bluuebunny/crossref_metadata_2025 huggingface dataset:
New Developments in Understanding Harper-Dorn, Five- power Law Creep and Power-law Breakdown
Authors: kassner michael
Published: September 2020

This paper discusses recent developments in creep, over a wide range of temperature, that mqy change our understanding of creep. The five-power law creep exponent (3.5 to 7) has never been explained in fundamental terms. The best the scientific community has done is to develop a natural three power-law creep equation that falls short of rationalizing the higher stress exponents that are typically five. This inability has persisted for many decades. Computational work examining the stress-dependence of the climb rate of edge dislocations we may rationalize the phenomenological creep equations. Harper-Dorn creep, “discovered” over 60 years ago has been immersed in controversy. Some investigators have insisted that a stress exponent of one is reasonable. Others believe that the observation of a stress exponent of one is a consequence of dislocation network frustration. Others believe the stress exponent is artificial due to the inclusion of restoration mechanisms such as dynamic recrystallization or grain growth that is not of any consequence in the five power-law regime. Also, the experiments in the Harper-Dorn regime, which accumulate strain very slowly (sometimes over a year) may not have attained a true steady state. New theories suggest that absence or presence of Harper-Dorn may be a consequence of the initial dislocation density. Novel experimental work suggests that power-law breakdown may be a consequence of a supersaturation of vacancies which increase self-diffusion.
Are Eastern and Western Monarch Butterflies Distinct Populations? A Review of Evidence for Ecological, Phenotypic, and Genetic Differentiation and Implications for Conservation
Authors: Freedman Micah , De Roode Jacobus , Forister Matthew , Kronforst Marcus , Pierce Amanda , Schultz Cheryl , Taylor Orley , Crone Elizabeth
Published: September 2020

Monarch butterflies are a species of conservation priority due to declining overwintering populations in both eastern and western North America. Declines in western overwintering monarchs—more than 99% since monitoring began—are especially acute. However, the degree to which the western monarch is a distinct biological entity is uncertain. In this review, we focus on phenotypic and genetic differentiation between eastern and western monarchs, with the goal of informing researchers and policy-makers who are interested in monarch conservation. Eastern and western monarchs occupy distinct environments and show some evidence for phenotypic differentiation—particularly for migration-associated traits—though population genetic and genomic studies suggest that they are genetically indistinguishable from one another. We suggest future studies that could improve our understanding of differences between eastern and western monarchs. We also discuss the concept of adaptive capacity in eastern and western monarchs as well as non-migratory populations outside of the monarch’s primary North American range.
Effects of Gender and Obesity on Daytime Sleepiness in Obstructive Sleep Apnoea Patients
Authors: Sah Sushil Kumar , Tan Hua Zhang , Yu Sun , Feng Jin , Zhang Yong Hong , Shah Anil Kumar
Published: September 2020

Objective: Identify factors associated with excessive day time sleepiness (EDS) in individuals with obstructive sleep apnea (OSA), and analyze the effects that obesity and gender have on excessive daytime sleepiness in such individuals. Methods: A total of 160 people were selected for this study. All the people have completed a clinical evaluation, and whose apnea-hypopnea index (AHI) > 10 events/hour of sleep on polysomnography were included in the study from the Department of otolaryngology. Results: The Mean age was 43.87±11.34 years, mean EDS score was 14.09± 4.91, and mean AHI was 43.88±20.66 events/hour of sleep. Male presented lower mean age, higher EDS scores, and more time in apnoea, whereas females presented with higher mean age, lower EDS scores, and less time in sleep apnea. The EDS score showed best correlation with duration of apnoea (r = 0.448; p < 0.01), peripheral oxygen saturation (SpO2; r = -0.458; p < 0.01) and AHI (r = 0.484; p < 0.01). The mean body mass index (BMI) was 27.41±3.86 kg/m2. Normal, Overweight, obese, and morbidly obese were observed in 20%, 61%, 18%, and 0.6% of cases, respectively. Severity of the disease best correlated with BMI (r = 0.421; p < 0.01). Conclusions: OSA is predominant in males (M/F 5:1), and obese population. Females diagnosed with OSA have higher mean age. However, EDS scores and time spent in sleep apnoea is lower in females. Higher BMI is associated with EDS, irrespective of gender.
Suitable Habitat Modeling of Prehistoric Antelope-like Bovid Duboisia Santeng in Java Island in The Early Pleistocene
Authors: Wibowo Andri
Published: September 2020

