bluuebunny/crossref_metadata_2025 huggingface dataset:
Students’ Perceptions in Online Physical Education Learning: Comparison Study of Autonomy, Competence, and Relatedness in Saudi Students during the COVID-19 Lockdown
Authors: Frikha Mohamed , Chaâri Nesrine , Mezghanni Nourhen , Alhumaid Majed M. , Alibrahim Mohammed S.
Published: November 2022

The interest in the efficiency of online learning was and remains a major concern to researchers especially during the worldwide pandemic crisis (COVID-19). Nonetheless, there is a lack of studies focusing on students’ perceptions in online physical education (PE) learning sessions. Based on the self-determination theory (SDT), the present investigation aimed to explore psychological need satisfaction (PNS) to understand the autonomy, competence, and relatedness of Saudi PE students during the online sessions undertaken during the COVID-19 pandemic lockdown. PE students (N = 321, 161 females and 160 males) completed an online questionnaire composed of demographic characteristics, grade point average (GPA), sleep and physical activity (PA) habits, and the physical education autonomy relatedness competence scales (PE-ARCS). A t-test and one-way ANOVA were conducted and revealed that female students presented higher PNS compared with males. Students practicing PA had higher autonomy values than those not practicing PA (p = 0.001). However, no differences were recorded concerning competence and relatedness perceptions. The groups practicing walking, aerobic exercise, muscular training, and specialty training had higher values in autonomy and relatedness. The groups that slept for more than six hours a night, had previous experience with online learning, and had a GPA of more than three recorded higher PNS values. Correlation analysis showed high interdependence of the three PNS variables as well as with the variables of gender, experience with online learning, sleep hours, and type of PA practiced, but not with GPA or frequency of PA practice. The PNS values regarding online PE sessions were (i) higher in female students compared with males and (ii) related to previous experience in online learning, GPA, sleep habits, and type of PA. Walking, aerobic exercise, muscular training, and training in a specialty affected both autonomy and competence perception; however, relatedness was mainly affected by walking activity. Therefore, it is necessary to support ICT knowledge of students with low GPAs and to encourage them to adopt balanced sleep and physical activity habits to increase their perceptions of autonomy, competence, and relatedness in online PE lessons.
Before-and-After Study of the First Four Years of the Enhanced Recovery after Surgery (ERAS®) Programme in Older Adults Undergoing Elective Colorectal Cancer Surgery
Authors: Martínez-Escribano Cristina , Arteaga Moreno Francisco , Cuesta Peredo David , Blanco Gonzalez Francisco Javier , De la Cámara-de las Heras Juan Maria , Tarazona Santabalbina Francisco J.
Published: November 2022

Background: The aim of this study was to determine whether the inclusion of older patients undergoing elective colorectal cancer resection in the Enhanced Recovery After Surgery (ERAS®) programme could improve clinical outcomes during hospital admission. Methods: A before-and-after study in ≥70-year-old patients electively admitted for colorectal cancer resection was designed. In total, 213 patients were included in the ERAS® group, and 158 were included in the control group. Results: The average age was 77.9 years old (SD 5.31) and 57.14% of them were men, with a Charlson Index score of 3.42 (SD 3.32). The ERAS® group presented a lower transfusion rate of 42 (19.7%), compared to 75 (47.5%) in the control group (p < 0.001). The crude odds ratio (OR) for transfusion was 0.27 (95% CI 0.17–0.43; p < 0.001), and the adjusted odds ratio was 0.26 (95% CI 0.14–0.48; p < 0.001). The ERAS® group had a lower percentage of patients with moderate–severe malnutrition on admission, at 23.4% (37 patients) against 36.2% in the control group (42 patients) (p = 0.023), with an OR of 0.47 (95% CI 0.29–0.75; p < 0.002) and an adjusted OR of 0.48 (95% CI 0.29–0.78; p = 0.003). The number of patients who required admission to the intensive care unit (ICU) was also markedly lower: 54 from the ERAS® group (25.4%) versus 71 from the control group (44.9%) (p < 0.001). Conclusions: The inclusion of ≥70-year-old adults in the ERAS® programme resulted in a decrease in transfusions, number of erythrocyte concentrates transfused, and number of ICU admissions, along with improved nutritional status.
Chronic Cadmium Exposure and Genetic Polymorphisms of MMP-2 and MMP-9 in a Population Exposed to Steel Slag in the State of Rio de Janeiro, Brazil: A Cross-Sectional Study
Authors: Perini Jamila A. , Silva Mayara C. da , Correa Lorena V. , Silva Yasmin M. , Borges Renato M. , Moreira Maria de Fátima R.
Published: November 2022

