bluuebunny/crossref_metadata_2025 huggingface dataset:
Gaps in Health Care Services for Refugees in Cologne, Germany – a Mixed Methods Analysis
Authors: Warmbein Angelika , Beiersmann Claudia , Eulgem Andrea , Demir Jaqueline , Neuhann Florian
Published: December 2020

Background: Ever since the peak in the number of refugees arriving in Germany in 2015, existing health care structures have faced major challenges. The city of Cologne developed ad-hoc new structures: a separate department for refugee medicine was set up. In the context of this study, the actual gaps in the health care of refugees in the city of Cologne were examined. The study provides lessons learnt for the health care of refugees.
Methods: The present study used an embedded mixed-methods approach using 20 semi-structured interviews and a database including 353 datasets with socio-demographic, health-related and resource-related information to cross-check the results of qualitative data.
Results: The qualitative data revealed gaps in providing health care to refugees. These gaps were found concerning approving health care services and medical aids by the municipality, communication and cooperation between the actors in care of refugees, undersupplies in mental health care and addictive disorders as well as improper housing situations for vulnerable groups of refugees with mental health issues, psychiatric disorders or elderly persons. Quantitative data confirmed the gap in approving health care services and medical aids, whilst no valid statement could be made about communication and cooperation. Undersupplies for mental health issues were confirmed, the gap for treatment of addictive disorders shows a divergence within the database. Improper housing situations for mentally ill persons were reflected, for elderly persons this did not appear in data.
Conclusion: Analysing the gaps can stimulate necessary changes to improve health services for refugees locally, while others are beyond the control of the local authority and require legislative and political action.
African Soil Properties and Nutrients Mapped at 30--m Spatial Resolution using Two-scale Ensemble Machine Learning
Authors: Hengl Tomislav , Miller Matthew , Krizan Josip , Shepherd Keith , Sila Andrew , Kilibarda Milan , Antonijevic Ognjen , Glusica Luka , Dobermann Achim , Haefele Stephan , McGrath Steve , Acquah Gifty , Collinson Jamie , Parente Leandro , Sheykhmousa Mohammadreza , Saito Kazuki , Johnson Jean-Martial , Chamberlin Jordan , Silatsa Francis , Yemefack Martin , MacMillan Robert , Wheeler Ichsani , Crouch Jonathan
Published: December 2020

Soil property and class maps for the continent of Africa were so far only available at very generalised scales, with many countries not mappedat all. Thanks to an increasing quantity and availability of soil samples collected at field point locations by various government and/or NGOfunded projects, it is now possible to produce detailed pan-African maps of soil nutrients, including micro-nutrients at fine spatial resolutions. Inthis paper we describe production of a 30 m resolution Soil Information System of the African continent using, to date, the most comprehensivecompilation of soil samples (N ≈ 150, 000) and Earth Observation data. We produced predictions for soil pH, organic carbon (C) and totalnitrogen (N), total carbon, Cation Exchange Capacity (eCEC), extractable — phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg),sulfur (S), sodium (Na), iron (Fe), zinc (Zn) — silt, clay and sand, stone content, bulk density and depth to bedrock, at three depths (0, 20 and50 cm) and using 2-scale 3D Ensemble Machine Learning framework implemented in the mlr (Machine Learning in R) package. As covariatelayers we used 250 m resolution (MODIS, PROBA-V and SM2RAIN products), and 30 m resolution (Sentinel-2, Landsat and DTM derivatives)images. Our 5–fold spatial Cross-Validation results showed varying accuracy levels ranging from the best performing soil pH (CCC=0.900) tomore poorly predictable extractable phosphorus (CCC=0.654) and sulphur (CCC=0.708) and depth to bedrock. Sentinel-2 bands SWIR (B11,B12), NIR (B09, B8A), Landsat SWIR bands, and vertical depth derived from 30 m resolution DTM, were the overall most important 30 mresolution covariates. Climatic data images — SM2RAIN, bioclimatic variables and MODIS Land Surface Temperature — however, remainedas the overall most important variables for predicting soil chemical variables at continental scale. The publicly available 30–m soil maps aresuitable for numerous applications, including soil and fertilizer policies and investments, agronomic advice to close yield gaps, environmentalprograms, or targeting of nutrition interventions.
Prevalence and Impact of Migraine among University Students in Bangladesh: Findings from a Cross-sectional Survey
Authors: Rafi Md. Abdur , Islam Md. Saiful , Hasan M. Tasdik , Hossain Md. Golam
Published: December 2020

