bluuebunny/crossref_metadata_2025 huggingface dataset:
The Second Highest Prevalence of Celiac Disease Worldwide: Genetic and Metabolic Insights in Southern Brazilian Mennonites
Authors: Oliveira Luana Caroline , Dornelles Amanda Coelho , Nisihara Renato Mitsunori , Bruginski Estevan Rafael Dutra , Santos Priscila Ianzen dos , Cipolla Gabriel Adelman , Boschmann Stefanie Epp , Messias-Reason Iara José de , Campos Francinete Ramos , Petzl-Erler Maria Luiza , Boldt Angelica Beate Winter
Published: May 2023

Celiac disease (CD), despite its high morbidity, is an often-underdiagnosed autoimmune enteropathy. Using a modified version of the Brazilian questionnaire of the 2013 National Health Survey, we interviewed 604 Mennonites of Frisian/Flemish origin that have been isolated for 25 generations. A subgroup of 576 participants were screened for IgA autoantibodies in serum, and 391 participants were screened for HLA-DQ2.5/DQ8 subtypes. CD seroprevalence was 1:29 (3.48%, 95% CI = 2.16–5.27%) and biopsy-confirmed CD was 1:75 (1.32%, 95% CI = 0.57–2.59%), which is superior to the highest reported global prevalence (1:100). Half (10/21) of the patients did not suspect the disease. HLA-DQ2.5/DQ8 increased CD susceptibility (OR = 12.13 [95% CI = 1.56–94.20], p = 0.003). The HLA-DQ2.5 carrier frequency was higher in Mennonites than in Brazilians (p = 7 × 10−6). HLA-DQ8 but not HLA-DQ2.5 carrier frequency differed among settlements (p = 0.007) and was higher than in Belgians, a Mennonite ancestral population (p = 1.8 × 10−6), and higher than in Euro-Brazilians (p = 6.5 × 10−6). The glutathione pathway, which prevents reactive oxygen species-causing bowel damage, was altered within the metabolic profiles of untreated CD patients. Those with lower serological positivity clustered with controls presenting close relatives with CD or rheumatoid arthritis. In conclusion, Mennonites have a high CD prevalence with a strong genetic component and altered glutathione metabolism that calls for urgent action to alleviate the burden of comorbidities due to late diagnosis.
Mendelian Randomization and Transcriptome-Wide Association Analysis Identified Genes That Were Pleiotropically Associated with Intraocular Pressure
Authors: Yang Zhikun , Zhang Zhewei , Zhu Yining , Yuan Guangwei , Yang Jingyun , Yu Weihong
Published: May 2023

Background: Intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. However, the mechanisms underlying the controlling of IOP remain to be elucidated. Objective: To prioritize genes that are pleiotropically associated with IOP. Methods: We adopted a two-sample Mendelian randomization method, named summary-based Mendelian randomization (SMR), to examine the pleiotropic effect of gene expression on IOP. The SMR analyses were based on summarized data from a genome-wide association study (GWAS) on IOP. We conducted separate SMR analyses using Genotype-Tissue Expression (GTEx) and Consortium for the Architecture of Gene Expression (CAGE) expression quantitative trait loci (eQTL) data. Additionally, we performed a transcriptome-wide association study (TWAS) to identify genes whose cis-regulated expression levels were associated with IOP. Results: We identified 19 and 25 genes showing pleiotropic association with IOP using the GTEx and CAGE eQTL data, respectively. RP11-259G18.3 (PSMR = 2.66 × 10−6), KANSL1-AS1 (PSMR = 2.78 × 10−6), and RP11-259G18.2 (PSMR = 2.91 × 10−6) were the top three genes using the GTEx eQTL data. LRRC37A4 (PSMR = 1.19 × 10−5), MGC57346 (PSMR = 1.19 × 10−5), and RNF167 (PSMR = 1.53 × 10−5) were the top three genes using the CAGE eQTL data. Most of the identified genes were found in or near the 17q21.31 genomic region. Additionally, our TWAS analysis identified 18 significant genes whose expression was associated with IOP. Of these, 12 and 4 were also identified by the SMR analysis using the GTEx and CAGE eQTL data, respectively. Conclusions: Our findings suggest that the 17q21.31 genomic region may play a critical role in the regulation of IOP.
Differential Methylation of Telomere-Related Genes Is Associated with Kidney Disease in Individuals with Type 1 Diabetes
Authors: Hill Claire , Duffy Seamus , Kettyle Laura M. , McGlynn Liane , Sandholm Niina , Salem Rany M. , Thompson Alex , Swan Elizabeth J. , Kilner Jill , Rossing Peter , Shiels Paul G. , Lajer Maria , Groop Per-Henrik , Maxwell Alexander Peter , McKnight Amy Jayne ,   on behalf of the GENIE Consortium
Published: May 2023