Genetic polymorphisms in the matrix metalloproteinases (MMPs) family genes may be associated with cadmium (Cd) levels and its adverse effects. This study investigated the impact of MMP-2 and MMP-9 polymorphisms on Cd levels in 238 residents of a condominium in Rio de Janeiro, Brazil, built over an industrial steel slag waste. Polymorphisms were genotyped using TaqMan validated assays, and the Cd levels were measured in blood (BCd) and urine (UCd) samples by atomic absorption spectrometry. Associations were evaluated by linear correlation coefficients and multiple logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 50 ± 15 years; 58% were female, 69% non-smokers. Mean concentrations for BCd and UCd were 0.70 ± 0.2 μg L−1 and 0.56 ± 0.55 μg L−1, respectively. Smoking status was associated with BCd ≥ 0.70 μg L−1 (OR = 2.9; 95% CI = 1.6–5.9). MMP-9 rs17576 A > G was associated with BCd ≥ 0.70 μg L−1 (OR = 2.11; 95% CI = 1.10–4.05) and UCd ≥ 0.56 μg L−1 (OR = 3.38; 95% CI = 1.82–7.65). Knowing possible individual predisposing factors is essential to understand Cd toxicity, and to improve the monitoring of high-risk populations.
SARS-CoV-2 in Pregnancy—A Retrospective Analysis of Selected Maternal and Fetal Laboratory Parameters
Authors: Sobkowski Maciej , Pięta Beata , Sowińska Anna , Grabowska Marlena , Koch-Brzozowska Katarzyna , Wilczak Maciej , Bień Agnieszka
Published: November 2022

Pregnant women and their neonates belong to the group of individuals with elevated risk for COVID-19 infection. Data on the course of the disease and how it affects the pregnancy and neonatal wellbeing remain conflicting. The aim of the study was to evaluate the effect of SARS CoV-2 infection on the mode of delivery, neonatal condition and selected maternal and fetal laboratory parameters. This was a single-center retrospective case–control study. This dataset was generated using electronic medical records collected by medical personnel. Two groups of patients, hospitalized between April, 2020 and February, 2021, were included in the study: study group (304)—pregnant women with SARS-CoV-2 and control group (N = 329)—healthy pregnant women or parturients. Mothers with a severe course of COVID-19 had higher activated partial thromboplastin—APTT (p = 0.02), C-Reactive Protein—CRP (p = 0.00) and procalcitonin (p = 0.032) levels as compared to pregnant women with mild or moderate course of the disease. Neonates born to SARS-CoV-2-infected mothers presented with worse condition at 1 and 5 minutes of life (p = 0.000 and 0.00, respectively) and lower Arterial Blood Gas—ABG pH scores (p = 0.016). Elective cesarean section is the most common mode of delivery for SARS-CoV2-infected mothers. Emergency cesarean sections are performed at earlier gestational age as compared to vaginal delivery and elective cesarean section. Lower Apgar scores were observed in neonates born to SARS-CoV-2-infected mothers who required oxygen therapy and whose procalcitonin levels were elevated. There is a relationship between more severe course of COVID-19 and APTT, as well as CRP and procalcitonin levels.
Well-Being, Physical Activity, and Social Support in Octogenarians with Heart Failure during COVID-19 Confinement: A Mixed-Methods Study
Authors: Marques-Sule Elena , Muñoz-Gómez Elena , Almenar-Bonet Luis , Moreno-Segura Noemi , Sánchez-Gómez María-Cruz , Deka Pallav , López-Vilella Raquel , Klompstra Leonie , Cabanillas-García Juan Luis
Published: November 2022

Background: This study aimed to compare well-being and physical activity (PA) before and during COVID-19 confinement in older adults with heart failure (HF), to compare well-being and PA during COVID-19 confinement in octogenarians and non-octogenarians, and to explore well-being, social support, attention to symptoms, and assistance needs during confinement in this population. Methods: A mixed-methods design was performed. Well-being (Cantril Ladder of Life) and PA (International Physical Activity Questionnaire) were assessed. Semi-structured interviews were performed to assess the rest of the variables. Results: 120 participants were evaluated (74.16 ± 12.90 years; octogenarians = 44.16%, non-octogenarians = 55.83%). Both groups showed lower well-being and performed less PA during confinement than before (p < 0.001). Octogenarians reported lower well-being (p = 0.02), higher sedentary time (p = 0.03), and lower levels of moderate PA (p = 0.04) during confinement. Most individuals in the sample considered their well-being to have decreased during confinement, 30% reported decreased social support, 50% increased their attention to symptoms, and 60% were not satisfied with the assistance received. Octogenarians were more severely impacted during confinement than non-octogenarians in terms of well-being, attention to symptoms, and assistance needs. Conclusions: Well-being and PA decreased during confinement, although octogenarians were more affected than non-octogenarians. Remote monitoring strategies are needed in elders with HF to control health outcomes in critical periods, especially in octogenarians.
The Implementation and Role of Antigen Rapid Test for COVID-19 in Hemodialysis Units
Authors: Qi Jing , Tan Jia Neng , Hui Soh Heng , Lim Neoh Choo , Lau Titus , Haroon Sabrina
Published: November 2022