Background: Migraine is one of the main causes of long-term morbidity, and it is one of the major contributors of all types of headaches in worldwide. Despite its disruptive effect, it is frequently underdiagnosed and undertreated in Bangladesh. The aim of the present study was to determine the prevalence of migraines and its impact on daily life of university students in Bangladesh.Methods: This cross-sectional study was conducted among 2,352 students of Rajshahi University and Jahangirnagar University during March 2020 through a self-administered online survey. ID MigraineTM scale and HIT-6 scale were used to screen migraine and its impact respectively. Frequency distribution, and Chi-square test, t-test along with multiple logistic regressions model were used to determine the prevalence and associated factors of migraine respectively. Results: The overall prevalence of migraine among the participants was 21.4%. The prevalence was higher among females (29%) than males (12%). A multivariable logistic regression model provided the following eight risk factors of migraine: (i) gender (p<0.01), (ii) family income (p<0.01), (iii) marital status (p<0.01), (iv) infrequent exercise (p<0.01), (v) family history of headache (p<0.01), (vi) high screen time (p<0.05), (vii) depressive symptoms (p<0.05) and (viii) anxiety disorder (p<0.01). More than two-thirds of the migraineurs reported more than five attacks during the past month with moderate to severe intense headache. Stress was the most reported trigger of migraine among university students (71%) followed by irregular sleep (47%), academic pressure (33%), and external noise (28%). Almost 37% of the participants who had migraines reported that headache caused severe impact in their day to day life. Conclusions: The prevalence of migraine among university students of Bangladesh is alarmingly high. Frequent migraine attacks and severe intensity of headache cause a substantial level of impact among the sufferers. Cautious avoidance of the triggering factors through appropriate interventions and prophylactic medication can mitigate the negative impact of migraine as well as improve the quality of life.
Labor Dystocia and Risk of Histological Chorioamnionitis and Funisitis: A Study from a Single Tertiary Referral Center
Authors: Kyozuka Hyo , Murata Tuyoshi , Fukuda Toma , Yasuda Shun , Kanno Aya , Yazawa Riho , Hashimoto Yuko , Yamaguchi Akiko , Fujimori Keiya
Published: December 2020

Background: Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of labor dystocia in histological chorioamnionitis and funisitis has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis.Methods: In this retrospective cohort study, the patients who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was graded as 0–3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2.Result: Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9-20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7-21.8), funisitis (adjusted odds ratio, 9.4; 95% confidence interval, 1.8-48.2), and funisitis stage ≥2 (adjusted odds ratio, 23.5; 95% confidence interval, 2.3-23.8). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7-7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2-7.9), and funisitis (adjusted odds ratio, 4.5; 95% confidence interval, 1.2-16.8). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia. Conclusion: Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.
Integrative Analyses of Key Genes Associated With Carotid Atherosclerosis Plaque Stability 
Authors: Guo Zhenyu , Yu Baixue , Wang Tao , Yang Xiaohu , Wang Chen , Fan Longhua
Published: December 2020

Carotid plaque rupture with thrombosis is responsible for the majority of acute cerebrovascular events. The study aimed to identify key genes associated with plaque destabilization. In our study, expression profiles regarding carotid plaque stability (GSE41571 and GSE120521) were obtained from the Gene Expression Omnibus (GEO) database and used to analyze differentially expressed genes (DEGs), key biological processes (BP) and intersecting pathways. And the expression of the DEGs was validated in clinical and cell samples. A total of 113 DEGs were identified and gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. Among the BP annotations, changes in “extracellular matrix (ECM) were closely related to plaque stability. “Focal adhesion”, ECM -receptor interaction”, “vascular smooth muscle contraction” and “regulation of actin cytoskeleton” were key pathways associated with plaque stability. Genes with top 15 scores (CytoHubba) were selected as hub genes, including ACTA2, MYLK, CALD1, MYH10, ACE, HMOX1, CYBA, NOX4, LUM, RAC2, COL4A5, SDC1, UCP2, SORBS1, and FCER1G. Pathway enrichment analysis showed that selected hub genes were also significantly enriched in “vascular smooth muscle contraction” and “focal adhesion”. Further detection in tissue and cell samples suggested MYLK, NOX4, COL4A5, SDC1 and CYBA might have potential clinical significance.
Recent Trends in the Incidence of Clear Cell Adenocarcinoma and Survival Outcomes: A SEER Analysis
Authors: Shrestha Anil , Maskey Niraj , Dong Xiaohui , Zheng Zongtai , Yang Fuhan , Wang Ruiliang , Ma Wenchao , Liu Ji , Li Cheng , Zhang Wentao , Mao Shiyu , Liu Shenghua , Yao Xudong , Guo Yadong
Published: December 2020

Objective. To investigate recent trends in the epidemiological and prognostic factors of clear cell adenocarcinoma (CCA) which is considered a relatively rare tumor with a glycogen-rich phenotype. Methods. Patients with CCA from years 2000 to 2016 were identified from the Surveillance, Epidemiological, and End Results (SEER) database. Relevant population data were used to analyze the rates age-adjusted incidence, age-standardized 3-year and 5-year relative survivals, and overall survival (OS). Results. Of the 104,206 CCA patients identified. The age-adjusted incidence of CCA increased 2.7-fold from the year 2000 (3.3/100,000) to 2016 (8.8/100,000). This increase occurred across all ages, races, stages, and grades. Of all these subgroups, the increase was largest in the grade IV group. The age-standardized 3-year and 5-year relative survivals increased during this study period, rising by 9.1% and 9.5% from 2000 to 2011, respectively. Among all the stages and grades, the relative survival increase was greatest in the grade IV group. According to multivariate analysis of all CCA patients, predictors of OS were: age, gender, year of diagnosis, marital status, race, grade, stage, and primary tumor site (P < 0.001). The OS of all CCA patients during the period 2008 to 2016 was significantly higher than that from 2000 to 2007 (hazard ratio [HR], 0.87; 95% CI: 0.85–0.89; P < 0.001). Conclusions. The incidence of CCA and survival of these patients improved over time. In particular, the highest increases were reported for grade IV CCA, which may be due to an earlier diagnosis and improved treatment.
Selective Retina Therapy and Thermal Stimulation of the Retina: Different Regenerative Properties - Implications for AMD Therapy
Authors: Richert Elisabeth , Papenkort Julia , Burchard Claus von der , Klettner Alexa , Arnold Philipp , Lucius Ralph , Brinkmann Ralf , Framme Carsten , Roider Johann , Tode Jan
Published: December 2020