The migration routes have facilitated the distribution of mammals from south east Asian mainland to the Sundaland including Java island in the early Pleistocene. One of species that has migrated through that route is antelope-like bovid Duboisia santeng. In the present study, the potential distribution areas and the suitable habitats of D. santeng have been projected and modeled. The modeled habitat was a forest river basin sizing 302.91 Ha in the central of Java island. The model has classified and reconstructed the habitat suitability ranged from low to high back to Pleistocene. The surrounding areas of forest were mostly classified as medium and low related to the limited tree covers. Most suitable habitats were identified in the middle of forest river basin where the tree covers were presented
Land Use Differences Across Socioeconomic Boundaries and Implications for Air Quality
Authors: Mendoza Daniel L.
Published: September 2020

Multiple social and environmental justice concerns are linked to urban form such as the distribution of socioeconomic class populations, healthcare spending, air pollution exposure, and human mobility. This study used 1m resolved LIDAR data to characterize land use in Salt Lake County, Utah and associate it with sociodemographic and air quality data at the census block group and zip code levels. We found that increasing tree cover was associated with higher per capita income and lower minority populations while increasing built cover was linked to lower per capita income and higher minority populations. Air quality showed less strong correlations, however, decreased non irrigated cover, increased built cover, and higher amounts of households living under poverty was related to higher long-term PM2.5 exposure. Several policy efforts have been undertaken to improve air quality and reduce negative health outcomes in Utah which are being informed by regulatory and research grade air quality sensors.
Foodborne Transmission of Sars-Cov-2 Is More Evident Than It Has Been Before
Authors: Aboubakr Hamada , Goyal Sagar
Published: September 2020

Background:Although highly strict social distancing and viral spread protection guidelines are in force, the reported numbers of COVID-19 cases across the world are still increasing. This indicates that we are still unable to completely understand the transmission routes of SARS-CoV-2. One of the possible routes that can play a significant role is the fecal-oral transmission since SARS-CoV-2 can replicate in the intestines as demonstrated by isolation of infectious virus from fecal samples of COVID-19 cases. Scope and approach:In this review, we compare the characteristics of SARS-CoV-2 with the distinctive characteristics of enteric foodborne viruses. We also discuss and respond to the arguments given in some reports that downplay the importance of foodborne transmission route of SARS-CoV-2. Key findings and conclusions:Enteric viruses such as human noroviruses (HuNoVs) and hepatitis A virus (HAV) are known to transmit through foods such as fresh produce and berries, leading to frequent multistate foodborne disease outbreaks all over the world. SARS-CoV-2 was found to share four distinctive characteristics of foodborne viruses that allow them to transmit through foods. This similarity in characteristics, recent report of detecting SARS-CoV-2 particles from frozen food packages in China, and recent suspected foodborne COVID-19 case in New Zealand, indicate that foodborne transmission of SARS-CoV-2 is more evident than previously thought possible. To support or deny this route of transmission, urgent research needs to be undertaken to answer two primary questions and many secondary ones as described in this review.
Evaluation of the Properties of an Electro-Sinter-Forged Bearing Steel
Authors: Bidulský Róbert , Gobber Federico Simone , Fais Alessandro , Bidulská Jana , Actis Grande Marco
Published: September 2020

In this study one of the most innovative sintering techniques up to date was evaluated: Electro-Sinter-Forging (ESF). Despite it has been proved to be effective in densifying several different metallic materials and composites, bearing steels such as 100Cr6 have never been processed so far. Pre-alloyed Astaloy CrM powders have been ad-mixed with either graphite or graphene and then processed by ESF to produce a 100Cr6 equivalent composition. Porosity has been evaluated by optical microscopy and compared to that one of 100Cr6 commercial samples. Mechanical properties such as hardness and transverse rupture strength were tested on samples produced by employing different process parameters and then submitted to different treatments (machining, heat treatment). The experimental characterization highlighted that porosity is the factor mostly affecting mechanical resistance of the samples, correlating linearly to the transverse rupture strength. Hardness on the other side does not correlate to the mechanical resistance because process related cracking has a higher effect on the final properties. Promising results were obtained that give room to the sinterability by ESF of materials difficult to sinter by conventional press and sinter techniques.
Three-Dimensional Modeling and Fluid Flow Simulation for the Quantitative Description of Permeability Anisotropy in Tidal Flat Carbonate
Authors: Eltom Hassan A. , Saraih Nabil A. , Esteva Oliver G. , Kusuma Lundi , Ahmed Saleh , Yassin Mohamed A.
Published: September 2020

