bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple Practical Guide to Genomic Diagnostics in a Pediatric Setting
Authors: Taylor Alan , Alloub Zeinab , Tayoun Ahmad Abou
Published: May 2021

With limited access to trained clinical geneticists and/or genetic counselors in the majority of healthcare systems globally, and the expanding use of genetic testing in all specialties of medicine, many healthcare providers do not receive the relevant support to order the most appropriate genetic test for their patients. Therefore, it is essential to educate all healthcare providers about the basic concepts of genetic testing and how to properly utilize this testing for each patient. Here, we review the various genetic testing strategies and their utilization based on different clinical scenarios, and test characteristics, such as the types of genetic variation identified by each test, turnaround time, and diagnostic yield for different clinical indications. Additional considerations such as test cost, insurance reimbursement, and interpretation of variants of uncertain significance are also discussed. The goal of this review is to aid healthcare providers in utilizing the most appropriate, fastest, and most cost-effective genetic test for their patients, thereby increasing the likelihood of a timely diagnosis and reducing the financial burden on the healthcare system by eliminating unnecessary and redundant testing.
Comparison of Selection Signatures between Korean Native and Commercial Chickens Using 600K SNP Array Data
Authors: Cho Sunghyun , Manjula Prabuddha , Kim Minjun , Cho Eunjin , Lee Dooho , Lee Seung Hwan , Lee Jun Heon , Seo Dongwon
Published: May 2021

Korean native chickens (KNCs) comprise an indigenous chicken breed of South Korea that was restored through a government project in the 1990s. The KNC population has not been developed well and has mostly been used to maintain purebred populations in the government research institution. We investigated the genetic features of the KNC population in a selection signal study for the efficient improvement of this breed. We used 600K single nucleotide polymorphism data sampled from 191 KNCs (NG, 38; NL, 29; NR, 52; NW, 39; and NY, 33) and 54 commercial chickens (Hy-line Brown, 10; Lohmann Brown, 10; Arbor Acres, 10; Cobb, 12; and Ross, 12). Haplotype phasing was performed using EAGLE software as the initial step for the primary data analysis. Pre-processed data were analyzed to detect selection signals using the ‘rehh’ package in R software. A few common signatures of selection were identified in KNCs. Most quantitative trait locus regions identified as candidate regions were associated with traits related to reproductive organs, eggshell characteristics, immunity, and organ development. Block patterns with high linkage disequilibrium values were observed for LPP, IGF11, LMNB2, ERBB4, GABRB2, NTM, APOO, PLOA1, CNTN1, NTSR1, DEF3, CELF1, and MEF2D genes, among regions with confirmed selection signals. NL and NW lines contained a considerable number of selective sweep regions related to broilers and layers, respectively. We recommend focusing on improving the egg and meat traits of KNC NL and NW lines, respectively, while improving multiple traits for the other lines.
Experimental and Numerical Assessment of Seismic Retrofit Solutions for Stone Masonry Buildings
Authors: Guerrini Gabriele , Salvatori Christian , Senaldi Ilaria , Penna Andrea
Published: May 2021

This paper presents an experimental and numerical study on different retrofit solutions for stone masonry buildings with timber diaphragms in earthquake-prone regions, aiming at enhancing wall-to-diaphragm connections, diaphragms’ stiffness, and masonry properties. The experimental results of incremental dynamic shake-table tests on three full-scale two-story buildings, complemented by material and component characterization tests, are initially summarized. The first building specimen was unstrengthened. The second one was retrofitted at the floor and roof levels with improved wall-to-diaphragm connections and a moderate increase in diaphragm stiffness. Connections were also improved in the third specimen together with a significant enhancement of diaphragm stiffness. The calibration of two numerical models, versus the experimental response of the retrofitted building specimens, is then presented. The models were further modified and reanalyzed to assess the effects of masonry mechanical upgrades, which could be achieved in practice through deep joint repointing or various types of jacketing. These solutions were simulated by applying correction coefficients to the masonry mechanical properties, as suggested by the Italian building code. The effectiveness of the experimentally implemented and numerically simulated interventions are discussed in terms of strength enhancement and failure modes.
Dramatic Increases in Telehealth-Related Tweets during the Early COVID-19 Pandemic: A Sentiment Analysis
Authors: Champagne-Langabeer Tiffany , Swank Michael , Manas Shruthi , Si Yuqi , Roberts Kirk
Published: May 2021

The COVID-19 pandemic resulted in a large expansion of telehealth, but little is known about user sentiment. Tweets containing the terms “telehealth” and “telemedicine” were extracted (n = 192,430) from the official Twitter API between November 2019 and April 2020. A random subset of 2000 tweets was annotated by trained readers to classify tweets according to their content, including telehealth, sentiment, user type, and relation to COVID-19. A state-of-the-art NLP model (Bidirectional Encoder Representations from Transformers, BERT) was used to categorize the remaining tweets. Following a low and fairly stable level of activity, telehealth tweets rose dramatically beginning the first week of March 2020. The sentiment was overwhelmingly positive or neutral, with only a small percentage of negative tweets. Users included patients, clinicians, vendors (entities that promote the use of telehealth technology or services), and others, which represented the largest category. No significant differences were seen in sentiment across user groups. The COVID-19 pandemic produced a large increase in user tweets related to telehealth and COVID-19, and user sentiment suggests that most people feel positive or neutral about telehealth
Anxiety, Post-Traumatic Stress, and Burnout in Health Professionals during the COVID-19 Pandemic: Comparing Mental Health Professionals and Other Healthcare Workers
Authors: Franzoi Isabella Giulia , Granieri Antonella , Sauta Maria Domenica , Agnesone Monica , Gonella Marco , Cavallo Roberto , Lochner Piergiorgio , Bragazzi Nicola Luigi , Naldi Andrea
Published: May 2021

