bluuebunny/crossref_metadata_2025 huggingface dataset:
Earthquake and Electrochemistry: Unraveling the Unpredictable
Authors: Das Atanu
Published: December 2020

Earthquakes are measured using well defined seismic parameters such as seismic moment (Mo), moment magnitude (Mw), and released elastic energy(E). How this tremendous amount of energy is accumulated silently deep inside the earth's crust? The most obvious question in seismic research remains unanswered. We found an inherent and intriguing connection between the released energy in an earthquake and electrochemical potential induced in an ultra-thin metal oxide electrode immersed in an aqueous pH solution, which leads us to understand the origin of the energy accumulation process in an earthquake.

A huge electrochemical potential is accumulated from numerous electrochemical cells formed in a unique layer structure of hydrated clay minerals (predominantly smectite), which resulted in a lightning-like discharge in the lithosphere (hypocenter). The subsequent thunder-like massive shockwave is produced, which initiates tectonic plate movement along a fault line, probably through acoustic fluidization (AF), and resulting seismic energy is transmitted as primary wave (P-wave), secondary wave (S-wave), and surface waves.

The presence of electrical voltage in the hypocenter directly supports the seismic electric signal (SES), further strengthening the VAN method of earthquake prediction. Our finding is supported by a plethora of research and observation devoted to seismic science. This study will find its significance if immediate action is implemented to monitor the evolution of electrochemical potential, seismic electrical signal (SES), and ionic activity in the fault zone at lithosphere as well as in the ionosphere for predicting an impending earthquake for saving human lives as early as possible.
A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyperactivation
Authors: Kang Sisi , Yang Mei , He Suhua , Wang Yueming , Chen Xiaoxue , chen Yao-Qing , Hong Zhongsi , Liu Jing , Jiang Guanmin , Chen Qiuyue , Zhou Ziliang , Zhou Zhechong , Huang Zhaoxia , Huang Xi , He Huanhuan , Zheng Weihong , Liao Hua-Xin , Xiao Fei , Shan Hong , Chen Shoudeng
Published: December 2020

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who had dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the mAb with the highest binding affinity (nCoV396) revealed changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyper-activation analysis demonstrated that nCoV396 specifically compromises the N protein-induced complement hyper-activation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.
Classification of unlabeled online media
Authors: Prakash Sakthi Kumar Arul , Tucker Conrad
Published: December 2020

This work investigates the ability to classify misinformation in online social media networks in a manner that avoids the need forground truth labels. Rather than approach the classification problem as a task for humans or machine learning algorithms, thiswork leverages user-user and user-media (i.e.,media likes) interactions to infer the type of information (fake vs. authentic) beingspread, without needing to know the actual details of the information itself. To study the inception and evolution of user-userand user-media interactions over time, we create an experimental platform that mimics the functionality of real world socialmedia networks. We develop a graphical model that considers the evolution of this network topology to model the uncertainty(entropy) propagation when fake and authentic media disseminates across the network. The creation of a real-world socialmedia network enables a wide range of hypotheses to be tested pertaining to users, their interactions with other users, andwith media content. The discovery that the entropy of user-user, and user-media interactions approximates fake and authenticmedia likes, enables us to classify fake media in an unsupervised learning manner.
Tests for Probability of A Reaction and Difference Between Reactions Where Treatment Increases Marker-Values of Particular Subjects but Decreases Others
Authors: Ishida Torao , Takagi Ken , Wang Gui-feng , Tanahashi Nobuyuki , Kawanokuchi Jun , Takagi Hisayo , Guo Yi , Ma Ning
Published: December 2020

PD-1 has a role in regulating the response of the immune system to the cells of the human body. Paris et al. reported that combination antiretroviral therapy did not change % CD4+ of PD-1highCTLA-4lowCD127high early/intermediated T cells of human immunodeficiency virus infected patients but increased the percent of the marker limited to initial CD4 counts <200 with Wilcoxon signed-rank test. We hypothesized that the treatment increased the marker value in patients whose initial marker value is less than a particular value and decreased the marker value in other patients and that the test misleadingly concluded that the treatment did not change the marker value. General subgroup analyses correctly estimate the statistical significance of such a reaction or difference between such reactions only when the reaction of both of subgroups or both difference between such subgroups is statistically significant. We propose Ishida’ t-test for paired samples that can correctly judge the probability without division of the group into subgroups, and Ishida’ t-test for unpaired samples that can correctly judge the statistical significance of the difference between such reactions. We also showed that many treatments cause such increase and decrease of marker values relating PD-1 of subjects.
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