As we move into the third year with COVID-19, many countries have attempted to manage the disease as an endemic. However, this is limited by the disease’s morbidity and mortality, the emergence of new strains, and the effectiveness of the vaccine. This brief report describes, evaluates, and discusses the implementation of regular antigen rapid tests (ARTs) for COVID-19 in hemodialysis units. We introduced ARTs during the surge in our hemodialysis units. As compliance with the test was mandatory by regulatory requirements, we surveyed patients and caregivers to measure their acceptability, appropriateness, and feasibility of the ART’s implementation. Acceptability measured confidence and level of comfort when performing ART tests, while appropriateness measured the perception of the necessity of ARTs, safety in the dialysis unit with the implementation of ARTs, and understanding using a Likert scale. Feasibility measured the perception of the timely start of dialysis treatment and the convenience of the test. Our survey found that ARTs were acceptable to 98% of patients and caregivers, with the majority reporting no discomfort. The majority of the patients agreed that ARTs were appropriate and feasible. We reported successful ART implementation in a healthcare setting with no false-positive or transmission within the unit during this period. Nevertheless, the long-term implementation outcome will require further evaluation.
The Effects of Ventilation, Humidity, and Temperature on Bacterial Growth and Bacterial Genera Distribution
Authors: Qiu Yujia , Zhou Yan , Chang Yanfen , Liang Xinyue , Zhang Hui , Lin Xiaorui , Qing Ke , Zhou Xiaojie , Luo Ziqiang
Published: November 2022

Background: Bacteria are readily nourished in airtight environments with high humidity, such as storage cabinets, clothing closets, and corners, where ventilation is normally low and humidity is high. Objectives: We characterized the role of humidity and ventilation in bacterial growth and genus distribution at different temperatures (26 °C and 34 °C). Methods: Fresh pork, which was used as the substrate for bacterial culture, was placed in storage cabinets. Bacterial growth and genera distribution on the surface of pork placed in a storage cabinet under different temperatures (26 °C and 34 °C); relative humidity levels (RH: 50%, 70%, 90%); and ventilation conditions (no ventilation and low, medium, and high levels of ventilation) were assessed by rDNA sequencing. Results: Increased ventilation and reduced humidity significantly decreased bacterial growth at 26 °C and 34 °C. The contribution of increased ventilation to the reduction in bacterial growth exceeded that of decreased humidity. Ventilation had the greatest effect on reducing bacterial growth compared to the unventilated conditions at 70% RH. At 34 °C, medium and high levels of ventilation were required to reduce bacterial growth. High temperatures greatly increased bacterial growth, but ventilation could reduce the degree of this increase.
Association between Perfluoroalkyl and Polyfluoroalkyl Substances and Women’s Infertility, NHANES 2013–2016
Authors: Tan Yuxuan , Zeng Zurui , Liang Huanzhu , Weng Xueqiong , Yao Huojie , Fu Yingyin , Li Yexin , Chen Jingmin , Wei Xiangcai , Jing Chunxia
Published: November 2022

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are widely used in consumer products. However, the role of PFAS in infertility is still poorly understood. A total of 788 women from the 2013–2016 nationally representative NHANES were included to explore the association between PFAS exposure and self-reported infertility. Six PFAS, including PFDE, PFNA, PFHxS, n-PFOA, n-PFOS, and Sm-PFOS, were detected by online SPE-HPLC-TIS-MS/MS. We used the generalized linear regression model (GLM), generalized additive models (GAM), and Bayesian kernel machine regression (BKMR) to assess the single effects, non-linear relationships, and mixed effects on women’s infertility, respectively. The prevalence of self-reported infertility was 15.54% in this study. In GLM, n-PFOA showed a negative association with self-reported infertility in women for the Q3 (OR: 0.396, 95% CI: 0.119, 0.788) and Q4 (OR: 0.380, 95% CI: 0.172–0.842) compared with Q1 (p for trend = 0.013). A negative trend was also observed in n-PFOS and ∑PFOS (p for trend < 0.05). In GAM, a non-linear relationship was revealed in Sm-PFOS, which exhibits a U-shaped relationship. The BKMR model indicated that there might be a joint effect between PFAS and women’s infertility, to which PFNA contributed the highest effect (PIP = 0.435). Moreover, age stratification analysis showed a different dose–response curve in under and above 35 years old. Women under the age of 35 have a more noticeable U-shaped relationship with infertility. Therefore, the relatively low level of mixed PFAS exposure was negatively associated with self-reported infertility in women in general, and the impact of PFAS on infertility may vary among women of different age groups. Further studies are needed to determine the etiological relationship.
Validation of the Novel Interprofessional Shared Decision-Making Questionnaire to Facilitate Multidisciplinary Team Building in Patient-Centered Care
Authors: Goto Yuko , Miura Hisayuki
Published: November 2022

To support patients in making complex and difficult decisions, it is necessary to form a team that comprises different specialists, the patient, and family members who have detailed information about the latter. Shared decision-making (SDM) is the foundation of patient-centered care; however, its structure in the context of multidisciplinary teams remains unclear. This cross-sectional study aimed to validate the novel interprofessional SDM measure (“Group’s SDM measure”). We used data of 175 participants who attended SDM Workshops for Advance Care Planning. The Group’s SDM measure included 10 Japanese items that could be used by small groups of multidisciplinary professionals, and the responses were rated using a 6-point Likert scale. The index exhibited a single-factor structure and high goodness of fit with residual correlation via factor analysis. We calculated Cronbach’s α (α = 0.948) and McDonald’s ω (ω = 0.948) and verified high internal consistency. The Group’s SDM measure can be used when evaluating the SDM process where multidisciplinary professionals are involved. We hope that in the future, it will lead to the promotion of interprofessional SDM through training with the use of this measure.
Health Equity Impact Assessment Related to Air Pollution Reduction
Authors: Deguen Séverine , Kihal-Talantikite Wahida
Published: November 2022