The psychological impact of the pandemic on healthcare workers has been assessed worldwide, but there are limited data on how mental health professionals (MHPs) have been affected. Thus, this paper aims to investigate anxiety, post-traumatic stress, and burnout in a sample of MHPs. We conducted a descriptive, cross-sectional study on 167 participants: 56 MHPs, 57 physicians working closely with COVID-19 patients, and 54 physicians not working closely with such patients. MHPs reported good overall mental health. Most MHPs reported no post-traumatic stress, and their scores were significantly lower compared to HPs working closely with COVID-19 patients. MHPs’ hyperarousal scores were also significantly lower compared to HPs working closely with COVID-19 patients, while their intrusion scores were statistically significantly lower than those of all other professionals. Multivariable logistic regressions showed that MHPs had lower odds of exhibiting state anxiety and low personal accomplishment compared to HPs not working closely with COVID-19 patients. In sum, MHPs seem to show almost preserved mental health. Thus, given the high mental healthcare demand during a pandemic, it would be useful to rely on these professionals, especially for structuring interventions to improve and support the mental health of the general population and other healthcare workers.
Gender-Specific Prevalence of Risk Factors for Non-Communicable Diseases by Health Service Use among Schoolteachers in Afghanistan
Authors: Alemi Sharifullah , Nakamura Keiko , Arab Ahmad Shekib , Mashal Mohammad Omar , Tashiro Yuri , Seino Kaoruko , Hemat Shafiqullah
Published: May 2021

Objectives of this study were: (1) to examine gender differences in biomedical indicators, lifestyle behaviors, self-health check practices, receipt of professional non-communicable disease (NCD)-related lifestyle advice, and the use of health services among teachers in Afghanistan; and (2) to seek the patterns of these indicators among users and non-users of health services among both male and female teachers. This cross-sectional study was carried out among 600 schoolteachers in Kabul city in February 2017. Gender differences in percentage distributions of abnormal biomedical indicators, lifestyle behaviors, self-health check practices, and receipt of professional lifestyle advice were examined. These patterns were further analyzed according to the use of health services in the previous 12 months by both genders. The results showed that male teachers had a higher prevalence of hypertension, increased serum triglycerides, physically active lifestyle, and tobacco use than female teachers (28.2/20.4, p = 0.038; 47.0/37.9, p = 0.040; 54.3/40.9, p = 0.002; 15.8/0.7, p < 0.001, respectively); female teachers had a higher prevalence of increased serum LDL cholesterol, overweight/obesity, and frequent consumption of fruits/vegetables than male teachers (61.3/50.8, p = 0.018; 64.7/43.5, p < 0.001; 71.4/53.8, p < 0.001, respectively). Female teachers were more likely to receive professional lifestyle advice related to NCDs than male teachers. Although users of health services practiced self-health checks and received professional lifestyle advice more frequently than non-users, abnormal biomedical indicators were similarly shown among users and non-users of health services in both genders. In conclusion, high prevalence of abnormal biomedical indicators was indicated in both male and female teachers, although the specific abnormal biomedical indicators differed by gender. Users and non-users of health services presented a similar prevalence of these abnormal indicators. Understanding the differences in patterns of NCD risk factors is essential when developing gender-informed policies.
Impact of 4th of July Fireworks on Spatiotemporal PM2.5 Concentrations in California Based on the PurpleAir Sensor Network: Implications for Policy and Environmental Justice
Authors: Mousavi Amirhosein , Yuan Yiting , Masri Shahir , Barta Greg , Wu Jun
Published: May 2021