BackgroundSelective Retina Therapy (SRT) and Thermal Stimulation of the Retina (TSR) have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration. MethodsFor PCR array, 6 eyes of apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation. ResultsTSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 hour after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, one hour after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells. ConclusionsSRT induces RPE cell death, followed by regeneration within a few days, accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation.
Time to resuscitate cardiopulmonary resuscitation! The 3R/CPR: Refill-Recoil-Rebound.
Authors: Nour Sayed
Published: December 2020

Sudden cardiac arrest (SCA) remains a major health issue worldwide with a gloomy outcome due to the inadequate organs’ perfusion during cardiopulmonary resuscitation (CPR). Alternatively, we aim through the present work to expose our visions of SCA management and propose a new technique of cardiac massage, urging CPR experts around the world to conduct their in-depth reviews for the sake of patients.
Correlation Between Uniocular Deviation and Duction Changes Following Different Decompression Surgeries in Thyroid Eye Disease
Authors: Guo Jie , Li Xiaofeng , Ma Ruiqi , Qian Jiang
Published: December 2020

Background: Postoperative ocular imbalance is an important problem for orbital decompression surgery in thyroid eye disease (TED). To evaluate the changes of unilateral ocular deviation and duction following orbital decompression and discuss the possible biomechanics of ocular imbalance.Methods: Fifty-four TED patients who underwent unilateral orbital decompression were included. 15 patients underwent 1-wall (deep lateral wall) decompression, 18 patients underwent 2-wall (deep lateral and medial wall) decompression and 21 patients underwent 3-wall (deep lateral, medial and inferior wall) decompression. Objective and subjective deviation of the operated eyes compared with the fellow eyes were evaluated using prism test and synoptophore, respectively. Ocular ductions were measured using Hirschberg’s method. The diameters of extraocular rectus were measured by computed tomography.Results: Ocular deviation and duction showed no significant difference after 1-wall decompression (p=0.25~0.89). Esotropia increased after 2-wall decompression (p=0.001~0.02). Hypotropia increased after 3-wall decompression (p=0.02). Adduction increased but abduction decreased following 2-wall and 3-wall decompression (p<0.05). Infraduction increased following 3-wall decompression (p<0.001). Additionally, the increase of esotropia had significant correlations with the increase of adduction and with the decrease of abduction (r=0.37~0.63, p<0.05). There were significant correlations between the diameter of medial rectus and the increase of esotropia, the increase of adduction and the decrease of abduction postoperatively (r=0.35~0.48, p<0.05).Conclusions: The changes in ocular deviation and duction were different after 1-wall, 2-wall and 3-wall orbital decompression. The expansion of orbital cavity and the increased contractile force of rectus might be important reasons for strabismus changes following decompression surgery.
Dealing With Unspecific Clinical Phenotypes in Molecular Autopsy - HPO-Driven Whole Exome Sequencing Analysis Versus Gene Panel Testing
Authors: Schoen Ulrike , Holzer Anna , Laner Andreas , Kleinle Stephanie , Scharf Florentine , Benet-Pagès Anna , Peschel Oliver , Holinski-Feder Elke , Diebold Isabel
Published: December 2020

Background: Molecular autopsy represents an efficient tool to save the diagnosis in up to one-third of sudden unexplained death (SUD). A defined gene panel is usually used for the examination. Alternatively, it is possible to carry out a comprehensive genetic assessment (Whole Exome Sequencing, WES), which also identifies rare, previously unknown variants. The disadvantage is that a dramatic number of variants must be assessed to identify the causal variant. To improve the evaluation of WES, the Human Phenotype Ontology (HPO) annotation is used internationally for deep phenotyping in the field of rare disease. However, a HPO-based evaluation of WES in SUD has not been described before.Methods: We performed WES in tissue samples from 16 people after SUD. Instead of a fixed gene panel, we defined a set of HPO terms and thus created a flexible “virtual gene panel”, with the advantage, that recently identified genes are automatically associated by HPO terms in the HPO database.Results: We obtained a median value of 68,947 variants per sample. Stringent filtering ended up in a median value of 276 variants per sample. Using the HPO-driven virtual gene panel we developed an algorithm that prioritized 1.4% of the variants. Variant interpretation resulted in eleven potentially causative variants in 16 individuals. Conclusion: Our data introduce an effective diagnostic procedure in molecular autopsy of SUD with a non-specific clinical phenotype.
Future Proofing Applied Epidemiology Workforce Training for Emergency Response. A Global Survey of Applied Epidemiologists, 2019-2020
Authors: Parry Amy Elizabeth , Kirk Martyn D , Durrheim David N , Olowokure Babatunde , Colquhoun Samantha , Housen Tambri
Published: December 2020