Despite considerable improvements in terms of prevention, management, and regulation, air pollution remains a leading environmental health issue worldwide [...]
Health Education Module Based on Information–Motivation–Behavioural Skills (IMB) for Reducing Depression, Anxiety, and Stress among Adolescents in Boarding Schools: A Clustered Randomised Controlled Trial
Authors: Dapari Rahmat , Bashaabidin Mohd Safrin Mohamad , Hassan Mohd Rohaizat , Dom Nazri Che , Rahim Syed Sharizman Syed Abdul , Wan Mahiyuddin Wan Rozita
Published: November 2022

Depression, anxiety, and stress (DAS) among adolescents have become a public health concern. The aim of this study was to develop, implement, and measure an IMB-based health education intervention module for reducing DAS among adolescents in boarding schools in the state of Negeri Sembilan, Malaysia. A single-blinded cluster randomised control trial (RCT) was conducted among students with abnormal DASS-21 scores. They were divided into an intervention group (three schools, 62 participants) and a control group (three schools, 57 participants). Participants in the intervention group received IMB-based health education, while participants in the control group underwent the standard care session. To determine the effectiveness of the intervention, the Generalised Linear Mixed Model (GLMM) analysis was conducted. A total of 119 students participated in this study, and no loss to follow-up was reported. Both intervention and control groups showed significantly reduced DAS scores (p < 0.005). However, the reduction of these scores was greater in the intervention group. The GLMM analysis revealed that the intervention was effective in reducing depression (ß = −2.400, t = −3.102, SE = 0.7735, p = 0.002, 95% CI = −3.921, −0.878), anxiety (ß = −2.129, t = −2.824, SE = 0.7541, p = 0.005, 95% CI = −3.612, −0.646), and stress (ß = −1.335, t = −2.457, SE = 0.536, p = 0.015, 95% CI = −2.045, −0.266) among adolescents. The IMB-based health education module was effective in reducing DAS among adolescents in boarding schools.
Well-Being and Mental Health in Teachers: The Life Impact of COVID-19
Authors: Flores Jerome , Caqueo-Urízar Alejandra , Escobar Michael , Irarrázaval Matías
Published: November 2022

The impact of the pandemic on teachers’ mental health has also been an important issue. The aim of the study was to analyze the vital impact of COVID-19, spirituality, and the use of social-emotional strategies on teacher well-being, mediated by mental health. The sample was non-random, inviting all teachers in a city North of Chile to participate in the study. The sample consisted of 624 teachers. A total of 74.4% were women and 25.6% were men. The mean age was 44.1 and the standard deviation was 11.9. A total of 56.4% belonged to public schools and 43.6% belonged to subsidized schools. Structural equations were used to analyze the data, finding a mental health mediating effect between the death of a close person, affected areas and family history with life satisfaction. Spirituality and the use of socio-emotional strategies self-applied by the teachers had no direct relationship with their mental health, so their mediating effect in relation to life satisfaction was discarded. Teachers who used social-emotional strategies, as well as those who reported higher levels of spirituality, obtained greater satisfaction with life, both general and specifically. Women had higher levels of depression, anxiety and stress symptomatology, but also higher levels of life satisfaction. The implications are discussed.
Spatial Pattern and Influencing Factors of Basic Education Resources in Rural Areas around Metropolises—A Case Study of Wuhan City’s New Urban Districts
Authors: Jiang Liang , Chen Jie , Tian Ye , Luo Jing
Published: November 2022

Basic education resources are basic urban and rural social public security resources, and their spatial distribution is an important issue related to people’s livelihoods and social justice. Taking Wuhan as a case study, this paper analyzed the spatial distribution characteristics of rural basic education resources based on the methods of the average nearest neighbor index, imbalance index, kernel density analysis and two-step floating catchment area and then used geographic detector analysis to detect its influencing factors. The following findings were obtained: (1) Rural kindergartens and elementary schools in Wuhan City’s new urban districts showed a clustered distribution pattern, while secondary schools showed a uniform distribution trend. The spatial distribution of rural basic education resources is poorly balanced, with a tendency to cluster in Huangpi District, Xinzhou District and Caidian District; the overall spatial distribution density of rural basic education resources showed the distribution characteristics of “block-like clustering and multicenter development”. (2) The spatial accessibility of kindergartens showed a spatial pattern of “large dispersion and small clustering”, with multiple high-value clustering areas; and the accessibility of elementary and secondary schools showed a spatial pattern of high in the south and low in the north. (3) The population, economy and education development level are the main factors affecting the spatial distribution of rural basic education resources, while the influence of infrastructure construction is weak. The core influencing factors of the spatial distribution of each type of basic education resource are both consistent and different. According to the interaction factor detection, the spatial distribution of rural basic education resources in Wuhan City’s new urban districts is the result of the combined effect of multiple factors.
Map Design and Usability of a Simplified Topographic 2D Map on the Smartphone in Landscape and Portrait Orientations
Authors: Medyńska-Gulij Beata , Gulij Jacek , Cybulski Paweł , Zagata Krzysztof , Zawadzki Jakub , Horbiński Tymoteusz
Published: November 2022