Fireworks are often used in celebration, causing short term, extremely high particulate matter air pollution. In recent years, the rapid development and expansion of low-cost air quality sensors by companies such as PurpleAir has enabled an understanding of air pollution at a much higher spatiotemporal resolution compared to traditional monitoring networks. In this study, real-time PM2.5 measurements from 751 PurpleAir sensors operating from June to July in 2019 and 2020 were used to examine the impact of 4th of July fireworks on hourly and daily PM2.5 concentrations at the census tract and county levels in California. American Community Survey (ACS) and CalEnviroScreen 3.0 data were used to identify correlations between PM2.5 measurements and socioeconomic status (SES). A two-step method was implemented to assure the quality of raw PM2.5 sensor data and sensor calibration against co-located reference instruments. The results showed that over 67% and 81% of counties experienced immediate impacts related to fireworks in 2019 and 2020, respectively. Relative to 2019, the peak PM2.5 concentrations on July 4th and 5th 2020 were, on average, over 50% higher in California, likely due to the COVID-19-related increase in the use of household-level fireworks. This increase was most pronounced in southern counties, which tend to have less strict firework-related regulations and a greater use of illegal fireworks. Los Angeles County experienced the highest July 4th daily PM2.5 levels both in 2019 (29.9 µg·m−3) and 2020 (42.6 µg·m−3). Spatial hot spot analyses generally showed these southern counties (e.g., Los Angeles County) to be regional air pollution hotspots, whereas the opposite pattern was seen in the north (e.g., San Francisco). The results also showed PM2.5 peaks that were over two-times higher among communities with lower SES, higher minority group populations, and higher asthma rates. Our findings highlight the important role that policy and enforcement can play in reducing firework-related air pollution and protecting public health, as exemplified by southern California, where policy was more relaxed and air pollution was higher (especially in 2020 when the 4th of July coincided with the COVID-19-lockdown period), and in disadvantaged communities where disparities were greatest.
One-Year Lesson: Machine Learning Prediction of COVID-19 Positive Cases with Meteorological Data and Mobility Estimate in Japan
Authors: Rashed Essam A. , Hirata Akimasa
Published: May 2021

With the wide spread of COVID-19 and the corresponding negative impact on different life aspects, it becomes important to understand ways to deal with the pandemic as a part of daily routine. After a year of the COVID-19 pandemic, it has become obvious that different factors, including meteorological factors, influence the speed at which the disease is spread and the potential fatalities. However, the impact of each factor on the speed at which COVID-19 is spreading remains controversial. Accurate forecasting of potential positive cases may lead to better management of healthcare resources and provide guidelines for government policies in terms of the action required within an effective timeframe. Recently, Google Cloud has provided online COVID-19 forecasting data for the United States and Japan, which would help in predicting future situations on a state/prefecture scale and are updated on a day-by-day basis. In this study, we propose a deep learning architecture to predict the spread of COVID-19 considering various factors, such as meteorological data and public mobility estimates, and applied it to data collected in Japan to demonstrate its effectiveness. The proposed model was constructed using a neural network architecture based on a long short-term memory (LSTM) network. The model consists of multi-path LSTM layers that are trained using time-series meteorological data and public mobility data obtained from open-source data. The model was tested using different time frames, and the results were compared to Google Cloud forecasts. Public mobility is a dominant factor in estimating new positive cases, whereas meteorological data improve their accuracy. The average relative error of the proposed model ranged from 16.1% to 22.6% in major regions, which is a significant improvement compared with Google Cloud forecasting. This model can be used to provide public awareness regarding the morbidity risk of the COVID-19 pandemic in a feasible manner.
The Impact of the COVID-19 Pandemic on Primary Emotional Systems and Emotional Regulation
Authors: Mariani Rachele , Renzi Alessia , Di Monte Cinzia , Petrovska Elena , Di Trani Michela
Published: May 2021

(1) Background: The COronaVIrus Disease 2019 (COVID-19) pandemic poses a unique challenge as a severe global crisis affecting physical and psychological health. The main purpose of this work is to study the impact of a traumatic event while also observing the human ability to adapt. One of the first theories to study the adaptive importance of the evolutionary lineage of the affective systems is referred to as BrainMind (Panksepp, 2010). This study aims to explore whether primary emotional systems (PES) and emotion regulation (ER) strategies show differences between the pre- and post- lockdown period; and if positive systems and specific emotion regulation pre-pandemic act as a protective or risk factor for mental and physical wellbeing. (2) Methods: 98 participants who had participated in a previous study before the pandemic were re-contacted to refill the Affective Neuroscience Personality Scale (ANPS) and the Emotion Regulation Questionnaire (ERQ) after the outbreak of the pandemic with the addition of the Symptom Checklist-90-Revised (SCL-90R). (3) Results: The results showed that the COVID-19 lockdown rules had an impact on Emotional Regulation and on a re-balancing of PES. Moreover, pre-pandemic expressive–suppressive ERQ strategies and ANPS SADNESS scores appeared as relevant risk factors, which predicted higher Global Severity Index (GSI) scores during lockdown. (4) Conclusions: The lockdown appears to have activated PLAY and CARE as protective systems, but has detuned the ability to positively reinterpret the situation.
Oral Health: Global Research Performance under Changing Regional Health Burdens
Authors: Ahmadi Salim , Klingelhöfer Doris , Erbe Christina , Holzgreve Fabian , Groneberg David A. , Ohlendorf Daniela
Published: May 2021

