bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge Gaps and Research Priorities on the Health Effects of Heatwaves: A Systematic Review of Reviews
Authors: Conti Andrea , Valente Martina , Paganini Matteo , Farsoni Marco , Ragazzoni Luca , Barone-Adesi Francesco
Published: May 2022

Although extreme weather events have played a constant role in human history, heatwaves (HWs) have become more frequent and intense in the past decades, causing concern especially in light of the increasing evidence on climate change. Despite the increasing number of reviews suggesting a relationship between heat and health, these reviews focus primarily on mortality, neglecting other important aspects. This systematic review of reviews gathered the available evidence from research syntheses conducted on HWs and health. Following the PRISMA guidelines, 2232 records were retrieved, and 283 reviews were ultimately included. Information was extracted from the papers and categorized by topics. Quantitative data were extracted from meta-analyses and, when not available, evidence was collected from systematic reviews. Overall, 187 reviews were non-systematic, while 96 were systematic, of which 27 performed a meta-analysis. The majority evaluated mortality, morbidity, or vulnerability, while the other topics were scarcely addressed. The following main knowledge gaps were identified: lack of a universally accepted definition of HW; scarce evidence on the HW-mental health relationship; no meta-analyses assessing the risk perception of HWs; scarcity of studies evaluating the efficacy of adaptation strategies and interventions. Future efforts should meet these priorities to provide high-quality evidence to stakeholders.
Patients with Musculoskeletal Disorders Presenting to the Emergency Department: The COVID-19 Lesson
Authors: Pasta Gianluigi , Polizzi Alberto , Annunziata Salvatore , Klersy Catherine , Fenech Lorenzo , Dermenaki Farahani Mohammad Reza , Ghiara Matteo , Castelli Alberto , Jannelli Eugenio , Grassi Federico Alberto , Mosconi Mario
Published: May 2022

Background: Musculoskeletal disorders (MSKDs) are the most common class of complaints among patients presenting for care in the Emergency Department (ED). There is a non-urgent patient population with musculoskeletal complaints attending ED services that creates a burgeoning waiting list and contributes to overcrowding in Emergency Departments (EDs), which is a major concern worldwide. The recent (Coronavirus disease-19) COVID-19 pandemic is an unprecedented challenge that is revealing the structural and situational strengths and weaknesses of healthcare systems. Methods: This study retrospectively and prospectively assessed patients presenting to the Emergency Department before and after the COVID-19 outbreak (from 21 February 2019 to 3 May 2019 and from 21 February 2020 to 3 May 2020) with non-traumatic or low-severity musculoskeletal conditions to test the hypothesis that these patients should have access to care outside the ED and that the COVID-19 outbreak has changed patients’ care and health perception. Results: A total of 613 patients were identified, and 542 of them (87.56%) participated in a personalized survey. From this number, 81.73% of the total accesses took place in 2019, and only 18.27% of the accesses took place during the first outbreak and lockdown. More than 90% of patients admitted to the ED accessed care during the day shift in both periods. A total of 87.30% of patients presenting to the ED with a MSKD followed their general practitioner’s (GP) advice/referral in 2019, and 73.87% did so in 2020. The differences in the means of transport to the ED was statistically significant (p-value 0.002). Conclusions: The outbreak and lockdown period confirmed that there is an inappropriate use of the ED related to patients with MSKD. However, the ED appears to be the only available solution for these patients. New services and pathways are therefore needed to enhance MSKD management and reduce ED crowding. Additional observational studies shall be developed to confirm and compare our findings with those of various EDs. The main limit of the inferential part of the study is probably due to the small sample of patients in 2020.
Towards Understanding Behaviour and Emotions of Children with CLN3 Disease (Batten Disease): Patterns, Problems and Support for Child and Family
Authors: Honingh Aline K. , Kruithof Yvonne L. , Kuper Willemijn F. E. , van Hasselt Peter M. , Sterkenburg Paula S.
Published: May 2022

The juvenile variant of Neuronal Ceroid Lipofuscinosis (CLN3 disease/Batten disease) is a rare progressive brain disease in children and young adults, characterized by vision loss, decline in cognitive and motor capacities and epilepsy. Children with CLN3 disease often show disturbed behaviour and emotions. The aim of this study is to gain a better understanding of the behaviour and emotions of children with CLN3 disease and to examine the support that the children and their parents are receiving. A combination of qualitative and quantitative analysis was used to analyse patient files and parent interviews. Using a framework analysis approach a codebook was developed, the sources were coded and the data were analysed. The analysis resulted in overviews of (1) typical behaviour and emotions of children as a consequence of CLN3 disease, (2) the support children with CLN3 disease receive, (3) the support parents of these children receive, and (4) the problems these parents face. For a few children their visual, physical or cognitive deterioration was found to lead to specific emotions and behaviour. The quantitative analysis showed that anxiety was reported for all children. The presented overviews on support contain tacit knowledge of health care professionals that has been made explicit by this study. The overviews may provide a lead to adaptable support-modules for children with CLN3 disease and their parents.
Current Artificial Intelligence (AI) Techniques, Challenges, and Approaches in Controlling and Fighting COVID-19: A Review
Authors: Albalawi Umar , Mustafa Mohammed
Published: May 2022