BackgroundRapid and effective emergency response to address health security relies heavily on a competent and suitably trained local and international workforce. The COVID-19 pandemic has highlighted the need to ensure that the health security workforce is well equipped to tackle current and future challenges. We conducted a survey to understand whether applied epidemiology training was meeting the needs of the field epidemiological workforce.MethodWe conducted a cross sectional online survey. Purposive sampling and snowballing techniques were used to identify survey respondents. Inclusion criterion was any person who self-identified as working in an applied epidemiology role. We recruited survey respondents through an online social media campaign and partnered with the Training Programs in Epidemiology and Public Health Interventions Network (TEPHINET) to directly reach field epidemiology training programme (FETP) alumni networks. Survey topics included participant demographics, technical background, formal education level, year of epidemiology training, topics studied during epidemiology training, years of experience as an epidemiologist, and their public health/epidemiology learning. The survey was available in English and French. ResultsWe received 282 responses from people with a range of formal public health and epidemiology training backgrounds. Applied epidemiology work experience of respondents spanned almost 30 years from across 64 countries. FETP alumni made up 74% (n=210) of the total. Basic outbreak and surveillance training was well reported by the respondents, however training in specialised techniques related to emergency response was not as common. Less than 50% of respondents reported receiving training in leadership and management. Training in emergency response and communications scored low across most categories. Fifty-six per cent of respondents reported learning evidence-based decision-making. FETP graduates reported higher levels of formal training in all survey topics. Conclusion﻿A specific aim of our survey was to identify the training needs of the applied epidemiology workforce. Training gaps identified included leadership, communication and social skills, as well as emergency response capacity. Our survey showed that applied epidemiology workforce training must evolve to remain relevant to current and future public health challenges.
Retention of Healthcare Workers One Year After Recruitment and Deployment in Rural Setting: an Experience Post-Ebola in Five Health Districts in Guinea
Authors: Kolie Delphin , Pas Remco Van De , Delamou Alexandre , Dioubaté Nafissatou , Beavogui Foromo Timothée , Bouedouno Patrice , Beavogui Abdoul Habib , Kaba Abdoulaye , Put Willem Van De , Damme Wim Van
Published: December 2020

IntroductionHealth workforce reform was undertaken in Guinea in 2016 following the Ebola outbreak to overcome the decades-long shortage and maldistribution of HCWs. This study aims to assess the effects of this programme on local health systems and its influence on HCWs turnover in rural Guinea. MethodsAn exploratory study design using a mixed-method approach was conducted in five rural health districts. Data were collected through a semi-structured questionnaire, in-depth interviews guides and documentary review. ResultsOut of the 611 HCWs officially deployed in the selected districts, 600 (98%) took-up duties. Female HCWs (64%), assistant nurses (39%), nurses (26%) and medical doctors (20%) represented the majority. Findings showed that 69% of HCWs were posted in health centres; the majority of which were medical doctors, nurses and midwives. The deployment has reportedly enhanced quality and timely data reporting. However, challenges were faced by local health authorities in the posting of HCWs including the unfamiliarity of some with primary healthcare delivery, collaboration conflicts between HCWs and the high feminization of the recruitment. One year after their deployment, 31% of the HCWs were absent from their posts. This included 59% of nurses, 29% of medical doctors and 11% of midwives. Main reasons for absenteeism were unknown (51%), continuing training (12%), illness (10%) and maternity leave (9%). Finding showed a confusion of roles and responsibilities between national and local actors in the management of HCWs; which was accentuated by lack of policy documents. ConclusionThe post-Ebola healthcare workers policy appears to have been successfully positive in the redistribution of HCWs, quality improvement of staffing levels in peripheral healthcare facilities, and the enhancing of district health offices capacities. However, greater attention should be given to the development of policy guidance documents with the full participation of all actors and a clear distinction of their roles and responsibilities for improved implementation and efficacy of this programme.
Characterization of Leading Dysregulated Plasma-Proteome Associated Genes in Patients with Gastro-Esophageal Cancers.
Authors: Vizeacoumar Frederick , Dwernychuk Lynn , Zaidi Adnan , Freywald Andrew , Vizeacoumar Franco , Ahmed Shahid
Published: December 2020

