bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capacity Building of Health Professionals on Genetics and Genomics Practice: Evaluation of the Effectiveness of a Distance Learning Training Course for Italian Physicians
Authors: Calabrò Giovanna Elisa , Tognetto Alessia , Mazzaccara Alfonso , Barbina Donatella , Carbone Pietro , Guerrera Debora , Di Pucchio Alessandra , Federici Antonio , Ricciardi Walter , Boccia Stefania 
Published: March 2021

BackgroundThe rapid spread of personalized medicine requires professionals to manage the “omics revolution.” Therefore, the genetics/genomics literacy of healthcare professionals should be in line with the continuous advances in this field, in order to implement its potential implications for diagnosis, control and treatment of diseases. The present study investigates the effectiveness of a distance learning course on genetics and genomics targeted at medical doctors.MethodsIn the context of a project funded by the Italian Ministry of Health, we developed a distance learning course, entitled Genetics and Genomics practice. The course focused on genetic/genomics testing, pharmacogenetics and oncogenomics and was developed according to andragogical training methods (Problem-based Learning and Case-based Learning). We used a pre-test vs. post-test study design to assess knowledge improvement on a set of 10 Multiple Choice Questions (MCQs). We analyzed the proportion of correct answers for each question pre and post-test and the mean score difference stratified by gender, age, professional status and medical discipline. Moreover, the test was submitted to the participants 8 months after the conclusion of the course (follow-up), in order to assess the retained knowledge.ResultsThe course was completed by 1,637 Italian physicians, most of which were primary care physicians (20.8%), public health professionals (11.5%) and specialist pediatricians (10.6%). The proportion of correct answers increased in the post-test for all the MCQs. The overall mean score significantly increased, from 59.46 in the pre-test to 71.42 in the post-test (p &lt; 0.0001). The comparison in test performance between follow-up and pre-test demonstrated an overall knowledge improvement.ConclusionGenomics literacy among healthcare professionals is essential to ensure optimal translation to healthcare delivery of research. The results of this course suggest that distance-learning training in genetic/genomics practice represents an effective method to improve physicians’ knowledge in the immediate and mid-term time scale. A preprint version of this paper is available at: https://www.researchsquare.com/article/rs-10083/v1.
Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity
Authors: Mawa Patrice A. , Kincaid-Smith Julien , Tukahebwa Edridah M. , Webster Joanne P. , Wilson Shona 
Published: March 2021

Schistosomiasis is the second most important human parasitic disease in terms of socioeconomic impact, causing great morbidity and mortality, predominantly across the African continent. For intestinal schistosomiasis, severe morbidity manifests as periportal fibrosis (PPF) in which large tracts of macro-fibrosis of the liver, visible by ultrasound, can occlude the main portal vein leading to portal hypertension (PHT), sequelae such as ascites and collateral vasculature, and ultimately fatalities. For urogenital schistosomiasis, severe morbidity manifests as pathology throughout the urinary system and genitals, and is a definitive cause of squamous cell bladder carcinoma. Preventative chemotherapy (PC) programmes, delivered through mass drug administration (MDA) of praziquantel (PZQ), have been at the forefront of schistosomiasis control programmes in sub-Saharan Africa since their commencement in Uganda in 2003. However, despite many successes, ‘biological hotspots’ (as distinct from ‘operational hotspots’) of both persistent high transmission and morbidity remain. In some areas, this failure to gain control of schistosomiasis has devastating consequences, with not only persistently high infection intensities, but both “subtle” and severe morbidity remaining prevalent. These hotspots highlight the requirement to revisit research into severe morbidity and its mechanisms, a topic that has been out of favor during times of PC implementation. Indeed, the focality and spatially-structured epidemiology of schistosomiasis, its transmission persistence and the morbidity induced, has long suggested that gene-environmental-interactions playing out at the host-parasite interface are crucial. Here we review evidence of potential unique parasite factors, host factors, and their gene-environmental interactions in terms of explaining differential morbidity profiles in the human host. We then take the situation of schistosomiasis mansoni within the Albertine region of Uganda as a case study in terms of elucidating the factors behind the severe morbidity observed and the avenues and directions for future research currently underway within a new research and clinical trial programme (FibroScHot).
Profiling Tissue and Biofluid miR-155-5p, miR-155*, and miR-146a-5p Expression in Graft vs. Host Disease
Authors: Crossland Rachel E. , Norden Jean , Ghimire Sakhila , Juric Mateja Kralj , Pearce Kim F. , Lendrem Clare , Collin Matthew , Mischak-Weissinger Eva , Holler Ernst , Greinix Hildegard T. , Dickinson Anne M. 
Published: March 2021