SARS-CoV-2 (COVID-19) has been one of the worst global health crises in the 21st century. The currently available rollout vaccines are not 100% effective for COVID-19 due to the evolving nature of the virus. There is a real need for a concerted effort to fight the virus, and research from diverse fields must contribute. Artificial intelligence-based approaches have proven to be significantly effective in every branch of our daily lives, including healthcare and medical domains. During the early days of this pandemic, artificial intelligence (AI) was utilized in the fight against this virus outbreak and it has played a major role in containing the spread of the virus. It provided innovative opportunities to speed up the development of disease interventions. Several methods, models, AI-based devices, robotics, and technologies have been proposed and utilized for diverse tasks such as surveillance, spread prediction, peak time prediction, classification, hospitalization, healthcare management, heath system capacity, etc. This paper attempts to provide a quick, concise, and precise survey of the state-of-the-art AI-based techniques, technologies, and datasets used in fighting COVID-19. Several domains, including forecasting, surveillance, dynamic times series forecasting, spread prediction, genomics, compute vision, peak time prediction, the classification of medical imaging—including CT and X-ray and how they can be processed—and biological data (genome and protein sequences) have been investigated. An overview of the open-access computational resources and platforms is given and their useful tools are pointed out. The paper presents the potential research areas in AI and will thus encourage researchers to contribute to fighting against the virus and aid global health by slowing down the spread of the virus. This will be a significant contribution to help minimize the high death rate across the globe.
Analysis of Electric Bicycle Riders’ Use of Mobile Phones While Riding on Campus
Authors: Yang Yanqun , Wang Linwei , Easa Said M. , Zheng Xinyi
Published: May 2022

Based on the theory of rational action (TRA), overconfidence theory (OT), and deterrence theory (DT), this study explores the reasons for mobile phone use by Chinese students riding electronic bicycles (e-bikes) in Fuzhou City. We tested the reliability and validity of an extended TPB, OT and DT questionnaire (with 531 eligible responses) and constructed a structural equation model of mobile phone use behavior while riding e-bikes, based on the improved model. The structural equation model (SEM) is used to evaluate the relationship between the internal factors of mobile phone riding behavior. The results show that the correlation among mobile phone dependence, punishment mechanism, attitude, and controllable operation impacts e-bike riders’ behavior when using mobile phones while riding.
Exercise Capacity and Cardiorespiratory Fitness in Children with Congenital Heart Diseases: A Proposal for an Adapted NYHA Classification
Authors: Neunhaeuserer Daniel , Battista Francesca , Mazzucato Barbara , Vecchiato Marco , Meneguzzo Giulia , Quinto Giulia , Niebauer Josef , Gasperetti Andrea , Vida Vladimiro , Di Salvo Giovanni , Varnier Maurizio , Ermolao Andrea
Published: May 2022

Objective: To propose and evaluate an adapted NYHA classification for children with congenital heart disease (CHD) as a feasible clinical tool for classifying patients’ fitness, cardiorespiratory efficiency and functional limitations during their ordinary daily activities, which are also characterized by vigorous and competitive physical exercise among peers. Methods: This cross-sectional investigation analyzed 332 patients (13.1 ± 3.01 y/o) who underwent surgical repair of CHD and performed Cardiopulmonary Exercise Testing (CPET). Patients were divided into NYHA class I, IIA and IIB by specific questioning regarding functional limitation and performance compared to peers and at strenuous intensity. Class IIA was characterized by slight exercise limitation only for strenuous/competitive activities, whereas IIB for already ordinary physical activities. These NYHA classes were compared with maximal CPET on treadmill. Results: Patients’ exercise capacity (exercise time, METs), aerobic capacity (VO2peak) and chronotropic response were found progressively impaired when NYHA class I was compared with IIA and IIB. Indeed, ventilatory-perfusion mismatch (PETCO2, VE/VCO2) significantly worsened from NYHA class I to IIA, while no difference was found between IIA and IIB. Conclusion: This adapted NYHA-CHD classification could allow regular functional evaluations and accurate assessments by clinicians, leading to facilitated clinical management and timely medical interventions.
At the Peak of the Second Wave of COVID-19, Did Millennials Show Different Emotional Responses from Older Adults?
Authors: Wagener Aurélie , Stassart Céline , Etienne Anne-Marie
Published: May 2022

The COVID-19 pandemic disturbs mental health. Indeed, higher levels of negative emotions and anxiety, along with lower levels of positive emotions and well-being, have been highlighted. As a result, individuals need to regulate these psychological states in a context of uncertainty and daily restrictions (e.g., access to leisure activities, social contacts) or modifications of livelihood (e.g., working modalities). Overall, psychological reactions to the pandemic have been shown to differ based on one’s age. The purpose of this research is to compare psychological reactions to the pandemic between Millennials (born between 1981 and 1996) and Older Adults. The generation’s prism seems relevant as members of specific generations are shaped (e.g., views of the world, the future) by their similar experiences. Ninety-four Millennials and 129 Older Adults, recruited in the general population, participated to an online survey assessing emotions, emotion regulation strategies, environmental satisfaction, and intolerance of uncertainty. Results show that Millennials experience higher levels of negative emotions along with higher levels of worry and rumination than Older Adults. Millennials also report a higher level of joy. Nonetheless, more Older Adults engage themselves in novel activities. Overall, findings confirm previous ones and indicate the need to offer effective clinicals tool to prevent mental health worsening.
The Pattern and Local Push Factors of Rural Depopulation in Less-Developed Areas: A Case Study in the Mountains of North Hebei Province, China
Authors: Yu Zhonglei , Zhang Hua , Sun Piling , Guo Yandi
Published: May 2022