Objectives: Inadequate oral hygiene still leads to many serious diseases all over the world. Therefore, this study aimed to analyze scientific research in the field of oral health in order to be able to comprehend their relevant subject areas, research connections, or developments. Methods: This study aimed to assess the global publication output on oral hygiene to create a world map that provides background information on key players, trends, and incentives of research. For this purpose, established bibliometric parameters were combined with state-of-the-art visualization techniques. Results: This study shows the actual key players of research on oral hygiene in high-income economies with only marginal participation from lower economies. This still corresponds to the current burden situations, but they are more and more shifting to the disadvantage of the low-income countries. There is a clear North–South and West–East gradient, with the USA and the Western European nations being the most publishing nations on oral hygiene. As an emerging country, Brazil plays a role in the research. Conclusions: The scientific power players were concentrated in high-income countries. However, the changing epidemiological situation requires a different scientific approach to oral hygiene. This requires an expansion of the international network to meet the demands of future global oral health burdens, which are mainly related to oral hygiene.
Differences in Neuropsychological Performance between Refugee and Non-Refugee Children in Palestine
Authors: Fasfous Ahmed F. , Pérez-Marfil María Nieves , Cruz-Quintana Francisco , Pérez-García Miguel , Al-Yamani Hala R. , Fernández-Alcántara Manuel
Published: May 2021

Neuropsychological studies on refugee children are scarce, but there are even less in the case of Palestinian children. This work aims to study the neuropsychological performance of Palestinian refugee children in Palestine compared to other Palestinian children living outside refugee camps. A comprehensive Neuropsychological battery was administrated to 584 Palestinian school children (464 refugees and 120 non-refugees) aged 6, 7, and 8 years old. Results showed that non-refugee children outperformed refugee children in sustained attention, verbal comprehension, verbal memory, and visual memory. This study is the first to have performed a comprehensive neuropsychological assessment, based on a standardized and validated battery with the Palestinian refugee children. It supports professionals in their evaluation of neurodevelopment and neuropsychological alterations in refugee and non-refugee children in Palestine.
Association between Job-Related Factors and Work-Related Anxiety, and Moderating Effect of Decision-Making Authority in Korean Wageworkers: A Cross-Sectional Study
Authors: Kim Sang-Woo , Ha Junghee , Lee June-Hee , Yoon Jin-Ha
Published: May 2021

Among the factors causing workers’ anxiety, job-related factors are important since they can be managed. Therefore, this study aimed to analyze the association between work-related anxiety and job-related factors among Korean wageworkers using data from the Fifth Korean Working Conditions Survey. Participants were 13,600 Korean wageworkers aged <65 years. We analyzed the association between job-related factors and work-related anxiety, and the moderating effect of decision-making authority. “Meeting precise quality standards,” “Solving unforeseen problems on your own,” “Complex tasks,” “Learning new things,” “Working at very high speed,” and “Working to tight deadlines” were positively associated with work-related anxiety. “Monotonous tasks” was negatively associated with work-related anxiety. The odds ratio (OR) of “Complex tasks” was higher in the group that had insufficient decision-making authority (OR 3.92, 95% confidential interval (CI) 2.40–6.42) compared to that with sufficient decision-making authority (OR 2.74, 95% CI 1.61–4.67). The risk of work-related anxiety was higher when the workers experienced time pressure, carried out tasks with high mental and physical demands, and dealt with unpredictable situations. This association was more pronounced when decision-making authority was insufficient.
Dimensions of Community Assets for Health. A Systematised Review and Meta-Synthesis
Authors: Sáinz-Ruiz Pablo Alberto , Sanz-Valero Javier , Gea-Caballero Vicente , Melo Pedro , Nguyen Tam H. , Suárez-Máximo Juan Daniel , Martínez-Riera José Ramón
Published: May 2021

Since Aaron Antonovsky’s salutogenesis theory and Morgan and Ziglio’s health assets model were first proposed, there has been a growing concern to define the resources available to the individual and the community to maintain or improve health and well-being. The aim of the present study was to identify the dimensions that characterise community assets for health. To this end, we conducted a systematised review with a meta-synthesis and content analysis of research or projects involving asset mapping in the community. Articles that met our eligibility criteria were: (1) based on the salutogenic approach and (2) described an assets mapping process and among their results, explained what, how and why particular community assets for health had been selected. The search included primary studies in the published and grey literature which were selected from websites and electronic databases (Web of Science, MEDLINE, Scopus, EBSCOhost, Dialnet, SciELO). Of the 607 records examined by a single reviewer, 34 were included in the content analysis and 14 in the qualitative synthesis. Using an inductive process, we identified 14 dimensions with 24 categories, for which in-depth literature reviews were then carried out to define specific indicators and items. These dimensions were: utility, intention, previous use, accessibility (“circumstances–opportunity–affordability”), proximity-walkability, connectivity, intelligibility (visibility, transparency), identity (uniqueness, appropriability, attachment), design (configuration, functionality, comfort), safety (objective/subjective), diversity, the dimension of public and private, and sustainability (which includes maintenance, profitability or economic sustainability, environmental sustainability, centrality-participation and equity-inclusiveness).
‘Difficult Conversations with Patients’—A Modified Group Objective Structured Clinical Experience for Medical Students
Authors: Przymuszała Piotr , Marciniak-Stępak Patrycja , Cerbin-Koczorowska Magdalena , Borowczyk Martyna , Cieślak Katarzyna , Szlanga Lidia , Zielińska-Tomczak Łucja , Marciniak Ryszard
Published: May 2021