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

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

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

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

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

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

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

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

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

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

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

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.
Characteristics and Costs of Prehospital Care for Chronic Kidney Disease Patients: A Longitudinal Cohort Study
Authors: Sarria-Guerrero José Antonio , Guix-Comellas Eva Maria , Jiménez-Fábrega Francesc Xavier , Benito-Aracil Llúcia , Sancho-Agredano Raül , Padrés Núria Fabrellas
Published: December 2020

Background The global cost associated with substitute treatment for patients with chronic kidney disease has been calculated, but there is a lack of information about the characteristics and costs deriving from pre-hospital care with transport and admission to hospital emergency services. Therefore, the aim of this study was to identify the characteristics of urgent telephone requests to Emergency Medical Services for patients with chronic kidney disease in Catalonia, Spain, and make a cost estimation of prehospital care and admission to the emergency department, grouped by comorbidities. Methods Retrospective longitudinal observational study. Patients who required urgent prehospital care based on telephone triage were enrolled. Sociodemographic, clinical, and financial variables were collected. The data were gathered by means of a review of the clinical records in the Emergency Medical Services database. To explore the possible relation among the qualitative variables the χ² test was used, for the relation between a quantitative variable and dichotomy qualitative variable the student t test was used with prior testing of the normal deviation of quantitative variables, and the Mann-Whitney U test was then employed if they did not fulfil normality criteria. For all calculations an alpha error of p <0.05 was assumed.Results A total of 252 phone calls were analyzed. Some 98.4% of patients (n=248) were prioritized through phone triage and classified as very severely ill: resuscitation or emergencies. The most prevalent initial diagnoses were intense dyspnoea, accidental fall, abdominal pain, and disease decompensation; there were 11 cases of cardio-respiratory arrest (4.36%), half of which were associated with hypertensive heart disease (HHDT). The average cost of prehospital care was €480.06/patient (SD=256.74), but in patients with comorbidities this rose to €550.77 for HHD and €508.73 for diabetes mellitus (DM). No statistically significant differences were found between total cost/patient and comorbidity (p=0.361), or between the costliest comorbidities, HHD and DM (p=0.330). Conclusions Patients telephoned for help when they were in serious condition, in line with the levels established by telephone triage. The cost of prehospital care was high, and this increased in the presence of comorbidities.
Service Acceptance of HIV Non-Occupational Post-Exposure Prophylaxis(nPEP) Among College Students: A Cross-Sectional Study in China
Authors: Liu Tongtong , Wang Xi , Li Aixin , Ye Jiangzhu , Shan Duo , Zhang Guang , Liu An
Published: December 2020

Background: College students are the key group we should pay more attention for acquired immune deficiency syndrome (AIDS) prevention and control in recent years in China, and few studies of HIV non-occupational post-exposure prophylaxis(nPEP) knowledge awareness and service acceptance have been conducted among them in China. This study conducted a cross-sectional survey to understand the service acceptance of nPEP and its influencing factors among college students in the three cities of China. Methods: A questionnaire survey was conducted to collect information on socio-demographic, behavioral characteristic, HIV/AIDS knowledge, nPEP knowledge, acceptance of nPEP services among the college students in Beijing, Shenzhen, and Kunming of China from March to April of 2019. Each participant completed a computer-assisted or mobile phone-assisted self-interview with informed consent and completed an anonymous questionnaire on line. Multivariable logistic regression analyses identified predictors for service acceptance of nPEP. Results A total of 4698 students were surveyed with the average age of 20 years old. 98.0% (4605/4698) of them were undergraduates, 21.8%(1022/4698) had sexual intercourse; 48.6% (2282/4698)had heard of nPEP, among which4.95%(113/2282) received nPEP services. The rate of AIDS knowledge awareness was 85.6% (5495/4698) with the differences statistically significant between the three cities. The nPEP knowledge awareness rate was 16.5% (774/4698). There were differences in receiving nPEP services among students of different ages, genders, sexual behaviors, and knowledge of AIDS by univariate analysis. Multivariable analyses indicated that age group of 18 and under (OR=2.551, 95% CI=1.153-5.646), male (OR=3.131, 95% CI=1.866-5.253), homosexual behavior (OR=4.661,95%CI=2.658-8.172), heterosexual behavior (OR=1.676, 95% CI=1.040-2.947), no awareness of AIDS (OR=3.882, 95% CI=2.371-6.356) and nPEP (OR=4.788, 95% CI=2.50-9.169) knowledge, were associated factors with the service acceptance of nPEP among the college students. Conclusion The low acceptance of nPEP services was mainly affected by nPEP knowledge awareness among the college students and further publicity and education of nPEP knowledge are necessary, as well as dissemination of knowledge of HIV/AIDS prevention and treatment. More attention should be paid to the factors associated with acceptance of nPEP services.
Neutrophil to lymphocyte ratio and Fibrinogen Values in predicting patients with type B aortic dissection
Authors: Li Shuangshuang , Yang Jin , Guo Renle , Dong Jian , Chang Sheng , Zhu Hongqiao , Li Zhaohui , Zhou Jian Jian , Jing Zaiping
Published: December 2020