Map design and usability issues are crucial when considering different device orientations. It is visible, especially in exploring the topographical space in landscape or portrait orientation on the mobile phone. In this study, we aim to reveal the main differences and similarities among participants’ performance in a map-based task. The study presents an original research scheme, including establishing conceptual assumptions, developing map applications with gaming elements, user testing, and visualizing results. It appears that the different phone orientation triggers different visual strategy. This transfers into decision-making about the path selection. It turned out that in landscape orientation, participants preferred paths oriented east–west. On the other hand, portrait orientation supported north–south path selection. However, considering the given task accomplishment, both mobile phones’ orientations are adequate for the exploration of topographical space.
ZmGLP1, a Germin-like Protein from Maize, Plays an Important Role in the Regulation of Pathogen Resistance
Authors: Mao Lixue , Ge Lijie , Ye Xinchun , Xu Li , Si Weina , Ding Ting
Published: November 2022

A gene encoding a protein similar to germin-like proteins (GLPs) was obtained from maize (Zea mays) and designated as ZmGLP1. Based on the ZmGLP1 conserved domain and phylogenetic status, ZmGLP1 was grouped into GLP subfamily b and has high similarity to OsGLP8-14 from Oryza sativa. ZmGLP1 is expressed in different maize tissues during different growth stages and is mainly expressed in the stems and leaves. The induced expression patterns confirmed that ZmGLP1 is differentially expressed under abiotic and hormone stress; it had an early response to jasmonic acid (JA) and ethephon (ET) but a late response to salicylic acid (SA) and was significantly upregulated under Bipolaris maydis infection. The overexpression of ZmGLP1 in Arabidopsis improved the resistance to biotrophic Pseudomonas syringae pv. tomato DC3000 (PstDC3000) and necrotrophic Sclerotinia sclerotiorum by inducing the expression of JA signaling-related genes. Moreover, the hydrogen peroxide (H2O2) content increased due to the overexpression of ZmGLP1 in Arabidopsis after pathogen infection. Compared to the wild-type control, the H2O2 content of ZmGLP1-overexpressing Arabidopsis infected by PstDC3000 increased significantly but was lower in transgenic plants infected with S. sclerotiorum. Furthermore, high-performance liquid chromatography–tandem mass (HPLC-MS/MS) spectrometry showed that the JA contents of ZmGLP1-overexpressing Arabidopsis markedly increased after pathogen infection. However, the improved resistance of ZmGLP1-overexpressing Arabidopsis pretreated with the JA biosynthetic inhibitor, sodium diethyldithiocarbamate trihydrate (DIECA), was suppressed. Based on these findings, we speculate that ZmGLP1 plays an important role in the regulation of Arabidopsis resistance to biotrophic PstDC3000 and necrotrophic S. sclerotiorum; the regulatory effects are achieved by inducing plant oxidative burst activity and activation of the JA signaling pathway.
Space Microgravity Alters Neural Stem Cell Division: Implications for Brain Cancer Research on Earth and in Space
Authors: Shaka Sophia , Carpo Nicolas , Tran Victoria , Cepeda Carlos , Espinosa-Jeffrey Araceli
Published: November 2022

Considering the imminence of long-term space travel, it is necessary to investigate the impact of space microgravity (SPC-µG) in order to determine if this environment has consequences on the astronauts’ health, in particular, neural and cognitive functions. Neural stem cells (NSCs) are the basis for the regeneration of the central nervous system (CNS) cell populations and learning how weightlessness impacts NSCs in health and disease provides a critical tool for the potential mitigation of specific mechanisms leading to neurological disorders. In previous studies, we found that exposure to SPC-µG resulted in enhanced proliferation, a shortened cell cycle, and a larger cell diameter of NSCs compared to control cells. Here, we report the frequent occurrence of abnormal cell division (ACD) including incomplete cell division (ICD), where cytokinesis is not successfully completed, and multi-daughter cell division (MDCD) of NSCs following SPC-µG as well as secretome exposure compared to ground control (1G) NSCs. These findings provide new insights into the potential health implications of space travel and have far-reaching implications for understanding the mechanisms leading to the deleterious effects of long-term space travel as well as potential carcinogenic susceptibility. Knowledge of these mechanisms could help to develop preventive or corrective measures for successful long-term SPC-µG exposure.
Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1
Authors: Ryu Kunhi , Heo Yunkyung , Lee Yechan , Jeon Hyejin , Namkung Wan
Published: November 2022

Chloroquine (CQ) is an antimalaria drug that has been widely used for decades. However, CQ-induced pruritus remains one of the major obstacles in CQ treatment for uncomplicated malaria. Recent studies have revealed that MrgprX1 plays an essential role in CQ-induced itch. To date, a few MrgprX1 antagonists have been discovered, but they are clinically unavailable or lack selectivity. Here, a cell-based high-throughput screening was performed to identify novel antagonists of MrgprX1, and the screening of 2543 compounds revealed two novel MrgprX1 inhibitors, berbamine and closantel. Notably, berbamine potently inhibited CQ-mediated MrgprX1 activation (IC50 = 1.6 μM) but did not alter the activity of other pruritogenic GPCRs. In addition, berbamine suppressed the CQ-mediated phosphorylation of ERK1/2. Interestingly, CQ-induced pruritus was significantly reduced by berbamine in a dose-dependent manner, but berbamine had no effect on histamine-induced, protease-activated receptors 2-activating peptide-induced, and deoxycholic acid-induced itch in mice. These results suggest that berbamine is a novel, potent, and selective antagonist of MrgprX1 and may be a potential drug candidate for the development of therapeutic agents to treat CQ-induced pruritus.
Polyphenon E Effects on Gene Expression in PC-3 Prostate Cancer Cells
Authors: Carastro L. , Vallebuona Ethan , Cordova Ricardo , Gannon Ashley , Kim Seung , Costello Corrine , Declet-Bauzo Ricardo , Kumar Nagi , Park Jong
Published: November 2022