This study presents a modified Group Objective Structured Clinical Experience (GOSCE) focused on difficult conversations, in which, due to limited time and financial resources, only some students could actively participate in scenarios. We aimed to evaluate the intervention, including differences between them and observers. The intervention was organized for sixth-year medical students at a Polish medical university. The study protocol assumed a pre-post analysis of students’ attitudes and self-efficacy of communication skills and their opinions about the intervention. Complete questionnaire pairs were returned by 126 students. The pre-post analysis revealed a significant improvement in their self-efficacy levels of almost all skills as well as their affective attitudes and belief in outcomes of communication learning. The improvement was significant among both the active participants and observers. It also showed a decrease in the motivation score, significant only in females. Regardless of their roles, students had positive opinions about the course and its particular aspects. The modified GOSCE may be an enjoyable and effective learning experience for students, especially in the light of limited resources. However, changes in their motivation score suggest the necessity to increase the importance of communication learning in the curriculum.
Next-Generation Sequencing Applications for Inherited Retinal Diseases
Authors: Dockery Adrian , Whelan Laura , Humphries Pete , Farrar G. Jane
Published: May 2021

Inherited retinal diseases (IRDs) represent a collection of phenotypically and genetically diverse conditions. IRDs phenotype(s) can be isolated to the eye or can involve multiple tissues. These conditions are associated with diverse forms of inheritance, and variants within the same gene often can be associated with multiple distinct phenotypes. Such aspects of the IRDs highlight the difficulty met when establishing a genetic diagnosis in patients. Here we provide an overview of cutting-edge next-generation sequencing techniques and strategies currently in use to maximise the effectivity of IRD gene screening. These techniques have helped researchers globally to find elusive causes of IRDs, including copy number variants, structural variants, new IRD genes and deep intronic variants, among others. Resolving a genetic diagnosis with thorough testing enables a more accurate diagnosis and more informed prognosis and should also provide information on inheritance patterns which may be of particular interest to patients of a child-bearing age. Given that IRDs are heritable conditions, genetic counselling may be offered to help inform family planning, carrier testing and prenatal screening. Additionally, a verified genetic diagnosis may enable access to appropriate clinical trials or approved medications that may be available for the condition.
The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications
Authors: Tsai Chang-Youh , Hsieh Song-Chou , Liu Chih-Wei , Lu Cheng-Hsun , Liao Hsien-Tzung , Chen Ming-Han , Li Ko-Jen , Wu Cheng-Han , Shen Cheih-Yu , Kuo Yu-Min , Yu Chia-Li
Published: May 2021

Rheumatoid arthritis (RA) is a typical autoimmune-mediated rheumatic disease presenting as a chronic synovitis in the joint. The chronic synovial inflammation is characterized by hyper-vascularity and extravasation of various immune-related cells to form lymphoid aggregates where an intimate cross-talk among innate and adaptive immune cells takes place. These interactions facilitate production of abundant proinflammatory cytokines, chemokines and growth factors for the proliferation/maturation/differentiation of B lymphocytes to become plasma cells. Finally, the autoantibodies against denatured immunoglobulin G (rheumatoid factors), EB virus nuclear antigens (EBNAs) and citrullinated protein (ACPAs) are produced to trigger the development of RA. Furthermore, it is documented that gene mutations, abnormal epigenetic regulation of peptidylarginine deiminase genes 2 and 4 (PADI2 and PADI4), and thereby the induced autoantibodies against PAD2 and PAD4 are implicated in ACPA production in RA patients. The aberrant expressions of non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) in the immune system undoubtedly derange the mRNA expressions of cytokines/chemokines/growth factors. In the present review, we will discuss in detail the expression of these ncRNAs and their target molecules participating in developing RA, and the potential biomarkers for the disease, its diagnosis, cardiovascular complications and therapeutic response. Finally, we propose some prospective investigations for unraveling the conundrums of rheumatoid pathogenesis.
High Doses of D-Chiro-Inositol Alone Induce a PCO-Like Syndrome and Other Alterations in Mouse Ovaries
Authors: Bevilacqua Arturo , Dragotto Jessica , Lucarelli Micaela , Di Emidio Giovanna , Monastra Giovanni , Tatone Carla
Published: May 2021

Administration of 1000–1500 mg/day D-Chiro-Inositol (DCIns) or a combination of Myo-Inositol (MyoIns) and DCIns in their plasma molar ratio (40:1) for three or more months are among recommended treatments for metabolic syndrome and/or Polycystic Ovary Syndrome (PCOS). We previously confirmed the efficacy of this formulation (8.2 mg/day MyoIns and 0.2 mg/day DCIns for 10 days) in a mouse PCOS model, but also observed negative effects on ovarian histology and function of formulations containing 0.4–1.6 mg/day DCIns. We therefore analyzed effects of higher doses of DCIns, 5, 10 and 20 mg/day, administered to young adult female mice for 21 days, on ovarian histology, serum testosterone levels and expression of the ovarian enzyme aromatase. Five mg/day DCIns (human correspondence: 1200 mg/day) altered ovarian histology, increased serum testosterone levels and reduced the amount of aromatase of negative controls, suggesting the induction of an androgenic PCOS model. In contrast, 10–20 mg/day DCIns (human correspondence: 2400–4800 mg/day) produced ovarian lesions resembling those typical of aged mice, and reduced serum testosterone levels without affecting aromatase amounts, suggesting a failure in steroidogenic gonadal activity. Notwithstanding physiological/biochemical differences between mice and humans, the observed pictures of toxicity for ovarian histology and function recommend caution when administering DCIns to PCOS patients at high doses and/or for periods spanning several ovulatory cycles.
mRNA Expression of SMPD1 Encoding Acid Sphingomyelinase Decreases upon Antidepressant Treatment
Authors: Rhein Cosima , Zoicas Iulia , Marx Lena M. , Zeitler Stefanie , Hepp Tobias , von Zimmermann Claudia , Mühle Christiane , Richter-Schmidinger Tanja , Lenz Bernd , Erim Yesim , Reichel Martin , Gulbins Erich , Kornhuber Johannes
Published: May 2021