Rural depopulation is the most significant geographical phenomenon in rural areas during the process of urbanization. Although many studies have investigated the driving force of rural depopulation based on rural-urban migration at the macro level, the local factors, and their impact on rural depopulation from the rural areas have been not fully revealed. This paper selected the northern mountains of China’s Hebei province as a study area to explore the pattern and local push factors of rural depopulation at the rural-township levels based on GeoDetector. The main findings are summarized as follows. (1) Rural depopulation varies substantially, demonstrates spatial correlation, and is distributed in clusters. From a dynamic perspective, compare that in years 2000–2010, the population growth areas during 2010–2017 have been significantly expanded, while the sharp depopulation areas and severe depopulation areas experienced shrinkage in our study area. (2) The pattern of rural depopulation is in accordance with terrain. Rural depopulation tends to be stronger in plateaus and mountains, while relatively milder in intermontane basins, hills, and piedmont plains. (3) The agricultural suitability of natural environmental and rural economic opportunities together with climate changes were the most important driving forces of rural depopulation at local levels. Location, sparse population, and inadequate public services also contributed to rural depopulation. However, the dominant driving factors are different in the different periods. Rural depopulation was mainly driven by arable land per capita and natural environmental variables in the years 2000–2010, while the population density, location, and off-farm economic opportunities played a decisive role in the years 2010–2017. (4) Rural depopulation is a complex, multi-dimensional process driven by a combination of multiple factors including different environmental factors, economic opportunities, and location. This paper reveals the push factors of rural depopulation in underdeveloped mountainous areas by a quantitative empirical approach, inspiring increased attention to the impacts of local factors and spatial correlations on rural depopulation, and has many implications for the policy design of China’s rural revitalization.
Do Budget Cigarettes Emit More Particles? An Aerosol Spectrometric Comparison of Particulate Matter Concentrations between Private-Label Cigarettes and More Expensive Brand-Name Cigarettes
Authors: Gerlach Greta , Braun Markus , Dröge Janis , Groneberg David A.
Published: May 2022

Private-label cigarettes are cigarettes that belong to the retailer itself. Private-label cigarettes from discounters or supermarkets are cheaper than brand-name cigarettes, and their lower price has allowed them to garner an ever-increasing share of the tobacco product market, especially among lower socioeconomic groups. Particulate matter (PM), a considerable component of air pollution, is a substantial health-damaging factor. Smoking is the primary source of PM in smokers’ homes. In a 2.88 m3 measuring chamber, the PM emission fractions PM10, PM2.5, and PM1 from three private-label cigarette brands and three brand-name cigarette brands with identical nicotine, tar, and carbon monoxide content were measured and compared to those of a reference cigarette by laser aerosol spectroscopy. All cigarette brands emitted PM in health-threatening quantities. The measurement results ranged from 1394 µg/m3 to 1686 µg/m3 PM10, 1392 µg/m3 to 1682 µg/m3 PM2.5, and 1355 µg/m3 to 1634 µg/m3 PM1, respectively. Only one private-label brand differed significantly (p < 0.001) from the other cigarette brands, which were tested with slightly lower PM levels. All other brands differed only marginally (not significant, p > 0.05) from one another. Significant (p < 0.05) negative correlations between private-label and brand-name cigarettes were found for PM10, PM2.5, and PM1 when accounting for tobacco filling densities, and for PM1 when accounting for filter lengths. The especially health-hazardous fraction PM1 accounted for the largest proportion of PM emissions from the cigarettes tested. The results of this study suggest that- cheaper tobacco products are as harmful as more expensive ones, at least regarding PM emissions. This highlights the importance of anti-smoking campaigns, especially for lower socioeconomic groups, where smoking is more widespread. Governments should reduce the price gap between cheap and more expensive tobacco products by implementing specific tobacco taxes. In such a case, at increasing prices of tobacco products, a downward shift to private-label cigarettes would probably decrease.
Spatial and Temporal Analysis of COVID-19 in the Elderly Living in Residential Care Homes in Portugal
Authors: De Mello-Sampayo Felipa
Published: May 2022