Background: Gastro-esophageal cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of gastro-esophageal cancers to identify new therapeutic targets and to yield predictive response to the available therapies. Our study aims to identify leading genes that are dysregulated (upregulated or downregulated) in patients with gastro-esophageal cancers.Methods: We examined gene expression data for those genes whose protein products can be detected in the plasma in 600 independent tumor samples and 46 matching normal tissue samples using the Cancer Genome Atlas (TCGA) to identify leading genes that are dysregulated in patients with gastro-esophageal cancers. Non-parametric Mann-Whitney-U test was used to evaluate differential expression of genes using a cut-off of P< 0.05.Results: The comparison between tumors sample and healthy tissue showed BIRC5 (p=2.61 E-08), APOC2 (p=3.23E-08), CENPF (p=4.38E-08), STMN1 (p=5.74E-08), and HNRPC (p=8.21E-08) were the leading genes significantly overexpressed in esophageal cancer whereas CST1 (p=3.97 E-21), INHBA (p=9.22E-20), ACAN (p=1.08E-19), HSP90AB1 (p=2.62E-19), and HSPD1 (p=3.91E-19) were the leading genes that were overexpressed in stomach cancer. Conversely, C16orf89 (9.78E-08), AR (1.01E-07), CKB (1.17E-07), ADH1B (1.79E-07), and NCAM1 (2.15E-07) were the leading gene that were significantly downregulated in esophageal cancer whereas GPX3 (1.65E-19), CLEC3B (5.70E-19), CFD (5.68E-18), GSN (4.5IE-17), and CCL14 (1.12E-16) were significantly downregulated in stomach cancer. Furthermore, Stage-based examination showed stage-specific differential expression of various genes as well as stage-wise increasing or decreasing up-regulation or down-regulation of selected genes, respectively. Conclusions: The present study identified leading upregulated and downregulated genes in gastro-esophageal cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted-treatment.
Organotypic modeling of SARS-CoV-2 lung and brainstem infection
Authors: Ferren Marion , Favede Valérie , Decimo Didier , Iampietro Mathieu , Lieberman Nicole A. P. , Weickert Jean-Luc , Pelissier Rodolphe , Mazelier Magalie , Terrier Olivier , Moscona Anne , Porotto Matteo , Greninger Alexander L. , Messaddeq Nadia , Horvat Branka , Mathieu Cyrille
Published: December 2020

SARS-CoV-2 has caused a global pandemic of Covid-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also lead to central nervous system infection and neurological sequelae. We developed and characterized two new organotypic cultures from hamster brainstem and lung tissues that offer the unique opportunity to study the early steps of the pathogenesis and screening of antivirals. Using these models, we validated the early tropism of the virus in the lung and demonstrated that SARS-CoV2 can infect brainstem and cerebellum, mainly by targeting granular neurons. Viral infection induced specific interferon and innate immune responses with patterns specific to each organ along with apoptotic, necroptotic, and pyroptotic cell death. Overall, our data illustrate the potential of rapidly modeling complex tissue level interactions of viral infection in a newly emerged virus.
Reliability of A Dried Urine Test for Comprehensive Assessment of Urine Hormones and Metabolites
Authors: Newman Mark , Curran Desmond
Published: December 2020

BackgroundMass spectrometry allows for analysis of multiple hormone and organic acid metabolites from small urine volumes; however, to assess the full extent of daily hormone production, 24-hour urine collections are usually required. The aims of this study were, first, to confirm that mass spectrometric analysis of an array of hormones and organic acids would yield similar results in both liquid and dried urine, and, second, to determine if collection of four dried spot urine samples could be substituted for a 24-hour collection when measuring reproductive hormones. MethodsTwo study populations were included in this prospective observational study. Twenty individuals collected both a spot liquid urine and dried urine on filter paper to analyze eight organic acids. A second group of 26 individuals collected both a 24-hour urine and four dried spot urines during waking hours throughout the same day for evaluation of 17 reproductive hormones and metabolites; data from 18 of these individuals were available to compare liquid versus dried urine results. Dried urine was extracted, hydrolyzed, and derivatized before analysis by mass spectrometry; all analytes from dried urine were normalized to urine creatinine. ResultsReproductive hormone results from dried and liquid urine were in excellent agreement with intraclass correlation coefficients (ICCs) greater than 0.90; comparison of dried to liquid urine for organic acids showed good to excellent agreement (ICC range: 0.75 to 0.99). Comparison between the 4-spot urine collection and 24-hour urine collection methods showed excellent agreement (ICC>0.9) for 14 of the 17 urine metabolites and good agreement for the others (ICC 0.78 to 0.85) with no systematic differences between the two methods of collection. ConclusionsThe burden of urine collection can be reduced using collection of four spot dried urines on filter paper without compromising comparability with hormone results from a 24-hour urine collection. A large number of urine analytes can be assessed from the dried urine with similar results to those from liquid urine. Given the ease of sample handling, this 4-spot dried urine assay would be useful for both clinical assessment of patients and for large epidemiologic studies.
How to Predict SARS-COV2 Infection in Patient Admitted in Emergency Department: A Prospective Cohort Study.
Authors: BALEN Frederic , CHAPENTIER Sandrine , AUBOIROUX Paul-Henri , NOEL-SAVINA Elise , SANS Nicolas , GROUTEAU Gaspard , RAYNAUD Anne , HEBRARD Manon , DUBUCS Xavier , HOUZE-CERFON Charles-Henri , COLINEAUX Hélène
Published: December 2020