Three-dimensional (3D) facies and petrophysical models were generated from previously published data of carbonate strata in the Dam Formation (eastern Saudi Arabia) to quantitatively investigate, describe, understand, model, and predict the permeability anisotropy of tidal flat carbonate within a sequence stratigraphic framework. The resulting 3D models were used to conduct fluid flow simulations to demonstrate how permeability anisotropy influences the production of hydrocarbons and ultimately affects decisions concerning future drilling in the exploration and development of carbonate reservoirs that have tidal flat strata. The constructed 3D facies model consists of four lithofacies associations, two of which were grain-dominated associations and two of which were mud-dominated associations. These lithofacies associations varied spatially in four reservoir zones (zones 1 to 4), which represent two fourth-order sequences in the uppermost part of the Dam Formation. Zones 1 and 3 consist of transgressive parasequences, and zones 2 and 4 consist of the regressive parasequences of these sequences. The 3D porosity and permeability models have a coherent match with the distribution of the lithofacies and the stratigraphic framework of the Dam Formation. The results suggested that the permeability anisotropy in zones 1 and 3 is controlled by the occurrence of the grain-dominated lithofacies associated with tidal flat channels. This lithofacies association overlies the sequence boundaries of sequences 1 and 3, forms reservoir bodies with relatively high permeability values, and is elongated perpendicular to the shoreline of the depositional environments. In contrast, permeability anisotropy in zones 2 and 4 is thought to be controlled by the occurrence of the grain-dominated lithofacies associated with the oolitic shoal. This lithofacies association overlies the maximum flooding surface of sequences 2 and 4, forms reservoir bodies with relatively high permeability values, and is elongated parallel to the shoreline of the depositional environments. Fluid flow simulation results suggested that the trend in hydrocarbon production from the constructed 3D models depends on permeability anisotropy in each reservoir zone. Thus, recognizing trends in permeability anisotropy, which might be predicted using sequences stratigraphy, could help to identify potential areas for future drilling.
Application of Stochastic Analysis in Project Economics
Authors: Mian M. A.
Published: September 2020

The oil and gas industry has come a long way by shifting from the deterministic methods of economic evaluations to probabilistic/stochastic methods. The time is right as the uncertainties keep on increasing and more sophisticated methods/calculations are required for decision-making. The industry is under pressure to maintain its key performance indicator of reserves-to-annual production ratio. New discoveries are becoming scarce, and the size of the discoveries keep on going down. The economics of many discoveries are marginal, and they will require prudent evaluation, planning, and synergies for viable development.

The industry has done a good job in advancing technology, but it is behind in commercial aspects of the business. Due to this lack of expertise, the industry adopts methods and calculations presented by financial/statistical/stock analysts. Although these methods and calculations may suit other industries, they are not directly applicable to the oil and gas industry. Using these methods, without adjusting them to the oil and gas industry’s environment could be damaging to decision-making. Use of methods that are not directly suited to our industry becomes merely an academic exercise and does not add value. In fact, they may have negative impacts on the perceived profitability and result in suboptimal investment decisions and portfolios.

This article shows one such method that is sometimes used by strategists, economists, and planners. The findings in this article will definitely raise concerns and make us think twice about adopting methods from other disciplines without deep scrutiny. The article provides recommendations to alleviate shortcomings in some of the methods applied.
Benchmarking of Pulsed Field Gradient Nuclear Magnetic Resonance as a Demulsifier Selection Tool with Arabian Light Crude Oils
Authors: Marques Debora Salomon , White Ramsey , Al-Khabaz Sajjad , Al-Talaq Mustafa , Al-Buainain Jabr
Published: September 2020