Background: The goal of this study is to identify geographic areas for priority actions in order to control COVID-19 among the elderly living in Residential Care Homes (RCH). We also describe the evolution of COVID-19 in RHC throughout the 278 municipalities of continental Portugal between March and December 2020. Methods: A spatial population analysis of positive COVID-19 cases reported by the Portuguese National Health Service (NHS) among the elderly living in RCH. The data are for COVID-19 testing, symptomatic status, comorbidities, and income level by municipalities. COVID-19 measures at the municipality level are the proportion of positive cases of elderly living in RCH, positive cases per elderly living in RCH, symptomatic to asymptomatic ratio, and the share of comorbidities cases. Spatial analysis used the Kernel density estimation (KDE), space-time statistic Scan, and geographic weighted regression (GWR) to detect and analyze clusters of infected elderly. Results: Between 3 March and 31 December 2020, the high-risk primary cluster was located in the regions of Braganca, Guarda, Vila Real, and Viseu, in the Northwest of Portugal (relative risk = 3.67), between 30 September and 13 December 2020. The priority geographic areas for attention and intervention for elderly living in care homes are the regions in the Northeast of Portugal, and around the large cities, Lisbon and Porto, which had high risk clusters. The relative risk of infection was spatially not stationary and generally positively affected by both comorbidities and low-income. Conclusion: The regions with a population with high comorbidities and low income are a priority for action in order to control COVID-19 in the elderly living in RCH. The results suggest improving both income and health levels in the southwest of Portugal, in the environs of large cities, such as Lisbon and Porto, and in the northwest of Portugal to mitigate the spread of COVID-19.
Resilience in the Ranks: Trait Mindfulness and Self-Compassion Buffer the Deleterious Effects of Envy on Mental Health Symptoms among Public Safety Personnel
Authors: Beshai Shadi , Mishra Sandeep , Feeney Justin R. , Summerfield Tansi , Hembroff Chet C. , Krätzig Gregory P.
Published: May 2022

Public safety personnel (PSP) face frequent stressors that increase their risk of developing symptoms of depression and anxiety. In addition to being exposed to potentially traumatic events, PSP trainees may face a compounded risk of developing mental health symptoms, as their training environments are conducive to social comparisons and the resultant painful emotion of envy. Envy is associated with numerous negative health and occupational outcomes. Fortunately, there are several individual difference factors associated with increased emotional regulation, and such factors may offer resilience against the damaging mental health effects of envy. In this study, we examined the interplay between dispositional mindfulness, self-compassion, and dispositional envy in predicting job satisfaction, stress, experience of positive and negative emotions, subjective resilience, and symptoms of depression and anxiety in a sample of police trainees (n = 104). A substantial minority of trainees reported clinically significant symptoms of depression (n = 19:18.3%) and anxiety (n = 24:23.1%) in accordance with the cut-off scores on screening measures. Consistent with hypotheses, dispositional envy was associated with lower job satisfaction, greater stress, and greater anxiety and depression. Furthermore, envy was associated with higher negative emotions, lower positive emotions, and lower subjective resilience. Dispositional mindfulness and self-compassion were associated with greater job satisfaction, lower stress, and reduced symptoms of depression and anxiety. Moreover, mindfulness and self-compassion were both associated with lower negative emotions, higher positive emotions, and subjective resilience. The associations between envy and the relevant job and mental health outcomes were significantly diminished after controlling for mindfulness and self-compassion. This suggests that these protective traits may serve as transdiagnostic buffers to the effects of envy on mental health. The results of this study confirmed the damaging effects of envy and suggested the potential remediation of these effects through the cultivation of mindfulness and self-compassion.
Circulating Trends of Influenza and Other Seasonal Respiratory Viruses among the US Department of Defense Personnel in the United States: Impact of the COVID-19 Pandemic
Authors: Hu Wenping , Fries Anthony C. , DeMarcus Laurie S. , Thervil Jeffery W. , Kwaah Bismark , Brown Kayla N. , Sjoberg Paul A. , Robbins Anthony S.
Published: May 2022

The objective of this study was to evaluate the impact of the COVID-19 pandemic on the circulation of influenza and other seasonal respiratory viruses in the United States. All data were obtained from the US Department of Defense Global Respiratory Pathogen Surveillance Program over five consecutive respiratory seasons from 2016–2017 through to 2020–2021. A total of 62,476 specimens were tested for seasonal respiratory viruses. The circulating patterns of seasonal respiratory viruses have been greatly altered during the pandemic. The 2019–2020 influenza season terminated earlier compared to the pre-pandemic seasons, and the 2020–2021 influenza season did not occur. Moreover, weekly test positivity rates dramatically decreased for most of the seasonal respiratory viruses from the start of the pandemic through spring 2021. After the easing of non-pharmaceutical interventions (NPIs), circulations of seasonal coronavirus, parainfluenza, and respiratory syncytial virus have returned since spring 2021. High rhinovirus/enterovirus activity was evident throughout the 2020–2021 respiratory season. The findings suggest a strong association between the remarkably changed activity of seasonal respiratory viruses and the implementation of NPIs during the COVID-19 pandemic. The NPIs may serve as an effective public health tool to reduce transmissions of seasonal respiratory viruses.
Intergenerational Transmission of Trauma: The Mediating Effects of Family Health
Authors: Reese Emma M. , Barlow Melissa Jane , Dillon Maddison , Villalon Sariah , Barnes Michael D. , Crandall AliceAnn
Published: May 2022