Major depressive disorder (MDD) is a severe psychiatric condition with key symptoms of low mood and lack of motivation, joy, and pleasure. Recently, the acid sphingomyelinase (ASM)/ceramide system has been implicated in the pathogenesis of MDD. ASM is a lysosomal glycoprotein that catalyzes the hydrolysis of sphingomyelin, an abundant component of membranes, into the bioactive sphingolipid ceramide, which impacts signaling pathways. ASM activity is inhibited by several common antidepressant drugs. Human and murine studies have confirmed that increased ASM activity and ceramide levels are correlated with MDD. To define a molecular marker for treatment monitoring, we investigated the mRNA expression of SMPD1, which encodes ASM, in primary cell culture models, a mouse study, and a human study with untreated MDD patients before and after antidepressive treatment. Our cell culture study showed that a common antidepressant inhibited ASM activity at the enzymatic level and also at the transcriptional level. In a genetically modified mouse line with depressive-like behavior, Smpd1 mRNA expression in dorsal hippocampal tissue was significantly decreased after treatment with a common antidepressant. The large human study showed that SMPD1 mRNA expression in untreated MDD patients decreased significantly after antidepressive treatment. This translational study shows that SMPD1 mRNA expression could serve as a molecular marker for treatment and adherence monitoring of MDD.
Bruton’s Tyrosine Kinase Targeting in Multiple Myeloma
Authors: Von Suskil Max , Sultana Kazi Nasrin , Elbezanti Weam Othman , Al-Odat Omar S. , Chitren Robert , Tiwari Amit K. , Challagundla Kishore B. , Srivastava Sandeep Kumar , Jonnalagadda Subash C. , Budak-Alpdogan Tulin , Pandey Manoj K.
Published: May 2021

Multiple myeloma (MM), a clonal plasma cell disorder, disrupts the bones’ hematopoiesis and microenvironment homeostasis and ability to mediate an immune response against malignant clones. Despite prominent survival improvement with newer treatment modalities since the 2000s, MM is still considered a non-curable disease. Patients experience disease recurrence episodes with clonal evolution, and with each relapse disease comes back with a more aggressive phenotype. Bruton’s Tyrosine Kinase (BTK) has been a major target for B cell clonal disorders and its role in clonal plasma cell disorders is under active investigation. BTK is a cytosolic kinase which plays a major role in the immune system and its related malignancies. The BTK pathway has been shown to provide survival for malignant clone and multiple myeloma stem cells (MMSCs). BTK also regulates the malignant clones’ interaction with the bone marrow microenvironment. Hence, BTK inhibition is a promising therapeutic strategy for MM patients. In this review, the role of BTK and its signal transduction pathways are outlined in the context of MM.
Therapies Targeted at Non-Coding RNAs in Prevention and Limitation of Myocardial Infarction and Subsequent Cardiac Remodeling—Current Experience and Perspectives
Authors: Kowara Michal , Borodzicz-Jazdzyk Sonia , Rybak Karolina , Kubik Maciej , Cudnoch-Jedrzejewska Agnieszka
Published: May 2021

Myocardial infarction is one of the major causes of mortality worldwide and is a main cause of heart failure. This disease appears as a final point of atherosclerotic plaque progression, destabilization, and rupture. As a consequence of cardiomyocytes death during the infarction, the heart undergoes unfavorable cardiac remodeling, which results in its failure. Therefore, therapies aimed to limit the processes of atherosclerotic plaque progression, cardiac damage during the infarction, and subsequent remodeling are urgently warranted. A hopeful therapeutic option for the future medicine is targeting and regulating non-coding RNA (ncRNA), like microRNA, circular RNA (circRNA), or long non-coding RNA (lncRNA). In this review, the approaches targeted at ncRNAs participating in the aforementioned pathophysiological processes involved in myocardial infarction and their outcomes in preclinical studies have been concisely presented.
Brain-Derived Neurotrophic Factor Signaling in the Pathophysiology of Alzheimer’s Disease: Beneficial Effects of Flavonoids for Neuroprotection
Authors: Numakawa Tadahiro , Odaka Haruki
Published: May 2021