The use of chemical demulsifiers in the treatment of crude oil emulsions is an essential step in processing facilities worldwide. Each production facility requires specific demulsifier reformulations as the crude characteristics change. The assessment of candidate demulsifiers before online field trials is currently done with bottle tests. Such tests are manual, based on water dropout visually measured by operators. The development of a method that can automatically determine the speed and amount of water dropout without the laborious need to manually record water separation would significantly decrease human error. Pulsed field gradient nuclear magnetic resonance (PFG-NMR) is used as a classification tool to qualitatively rank the efficiency of different demulsifiers in breaking Arabian Light emulsions. This imaging method can evaluate demulsifier action based on the emulsion characteristics; for example, rate of sedimentation and coalescence and formation of a dense packed zone (rag layer). The results are validated against field trials performed in gas-oil separation plants (GOSPs) at two Saudi Arabian facilities. There was good agreement between the PFG-NMR method and field trials. The results were found to correspond to the water dropout in the first stage of crude oil treatment in processing plants (production traps).
Does socioeconomic status have any influence on success at the national ranking exam?, a prospective survey
Authors: Bouchghoul Hanane , Teboul Jean-Louis , Senat Marie-Victoire , Vigoureux Solene
Published: September 2020

Background: The weight of social inequalities during education is a reality. Students of lower socioeconomic status may have less chance of success in higher education, particularly in medical studies. However, the role of students' socioeconomic factors, such as their parents' profession, in their success in the national ranking exam (NRE) has not been studied.Our aim was to investigate the association between socioeconomic factors and success in the national ranking exam among sixth year medical students at the Paris-Sud Faculty of Medicine.Methods: This was a prospective survey of all sixth-year medical students at the Paris-Sud Faculty of Medicine, using a questionnaire on socioeconomic factors, which were compared according to NRE ranking.Results: Of 172 sixth year medical students, 110 completed the questionnaire. Their ranking ranged from 20 to 7695, with a median of 2815 (interquartile range: 1029-4581). The factors associated with the NRE ranking were a high school diploma (baccalauréat) A or B grade, success at the first attempt in the first-year medical examination, and enrollment in the NRE preparatory lectures during the sixth year of medical training (linear regression, p<0.001). The educational status and socio-professional category of the parents were not associated with the NRE ranking (linear regression, p=0.92).Conclusion: At the Paris-Sud Faculty of Medicine, there was no association between parental socioeconomic status and sixth year students' success in the NRE.
A New Efficient Method to Detect Genetic Interactions for Lung Cancer GWAS
Authors: Luyapan Jennifer , Ji Xuemei , Li Siting , Xiao Xiangjun , Zhu Dakai , Duell Eric J. , Christiani David C. , Schabath Matthew B. , Arnold Susanne M. , Zienolddiny Shanbeh , Brunnström Hans , Melander Olle , Thornquist Mark D. , MacKenzie Todd A. , Amos Christopher I. , Gui Jiang
Published: September 2020

Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset.Methods: To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data.Results: Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR = 1.24, P = 3.15 x 10-15), as the top marker to predict age of lung cancer onset.Conclusions: From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.
Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions
Authors: Akahane Toshiaki , Kanomata Naoki , Harada Oi , Yamashita Tetsumasa , Kurebayashi Junichi , Tanimoto Akihide , Moriya Takuya
Published: September 2020

Background: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.Methods: Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but onepatient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.Conclusions: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.
Predicting and Clustering Plant CLE Genes with a New Method Developed Specifically for Short Amino Acid Sequences
Authors: Zhang Zhe , Liu Lei , Kucukoglu Melis , Tian Dongdong , Larkin Robert M. , Shi Xueping , Zheng Bo
Published: September 2020

Background: The CLV3/ESR-RELATED (CLE) gene family encodes small secreted peptides (SSPs) and plays vital roles in plant growth and development by promoting cell-to-cell communication. The prediction and classification of CLE genes is challenging because of their low sequence similarity. Results: We developed a machine learning-aided method for predicting CLE genes by using a CLE motif-specific residual score matrix and a novel clustering method based on the Euclidean distance of 12 amino acid residues from the CLE motif in a site-weight dependent manner. In total, 2156 CLE candidates—including 627 novel candidates—were predicted from 69 plant species. The results from our CLE motif-based clustering are consistent with previous reports using the entire pre-propeptide. Characterization of CLE candidates provided systematic statistics on protein lengths, signal peptides, relative motif positions, amino acid compositions of different parts of the CLE precursor proteins, and decisive factors of CLE prediction. The approach taken here provides information on the evolution of the CLE gene family and provides evidence that the CLE and IDA/IDL genes share a common ancestor. Conclusions: Our new approach is applicable to SSPs or other proteins with short conserved domains and hence, provides a useful tool for gene prediction, classification and evolutionary analysis.
Changes in 3-month mineral and bone disorder patterns were associated with all-cause mortality in prevalent hemodialysis patients with secondary hyperparathyroidism
Authors: Kato Chihiro , Fujii Naohiko , Miyakoshi Chisato , Asada Shinji , Onishi Yoshihiro , Fukuma Shingo , Takanobu Nomura , Michihito Wada , Fukagawa Masafumi , Fukuhara Shunichi , Akizawa Tadao
Published: September 2020