Family health is important to the well-being of individual family members and the collective family unit, and as such, may serve as a mediator for the intergenerational transmission of trauma (ITT). This study aimed to understand the intergenerational impact of parent’s adverse and positive childhood experiences (ACEs and PCEs) on their children’s adverse family experiences (AFEs) and how family health mediated those relationships. The sample consisted of 482 heterosexual married or cohabiting couples (dyads) in the United States who had a child between the ages of 3 and 13 years old. Each member of the dyad completed a survey, and data were analyzed using structural equation modeling. Parental ACEs were associated with more AFEs. The fathers’, but not the mothers’, ACEs were associated with worse family health. Parental PCEs were associated with better family health, and family health was associated with lower AFE scores. Indirect effects indicated that parental PCEs decreased AFEs through their impact on family health. Family health also mediated the relationship between the father’s ACEs and the child’s AFEs. Interventions designed to support family health may help decrease child AFEs.
Tumor Promoting Effects of Sulforaphane on Diethylnitrosamine-Induced Murine Hepatocarcinogenesis
Authors: Zheng Jie , Kim Do-Hee , Fang Xizhu , Kim Seong Hoon , Saeidi Soma , Kim Su-Jung , Surh Young-Joon
Published: May 2022

Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor involved in protection against initiation of carcinogenesis in normal cells. Notably, recent studies have demonstrated that aberrant activation of NRF2 accelerates the proliferation and progression of cancer cells. The differential effects of NRF2 on multi-stage carcinogenesis have raised a concern about the validity of NRF2 activators for chemoprevention. This prompted us to assess the effects of sulforaphane (SFN), a prototypic NRF2 activating chemopreventive phytochemical, on experimentally induced carcinogenesis. In the present study, SFN was daily injected intraperitoneally (25 mg/kg) for 3 months to male C57BL/6 mice at 6 months after single intraperitoneal administration of a hepatocarcinogen, diethylnitrosamine (DEN). The liver to body weight ratio, tumor growth, and the number and the size of hepatomas measured at 9 months after DEN administration were significantly higher in SFN-treated mice than those in vehicle-treated mice. Moreover, the expression of NRF2, its target protein NAD(P)H:quinone oxidoreductase 1, and the cell proliferation marker, proliferating cell nuclear antigen was further elevated in DEN plus SFN-treated mice. These results suggest that once hepatocarcinogenesis is initiated, SFN may stimulate tumor progression.
The Aryl Hydrocarbon Receptor Ligand FICZ Improves Left Ventricular Remodeling and Cardiac Function at the Onset of Pressure Overload-Induced Heart Failure in Mice
Authors: Tamayo María , Martín-Nunes Laura , Piedras María José , Martin-Calvo María , Martí-Morente Daniel , Gil-Fernández Marta , Gómez-Hurtado Nieves , Moro María Ángeles , Bosca Lisardo , Fernández-Velasco María , Delgado Carmen
Published: May 2022

Adverse ventricular remodeling is the heart’s response to damaging stimuli and is linked to heart failure and poor prognosis. Formyl-indolo [3,2-b] carbazole (FICZ) is an endogenous ligand for the aryl hydrocarbon receptor (AhR), through which it exerts pleiotropic effects including protection against inflammation, fibrosis, and oxidative stress. We evaluated the effect of AhR activation by FICZ on the adverse ventricular remodeling that occurs in the early phase of pressure overload in the murine heart induced by transverse aortic constriction (TAC). Cardiac structure and function were evaluated by cardiac magnetic resonance imaging (CMRI) before and 3 days after Sham or TAC surgery in mice treated with FICZ or with vehicle, and cardiac tissue was used for biochemical studies. CMRI analysis revealed that FICZ improved cardiac function and attenuated cardiac hypertrophy. These beneficial effects involved the inhibition of the hypertrophic calcineurin/NFAT pathway, transcriptional reduction in pro-fibrotic genes, and antioxidant effects mediated by the NRF2/NQO1 pathway. Overall, our findings provide new insight into the role of cardiac AhR signaling in the injured heart.
Golden and Silver–Golden Chitosan Hydrogels and Fabrics Modified with Golden Chitosan Hydrogels
Authors: Kozicki Marek , Pawlaczyk Aleksandra , Adamska Aleksandra , Szynkowska-Jóźwik Małgorzata Iwona , Sąsiadek-Andrzejczak Elżbieta
Published: May 2022

Golden and silver–golden chitosan hydrogels and hydrogel-modified textiles of potential biomedical applications are investigated in this work. The hydrogels are formed by reactions of chitosan with HAuCl4·xH2O. For above the critical concentration of chitosan (c*), chitosan–Au hydrogels were prepared. For chitosan concentrations lower than c*, chitosan–Au nano- and microgels were formed. To characterise chitosan–Au structures, sol–gel analysis, UV–Vis spectrophotometry and dynamic light scattering were performed. Au concentration in the hydrogels was determined by the flame atomic absorption spectrophotometry. Colloidal chitosan–Au solutions were used for the modification of fabrics. The Au content in the modified fabrics was quantified by inductively coupled plasma mass spectrometry technique. Scanning electron microscopy with energy dispersion X-ray spectrometer was used to analyse the samples. Reflectance spectrophotometry was applied to examine the colour of the fabrics. The formation of chitosan–Au–Ag hydrogels by the competitive reaction of Au and Ag ions with the chitosan macromolecules is reported.
Interactions between Macrophages and Mast Cells in the Female Reproductive System
Authors: Lampiasi Nadia
Published: May 2022

