclusions: Patients with epidural labor analgesia were associated with lower incidence of PPD compare to those with cesarean section with epidural anesthesia. Epidural labor analgesia, family income and EPDS scores in the early postpartum period were the independent predictors of PPD. Trial registration: This clinical trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx). Number: ChiCTR1900020510. Registered on: 3/1/2019.
Comparison of long-term outcomes between minimally invasive pulmonary resection combined with and without video-assisted mediastinoscopic lymphadenectomy for left-sided lung cancer
Authors: Yun Jae Kwang , Lee Geun Dong , Choi Sehoon , Kim Hyeong Ryul , Kim Dong Kwan , Park Seung-Il , Kim Yong-Hee 
Published: December 2020

Abstract
This study aimed to assess the long-term outcomes of video-assisted mediastinoscopic lymphadenectomy (VAMLA) combined with video-assisted thoracic surgery (VATS) for left-sided lung cancer pulmonary resection. We retrospectively reviewed 1194 consecutive patients who underwent VATS anatomical resection for left-sided lung cancer between January 2007 and December 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative outcomes and long-term survival outcomes were compared. Among 1194 patients, 295 (24.7%) underwent additional VAMLA (VATS + VAMLA group) and 899 patients (75.3%) underwent VATS only (VATS group). After IPTW adjustment, all baseline profiles between the two groups became similar. The long-term overall survival (OS) was similar between the VATS + VAMLA group and the VATS group (5-year OS, 77.8% vs. 79.3%, P = .957). However, among patients with borderline pulmonary function (FEV1 ≤ 60% or DLCO ≤ 60%), the VATS + VAMLA group (n=23) had slightly better prognosis than the VATS group (n=36) (5-year OS, 67.4% vs. 46.7%, P = .055). VAMLA can be a good complement to VATS for left-sided lung cancer, wherein optimal mediastinal lymph node dissection is not feasible under one-lung ventilation, such as when patients have borderline pulmonary function.
Extracellular DNA of slow growers of mycobacteria and its contribution to biofilm formation and drug tolerance
Authors: Ilinov Aleksandr , Nishiyama Akihito , Namba Hiroki , Fukushima Yukari , Takihara Hayato , Nakajima Chie , Savitskaya Anna , Kaboso Amina , Vinnik Yuri , Gebretsadik Gebremichal , Hakamata Mariko , Ozeki Yuriko , Tateishi Yoshitaka , Okuda Shujiro , Suzuki Yasuhiko , Matsumoto Sohkichi 
Published: December 2020

Abstract
DNA is basically an intracellular molecule that stores genetic information and carries instructions for growth and reproduction in all cellular organisms. However, in some bacteria, DNA has additional roles on the outside as an extracellular DNA (eDNA), an essential component for the formation of antibiotic tolerance bacteria in biofilm. Mycobacteria include life-threating human pathogens, most of which are slow growers. However, little is known about the nature of pathogenic mycobacteria’s eDNA. Here we found that eDNA is present in slow growers of mycobacterial pathogens, such as Mycobacterium tuberculosis, M. intracellulare, and M. avium at exponential growth phase. In contrast, eDNA is little in all tested rapid growers of mycobacteria. The physiological impact of disrupted eDNA on slow growers of mycobacteria include reduced formation of pellicle, a floating biofilm, and enhanced susceptibility to isoniazid and amikacin. Isolation and sequencing of eDNA revealed that it is identical to the genomic DNA in M. tuberculosis and M. intracellulare. In contrast, accumulation of phage DNA in eDNA of M. avium, suggests that the DNA released differs among mycobacterial species. Our data show important functions of eDNA for biofilm formation and drug tolerance in slow growers of mycobacteria.
Blood tryptase and thymic stromal lymphopoietin levels predict the risk of exacerbation in severe asthma
Authors: Cheng Shih-Lung , Lin Ching-Hsiung , Lin Sheng-Hao , Hsiao Yi-Han , Su Kang-Cheng , Yu Chong-Jen , Wang Hao-Chien , Sheu Chau-Chyun , Chiu Kuo-Chin , Perng Diahn-Warng , Ko Hsin-Kuo 
Published: December 2020