Background. There is limited evidence on the association between short-term changes in mineral and bone disorder parameters and survival in maintenance hemodialysis patients.
Methods. We investigated the association between changing patterns of phosphorus, calcium and intact parathyroid hormone levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism. Each parameter was divided into three categories (low [L], middle [M] and high [H]), and the changing patterns between two consecutive visits at 3-month intervals were categorized into nine groups (e.g., L-L and M-H). The middle category was defined as 4.0-7.0 mg/dL for phosphorous, 8.5-9.5 mg/dL for calcium and 200-500 pg/mL for intact parathyroid hormone. Adjusted incidence rates and rate ratios were analyzed by weighted Poisson regression models accounting for time-dependent exposures.
Results. For phosphorus, shifts from low/high to middle category (L-M/H-M) were associated with a lower mortality compared with the L-L and H-H groups, whereas shifts from middle to low/high category (M-L/M-H) were associated with a higher mortality compared with the M-M group. For calcium, shifts from low/middle to high category (L-H/M-H) were associated with a higher mortality compared with the L-L and M-M groups, whereas shifts from high to middle category (H-M) were associated with a lower mortality compared with the H-H group. For intact parathyroid hormone, shifts from low to middle category (L-M) were associated with a lower mortality compared with the L-L group.
Conclusions. Changes in the 3-month patterns of phosphorus and calcium toward the middle category were associated with lower mortality. Our study also suggests the importance of avoiding hypercalcemia.
Profiles of autophagy-related genes in esophageal adenocarcinoma
Authors: Zhu Lei , Dong Lin , Feng Minghao , Yang Fugui , Jiang Wenhao , Huang Zhiyuan , Liu Fabing , Wang Lingwei , Wang Guangxue , Li Qinchuan
Published: September 2020

Background: Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. Methods: Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition， significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues. Results: Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR=0.321, P=0.046), DAPK1 (HR=0.636, P=0.025) and CAPN1 (HR=0.395, P=0.004) played protective roles in survival. Gender (HR=0.225, P=0.032), stage (HR=5.841, P=0.008) and risk score (HR=1.131, P＜0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P ＜0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P＜0.05). Conclusion: Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.
Weight gain in patients with severe atopic dermatitis treated with dupilumab: a cohort study
Authors: Johansson Emma Kristin , Ivert Lina Ulrika , Bradley Baltzar , Lundqvist Maria , Bradley Maria
Published: September 2020

Background Dupilumab, targeting the interleukin-4α receptor and inhibiting the action of interleukin-4 and interleukin-13, was recently approved for treatment of moderate to severe atopic dermatitis. There is limited data on long-term effects and safety among patients with severe atopic dermatitis treated with dupilumab. Weight gain was observed among patients treated with dupilumab in our clinic. The aim was to describe weight change in a cohort study of patients with severe atopic dermatitis treated with dupilumab from baseline to follow-up after 12 months, and to analyze if weight change was associated with effect of treatment, reported appetite, and/or disturbed night sleep due to itching.Methods All patients with atopic dermatitis receiving systemic treatment at the Unit of Dermatology, Karolinska University Hospital, have been registered and monitored consecutively since January 2017. This cohort constituted all patients who started treatment on dupilumab or methotrexate between 10 January 2017 and 30 June 2019 with at least 6 months of follow-up within the study period. The following variables were monitored at start of and during treatment: Eczema Severity Score Index, Patient-Oriented Eczema Measure, visual analogue scale for pruritus 10cm, Montgomery-Åsberg Depression Rating Scale, Dermatology Life Quality Index, and weight. Data analyses were performed using two-sample Wilcoxon-Mann-Whitney rank-sum test, or the Wilcoxon matched-pairs sign-rank test with a p-value <0.05 considered as statistically significant.Results Patients treated with dupilumab (n=12) gained weight (mean 6.1 kg, range [0.1–18.0], p=0.002) after one year on treatment. The majority of patients showed a good response to treatment with dupilumab (n=11); at follow-up at 6, 9, or 12 months, they reached EASI-90 (n=6), EASI-75 (n=4), or EASI-50 (n=1). There was no significant association between weight gain and treatment response, reported appetite, or disturbed night-sleep due to itch. Patients treated with methotrexate showed no significant weight change (n=8). Conclusions To our knowledge, this is the first report on a possible association between weight gain and dupilumab treatment; the extent of the association is yet to be seen, as is the mechanism behind this finding.
Nosocomial Tuberculosis Transmission from 2006 to 2018 in Beijing Chest Hospital, China
Authors: Xie Zhongyao , Zhou Ning , Chi Yuqing , Huang Guofang , Wang Jingping , Gao Hui , Xie Na , Ma Qianhui , Yang Nan , Nie Wenjuan , Sun Zhaogang , Chu Naihui
Published: September 2020