Mast cells (MCs) and macrophages (Mϕs) are innate immune cells that differentiate from early common myeloid precursors and reside in all body tissues. MCs have a unique capacity to neutralize/degrade toxic proteins, and they are hypothesized as being able to adopt two alternative polarization profiles, similar to Mϕs, with distinct or even opposite roles. Mϕs are very plastic phagocytic cells that are devoted to the elimination of senescent/anomalous endogenous entities (to maintain tissue homeostasis), and to the recognition and elimination of exogenous threats. They can adopt several functional phenotypes in response to microenvironmental cues, whose extreme profiles are the inflammatory/killing phenotype (M1) and the anti-inflammatory/healing phenotype (M2). The concomitant and abundant presence of these two cell types and the partial overlap of their defensive and homeostatic functions leads to the hypothesis that their crosstalk is necessary for the optimal coordination of their functions, both under physiological and pathological conditions. This review will examine the relationship between MCs and Mϕs in some situations of homeostatic regulation (menstrual cycle, embryo implantation), and in some inflammatory conditions in the same organs (endometriosis, preeclampsia), in order to appreciate the importance of their cross-regulation.
Nanobody Paratope Ensembles in Solution Characterized by MD Simulations and NMR
Authors: Fernández-Quintero Monica L. , DeRose Eugene F. , Gabel Scott A. , Mueller Geoffrey A. , Liedl Klaus R.
Published: May 2022

Variable domains of camelid antibodies (so-called nanobodies or VHH) are the smallest antibody fragments that retain complete functionality and therapeutic potential. Understanding of the nanobody-binding interface has become a pre-requisite for rational antibody design and engineering. The nanobody-binding interface consists of up to three hypervariable loops, known as the CDR loops. Here, we structurally and dynamically characterize the conformational diversity of an anti-GFP-binding nanobody by using molecular dynamics simulations in combination with experimentally derived data from nuclear magnetic resonance (NMR) spectroscopy. The NMR data contain both structural and dynamic information resolved at various timescales, which allows an assessment of the quality of protein MD simulations. Thus, in this study, we compared the ensembles for the anti-GFP-binding nanobody obtained from MD simulations with results from NMR. We find excellent agreement of the NOE-derived distance maps obtained from NMR and MD simulations and observe similar conformational spaces for the simulations with and without NOE time-averaged restraints. We also compare the measured and calculated order parameters and find generally good agreement for the motions observed in the ps–ns timescale, in particular for the CDR3 loop. Understanding of the CDR3 loop dynamics is especially critical for nanobodies, as this loop is typically critical for antigen recognition.
Lysozyme Amyloid Fibril Structural Variability Dependence on Initial Protein Folding State
Authors: Mikalauskaite Kamile , Ziaunys Mantas , Smirnovas Vytautas
Published: May 2022

Amyloid fibril formation is associated with several amyloidoses, including neurodegenerative Alzheimer’s or Parkinson’s diseases. The process of such fibrillar structure formation is still not fully understood, with new mechanistic insights appearing on a regular basis. This, in turn, has limited the development of potential anti-amyloid compounds, with only a handful of effective cures or treatment modalities available. One of the multiple amyloid aggregation factors that requires further examination is the ability of proteins to form multiple, structurally distinct aggregates, based on the environmental conditions. In this work, we examine how the initial folding state affects the fibrilization of lysozyme—an amyloidogenic protein, often used in protein aggregation studies. We show that there is a correlation between the initial state of the protein and the aggregate formation lag time, rate of elongation, resulting aggregate structural variability and dye-binding properties, as well as formation lag time and rate of elongation.
Molecular and Biochemical Mechanism of Cannabidiol in the Management of the Inflammatory and Oxidative Processes Associated with Endometriosis
Authors: Genovese Tiziana , Cordaro Marika , Siracusa Rosalba , Impellizzeri Daniela , Caudullo Sebastiano , Raffone Emanuela , Macrí Francesco , Interdonato Livia , Gugliandolo Enrico , Interlandi Claudia , Crupi Rosalia , D’Amico Ramona , Fusco Roberta , Cuzzocrea Salvatore , Di Paola Rosanna
Published: May 2022

Endometriosis is usually associated with inflammation and chronic pelvic pain. This paper focuses the attention on the anti-inflammatory, anti-oxidant and analgesic effects of cannabidiol (CBD) and on its potential role in endometriosis. We employed an in vivo model of endometriosis and administered CBD daily by gavage. CBD administration strongly reduced lesions diameter, volume and area. In particular, it was able to modify lesion morphology, reducing epithelial glands and stroma. CBD showed anti-oxidant effects reducing lipid peroxidation, the expression of Nox-1 and Nox-4 enzymes. CBD restored the oxidative equilibrium of the endogenous cellular defense as showed by the SOD activity and the GSH levels in the lesions. CBD also showed important antifibrotic effects as showed by the Masson trichrome staining and by downregulated expression of MMP-9, iNOS and TGF-β. CBD was able to reduce inflammation both in the harvested lesions, as showed by the increased Ikb-α and reduced COX2 cytosolic expressions and reduced NFkB nuclear localization, and in the peritoneal fluids as showed by the decreased TNF-α, PGE2 and IL-1α levels. CBD has important analgesic effects as showed by the reduced mast cells recruitment in the spinal cord and the reduced release of neuro-sensitizing and pro-inflammatory mediators. In conclusion, the collected data showed that CBD has an effective and coordinated effects in endometriosis suppression.
Improving Printability of Digital-Light-Processing 3D Bioprinting via Photoabsorber Pigment Adjustment
Authors: Seo Jeong Wook , Kim Gyu Min , Choi Yejin , Cha Jae Min , Bae Hojae
Published: May 2022