Polyphenon E (Poly E) is a standardized, caffeine-free green tea extract with defined polyphenol content. Poly E is reported to confer chemoprotective activity against prostate cancer (PCa) progression in the TRAMP model of human PCa, and has shown limited activity against human PCa in human trials. The molecular mechanisms of the observed Poly E chemopreventive activity against PCa are not fully understood. We hypothesized that Poly E treatment of PCa cells induces gene expression changes, which could underpin the molecular mechanisms of the limited Poly E chemoprevention activity against PCa. PC-3 cells were cultured in complete growth media supplemented with varied Poly E concentrations for 24 h, then RNA was isolated for comparative DNA microarray (0 vs. 200 mg/L Poly E) and subsequent TaqMan qRT-PCR analyses. Microarray data for 54,613 genes were filtered for >2-fold expression level changes, with 8319 genes increased and 6176 genes decreased. Eight genes involved in key signaling or regulatory pathways were selected for qRT-PCR. Two genes increased expression significantly, MXD1 (13.98-fold; p = 0.0003) and RGS4 (21.98-fold; p = 0.0011), by qRT-PCR. MXD1 and RGS4 significantly increased gene expression in Poly E-treated PC-3 cells, and the MXD1 gene expression increases were Poly E dose-dependent.
Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis
Authors: Arteaga-Henríquez Gara , Lugo-Marín Jorge , Gisbert Laura , Setién-Ramos Imanol , Martínez-Gallo Mónica , Pujol-Borrell Ricardo , Ramos-Quiroga Josep Antoni
Published: November 2022

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and/or medical conditions are urgently needed to confirm the findings.
The Role of the Gallbladder, the Intestinal Barrier and the Gut Microbiota in the Development of Food Allergies and Other Disorders
Authors: Abril Ana G. , Villa Tomás G. , Sánchez-Pérez Ángeles , Notario Vicente , Carrera Mónica
Published: November 2022

The microbiota present in the gastrointestinal tract is involved in the development or prevention of food allergies and autoimmune disorders; these bacteria can enter the gallbladder and, depending on the species involved, can either be benign or cause significant diseases. Occlusion of the gallbladder, usually due to the presence of calculi blocking the bile duct, facilitates microbial infection and inflammation, which can be serious enough to require life-saving surgery. In addition, the biliary salts are secreted into the intestine and can affect the gut microbiota. The interaction between the gut microbiota, pathogenic organisms, and the human immune system can create intestinal dysbiosis, generating a variety of syndromes including the development of food allergies and autoimmune disorders. The intestinal microbiota can aggravate certain food allergies, which become severe when the integrity of the intestinal barrier is affected, allowing bacteria, or their metabolites, to cross the intestinal barrier and invade the bloodstream, affecting distal body organs. This article deals with health conditions and severe diseases that are either influenced by the gut flora or caused by gallbladder obstruction and inflammation, as well as putative treatments for those illnesses.
Talazoparib Does Not Interact with ABCB1 Transporter or Cytochrome P450s, but Modulates Multidrug Resistance Mediated by ABCC1 and ABCG2: An in Vitro and Ex Vivo Study
Authors: Sabet Ziba , Vagiannis Dimitrios , Budagaga Youssif , Zhang Yu , Novotná Eva , Hanke Ivo , Rozkoš Tomáš , Hofman Jakub
Published: November 2022

Talazoparib (Talzenna) is a novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that is clinically used for the therapy of breast cancer. Furthermore, the drug has shown antitumor activity against different cancer types, including non-small cell lung cancer (NSCLC). In this work, we investigated the possible inhibitory interactions of talazoparib toward selected ATP-binding cassette (ABC) drug efflux transporters and cytochrome P450 biotransformation enzymes (CYPs) and evaluated its position in multidrug resistance (MDR). In accumulation studies, talazoparib interacted with the ABCC1 and ABCG2 transporters, but there were no significant effects on ABCB1. Furthermore, incubation assays revealed a negligible capacity of the tested drug to inhibit clinically relevant CYPs. In in vitro drug combination experiments, talazoparib synergistically reversed daunorubicin and mitoxantrone resistance in cells with ABCC1 and ABCG2 expression, respectively. Importantly, the position of an effective MDR modulator was further confirmed in drug combinations performed in ex vivo NSCLC patients-derived explants, whereas the possible victim role was refuted in comparative proliferation experiments. In addition, talazoparib had no significant effects on the mRNA-level expressions of MDR-related ABC transporters in the MCF-7 cellular model. In summary, our study presents a comprehensive overview on the pharmacokinetic drug–drug interactions (DDI) profile of talazoparib. Moreover, we introduced talazoparib as an efficient MDR antagonist.
Polyglycerol Adipate-Grafted Polycaprolactone Nanoparticles as Carriers for the Antimicrobial Compound Usnic Acid
Authors: Taresco Vincenzo , Tulini Isotta , Francolini Iolanda , Piozzi Antonella
Published: November 2022