The aim of this study is to detect the diagnosis value of neutrophil lymphocyte ratio (NLR) and fibrinogen (FIB) in type B aortic dissection (TBAD) patients. This retrospective observation study consisted patients with TBAD, aortic aneurysm and physical examination between January 1, 2016 and December 31, 2019. Demographic and clinical information after the first admission were collected. Multivariate logistic regression analysis was performed to explore the correlational relationship between NLR, FIB and TBAD. Receiver Operating Characteristic Curve (ROC) was performed to evaluate the diagnostic implication of NLR and FIB in TBAD patients. Six hundred and six patients who were first diagnosed with TBAD were included. Control groups were 202 aortic aneurysm and 140 physical examination subjects. The level of NLR and FIB in aortic dissection patients was significantly higher than aortic aneurysm patients and healthy group (P < 0.001). According to the results of multivariate logistic regression analysis, NLR and FIB were independent risk factors of aortic dissection, and the odds ratio (OR) and 95% confidence interval (CI) value of NLR and FIB were 1.499(1.126-1.738) and 1.914(1.475-2.485), respectively. The area under the curve (AUC) was 0.836 of NLR and 0.756 of FIB. NLR and FIB showed high specificity, 89% and 83% respectively. This is the first study provided information on the diagnosis performance of NLR and FIB in TBAD patients. NLR and FIB showed high specificity, which may be a valuable tool for the diagnosis of TBAD.
Secondary Prevention Post Stroke in Primary Care in an Asian Setting: A Retrospective Cohort Study
Authors: Bansal Vivek , Lee Eng Sing , Smith Helen
Published: December 2020

Background: Stroke is one of the top contributors to burden of disability-adjusted life-years worldwide. Family physicians have key role in optimal secondary prevention post-stroke helping patients make appropriate lifestyle changes and take medication in accordance with the recommended clinical practice guidelines.Methods: Our aim was to characterize the profile of patients who were being managed in primary care setting for secondary prevention of stroke. Our specific objectives were: (i) to examine the level of overall and individual risk factors control after an index-stroke event in patients visiting the primary care setting and (ii) to describe the factors associated with the achievement of overall risk factors control in post-stroke patients.Study Design: Retrospective cohort study.We conducted a study looking retrospectively at records from our electronic chronic disease database. Our study included post-stroke patients who visited public primary care setting in Singapore between 1st January 2012 to 31st December 2016. Based on AHA Stroke guidelines, we operationalized our outcome of secondary prevention post-stroke as overall control, which comprised of patients having blood pressure, lipids, and glucose reading (for those who had diabetes) all well-controlled. We conducted descriptive analysis and performed multivariable logistic analysis to determine factors associated with overall control.Results: There were 24,240 patients in our study. Overall control was better in post-stroke patients without diabetes (49.2%) as compared to those with diabetes (28.1%).Among post-stroke patients without diabetes, factors significantly associated with overall control were sex [OR: 1.23, 95% CI: 1.10, 1.39], ethnicity [OR: 0.72, 95% CI: 0.58, 0.90], BMI [OR: 0.72, 95% CI: 0.62, 0.84) and atrial fibrillation [OR: 1.47, 95% CI: 1.21, 1.78].Among post-stroke patients with diabetes, factors significantly associated with overall control were sex [OR: 1.28, 95% CI: 1.12, 1.46], ethnicity, BMI, atrial fibrillation[OR: 1.24; 95% CI: 1.02, 1.51], chronic kidney disease and smoking status.Conclusion: We reported a sub-optimal level of overall control. Among post-stroke patients, those with diabetes had a higher proportion of sub-optimal control as compared to those without diabetes. Irrespective of diabetic status, being female, having high BMI, and of Malay ethnicity were associated with poor overall control compared to Chinese.
Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia
Authors: Liu Can , Lee Chia-Ying , Asher Greg , Cao Liqin , Terakoshi Yuka , Cao Peng , Kobayakawa Reiko , Kobayakawa Ko , Sakurai Katsuyasu , Liu Qinghua
Published: December 2020