Introduction: Acute graft vs. host disease (aGvHD) is a frequent complication following allogeneic haematopoeitic transplantation (HSCT). Despite recent advances, there are no universally accepted biomarkers to determine development of aGvHD. MicroRNAs miR-146a and miR-155 have been previously associated with aGvHD and show promise as clinically translatable biomarkers. In this study, we performed comprehensive expression profiling of miR-146a, miR-155, and miR-155* expression in aGvHD target tissue and biofluids and relate expression to post-HSCT outcomes.Materials and Methods: MicroRNA expression was assessed by qRT-PCR in gastrointestinal (n = 31) and skin (n = 31) biopsies as well as serum (exploratory cohort n = 34, verification cohort n = 81, diagnostic cohort n = 65) and urine (exploratory cohort n = 30, verification cohort n = 56, diagnostic cohort n = 20) biofluids, including extracellular vesicle (EV) cohorts (serum EV n = 15, urine EV n = 30). Expression was related to aGvHD incidence, severity and overall survival.Results: In GI samples, expression of miR-155 (p = 0.03) and miR-146a (p = 0.03) was higher at aGvHD onset compared to patients with no GvHD. In skin biopsies, expression of miR-155 (p = 0.004) was upregulated in aGvHD patients compared to normal control skin. Expression of miR-146a was higher in aGvHD compared to no aGvHD biopsies (p = 0.002). In serum, miR-155 (p = 0.03) and miR-146a (p = 0.02) expression was higher at day 14 (D14), while in urine expression was elevated at D7 post-HSCT in patients who developed aGvHD compared to those disease-free. This was verified in an independent serum (miR-155 p = 0.005, miR-146a p = 0.003) and urine (miR-155 p = 0.02, miR-146a p = 0.04) cohort, where both microRNAs were also associated with aGvHD by ROC analysis. In serum and urine samples taken at the time of aGvHD symptoms, expression of miR-155 and miR-146a was also elevated (serum miR-155 p = 0.03, miR-146a p &lt; 0.001; urine miR-155 p = 0.02, miR-146a p = 0.02). In contrast, miR-146a and miR-155 were downregulated at D14 in serum EVs and at D7 in urine EVs in patients who developed aGvHD compared to those that remained disease-free, in both an exploratory (serum miR-155 p = 0.02, miR-146a p = 0.06; urine miR-155 p = 0.02, miR-146a p = 0.07) and an independent cohort (serum miR-155 p = 0.01, miR-146a p = 0.02).Conclusions: These results further support a role for miR-155 and miR-146a as non-invasive, clinically relevant biomarkers for aGvHD. However, the link between their involvement in generalized inflammation and in specific pathophysiology requires further investigation at a systemic level.
Effector T Helper Cells Are Selectively Controlled During Pregnancy and Related to a Postpartum Relapse in Multiple Sclerosis
Authors: Koetzier Steven C. , Neuteboom Rinze F. , Wierenga-Wolf Annet F. , Melief Marie-José , de Mol C. Louk , van Rijswijk Angelique , Dik Willem A. , Broux Bieke , van der Wal Ronald , van den Berg Sjoerd A. A. , Smolders Joost , van Luijn Marvin M. 
Published: March 2021

Background: Multiple sclerosis (MS) patients are protected from relapses during pregnancy and have an increased relapse risk after delivery. It is unknown how pregnancy controls disease-contributing CD4+ T helper (Th) cells and whether this differs in MS patients who experience a postpartum relapse. Here, we studied the effector phenotype of Th cells in relation to pregnancy and postpartum relapse occurrence in MS.Methods: Memory skewing and activation of effector Th subsets were analyzed in paired third trimester and postpartum blood of 19 MS patients with and without a postpartum relapse and 12 healthy controls. Ex vivo results were associated with circulating levels of pregnancy-induced hormones and mirrored in vitro by exposing proliferating Th cells to corresponding serum samples.Results: Based on HSNE-guided analyses, we found that effector memory proportions of Th cells were increased in postpartum vs. third trimester samples from MS patients without a postpartum relapse. This was not seen for relapsing patients or healthy controls. CXCR3 was upregulated on postpartum memory Th cells, except for relapsing patients. These changes were verified by adding sera from the same individuals to proliferating Th cells, but did not associate with third trimester cortisol, estradiol or progesterone levels. For relapsing patients, activated memory Th cells of both third trimester and postpartum samples produced higher levels of pro-inflammatory cytokines.Conclusion: Effector Th cells are differentially regulated during pregnancy in MS patients, likely via serum-related factors beyond the studied hormones. The pro-inflammatory state of memory Th cells during pregnancy may predict a postpartum relapse.
MRI T1 Contrast-Enhanced Signal Intensity Is a Prognostic Indicator of Imatinib Therapy in Desmoid-Type Fibromatosis
Authors: Zhu Hui Ci , Xu Shi Xing , Li Xiao Ting , Guan Zhen , Li Shu , Sun Ying-Shi 
Published: March 2021