Nanoparticle (NP) drug delivery systems are known to potentially enhance the efficacy of therapeutic agents. As for antimicrobial drugs, therapeutic solutions against drug-resistant microbes are urgently needed due to the worldwide antimicrobial resistance issue. Usnic acid is a widely investigated antimicrobial agent suffering from poor water solubility. In this study, polymer nanoparticles based on polyglycerol adipate (PGA) grafted with polycaprolactone (PCL) were developed as carriers for usnic acid. We demonstrated the potential of the developed systems in ensuring prolonged bactericidal activity against a model bacterial species, Staphylococcus epidermidis. The macromolecular architecture changes produced by PCL grafted from PGA significantly influenced the drug release profile and mechanism. Specifically, by varying the length of PCL arms linked to the PGA backbone, it was possible to tune the drug release from a burst anomalous drug release (high PCL chain length) to a slow diffusion-controlled release (low PCL chain length). The developed nanosystems showed a prolonged antimicrobial activity (up to at least 7 days) which could be used in preventing/treating infections occurring at different body sites, including medical device-related infection and mucosal/skin surface, where Gram-positive bacteria are commonly involved.
Targeted NGS in Diagnostics of Genodermatosis Characterized by the Epidermolysis Bullosa Symptom Complex in 268 Russian Children
Authors: Savostyanov Kirill , Murashkin Nikolay , Pushkov Alexander , Zhanin Ilya , Suleymanov Elkhan , Akhkiamova Mariya , Shchagina Olga , Balanovska Elena , Epishev Roman , Polyakov Aleksander , Fisenko Andrey
Published: November 2022

The pathogenic variants of genes encoding proteins, participating in the formation and functioning of epidermis and dermo-epidermal junctions, create a large variety of clinical phenotypes from: small localized to severe generalized dermatitis, as well as early, or even, prenatal death due to extensive epidermis loss. The diagnostic panel in this study was developed for the purposes of identifying these pathogenic genetic variants in 268 Russian children, who possessed the epidermolysis bullosa symptom complex in a selection of 247 families. This panel included the targeted areas of 33 genes, which are genetic variants that can lead to the development of the phenotype mentioned above. The usage of next generation sequencing allowed the revelation of 192 various altered alleles (of which 109 alleles were novel, i.e., had not been described previously). In addition, it allowed the definition of the genetic variants that are both typical for most of the examined children and for the separate ethnic groups inhabiting modern Russia. We found that the most characteristic mutations for the Dargin and Chechen ethnic groups are the c.3577del deletion in the COL7A1 gene and the c.2488G>A missense mutation in the COL17A1 gene, respectively. In addition, the study of haplotypes of microsatellite markers, which we managed to conduct in the Dargin population, confirmed the presence of the founder effect.
Reliability of Rodent and Rabbit Models in Preeclampsia Research
Authors: Sakowicz Agata , Bralewska Michalina , Kamola Piotr , Pietrucha Tadeusz
Published: November 2022

In vivo studies on the pathology of gestation, including preeclampsia, often use small mammals such as rabbits or rodents, i.e., mice, rats, hamsters, and guinea pigs. The key advantage of these animals is their short reproductive cycle; in addition, similar to humans, they also develop a haemochorial placenta and present a similar transformation of maternal spiral arteries. Interestingly, pregnant dams also demonstrate a similar reaction to inflammatory factors and placentally derived antiangiogenic factors, i.e., soluble fms-like tyrosine kinase 1 (sFlt-1) or soluble endoglin-1 (sEng), as preeclamptic women: all animals present an increase in blood pressure and usually proteinuria. These constitute the classical duet that allows for the recognition of preeclampsia. However, the time of initiation of maternal vessel remodelling and the depth of trophoblast invasion differs between rabbits, rodents, and humans. Unfortunately, at present, no known animal replicates a human pregnancy exactly, and hence, the use of rabbit and rodent models is restricted to the investigation of individual aspects of human gestation only. This article compares the process of placentation in rodents, rabbits, and humans, which should be considered when planning experiments on preeclampsia; these aspects might determine the success, or failure, of the study. The report also reviews the rodent and rabbit models used to investigate certain aspects of the pathomechanism of human preeclampsia, especially those related to incorrect trophoblast invasion, placental hypoxia, inflammation, or maternal endothelial dysfunction.
Molecule(s) of Interest: I. Ionic Liquids–Gateway to Newer Nanotechnology Applications: Advanced Nanobiotechnical Uses’, Current Status, Emerging Trends, Challenges, and Prospects
Authors: Khan Riaz A. , Mohammed Hamdoon A. , Sulaiman Ghassan M. , Subaiyel Amal Al , Karuppaiah Arjunan , Rahman Habibur , Makhathini Sifiso , Ramburrun Poornima , Choonara Yahya E.
Published: November 2022