Diabetic kidney disease (DKD) represents a major global health problem. Accelerated ageing is a key feature of DKD and, therefore, characteristics of accelerated ageing may provide useful biomarkers or therapeutic targets. Harnessing multi-omics, features affecting telomere biology and any associated methylome dysregulation in DKD were explored. Genotype data for nuclear genome polymorphisms in telomere-related genes were extracted from genome-wide case–control association data (n = 823 DKD/903 controls; n = 247 end-stage kidney disease (ESKD)/1479 controls). Telomere length was established using quantitative polymerase chain reaction. Quantitative methylation values for 1091 CpG sites in telomere-related genes were extracted from epigenome-wide case–control association data (n = 150 DKD/100 controls). Telomere length was significantly shorter in older age groups (p = 7.6 × 10−6). Telomere length was also significantly reduced (p = 6.6 × 10−5) in DKD versus control individuals, with significance remaining after covariate adjustment (p = 0.028). DKD and ESKD were nominally associated with telomere-related genetic variation, with Mendelian randomisation highlighting no significant association between genetically predicted telomere length and kidney disease. A total of 496 CpG sites in 212 genes reached epigenome-wide significance (p ≤ 10−8) for DKD association, and 412 CpG sites in 193 genes for ESKD. Functional prediction revealed differentially methylated genes were enriched for Wnt signalling involvement. Harnessing previously published RNA-sequencing datasets, potential targets where epigenetic dysregulation may result in altered gene expression were revealed, useful as potential diagnostic and therapeutic targets for intervention.
Homolog of Pea SGR Controls Stay-Green in Faba Bean (Vicia faba L.)
Authors: Chen Jingbin , Zhou Huimin , Yuan Xingxing , He Yaming , Yan Qiang , Lin Yun , Wu Ranran , Liu Jinyang , Xue Chenchen , Chen Xin
Published: May 2023

Faba bean is an important legume crop consumed as a vegetable or snack food, and its green cotyledons could present an attractive color for consumers. A mutation in SGR causes stay-green in plants. In this study, vfsgr was identified from a green-cotyledon-mutant faba bean, SNB7, by homologous blast between the SGR of pea and the transcriptome of faba bean. Sequence analysis revealed that a SNP at position 513 of the CDS of VfSGR caused a pre-stop codon, resulting in a shorter protein in the green-cotyledon faba bean SNB7. A dCaps marker was developed according to the SNP that caused the pre-stop, and this marker was completely associated with the color of the cotyledon of faba bean. SNB7 stayed green during dark treatment, while the expression level of VfSGR increased during dark-induced senescence in the yellow-cotyledon faba bean HST. Transient expression of VfSGR in Nicotiana. benthamiana leaves resulted in chlorophyll degradation. These results indicate that vfsgr is the gene responsible for the stay-green of faba bean, and the dCaps marker developed in this study provides a molecular tool for the breeding of green-cotyledon faba beans.
A Novel 13q12 Microdeletion Associated with Familial Syndromic Corneal Opacification
Authors: Serpen Jasmine Y. , Presley William , Beil Adelyn , Armenti Stephen T. , Johnson Kayla , Mian Shahzad I. , Innis Jeffrey W. , Prasov Lev
Published: May 2023

Progressive corneal opacification can result from multiple etiologies, including corneal dystrophies or systemic and genetic diseases. We describe a novel syndrome featuring progressive epithelial and anterior stromal opacification in a brother and sister and their mildly affected father, with all three family members having sensorineural hearing loss and two also with tracheomalacia/laryngomalacia. All carried a 1.2 Mb deletion at chromosome 13q12.11, with no other noteworthy co-segregating variants identified on clinical exome or chromosomal microarray. RNAseq analysis from an affected corneal epithelial sample from the proband’s brother revealed downregulation of XPO4, IFT88, ZDHHC20, LATS2, SAP18, and EEF1AKMT1 within the microdeletion interval, with no notable effect on the expression of nearby genes. Pathway analysis showed upregulation of collagen metabolism and extracellular matrix (ECM) formation/maintenance, with no significantly down-regulated pathways. Analysis of overlapping deletions/variants demonstrated that deleterious variants in XPO4 were found in patients with laryngomalacia and sensorineural hearing loss, with the latter phenotype also being a feature of variants in the partially overlapping DFNB1 locus, yet none of these had reported corneal phenotypes. Together, these data define a novel microdeletion-associated syndromic progressive corneal opacification and suggest that a combination of genes within the microdeletion may contribute to ECM dysregulation leading to pathogenesis.
Fluid Redox Fingerprint of the CaCO3+Antigorite Dehydration Reaction in Subducted Metacarbonate Sediments
Authors: Maffeis Andrea , Ferrando Simona , Connolly James Alexander Denis , Frezzotti Maria Luce , Castelli Daniele
Published: May 2023