ObjectiveTo investigate the efficiency of pre-therapy magnetic resonance imaging (MRI) features in predicting the prognosis of desmoid-type fibromatosis patients treated with imatinib.Materials and MethodsA total of 38 desmoid-type fibromatosis patients treated with imatinib were collected in this retrospective study. The high signal intensity on pre-therapy MRI was evaluated on axial T2 and T1 contrast-enhanced sequences with fat suppression. Cox regression and Kaplan–Meier analyses explored the correlation between clinical or radiographic characteristics and progression-free survival (PFS).ResultsHyperintense T1 contrast enhancement (CE) proportion (≥ 75%) was identified as an independent predictor for PFS. Patients with hyperintense T1 CE proportion &lt;75% demonstrated no progression, while patients with hyperintense T1 CE proportion ≥75% demonstrated a progression rate of 78.4%.ConclusionHyperintense T1 CE proportion in the tumor is a potential predictor of disease progression in patients with desmoid-type fibromatosis treated with imatinib. Hyperintense T1 CE proportion &lt;75% indicates progression-free during treatment.
Subgroup-Independent Mapping of Renal Cell Carcinoma—Machine Learning Reveals Prognostic Mitochondrial Gene Signature Beyond Histopathologic Boundaries
Authors: Marquardt André , Solimando Antonio Giovanni , Kerscher Alexander , Bittrich Max , Kalogirou Charis , Kübler Hubert , Rosenwald Andreas , Bargou Ralf , Kollmannsberger Philip , Schilling Bastian , Meierjohann Svenja , Krebs Markus 
Published: March 2021

Background: Renal cell carcinoma (RCC) is divided into three major histopathologic groups—clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC). We performed a comprehensive re-analysis of publicly available RCC datasets from the TCGA (The Cancer Genome Atlas) database, thereby combining samples from all three subgroups, for an exploratory transcriptome profiling of RCC subgroups.Materials and Methods: We used FPKM (fragments per kilobase per million) files derived from the ccRCC, pRCC and chRCC cohorts of the TCGA database, representing transcriptomic data of 891 patients. Using principal component analysis, we visualized datasets as t-SNE plot for cluster detection. Clusters were characterized by machine learning, resulting gene signatures were validated by correlation analyses in the TCGA dataset and three external datasets (ICGC RECA-EU, CPTAC-3-Kidney, and GSE157256).Results: Many RCC samples co-clustered according to histopathology. However, a substantial number of samples clustered independently from histopathologic origin (mixed subgroup)—demonstrating divergence between histopathology and transcriptomic data. Further analyses of mixed subgroup via machine learning revealed a predominant mitochondrial gene signature—a trait previously known for chRCC—across all histopathologic subgroups. Additionally, ccRCC samples from mixed subgroup presented an inverse correlation of mitochondrial and angiogenesis-related genes in the TCGA and in three external validation cohorts. Moreover, mixed subgroup affiliation was associated with a highly significant shorter overall survival for patients with ccRCC—and a highly significant longer overall survival for chRCC patients.Conclusions: Pan-RCC clustering according to RNA-sequencing data revealed a distinct histology-independent subgroup characterized by strengthened mitochondrial and weakened angiogenesis-related gene signatures. Moreover, affiliation to mixed subgroup went along with a significantly shorter overall survival for ccRCC and a longer overall survival for chRCC patients. Further research could offer a therapy stratification by specifically addressing the mitochondrial metabolism of such tumors and its microenvironment.
Evaluation of the Current Therapeutic Approaches for COVID-19: A Systematic Review and a Meta-analysis
Authors: Abdelrahman Zeinab , Liu Qian , Jiang Shanmei , Li Mengyuan , Sun Qingrong , Zhang Yue , Wang Xiaosheng 
Published: March 2021