Digital-light-processing (DLP) three-dimensional (3D) bioprinting, which has a rapid printing speed and high precision, requires optimized biomaterial ink to ensure photocrosslinking for successful printing. However, optimization studies on DLP bioprinting have yet to sufficiently explore the measurement of light exposure energy and biomaterial ink absorbance controls to improve the printability. In this study, we synchronized the light wavelength of the projection base printer with the absorption wavelength of the biomaterial ink. In this paper, we provide a stepwise explanation of the challenges associated with unsynchronized absorption wavelengths and provide appropriate examples. In addition to biomaterial ink wavelength synchronization, we introduce photorheological measurements, which can provide optimized light exposure conditions. The photorheological measurements provide precise numerical data on light exposure time and, therefore, are an effective alternative to the expendable and inaccurate conventional measurement methods for light exposure energy. Using both photorheological measurements and bioink wavelength synchronization, we identified essential printability optimization conditions for DLP bioprinting that can be applied to various fields of biological sciences.
Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes
Authors: Di Meo Camilla , Tortolani Daniel , Standoli Sara , Angelucci Clotilde Beatrice , Fanti Federico , Leuti Alessandro , Sergi Manuel , Kadhim Salam , Hsu Eric , Rapino Cinzia , Maccarrone Mauro
Published: May 2022

The decriminalization and legalization of cannabis has paved the way for investigations into the potential of the use of phytocannabinoids (pCBs) as natural therapeutics for the treatment of human diseases. This growing interest has recently focused on rare (less abundant) pCBs that are non-psychotropic compounds, such as cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) and cannabigerolic acid (CBGA). Notably, pCBs can act via the endocannabinoid system (ECS), which is involved in the regulation of key pathophysiological processes, and also in the skin. In this study, we used human keratinocytes (HaCaT cells) as an in vitro model that expresses all major ECS elements in order to systematically investigate the effects of CBG, CBC, THCV and CBGA. To this end, we analyzed the gene and protein expression of ECS components (receptors: CB1, CB2, GPR55, TRPV1 and PPARα/γ/δ; enzymes: NAPE-PLD, FAAH, DAGLα/β and MAGL) using qRT-PCR and Western blotting, along with assessments of their functionality using radioligand binding and activity assays. In addition, we quantified the content of endocannabinoid(-like) compounds (AEA, 2-AG, PEA, etc.) using UHPLC-MS/MS. Our results demonstrated that rare pCBs modulate the gene and protein expression of distinct ECS elements differently, as well as the content of endocannabinoid(-like) compounds. Notably, they all increased CB1/2 binding, TRPV1 channel stimulation and FAAH and MAGL catalytic activity. These unprecedented observations should be considered when exploring the therapeutic potential of cannabis extracts for the treatment of human skin diseases.
Analytical and Theoretical Studies of Antioxidant Properties of Chosen Anthocyanins; A Structure-Dependent Relationships
Authors: Dudek Anita , Spiegel Maciej , Strugała-Danak Paulina , Gabrielska Janina
Published: May 2022

The relationship between the structure and the antiradical and antioxidant activities of three anthocyanidins, namely peonidin, petunidin, and delphinidin, and their glucosides was investigated in this study. The ability of anthocyanins to scavenge free radicals was determined using DPPH● assay, whereas the inhibition of peroxidation in liposomes in relation to a model membrane that imitated the composition of a lipid membrane in tumor cells was specified using the fluorimetric method. To explore this issue at the atomistic level, density functional theory studies were applied. It was shown that glycosides performed better than anthocyanidins in protecting membranes against oxidation. The highest redox potential was demonstrated by anthocyanidins with the highest number of hydroxyl groups in the B ring in the order as follows: (Dp > Pt > Pn), and the same relationship was proven for their glucosides. The majority of the compounds studied here proved to be better antioxidants than ascorbic acid. They showed consistent electrodonating properties and though the f-HAT mechanism became more feasible with each consecutive deprotonation. Glycosylation did not have a direct impact on reactivity, apart from peonidin and petunidin in the study of which it was found that this process was responsible for lifting off steric hindrance between B and C rings and rendering certain pathways more feasible. Kinetic and molecular dynamics are essential to properly describe the membrane’s lipid oxidation.
Characterization of Phytohormones and Transcriptomic Profiling of the Female and Male Inflorescence Development in Manchurian Walnut (Juglans mandshurica Maxim.)
Authors: Li Xiang , Han Rui , Cai Kewei , Guo Ruixue , Pei Xiaona , Zhao Xiyang
Published: May 2022