Background. In order to rapidly identifying patients with a low probability of being infected by COVID19 to quickly refer them to specialized departments, the objective of our study was to develop a clinical predictive model of infection by COVID19 in patients attending the ED for respiratory symptoms or unexplained fever.Methods. We included all patients over 15 years old, admitted in one of the 2 emergency departments of Toulouse University Hospital between March 13 and March 31 for respiratory symptoms (dyspnea, cough), or fever (or sensation of fever) of unknown origin, and potentially requiring hospitalization. COVID19 infection was assessed by CT-SCAN and RT-PCR. All the candidate predictors were variables collected during the first clinical examination. Internal validation of the final model was performed using the bootstrap procedure. We performed a temporal validation in the same way on patients included between April 1 and April 13.Results. 772 patients were included. The prevalence of COVID19 was 25.5%. There were 19 predictors in the final model. The corrected-by-optimism area under the curve was 0.86 (95%CI = [0.83;0.89]). For a threshold at 10%, the sensitivity was 92%., the specificity was 56%, and the false negative rate was 5%. In secondary data, including 387 patients, the prevalence of COVID19 was 15%. The area under the curve was 0.73 (95%CI = [0.63;0.83]). For the same threshold, the sensitivity was 78%, the specificity was 48%, and the false negative rate was 7%Conclusion. We have developed a predictive tool of COVID19 infection for patients attending the ED. It could safely reduce admission in COVID19 dedicated unit in ED and prevent its overcrowding.Trial registration number: NCT: RC31/20/0149
High Prevalence of Germline Mutations in Cancer Susceptibility Genes in Thai Patients with Clinical Spectrum of Hereditary Breast-Ovarian Cancer Syndrome
Authors: Lertwilaiwittaya Pongtawat , Roothumnong Ekkapong , Nakthong Panee , Dungort Peerawat , Meesamarnpong Chutima , Tansa-Nga Warisara , Pongsuktavorn Khontawan , Wiboonthanasarn Supakit , Tititumjariya Warunya , Thongnoppakhun Wanna , Chanprasert Sirisak , Limwongse Chanin , Pithukpakorn Manop
Published: December 2020

Background: Germline genetic mutation plays a significant role in breast cancer susceptibility. The strength of such predisposition varies among ethnic groups across the globe, and clinical data from Asian population to develop a strategic approach to who should undergo a genetic test are lacking. Methods: We performed a multigene test with next generation sequencing in our 5-year hereditary breast-ovarian cancer spectrum cohort consists of 306 breast cancer patients, 62 ovarian cancer patients, 14 pancreatic cancer patients and 7 prostatic cancer patients. Results: There were 83 pathogenic/likely pathogenic (P/LP) variants identified in 104 patients, 44 of these P/LP variants were novel. We reported a high rate of germline P/LP variants in breast cancer (24%), ovarian cancer (37%), pancreatic cancer (14%), and prostatic cancer (29%). Germline P/LP variants in BRCA1 and BRCA2 accounted for 80% of P/LP variants found in breast cancer and 57% of P/LP variants found in ovarian cancer. The detection rate of NCCN 2019 guideline for genetic/familial high-risk assessment of breast and ovarian cancers was 22-40%. Conclusion: Overall, the data from this study strongly support the consideration of multigene panel test as a diagnostic tool for patients with hereditary breast-ovarian cancer spectrum in Thailand.
Catalyst-loaded Micro-encapsulated Phase Change Material for Thermal Control of Exothermic Reaction
Authors: Takahashi Tatsuya , Koide Hiroaki , Sakai Hiroki , Ajito Daisuke , Kurniawan Ade , Kunisada Yuji , Nomura Takahiro
Published: December 2020

CO2 methanation is a promising technology to enable the use of CO2 as a resource. Thermal control of CO2 methanation, which is a highly active exothermic reaction, is important to avoid thermal runaway and subsequent degradation of the catalyst. Using the heat storage capacity of a phase change material (PCM) for thermal control of the reaction is a novel passive approach. In this study a novel structure was developed, wherein catalysts were directly loaded onto a micro-encapsulated PCM (MEPCM). The MEPCM was prepared in three steps consisting of a boehmite treatment, precipitation treatment, and heat oxidation treatment, and an impregnation process was adopted to prepare a Ni catalyst. The catalyst-loaded MEPCM did not show any breakage or deformation of the capsule or a decrease in the heat storage capacity after the impregnation treatment. MEPCM demonstrated a higher potential as an alternative catalyst support in CO2 methanation than the commercially available α-Al2O3 particle. In addition, the heat storage capacity of the catalyst-loaded MEPCM suppressed the temperature rise of the catalyst bed at a high heat absorption rate (2.4 MW m-3). In conclusion, ​the catalyst-loaded MEPCM is a high-speed, high-precision thermal control device because of its high-density energy storage and resolution of a spatial gap between the catalyst and cooling devices. This novel concept has the potential to overcome the technical challenges faced by efficiency enhancement of industrial chemical reactions.
Co-reactant Free Novel Self-enhanced Solid-state ECL Platform of Polyluminol-gold Nanocomposite for Highly Selective and Sensitive Signal-on Detection of Hg2+ ion
Authors: Chikkili Venkateswara Raju , Shanmugam Senthil Kumar
Published: December 2020