Introduction: Strong evidence is lacking to support effectiveness of currently implemented tuberculosis infection prevention control (TB-IPC) measures for preventing nosocomial tuberculosis (TB) transmission. This 13-year analysis is the longest follow-up investigation to date to identify risk factors underlying nosocomial TB transmission. Methods: We monitored all staff of Beijing Chest Hospital each year from 2006 to 2018. Age, gender, duration, department, education, income, respirator, ultraviolet, and ventilation were chosen as variables. Univariate cox regression, correlation analysis, and multivariate cox regression were analyzed sequentially.Results: Using multivariable cox regression analysis, variables of income, ultraviolet germicidal irradiation (UVGI), natural ventilation and mechanical ventilation conferred significant protective effects, with odds ratios (ORs) of 0.499, 0.058, 0.003, and 0.015, respectively (P<0.05). Medical N95 respirator conferred an excellent protective effect, with an associated TB infection rate of 0%. Notably, inadequately maintained mechanical ventilation systems were less protective than natural ventilation systems.Conclusions: UVGI, adequate ventilation, and use of medical N95 respirator may be risk factors of nosocomial TB transmission.
Schistosoma mansoni-related periportal fibrosis; can we use APRI and PSDR levels in the real-time selection of patients for targeted endoscopy in a resource-limited setting? A case-control study
Authors: Gunda Daniel W. , Mtui Elizabeth F. , Manyiri Paulina M. , Majinge David C. , Kilonzo Semvua B. , Mazigo Humphrey D. , Kidenya Benson R.
Published: September 2020

Background Schistosoma mansoni related hepatic fibrosis is usually associated with hemodynamic alteration with increased mortality due to bleeding varices. The diagnosis of varices before bleeding imposes a big challenge in resource-limited countries using endoscopy. Published evidence on the utility of non-invasive clinical tools in predicting the presence of varices among patients with S. mansoni related periportal fibrosis is still inadequate including Aspartate to platelet ratio index (APRI) and Platelet to splenic diameter ratio (PSDR) levels. This study describes the determinants of portal varices and assesses the potential utility of the APRI and PSDR level in the discrimination of portal varices among patients with S. mansoni related periportal fibrosis (PPF). Methods A case-control study using cross-sectional data was done among patients with Schistosoma mansoni related periportal fibrosis at Bugando Medical Centre, in Mwanza Tanzania. Socio-demographic, laboratory, ultrasound, and upper digestive endoscopic information were collected for analysis using STATA 13. The prevalence of varices was calculated and its associated factors were determined by logistic regression. The sensitivity and specificity of independent factors were determined to assess their potential utility in discriminating the presence of portal varices in patients with PPF.Results In total, 250 patients were included in this study, 109 (43.6%; 95%CI: 37.3-.49.9) of them had varices. On multivariate analysis the odds of having varices were independently increased among patients with higher APRI levels than 1.51, (AOR: 5.8; 95%CI: 3.1-11.1; p<0.001) and PSDR levels that were lower than 5700 (AOR: 5.9; 95%CI: 3.2-11.2; p<0.001). Both APRI and PSDR levels had significantly high sensitivity and specificity in predicting the presence of esophageal varices. However, the combined values of APRI and PSDR had higher specificity than any of the two markersConclusions This study indicates that varices are a common encounter among patients with S. mansoni related periportal fibrosis and it is independently associated with higher APRI and lower PSDR levels suggesting that these tools are potential discriminators of varices in this subgroup of patients. The reproducibility of these results should further be assessed longitudinally as potential non-invasive tools in selecting patients at high risk of having esophageal varices who could benefit from the targeted endoscopic intervention in a resource-limited setting like ours.
The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm
Authors: Miyamoto Kazuya , Matsumoto Kazuyuki , Kato Hironari , Yoshida Ryuichi , Umeda Yuzo , Inoue Hirohumi , Tanaka Takehiro , Matsumi Akihiro , Saragai Yosuke , Fujii Yuki , Yamazaki Tatsuhiro , Uchida Daisuke , Tomoda Takeshi , Horiguchi Shigeru , Yagi Takahito , Okada Hiroyuki
Published: September 2020