Mammals normally maintain a constant body temperature irrespective of their environmental temperature. However, emotions such as fear can trigger acute changes in body temperature accompanying defensive behaviors to enhance survival in life-threatening conditions. The neural mechanisms of fear-associated thermoregulation remain unclear. Here, we find that innate fear odor 2-methyl-2-thiazoline (2MT) evokes rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1, the chemosensor for 2MT. Following 2MT exposure, wild-type but not Trpa1-/- mice exhibit high c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel), and nucleus of the solitary tract (NTS). Tetanus toxin light chain (TeLC)-mediated inactivation of NTS-projecting PSTh neurons blunts 2MT-evoked hypothermia and abrogated tail temperature increase. Optogenetic activation of the PSTh-rostral NTS (RNTS) pathway specifically induces hypothermia and elevated tail temperature. Moreover, selective opto-stimulation of 2MT-activated PSTh-projecting PBel neurons, by capturing activated neuronal ensembles (CANE), induces hypothermia and elevated tail temperature. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel and PSTh or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail temperature increment. Taken together, these results uncover a novel PBel-PSTh-NTS neural pathway that underlies 2MT-evoked innate fear-associated hypothermia and tail vasodilation.
Bacterial Diversity and Predicted Enzymatic Function in a Multipurpose Surface Water System – From Wastewater Effluent Discharges to Drinking Water Production
Authors: Tiwari Ananda , Hokajärvi Anna-Maria , Domingo Jorge Santo , Elk Michael , Jayaprakash Balamuralikrishna , Ryu Hodon , Siponen Sallamaari , Vepsäläinen Asko , Kauppinen Ari , Puurunen Osmo , Artimo Aki , Perkola Noora , Huttula Timo , Miettinen Ilkka T. , Pitkänen Tarja
Published: December 2020

BackgroundRivers and lakes are used for multiple purposes such as for drinking water (DW) production, recreation, and as recipients of wastewaters from various sources. The understanding of the seasonal dynamics of bacterial communities on such waters may help for protecting human health and the environment. This study analyzed 16S rRNA-gene high-throughput sequence data for determining the spatial and seasonal dynamics of bacterial communities, their predicted functions, and potential health-related bacterial (PHRB) reads within the Kokemäenjoki River watershed in south-west Finland. Water samples were collected from various sampling points of the watershed, from its major pollution sources (sewage influent and effluent, industrial effluent, mine runoff) and different stages of the DW treatment process (pre-treatment, groundwater observation well, DW production well) by using the river water as raw water with artificial groundwater recharge (AGR). ResultsThe beta-diversity analysis revealed that bacterial communities were highly varied among sample groups (R = 0.92, p < 0.001, ANOSIM). The species richness and evenness indices were highest in surface water (Chao1; 920±10) among sample groups and gradually decreased along the DW treatment process (DW production well; Chao1: 320±20). Although the phylum Proteobacteria was omnipresent, its relative abundance was higher in sewage and industrial effluents (66-80%) than in surface water (55%). Phyla Firmicutes and Fusobacteria were only detected in sewage samples. Actinobacteria was more abundant in the surface water (≥13%) than in other groups (≤3%). Acidobacteria was more abundant in the DW treatment process (≥13%) than in others (≤2%). In total, the share of PHRB reads was higher in sewage and surface water than in the DW treatment samples. In surface water, the recorded richness indices and the share of PHRB reads were lowest during summer than other seasons. When all sample groups were considered together, the predicted enzymatic function was lowest during spring than other seasons. Conclusions The significantly different bacterial communities at the pollution sources as compared to surface water highlight the importance of effective wastewater treatment for protecting surface water quality. The low bacterial diversity and absence of PHRB reads in the DW samples indicate AGR is able to produce biologically stable and microbiologically safe drinking water.
L-Fuzzy Concept Analysis as a Decision-Making Tool in the Development of Bio-Based Materials
Authors: Leceta Itsaso , Alcalde Cristina , Urdanpilleta Marta , Guerrero Pedro , Caba Koro de la , Burusco Ana
Published: December 2020