Development of self-enhanced solid-state ECL platform creates a straightforward experimental design for the fabrication of point-of-care applications. Herein, we develop a promising method for self-enhanced solid-state ECL platform of polyluminol gold nanocomposite on glassy carbon electrode ((PL-Au)nano/GCE) via simple one step electrochemical deposition process without involving any additional co-reactants. The presence of AuNPs augments the electron transfer kinetics of PL and enhances the solid-state ECL intensity and promotes label free, excellent sensitivity, and selectivity to detect Hg2+ in physiological pH through signal-on mode. Unlike pristine PL/GCE, electrochemically co-deposited AuNPs in the (PL-Au)nano/GCE composite, enable the co-reactant accelerator by improving the catalytic activity of PL towards oxygen reduction reaction (ORR) yielding in-situ ROS (co-reactant) generation. Further, the ECL intensity of (PL-Au)nano/GCE composite, gradually increases by each addition of Hg2+ ion. This is because of the formation of an amalgamation of Au-Hg on (PL-Au)nano/GCE composite surface which further accelerate the yield of in-situ ROS and enhance the intensity of ECL. Whereas no ECL signals changes were observed for PL/GCE composite. The proposed self-enhanced solid-state ECL platform is selectively sensing the Hg2+ ion in the linear range of 0.3 nM to 200 nM with a detection limit of 0.1 nM. The demonstrated (PL-Au)nano/GCE platform might pave new avenues for further studies in the solid-state ECL platform which could be more useful in on-site monitoring of clinical bioassay and immunosensors.
Clinical and Molecular Findings in Early Infant Death Associated with Genetic Diseases: A Multicenter Cohort Study in China
Authors: Wang Xia , Zhu Tianwen , Gong Xiaohui , Bei Fei , Ma Li , Chen Yan , Zhao Dongying , Sun Jingjing , Wang Jian , Qiu Gang , Sun Jianhua , Sun Yu , Zhang yongjun
Published: December 2020

Background To investigate the impact of exome sequencing in critically ill infants and find out high-risk patients with genetic diseases for the 180-day mortality rate. Results A molecular diagnosis rate achieved in 203 of 439 (46.2%) sequenced infants. 60 of 203 (29.5%) diagnosed patients died before 180 days of life. Compared to the undiagnosed-cases, patients with genetic findings in metabolic-endocrine disorders (OR=2.89, 95% CI: 1.51-5.52), primary immunodeficiencies (OR=3.79, 95% CI: 1.25-11.53), and early-onset muscle disease (OR=6.49, 95% CI: 2.28-18.48) had high odds ratios of 180-day mortality. Based on the functions of the defective genes, infants with catalytic activity deficiency (OR=3.07, 95% CI: 1.51-6.25) and transporter activity deficiency (OR=4.15, 95% CI: 1.80-9.56) also had a high risk of 180-day mortality. Furthermore, the proportion of medical management correspondence to genetic findings increased from 22.4% to 40.3% (p=0.06), and the 180-day mortality rate decreased from 35.9% to 29.6% showing a moderate decreased trend (p trend =0.08) over 4 years.Conclusions Our study shows that patients with genetic findings in metabolic-endocrine disorders, primary immunodeficiencies and early-onset muscle disease are related to 180-day mortality, which are of great significance for improve the prognosis.
Differences in Health Care Experiences Between Rare Cancer and Common Cancer Patients: Results From a National Cross-Sectional Survey
Authors: Heus Eline de , Engelen Vivian , Dingemans Irene , Richel Carol , Schrieks Marga , Zwan Jan Maarten van der , Besselink Marc G. , Henegouwen Mark I. van Berge , Herpen Carla M.L. van , Duijts Saskia F.A.
Published: December 2020

Background Patients with rare cancers face challenges in the diagnostic and treatment phase, and in access to clinical expertise. Since studies on health care experiences of these patients in comparison to patients with more common cancers are scarce, we aimed to explore these differences.Methods Data were cross-sectionally collected among (former) cancer patients through a national online survey in the Netherlands (October 2019). Descriptive statistics were reported and subgroups (rare vs. common patients) were compared.Results In total, 7,343 patients (i.e., 1,856 rare and 5,487 common cancer patients) participated. Rare cancer patients were more often diagnosed and treated in different hospitals compared to common cancer patients (67% vs. 59%, p<0.001). Rare cancer patients received treatment more often in a single hospital (60% vs. 57%, p=0.014), but reported more negative experiences when treated in multiple hospitals than common cancer patients (14% vs. 9%, p<0.001). They also more often received advise from their physician about the hospital to go to for a second opinion (50% vs. 36%, p<0.001), were more likely to choose a hospital specialized in their cancer type (33% vs. 22%, p<0.001), and were more willing to travel as long as necessary to receive specialized care than common cancer patients (55% vs. 47%, p<0.001).Conclusions Rare and common cancer patients differ in their health care experiences. Health care for rare cancer patients can be further improved by proper referral to centers of expertise and building a clinical network specifically for rare cancers.
The Interoperability Between the Spanish Version of the International Classification of Diseases and ORPHAcodes: Towards Better Identification of Rare Diseases
Authors: Rico Juan , de Garibay Luis Javier Echevarría González , López María García , Vilarroig Sandra Guardiola , Roldán Luis Alberto Maceda , Zurriaga Óscar , Carbonell Clara Cavero
Published: December 2020