Ionic liquids are a potent class of organic compounds exhibiting unique physico-chemical properties and structural compositions that are different from the classical dipolar organic liquids. These molecules have found diverse applications in different chemical, biochemical, biophysical fields, and a number of industrial usages. The ionic liquids-based products and procedural applications are being developed for a number of newer industrial purposes, and academic uses in nanotechnology related procedures, processes, and products, especially in nanobiotechnology and nanomedicine. The current article overviews their uses in different fields, including applications, functions, and as parts of products and processes at primary and advanced levels. The application and product examples, and prospects in various fields of nanotechnology, domains of nanosystem syntheses, nano-scale product development, the process of membrane filtering, biofilm formation, and bio-separations are prominently discussed. The applications in carbon nanotubes; quantum dots; and drug, gene, and other payload delivery vehicle developments in the nanobiotechnology field are also covered. The broader scopes of applications of ionic liquids, future developmental possibilities in chemistry and different bio-aspects, promises in the newer genres of nanobiotechnology products, certain bioprocesses controls, and toxicity, together with emerging trends, challenges, and prospects are also elaborated.
Evaluation of Various Alternative Economical and High Throughput SARS-CoV-2 Testing Methods within Resource-Limited Settings
Authors: Duma Zamathombeni , Ramsuran Veron , Chuturgoon Anil A. , Edward Vinodh A. , Naidoo Pragalathan , Mkhize-Kwitshana Zilungile L.
Published: November 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak posed a challenge for diagnostic laboratories worldwide, with low-middle income countries (LMICs) being the most affected. The polymerase chain reaction (PCR) is the gold standard method for detecting SARS-CoV-2 infection. However, the challenge with this method is that it is expensive, which has resulted in under-testing for SARS-CoV-2 infection in many LMICs. Hence, this study aimed to compare and evaluate alternative methods for the mass testing of SARS-CoV-2 infection in laboratories with limited resources to identify cost-effective, faster, and accurate alternatives to the internationally approved kits. A total of 50 residual nasopharyngeal swab samples were used for evaluation and comparison between internationally approved kits (Thermo Fisher PureLink™ RNA Isolation Kit and Thermo Fisher TaqPath™ COVID-19 Assay Kit) and alternative methods (three RNA extraction and four commercial SARS-CoV-2 RT-PCR assay kits) in terms of the cost analysis, diagnostic accuracy, and turnaround time. In terms of performance, all of the alternative RNA extraction methods evaluated were comparable to the internationally approved kits but were more cost-effective (Lucigen QuickExtract™ RNA Extraction Kit, Bosphore EX-Tract Dry Swab RNA Solution and Sonicator method) and four commercial SARS-CoV-2 RT-PCR assay kits (Nucleic Acid COVID-19 Test Kit (SARS-CoV-2), abTESTM COVID-19 qPCR I Kit, PCL COVID19 Speedy RT-PCR Kit, and PCLMD nCoV One-Step RT-PCR Kit) with a sensitivity range of 76–100% and specificity of 96–100%. The cost per sample was reduced by more than 50% when compared to internationally approved kits. When compared to the Thermo Fisher PureLink™ Kit and Thermo Fisher TaqPath™ COVID-19 Assay Kit, the alternative methods had a faster turnaround time, indicating that laboratories with limited resources may be able to process more samples in a day. The above-mentioned cost-effective, fast, and accurate evaluated alternative methods can be used in routine diagnostic laboratories with limited resources for mass testing for SARS-CoV-2 because these were comparable to the internationally approved kits, Thermo Fisher PureLink™ Kit and Thermo Fisher TaqPath™ COVID-19 Assay Kit. The implementation of alternative methods will be the most cost-effective option for testing SARS-CoV-2 infection in LMICs.
Natural Inhibitors Targeting the Localization of Lipoprotein System in Vibrio parahaemolyticus
Authors: Liu Jiawen , Tong Jinrong , Wu Qian , Liu Jing , Yuan Mengqi , Tian Cuifang , Xu Huan , Malakar Pradeep K. , Pan Yingjie , Zhao Yong , Zhang Zhaohuan
Published: November 2022

The localization of lipoprotein (Lol) system is responsible for the transport of lipoproteins in the outer membrane (OM) of Vibrio parahaemolyticus. LolB catalyzes the last step in the Lol system, where lipoproteins are inserted into the OM. If the function of LolB is impeded, growth of V. parahaemolyticus is inhibited, due to lack of an intact OM barrier for protection against the external environment. Additionally, it becomes progressively harder to generate antimicrobial resistance (AMR). In this study, LolB was employed as the receptor for a high-throughput virtual screening from a natural compounds database. Compounds with higher glide score were selected for an inhibition assay against V. parahaemolyticus. It was found that procyanidin, stevioside, troxerutin and rutin had both exciting binding affinity with LolB in the micromolar range and preferable antibacterial activity in a concentration-dependent manner. The inhibition rates of 100 ppm were 87.89%, 86.2%, 91.39% and 83.71%, respectively. The bacteriostatic mechanisms of the four active compounds were explored further via fluorescence spectroscopy and molecular docking, illustrating that each molecule formed a stable complex with LolB via hydrogen bonds and pi–pi stacking interactions. Additionally, the critical sites for interaction with V. parahaemolyticus LolB, Tyr108 and Gln68, were also illustrated. This paper demonstrates the inhibition of LolB, thus, leading to antibacterial activity, and identifies LolB as a promising drug target for the first time. These compounds could be the basis for potential antibacterial agents against V. parahaemolyticus.