Background: Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern.Objective and Methods: To estimate the efficacy and safety of COVID-19 therapeutics, we performed meta-analyses of the studies reporting clinical features and treatments of COVID-19 published from January 21 to September 6, 2020.Results: We included 136 studies that involved 102,345 COVID-19 patients. The most prevalent treatments were antibiotics (proportion: 0.59, 95% CI: [0.51, 0.67]) and antivirals (proportion: 0.52, 95% CI: [0.44, 0.60]). The combination of lopinavir/ritonavir and Arbidol was the most effective in treating COVID-19 (standardized mean difference (SMD) = 0.68, 95% CI: [0.15, 1.21]). The use of corticosteroids was associated with a small clinical improvement (SMD = −0.40, 95% CI: [−0.85, −0.23]), but with a higher risk of disease progression and death (mortality: RR = 9.26, 95% CI: [4.81, 17.80]; hospitalization length: RR = 1.54, 95% CI: [1.39, 1.72]; severe adverse events: RR = 2.65, 95% CI: [2.09, 3.37]). The use of hydroxychloroquine was associated with a higher risk of death (RR = 1.68, 95% CI: [1.18, 2.38]). The combination of lopinavir/ritonavir, ribavirin, and interferon-β (RR = 0.34, 95% CI: [0.22, 0.54]); hydroxychloroquine (RR = 0.58, 95% CI: [0.39, 0.58]); and lopinavir/ritonavir (RR = 0.72, 95% CI: [0.56, 0.91]) was associated with reduced hospitalization length. Hydrocortisone (RR = 0.05, 95% CI: [0.03, 0.10]) and remdesivir (RR = 0.74, 95% CI: [0.62, 0.90]) were associated with lower incidence of severe adverse events. Dexamethasone was not significant in reducing disease progression (RR = 0.45, 95% CI: [0.16, 1.25]) and mortality (RR = 0.90, 95% CI: [0.70, 1.16]). The estimated combination of corticosteroids with antivirals was associated with a better clinical improvement than antivirals alone (SMD = −1.09, 95% CI: [−1.64, −0.53]).Conclusion: Antivirals are safe and effective in COVID-19 treatment. Remdesivir cannot significantly reduce COVID-19 mortality and hospitalization length, while it is associated with a lower incidence of severe adverse events. Corticosteroids could increase COVID-19 severity, but it could be beneficial when combined with antivirals. Our data are potentially valuable for the clinical treatment and management of COVID-19 patients.
Underwater Docking Approach and Homing to Enable Persistent Operation
Authors: Page Brian R. , Lambert Reeve , Chavez‐Galaviz Jalil , Mahmoudian Nina 
Published: March 2021

One of the main limiting factors in deployment of marine robots is the issue of energy sustainability. This is particularly challenging for traditional propeller-driven autonomous underwater vehicles which operate using energy intensive thrusters. One emerging technology to enable persistent performance is the use of autonomous recharging and retasking through underwater docking stations. This paper presents an integrated navigational algorithm to facilitate reliable underwater docking of autonomous underwater vehicles. Specifically, the algorithm dynamically re-plans Dubins paths to create an efficient trajectory from the current vehicle position through approach into terminal homing. The path is followed using integral line of sight control until handoff to the terminal homing method. A light tracking algorithm drives the vehicle from the handoff location into the dock. In experimental testing using an Oceanserver Iver3 and Bluefin SandShark, the approach phase reached the target handoff within 2 m in 48 of 48 tests. The terminal homing phase was capable of handling up to 5 m offsets with approximately 70% accuracy (12 of 17 tests). In the event of failed docking, a Dubins path is generated to efficiently drive the vehicle to re-attempt docking. The vehicle should be able to successfully dock in the majority of foreseeable scenarios when re-attempts are considered. This method, when combined with recent work on docking station design, intelligent cooperative path planning, underwater communication, and underwater power transfer, will enable true persistent undersea operation in the extremely dynamic ocean environment.
URGENSI PENDIDIKAN ANTIKORUPSI TERHADAP PENCEGAHAN KORUPSI DALAM PENDIDIKAN DASAR
Authors: Widiartana Gregorius , Setyawan Vincentius Patria 
Published: March 2021