Abstract
Some patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or resistant to corticosteroids. We aimed to identify the independent factors predictive for the future risk of exacerbation in patients with severe asthma. In this multi-center prospective observational study, 132 patients with severe asthma were enrolled and divided into exacerbation (n = 52) and non-exacerbation (n = 80) groups on the basis of exacerbation rate after a 1-year follow-up period. We found that previous history of severe-to-serious exacerbation, baseline blood eosinophil counts (≥291cells/mL), and serum tryptase (≤1448pg/mL) and thrymic stromal lymphopoietin (TSLP) levels (≥25pg/mL) independently predicted the future development of exacerbation with adjusted odds ratios (AOR) of 3.27, 6.04, 2.53 and 8.67, respectively. Notably, the patients with high blood eosinophil counts and low tryptase levels were likely to have more exacerbations than those with low blood eosinophil counts and high tryptase levels (AOR 16.9). TSLP and tryptase levels may be implicated in steroid resistance and responsiveness in the asthma inflammatory process. High blood eosinophil counts and low serum tryptase levels predict a high probability of future asthma exacerbation.
Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection
Authors: Yang Ning , Luna Joseph , Dai Peihong , Wang Yi , Rice Charles , Deng Liang 
Published: December 2020

Abstract
The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How these immune components communicate during an acute poxvirus infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we provide evidence that type II alveolar epithelial cells (AECIIs) function as the sentinels of pulmonary infection of vaccinia virus by inducing IFN-β and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways and the type I IFN positive feedback loop. This leads to the recruitment and activation of CCR2+ inflammatory monocytes in the infected lungs and their differentiation into Lyve1- interstitial macrophages (Lyve1- IMs), which efficiently engulf viral particles and block viral replication. Our results provide novel insights into how innate immune-sensing of viral infection by lung AECIIs influences the activation and differentiation of CCR2+ inflammatory monocytes to defend pulmonary poxvirus infection.
High Sensitivity Sanger Sequencing Detection of BRAF Mutations in Metastatic Melanoma FFPE Tissue Specimens
Authors: Cheng Lauren , Haydu Lauren , Song Ping , Nie Jianyi , Tetzlaff Michael , Kwong Lawrence , Gershenwald Jeffrey , Davies Michael , Zhang David 
Published: December 2020

Abstract
Mutations in the BRAF gene at or near the p. V600 locus are informative for therapy selection, but current methods for analyzing FFPE tissue DNA generally have a limit of detection of 5% variant allele frequency (VAF), or are limited to the single variant (V600E). These can result in false negatives for samples with low VAFs due to low tumor content or subclonal heterogeneity, or harbor non-V600 mutations. Here, we show that Sanger sequencing using the NuProbe VarTraceTM BRAF assay, based on the Blocker Displacement Amplification (BDA) technology, is capable of detecting BRAF V600 mutations down to 0.26% VAF from FFPE lymph node tissue samples. Comparison experiments on adjacent tissue sections using BDA Sanger, immunohistochemistry (IHC), digital droplet PCR (ddPCR), and NGS showed 100% concordance among all 4 methods for samples with BRAF mutations at ≥1% VAF, though ddPCR did not distinguish the V600K mutation from the V600E mutation. BDA Sanger, ddPCR, and NGS (with orthogonal confirmation) were also pairwise concordant for lower VAF mutations down to 0.26% VAF, but IHC produced a false negative. Thus, we have shown that Sanger sequencing can be effective for rapid detection and quantitation of multiple low VAF BRAF mutations from FFPE samples. BDA Sanger method also enabled detection and quantitation of less frequent, potentially actionable non-V600 mutations as demonstrated by synthetic samples.