The function of the brain-derived neurotrophic factor (BDNF) via activation through its high-affinity receptor Tropomyosin receptor kinase B (TrkB) has a pivotal role in cell differentiation, cell survival, synaptic plasticity, and both embryonic and adult neurogenesis in central nervous system neurons. A number of studies have demonstrated the possible involvement of altered expression and action of the BDNF/TrkB signaling in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). In this review, we introduce an essential role of the BDNF and its downstream signaling in neural function. We also review the current evidence on the deregulated the BDNF signaling in the pathophysiology of AD at gene, mRNA, and protein levels. Further, we discuss a potential usefulness of small compounds, including flavonoids, which can stimulate BDNF-related signaling as a BDNF-targeting therapy.
Sound Waves Promote Arabidopsis thaliana Root Growth by Regulating Root Phytohormone Content
Authors: Kim Joo Yeol , Lee Hyo-Jun , Kim Jin A , Jeong Mi-Jeong
Published: May 2021

Sound waves affect plants at the biochemical, physical, and genetic levels. However, the mechanisms by which plants respond to sound waves are largely unknown. Therefore, the aim of this study was to examine the effect of sound waves on Arabidopsis thaliana growth. The results of the study showed that Arabidopsis seeds exposed to sound waves (100 and 100 + 9k Hz) for 15 h per day for 3 day had significantly longer root growth than that in the control group. The root length and cell number in the root apical meristem were significantly affected by sound waves. Furthermore, genes involved in cell division were upregulated in seedlings exposed to sound waves. Root development was affected by the concentration and activity of some phytohormones, including cytokinin and auxin. Analysis of the expression levels of genes regulating cytokinin and auxin biosynthesis and signaling showed that cytokinin and ethylene signaling genes were downregulated, while auxin signaling and biosynthesis genes were upregulated in Arabidopsis exposed to sound waves. Additionally, the cytokinin and auxin concentrations of the roots of Arabidopsis plants increased and decreased, respectively, after exposure to sound waves. Our findings suggest that sound waves are potential agricultural tools for improving crop growth performance.
Constructing Crop Portraits Based on Graph Databases Is Essential to Agricultural Data Mining
Authors: Shi Yue-Xin , Zhang Bo-Kai , Wang Yong-Xiang , Luo Han-Qian , Li Xiang
Published: May 2021

Neo4j is a graph database that can use not only data, but also data relationships. Crop portraits, a kind of property graph, model the crop entity in the real world based on data to realize the networked management of crop knowledge. The existing crop knowledge base has shortcomings such as single crop variety, incomplete description, and lack of agricultural knowledge. Constructing crop portraits can provide a comprehensive description of crops and make up for these shortcomings. This research used agricultural question-and-answer data and popular science data obtained by text crawling as the original data, selected labels to establish a crop portrait that including three categories (crops, pesticides, and diseases and pests), and used the graph database (Neo4j) to store and display these portrait data. Information mining found that the crop portrait revealed the occurrence trend of diseases and pests, exhibited a nonintrinsic connection between different diseases and pests, and provided a variety of pesticides to choose from for control of diseases and pests. The results showed that constructing crop portraits is beneficial to agricultural analysis, and has practical application values and theoretical research prospects in the field of big data analytics.
Improved Relief Weight Feature Selection Algorithm Based on Relief and Mutual Information
Authors: Wang Hongbin , Wang Pengming , Deng Shengchun , Li Haoran
Published: May 2021

As the classic feature selection algorithm, the Relief algorithm has the advantages of simple computation and high efficiency, but the algorithm itself is limited to only dealing with binary classification problems, and the comprehensive distinguishing ability of the feature subsets composed of the former K features selected by the Relief algorithm is often redundant, as the algorithm cannot select the ideal feature subset. When calculating the correlation and redundancy between characteristics by mutual information, the computation speed is slow because of the high computational complexity and the method’s need to calculate the probability density function of the corresponding features. Aiming to solve the above problems, we first improve the weight of the Relief algorithm, so that it can be used to evaluate a set of candidate feature sets. Then we use the improved joint mutual information evaluation function to replace the basic mutual information computation and solve the problem of computation speed and correlation, and redundancy between features. Finally, a compound correlation feature selection algorithm based on Relief and joint mutual information is proposed using the evaluation function and the heuristic sequential forward search strategy. This algorithm can effectively select feature subsets with small redundancy and strong classification characteristics, and has the excellent characteristics of faster calculation speed.
The eSpiro Ventilator: An Open-Source Response to a Worldwide Pandemic
Authors: Terzi Nicolas , Rastello Fabrice , Déhan Christophe , Roux Marion , Sigaud Florian , Rigault Guillaume , Fromentin Cyril , Farrugia Adrien , Guérin Claude
Published: May 2021