Corruption eradication in Indonesia is still not optimal and still prioritizes repressive actions against corruption cases that have occurred. The implementation of such efforts is ineffective in eradicating corruption because corruption has taken root in the legal culture of society. One of the ways that can be implemented in efforts to eradicate corruption is to prevent corruption which can be done by providing anti-corruption education, especially for students at the primary education level. Primary education is the focus of providing anti-corruption education because it is at this level that the character building of a person, and anti-corruption education is actually character education. Keywords : Corruption Prevention, Corruption Crime, Anti-Corruption Education.
On the development of Technical Regulations on the safety of water distribution and sewer networks of public water supply and wastewater disposal systems
Authors: Примин О.Г. 
Published: March 2021

Рассмотрены вопросы надежности трубопроводов сетей водоснабжения и водоотведения городов и поселений России. Приведены соображения (в порядке дискуссии) о необходимости разработки и принятия Технического регламента о безопасности сетей водоснабжения и водоотведения централизованных систем водоснабжения и водоотведения. Технический регламент установит требования к сетям водоснабжения и водоотведения, обязательные для применения и исполнения на территории РФ. Отмечено, что в водной отрасли России в настоящее время отсутствует единая система, выработанная на основе практики применения обязательных требований к трубной продукции, используемой в сетях водоснабжения и водоотведения, и обязательной сертификации (декларирования). Предлагается область применения такого Технического регламента – сети централизованных систем холодного водоснабжения и водоотведения (канализации) на всех этапах их жизненного цикла, а также материалы и изделия, трубы, арматура, колодцы и связанные с ними процессы проектирования, строительства, эксплуатации, технического обслуживания, текущего и капитального ремонта, консервации и ликвидации сетей водоснабжения и водоотведения (канализации).
The issues of reliability of pipelines of water and sewer networks of Russian cities and settlements are considered. Considerations (by way of discussion) on the need for the development and adoption of Technical Regulations on the safety of water and sewer networks of public water supply and wastewater disposal systems are presented. The Technical Regulations will establish the requirements to water and sewer networks that will be mandatory for use and compliance on the territory of the Russian Federation. It is noted that the water industry in Russia is currently lacking a uniform system developed on the basis of the practice of applying mandatory requirements to pipe products used in water and sewer networks and their mandatory certification. The scope of application of such Technical Regulations is proposed, i. e. networks of public systems of cold water supply and wastewater disposal (sewerage) at all stages of their life cycle, as well as materials and articles, pipes, fittings, manholes and related processes of design, construction, operation, maintenance, current repairs and overhaul works, conservation and abandonment of water supply and sewer networks.
Enhanced performance of solution-processable floating-gate organic phototransistor memory for organic image sensor applications
Authors: Abe Hayato , Hattori Reitaro , Nagase Takashi , Higashinakaya Miho , Tazuhara Shion , Shiono Fumiya , Kobayashi Takashi , Naito Hiroyoshi 
Published: March 2021

Abstract
This paper reports on the memory characteristics of solution-processed organic phototransistors (OPTs) based on poly(3-hexylthiophene) with organic semiconductor floating gates and their application to image sensors. The addition of a small amount of soluble fullerene to the floating-gate layer enhances the erasing characteristics, which helps increase the on- and off-current ratio of the OPT memories. Furthermore, the OPT memories can achieve a long extrapolated retention time (>109 s) and high photosensitivity upon illumination of as weak as 10 μW cm‒2. A black and white pattern printed on paper can be imaged using the solution-processed OPT memory array.
Efficient terahertz wave generation of diabolo-shaped Fe/Pt spintronic antennas driven by a 780 nm pump beam
Authors: Talara Miezel , Bulgarevich Dmitry S. , Tachioka Chiyaka , Mag-usara Valynn Katrine , Muldera Joselito , Furuya Takashi , Kitahara Hideaki , Escaño Mary Clare , Guo Qixin , Nakajima Makoto , Torosyan Garik , Beigang René , Watanabe Makoto , Tani Masahiko 
Published: March 2021

Abstract
We report on efficient terahertz (THz) wave generation of Fe/Pt diabolo-shaped spintronic antennas with different Pt thicknesses fabricated on MgO substrates. Compared with the antenna-free spintronic bilayer, ∼45% and ∼98% emission amplitude improvements were obtained when using the antennas with thin and thick Pt, respectively, as THz radiation sources. The improvement can be attributed to the enhanced outcoupling of THz radiation to free space and to the enhanced THz emission with the deposition of thicker Pt layer at the displacement current direction. Our results suggest that efficient spintronic radiation sources can be obtained with proper design of these THz emitters.