Flowers are imperative reproductive organs and play a key role in the propagation of offspring, along with the generation of several metabolic products in flowering plants. In Juglans mandshurica, the number and development of flowers directly affect the fruit yield and subsequently its commercial value. However, owing to the lack of genetic information, there are few studies on the reproductive biology of Juglans mandshurica, and the molecular regulatory mechanisms underlying the development of female and male inflorescence remain unclear. In this study, phytohormones and transcriptomic sequencing analyses at the three stages of female and male inflorescence growth were performed to understand the regulatory functions underlying flower development. Gibberellin is the most dominant phytohormone that regulates flower development. In total, 14,579 and 7188 differentially expressed genes were identified after analyzing the development of male and female flowers, respectively, wherein, 3241 were commonly expressed. Enrichment analysis for significantly enriched pathways suggested the roles of MAPK signaling, phytohormone signal transduction, and sugar metabolism. Genes involved in floral organ transition and flowering were obtained and analyzed; these mainly belonged to the M-type MADS-box gene family. Three flowering-related genes (SOC1/AGL20, ANT, and SVP) strongly interacted with transcription factors in the co-expression network. Two key CO genes (CO3 and CO1) were identified in the photoperiod pathway. We also identified two GA20xs genes, one SVP gene, and five AGL genes (AGL8, AGL9, AGL15, AGL19, and AGL42) that contributed to flower development. The findings are expected to provide a genetic basis for the studies on the regulatory networks and reproductive biology in inflorescence development for J. mandshurica.
Lactoferrin Inhibition of the Complex Formation between ACE2 Receptor and SARS CoV-2 Recognition Binding Domain
Authors: Piacentini Roberta , Centi Laura , Miotto Mattia , Milanetti Edoardo , Di Rienzo Lorenzo , Pitea Martina , Piazza Paolo , Ruocco Giancarlo , Boffi Alberto , Parisi Giacomo
Published: May 2022

The present investigation focuses on the analysis of the interactions among human lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. In particular, kinetic and thermodynamic parameters for the pairwise interactions among the three proteins were measured via two independent techniques, biolayer interferometry and latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no binding to the RBD was observed up to the maximum “physiological” lactoferrin concentration range. Lactoferrin, above 1 µM concentration, thus appears to directly interfere with RBD–ACE2 binding, bringing about a measurable, up to 300-fold increase of the KD value relative to RBD–ACE2 complex formation.
Design of Rational JAK3 Inhibitors Based on the Parent Core Structure of 1,7-Dihydro-Dipyrrolo [2,3-b:3′,2′-e] Pyridine
Authors: Li Yihao , Meng Dan , Xie Jiali , Li Ruoyu , Wang Zifan , Li Jinlong , Mou Lin , Deng Xinhao , Deng Ping
Published: May 2022

JAK3 differs from other JAK family members in terms of tissue distribution and functional properties, making it a promising target for autoimmune disease treatment. However, due to the high homology of these family members, targeting JAK3 selectively is difficult. As a result, exploiting small changes or selectively boosting affinity within the ATP binding region to produce new tailored inhibitors of JAK3 is extremely beneficial. PubChem CID 137321159 was used as the lead inhibitor in this study to preserve the characteristic structure and to collocate it with the redesigned new parent core structure, from which a series of 1,7-dihydro-dipyrrolo [2,3-b:3′,2′-e] pyridine derivatives were obtained using the backbone growth method. From the proposed compounds, 14 inhibitors of JAK3 were found based on the docking scoring evaluation. The RMSD and MM/PBSA methods of molecular dynamics simulations were also used to confirm the stable nature of this series of complex systems, and the weak protein–ligand interactions during the dynamics were graphically evaluated and further investigated. The results demonstrated that the new parent core structure fully occupied the hydrophobic cavity, enhanced the interactions of residues LEU828, VAL836, LYS855, GLU903, LEU905 and LEU956, and maintained the structural stability. Apart from this, the results of the analysis show that the binding efficiency of the designed inhibitors of JAK3 is mainly achieved by electrostatic and VDW interactions and the order of the binding free energy with JAK3 is: 8 (−70.286 kJ/mol) > 11 (−64.523 kJ/mol) > 6 (−51.225 kJ/mol) > 17 (−42.822 kJ/mol) > 10 (−40.975 kJ/mol) > 19 (−39.754 kJ/mol). This study may provide a valuable reference for the discovery of novel JAK3 inhibitors for those patients with immune diseases.
A Hierarchical Genotyping Framework Using DNA Melting Temperatures Applied to Adenovirus Species Typing
Authors: Galvin Ben , Jones Jay , Powell Michaela , Olin Katherine , Jones Matthew , Robbins Thomas
Published: May 2022

Known genetic variation, in conjunction with post-PCR melting curve analysis, can be leveraged to provide increased taxonomic detail for pathogen identification in commercial molecular diagnostic tests. Increased taxonomic detail may be used by clinicians and public health decision-makers to observe circulation patterns, monitor for outbreaks, and inform testing practices. We propose a method for expanding the taxonomic resolution of PCR diagnostic systems by incorporating a priori knowledge of assay design and sequence information into a genotyping classification model. For multiplexed PCR systems, this framework is generalized to incorporate information from multiple assays to increase classification accuracy. An illustrative hierarchical classification model for human adenovirus (HAdV) species was developed and demonstrated ~95% cross-validated accuracy on a labeled dataset. The model was then applied to a near-real-time surveillance dataset in which deidentified adenovirus detected patient test data from 2018 through 2021 were classified into one of six adenovirus species. These results show a marked change in both the predicted prevalence for HAdV and the species makeup with the onset of the COVID-19 pandemic. HAdV-B decreased from a pre-pandemic predicted prevalence of up to 40% to less than 5% in 2021, while HAdV-A and HAdV-F species both increased in predicted prevalence.