Background: Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. Methods: We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017.Results: Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). Conclusions: LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.
Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
Authors: Marçal Pedro Henrique Ferreira , Gama Rafael Silva , Pereira Lorena Bruna de Oliveira , Filho Olindo Assis Martins , Pinheiro Roberta Olmo , Sarno Euzenir Nunes , Moraes Milton Ozório , Fraga Lucia Alves de Oliveira
Published: September 2020

Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes: paucibacillary (PB) and multibacillary (MB), closely related to the host immune responses. In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts. Methods: The main goal of the present study was to characterize the global cytokine signatures of CD4+ and CD8+ T-cells from leprosy patients with distinct clinical forms and their respective household contacts (HHC) upon in vitro antigen-specific stimuli. Short-term culture of peripheral blood mononuclear cells was done. After incubation, cells were harvested and prepared for surface and intracytoplasmic cytokine staining Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets, with increased frequency of IFN-g+ T-cell subsets along with IL-10+ and IL-4+ from CD4+ T-cells. Moreover, L(PB) displayed a polyfunctional profile characterized by enhanced percentage of IFN-g+, IL-10+ and IL-4+ produced by most T-cell subsets, as compared to L(MB) that presented a more restricted cytokine functional profile mediated by IL-10+ and IL-4+ T-cells with minor contribution of IFN-g produced by CD4+ T-cells. Noteworthy was that HHC(MB) exhibited enhanced frequency of IFN-g+ T-cells, contrasting with HHC(PB) that presented a cytokine profile limited to IL-10 and IL-4. Conclusions: Together, our findings provide additional immunological features associated with leprosy and household contacts. These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.
The Trends and Efficacy of Operation in the Treatment of Hepatocellular Carcinoma
Authors: Chen Lei , Chen Shi , Sun Tao , Yang Fan , Zheng Chuansheng
Published: September 2020

BackgroundOperation for the treatment of hepatocellular carcinoma (HCC) is limited. Recently, the possibility was advanced that operation (including surgery, transplantation, and ablation et, al) could be applied in HCC patients more widely. To address this issue, the trend in the use of operation and surgery for the treatment of HCC with time was analyzed. Additionally, whether patients gain a better survival benefit from surgery than other treatments was also evaluated.MethodsData from SEER registries were used to analyze the trends in the use operation and surgery for HCC and the survival benefits of these procedures. The study included patients between the ages of 35 and 84 years diagnosed as HCC between 2004 and 2015 (n=64019). Propensity score matching (PSM) analysis was used to reduce selection bias.Results From 2004 to 2015, the rate of operation for HCC decreased in the localized group (P<0.001), the regional and distant group (P<0.001). Surgery rate in the localized, regional, and distant group also declined (P=0.016, P=0.009, and P=0.018, respectively). Non-operation rate increased in the localized, regional, and distant group (all P<0.001). The median overall survival (mOS) of patients in the localized, regional group who underwent surgery was longer than that of patients with non-surgery operation and non-operation. Similar survival results were obtained in the analysis of patients with single tumor larger than 5 cm and 2-3 tumors larger than 3 cm. ConclusionAlthough surgery rate declined from 2004 to 2015 in all HCC patients, it might be used more widely in patients with localized and regional tumors. And the treatment of surgery in patients with single tumor larger than 5 cm or patients with 2-3 tumors larger than 3 cm was worth trying.
Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women
Authors: Lee Siew-Siew , Ling King-Hwa , Tusimin Maiza , Subramaniam Raman , Rahim Kartini Farah , Loh Su-Peng
Published: September 2020