The use of L-fuzzy concept analysis for the determination of the formulations of gelatin-based films that fulfillspecifc functional properties is reported. The requirements of water contact angle (CA), water vapourtransmission rate (WVTR), L* and b* colour values, tensile strength (TS), elongation at break (EB) and glossvalues were specified for both fatty food packaging and wound healing applications. Once the requiredformulations were estimated by L-fuzzy concepts, the experimental results showed a high accordance with thepredicted values of the nal properties, as well as with the requirements. The errors were lower than 20% in allcases, except in colour (for food packaging) and gloss and elongation at break (for wound healing), in whichthe nal properties were even better that the estimations. This analysis allowed nding the requiredformulations in a highly cost-effective way.
Identification of Prognosis-related RBPs to Reveal the Role of RNA Binding Proteins in the Progression and Prognosis of Wilms’ Tumor
Authors: Qi Xuejiao , Dong Yihui , Lin Xiaojie , Chen Jingqiu
Published: December 2020

BackgroundRNA-binding proteins (RBPs), the ubiquitous regulators that can bind to RNA, mediate the function of RNA in the process of its maturation, translation, transport and localization [1, 2]. Despite the various key functions of RBPs in posttranscriptional events, the mechanism of their influence on Wilms’ tumor has not been well elucidated. So we construct the research to identify several RBPs related to Wilmes’ tumor progression and prognosis, for the better understanding of RBPs’ role in the occurrence and development of Wilmes’ tumor, and to provide effective reference targets for new drug development.MethodsA total of 127 samples of different clinical characteristics including gender, race and stage were selected from TCGA to carry out our study. After the gene functional enrichment pathways, univariate Cox regression analysis and lasso regression analysis were performed to test the prognostic effect of the differentially-expressed genes and establish the prognostic index . Further Cox regression analyses were utilized to identify the independence of our model and to analyze the relationship between our model and clinical parameters. What’s more, gene set enrichment analysis (GSEA) was also performed to elucidate the biological characteristics of genes involved in Wilms’ tumor. P< 0.05 was considered to be statistically significant.Results26 RBPs were statistically correlated with Wilms’ tumor. After the construction of a prognostic index , patients were divided into high-and low-risk scores group. Kaplan-Meier (K-M) analyses showed that patients with high risk scores possessed poorer survival probability than patients with low risk scores in both training group and test group. Furthermore, multivariate Cox regression analysis explored the relationship between our prognostic model and clinical parameters and confirmed that our model was an independent predicted factor for Wilms’ tumor. ConclusionOur study clarifies the application of RBPs in the prognosis of Wilms’ tumor. We are confident that our risk scoring model can provide ideas for the development of new targets for broad-spectrum anticancer drugs and has great potential in clinical practice.Trial registrationretrospectively registered
Genetic Polymorphisms of Plasmodium Falciparum Isolates From Melka-werer, North East Ethiopia Based on the Merozoite Surface Protein-2 (msp-2) Gene as a Molecular Marker
Authors: Ali Hussein Mohammed , Assefa Ashenafi , Chernet Melkie , Wulataw Yonas , Commons Robert J
Published: December 2020

Background: The characterization of parasite populations circulating in malaria endemic areas is necessary to evaluate the success of ongoing interventions and malaria control strategies. This study was designed to investigate the genetic diversity of Plasmodium falciparum isolates from the semi-arid area in North East Ethiopia, using the highly polymorphic merozoite surface protein-2 (msp2) gene as a molecular marker. Methods: Dried blood spot isolates were collected from patients with Plasmodium falciparum infection between September 2014 and January 2015 from Melka-Werer, North East Ethiopia. Parasite DNA was extracted and genotyped using allele-specific nested polymerase chain reactions for msp2. Results: 52 isolates were collected with msp2 identified in 41 (78.8%) isolates. Allele typing of the msp2 gene detected the 3D7/IC allelic family in 54% and FC27 allelic family in 46%. A total of 14 different msp2 genotypes were detected including 6 belonging to the 3D7/IC family and 8 to the FC27 family. Forty percent of isolates had multiple genotypes and the overall mean multiplicity of infections (MOI) was 1.2 (95%CI 0.96-1.42). The heterozygosity index was 0.50 for the msp2 locus. There was no difference in MOI between age groups. A negative correlation between parasite density and multiplicity of infection was found (p = 0.02).Conclusion: P. falciparum isolates from the semi-arid area of North East Ethiopia are mainly monoclonal with low MOI and limited genetic diversity in the study population.