BackgroundRare diseases present a wide spectrum of clinical manifestations and severity levels, and their main common trait is the low prevalence, making them difficult to classify. Diagnoses are usually coded using the International Classification of Diseases (ICD), with its different versions. In Spain, the ICD-10-ES (stem from the ICD-10-CM–Clinical Modification) is used throughout the National Healthcare System since 2016, indistinctively including rare diseases that often lack a specific code. ORPHAcode aims to provide high-quality resources on rare diseases. The goal was to interrelate the ORPHAcode classification with the ICD-10-ES in order to engage a tool to track rare diseases diagnosis and characterize the improvement space for the identification of rare diseases in the Spanish Healthcare System.Methods5,775 disorder level ORPHAcodes were mapped to ICD-10-ES codes by comparing the descriptors associated in both classifications. ORPHAcodes were then clustered based on their assigned ICD-10-ES chapter and the redundancy of each individual ICD-10-ES code was calculated by counting the ORPHAcodes they mapped to. Three groups were established: Group 1 (1 ORPHAcode per ICD-10-ES), Group 2 (between 2-49 ORPHAcodes per ICD-10-ES) and Group 3 (≥50 ORPHAcodes per ICD-10-ES).ResultsEquivalences to 1,700 ICD-10-ES codes were established for 5,664 ORPHAcodes. The ORPHAcodes distribution within the ICD-10-ES showed an aggregation in the “Q” (>40%), “G” (>14%), and “E” (12%) chapters. The availability of ICD-10-ES codes to map ORPHAcodes reached its lowest at the “G” and “Q” chapters with less than 0.2 ICD-10-ES codes available per ORPHAcode. Global ICD-10-ES codes redundancy analysis revealed that only 1,055 of the equivalences pertain to group 1. Group 2 contained 3,358 equivalences with 634 ICD-10-ES codes while 1,322 equivalences were group 3 (11 ICD-10-ES). Within ICD-10-ES chapters, “G” and “Q” contained over 30% and 45% of their own equivalences in the highest redundancy level (group 3) respectively, but under 10% one to one equivalences each (group 1).Conclusions﻿ICD-10-ES codes have not enough specificity to identify rare diseases. Direct mapping between ICD and ORPHAcodes or the integration of ORPHAcodes at the healthcare system for diagnoses codification would enable better detection and epidemiological analysis of rare diseases.
Use of Anti-Epileptic Drugs During Adjuvant Chemo-Radiotherapy is Associated with Increased Mortality in Patients with Glioblastoma: A Nationwide Population-Based Cohort Study
Authors: Lee Peng-Yi , Chao KS Clifford , Wei Yu-Ting , Chu Chin-Nan , Chuang Hao-Che , Chung Wen-Hui , Wang Ti-Hao
Published: December 2020

BackgroundThere are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radiosensitizers to improve survival in glioblastoma (GBM) patients. We conducted a population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy (CCRT) on outcome.Methods1057 GBM patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant RT and temozolomide (TMZ), and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during CCRT (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for valproic acid (VPA), levetiracetam (LEV), and phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. ResultsThere were 642 patients in the AED group while 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs. (22.6% vs 18%, p=0.078). Overall, the AED group had significantly increased risk of mortality (HR=1.18, p=0.016). In subgroup analyses, the significant detrimental effect was demonstrated in VPA (HR=1.29, p=0.0002), but not in LEV (HR=1.18, p=0.079) and phenytoin (HR = 0.98, p=0.862). When stratified by sex and age, this detrimental effect was seen in male and patients less than 65 years old in the VPA group.Conclusion:Survival was not improved and even worse in patients with AEDs during CCRT in this nationwide population-based study. Our real-world data did not support prophylactic use of AEDs for GBM.
A newly isolated Cerrena unicolor capable of laccase production and lignin degradation in agricultural wastes
Authors: Tian Jiahui , Feng Jiali , Wang Ying , Lu Junhua , Mao Linjing , Chu Jie
Published: December 2020

Lignin is main residue of agro-industrial biomass which can be decomposed through enzymatic hydrolysis by fungi. In this study, a strain was isolated from birch forest and identified as Cerrena unicolor GC.u01 by 18S rDNA gene-sequencing technology. The activity of laccase (Lac) reached maximum 1605.28 ± 32.21 U·L-1 at 8th day via submerged fermentation, while the highest Lac activity by solid-state fermentation 1280.04 ± 48.11 U·g-1 with rice stalks and 566.83 ± 47.02 U·g-1 with wheat stalks were both obtained at 10th day, and 2677.50 ± 49.38 U·g-1 with corn stalks at 12th day. Then the lignin degradation ratios were up to 24.3%, 34.3% and 26.2% in wheat stalks, rice stalks and corn stalks, respectively, suggesting that the newly isolated Cerrena unicolor GC.u01 is potential for laccase production and lignin degradation by solid-state fermentation.