Background: Vitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women.Method: Information on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using a Ultra-High-Performance Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique.Results: Results showed that 50.2% of pregnant women were vitamin D deficient (25OHD <30 nmol/L). VDD (25OHD <30 nmol/L) was significantly associated with age, veiled clothing, maternal vitamin D intakes, from both food and supplements, and GC rs7041(and GC diplotypes). In contrast to previous studies that reported for non-pregnant population, significant positive association was found between CC genotype for SNP GC rs7041, GC 1s-1s and GC If-2 with risk of VDD (25OHD <30 nmol/L). Conclusions: The high prevalence of maternal VDD found in this study suggests the need for urgent development and implementation of vitamin D supplementation or fortification strategies to reduce VDD among pregnant women. The discrepancy in the association between GC rs7041 gene polymorphism and VDD reflects the variation in the factors associated with VDD in pregnancy compared to non-pregnant state
Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril
Authors: Zhang Keyu , Wang Xiaoyang , Wei Shuya , Wang Chunmei , Wang Mi , Liu Yingchun , Zhang Lifang , Xue Feiqun , Tang Shusheng
Published: September 2020

Background: Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. To support the safety assessment of the new potent anticoccidial agent, the subchronic toxicity of ethanamizuril was studied in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days.Results: Ethanamizuril was well tolerated at low and middle dosages and there were no ethanamizuril related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. The ethanamizuril related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both sexes. However, the characteristic toxicities of ethanamizuril in kidneys are recoverable in convalescence dogs of 300 mg/kg/day group. Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.
Uncovering fungal community composition in natural habitat of Ophiocordyceps sinensis using high-throughput sequencing and culture-dependent approaches
Authors: Zhang Chuanbo , Ren Chao-Hui , Wang Yan-Li , Wang Qi-Qi , Wang Yun-Sheng , Weng Qing-Bei
Published: September 2020

Background: The fungal communities inhabiting natural Ophiocordyceps sinensis play critical ecological roles in alpine meadow ecosystem, contribute to infect host insect, influence the occurrence of O. sinensis, and are repertoire of potential novel metabolites discovery. However, a comprehensive understanding of fungal communities of O. sinensis remain elusive. Therefore, the present study aimed to unravel fungal communities of natural O. sinensis using combination of high-throughput sequencing and culture-dependent approaches. Results: A total of 280,519 high-quality sequences, belonging to 5 fungal phyla, 15 classes, 41 orders, 79 families, 112 genera, and 352 putative operational taxonomic units (OTUs) were obtained from natural O. sinensis using high-throughput sequencing. Among of which, 43 genera were identified in external mycelial cortices, Ophiocordyceps, Sebacinia, Archaeorhizomyces were predominant genera with the abundance of 95.86%, 1.14%, 0.85%, respectively. A total of 66 genera were identified from soil microhabitat, Inocybe, Archaeorhizomyces, unclassified Thelephoraceae, Tomentella, Thelephora, Sebacina, unclassified Ascomycota, unclassified Fungi were predominant genera with an average abundance of 53.32%, 8.69%, 8.12%, 8.12%, 7.21%, 4.6%, 3.08% and 3.05%, respectively. The fungal communities in external mycelial cortices were significantly distinct from the soil microhabitat. Meanwhile, seven types of culture media were used to isolate culturable fungi at 16°C, resulted in 77 fungal strains isolated by rDNA ITS sequence analysis, belonging to 33 genera, including Ophiocordyceps, Trichoderma, Cytospora, Truncatella, Dactylonectria, Isaria, Cephalosporium, Fusarium, Cosmospora and Paecilomyces, etc.. Among all culturable fungi, Mortierella and Trichoderma were predominant genera. Conclusions: The significantly differences and overlap in fungal community structure between two approaches highlight that the integration of high-throughput sequencing and culture-dependent approaches would generate more information. Our result reveal a comprehensive understanding of fungal community structure of natural O. sinensis, provide new insight into O. sinensis associated fungi, and support that microbiota of natural O. sinensis is an untapped source for novel bioactive metabolites discovery.