Objective: To address the issue of ventilator shortages, our group (eSpiro Network) developed a freely replicable, open-source hardware ventilator. Design: We performed a bench study. Setting: Dedicated research room as part of an ICU affiliated to a university hospital. Subjects: We set the lung model with three conditions of resistance and linear compliance for mimicking different respiratory mechanics of representative intensive care unit (ICU) patients. Interventions: The performance of the device was tested using the ASL5000 lung model. Measurements and Main Results: Twenty-seven conditions were tested. All the measurements fell within the ±10% limits for the tidal volume (VT). The volume error was influenced by the mechanical condition (p = 5.9 × 10−15) and the PEEP level (P = 1.1 × 10−12) but the clinical significance of this finding is likely meaningless (maximum −34 mL in the error). The PEEP error was not influenced by the mechanical condition (p = 0.25). Our experimental results demonstrate that the eSpiro ventilator is reliable to deliver VT and PEEP accurately in various respiratory mechanics conditions. Conclusions: We report a low-cost, easy-to-build ventilator, which is reliable to deliver VT and PEEP in passive invasive mechanical ventilation.
Post-Diagnostic Statin Use Reduces Mortality in South Korean Patients with Dyslipidemia and Gastrointestinal Cancer
Authors: Han Kyu-Tae , Kim Seungju
Published: May 2021

Background: Statins play a role in lowering serum cholesterol and are known to have pleiotropic effects in a variety of diseases, including cancer. Despite the beneficial effects of statins in dyslipidemia patients, the treatment rate for dyslipidemia in Korea remains low, and evidence supporting the continued use of statins is lacking. The purpose of this study was to evaluate the effect of continued statin use and dosage on patient mortality after diagnosis of dyslipidemia and gastrointestinal (GI) cancer. Methods: We used data from the National Health Insurance Sampling (NHIS) cohort to evaluate patients diagnosed with dyslipidemia from 2002 to 2015. A total of 901 GI cancer patients with dyslipidemia and 62,727 non-cancer dyslipidemia patients were included in the study. During the study period, each patient’s medication possession ratio (MPR) after diagnosis was evaluated as a measure of continued statin use. Statin dosage was measured based on a defined daily dose (DDD). Finally, we used Cox-proportional hazard ratios to identify associations between the continual use of statins and mortality in patients with dyslipidemia and GI cancer. Results: In our study, mortality decreased with increasing MPR and reached significance in MPRs exceeding 50% for GI cancer patients and 75% for dyslipidemia patients compared to patients that did not use statins. Moreover, patients with high MPRs had significantly reduced 5-year mortality compared to non-users, and cause-specific mortality analyses revealed that high MPR was associated with decreased colorectal cancer death. We did not find a significant dose–response relationship between statins and mortality. Conclusion: Our findings suggest that continued statin use after diagnosis is associated with reduced patient mortality. Altogether, these results support the continued use of statins in dyslipidemia patients with and without GI cancer and highlight the importance of patient education by healthcare providers.
Arthroscopic Treatment Results of Triangular Fibrocartilage Complex Tears in Adolescents: A Systematic Review
Authors: Schachinger Florian , Farr Sebastian
Published: May 2021

Introduction: Injury to the triangular fibrocartilage complex (TFCC) may cause chronic wrist pain and instability if left untreated. The current literature of adult cases suggests that arthroscopic treatment offers favorable outcomes and is associated with a low complication rate. This systematic review evaluated the outcomes of arthroscopic TFCC surgery in adolescents. Materials and Methods: A PRISMA-guided literature search of PubMed, Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Cochrane Clinical Answers was conducted in May 2020. All studies reporting on (1) arthroscopic TFCC repair or debridement in (2) patients under the age of 19 years with (3) a minimum case number of four patients were extracted by two independent observers. The level of evidence of each study was assessed according to the Oxford Centre for Evidence-Based Medicine, and study quality was graded according to the Modified Coleman Methodology Score and the MINORS criteria. Clinical outcome scores, functional parameters, and any complications were reviewed. Results: The selected search terms initially resulted in a total of 986 possible articles. The authors eventually identified eight papers (all LoE IV) for inclusion in this systematic review. A total of 254 patients with verified TFCC tears and a mean age of 16 years (range, 7–19) received arthroscopic repair (162 patients, 67.1% of total) or debridement (77 patients, 29.7% of total). Arthroscopic treatment resulted in low pain levels, high patient satisfaction, and a fast return to sport. Complications overall were sparse and consisted mainly of persistent wrist pain (n = 31) and temporary paresthesia (n = 6) of the dorsal sensory branch of the ulnar nerve. Recurrent tears were sparse, with only four reported cases due to sports participation. Conclusion: Wrist arthroscopy is a reliable surgical option for treating TFCC tears in adolescents. The results obtained are comparable to those published in the literature. However, the variety of repair techniques and the low level of evidence across all included articles demand further prospective studies.
Endometrial Perivascular Progenitor Cells and Uterus Regeneration
Authors: Li Shiyuan , Ding Lijun
Published: May 2021

Ovarian steroid-regulated cyclical regeneration of the endometrium is crucial for endometrial receptivity and embryo implantation, and it is dependent on the dynamic remodeling of the endometrial vasculature. Perivascular cells, including pericytes surrounding capillaries and microvessels and adventitial cells located in the outermost layer of large vessels, show properties of mesenchymal stem cells, and they are thus promising candidates for uterine regeneration. In this review, we discuss the structure and functions of the endometrial blood vasculature and their roles in endometrial regeneration, the main biomarkers and characteristics of perivascular cells in the endometrium, and stem cell-based angiogenetic therapy for Asherman’s syndrome.