Antigorite dehydration is a process able to release, in comparison with other minerals, the highest amount of H2O from a subducting slab. The released fluid delivers critical elements (e.g., S, Cu, and REE) to the overlying subarc mantle, modifying the mantle source of arc magmas and related ore deposits. Whether antigorite breakdown produces oxidising or reducing fluids is debated. Whereas previous studies have investigated antigorite dehydration in serpentinites (i.e., in a (C)AMFS-H2O system), this contribution is devoted to the CMFS-COHS carbonate system, which is representative of the metacarbonate sediments (or carbonate-dominated ophicarbonate rocks) that sit atop the slab. Thermodynamic modelling is used to investigate the redox effect of the carbonate-buffered antigorite dehydration reactions (i.e., brucite breakdown and antigorite breakdown) on electrolytic fluid geochemistry as a function of P-T-fO2. The influence of P-T-fO2 conditions on the solubility of C and S, solute-bound H2 and O2, fluid pH, the average valence states of dissolved C and S, and the fluid redox budget indicates that, in metacarbonate sediments, the CaCO3+antigorite reaction tends to produce reducing fluids. However, the redox state of such fluids is buffered not only by the redox state of the system but also, most importantly, by concomitantly dissolving redox-sensitive minerals (i.e., carbonates, graphite, pyrite, and anhydrite). A qualitative correlation between the redox state of the system and the possible depth of fluid release into the mantle wedge is also derived.
Geological Uniqueness and Potential Geotouristic Appeal of Murge and Premurge, the First Territory in Puglia (Southern Italy) Aspiring to Become a UNESCO Global Geopark
Authors: Tropeano Marcello , Caldara Massimo A. , De Santis Vincenzo , Festa Vincenzo , Parise Mario , Sabato Luisa , Spalluto Luigi , Francescangeli Ruggero , Iurilli Vincenzo , Mastronuzzi Giuseppe A. , Petruzzelli Marco , Bellini Filippo , Cicala Marianna , Lippolis Elio , Petti Fabio M. , Antonelli Matteo , Cardia Stefano , Conti Jacopo , La Perna Rafael , Marino Maria , Marsico Antonella , Sacco Enrico , Fiore Antonello , Simone Oronzo , Valletta Salvatore , D’Ettorre Umberto S. , De Giorgio Vincenzo , Liso Isabella S. , Stigliano Eliana
Published: May 2023

At the end of November 2021, a large area of Puglia (an administrative region in Southern Italy) was officially nominated as new aUGGp (aspiring UNESCO Global Geopark) by the Italian National Commission of UNESCO. This area comprises the northwestern part of the Murge territory, where a Cretaceous sector of the Apulia Carbonate Platform crops out, and part of the adjacent Premurge territory, where the southwestward lateral continuation of the same platform (being flexed toward the Southern Apennines Chain) is covered by thin Plio-Quaternary foredeep deposits. The worldwide geological uniqueness of the aspiring Geopark (Murge aUGGp) is that the area is the only in situ remnant of the Adria Plate, the old continental plate almost entirely squeezed between the Africa and Eurasia Plates. In such a context, the Murge area (part of the Apulia Foreland) is a virtually undeformed sector of Adria, while other territories of the plate are and/or were involved in the subduction/collision processes. In the aspiring Geopark, the crust of Adria is still rooted to its mantle, and the Cretaceous evolution of the continent is widely recorded in the Murge area thanks to the shallow-water carbonate succession of one of the largest peri-Tethys carbonate platforms (the Apulia Carbonate Platform). The aspiring Geopark also comprises the Premurge area, which represents the outer Southern Apennines foredeep, whose Plio-Quaternary evolution is spectacularly exposed thanks to an “anomalous” regional middle-late Quaternary uplift. Despite the presence of numerous geological singularities of international importance, it would be important, from a geotourist point of view, to propose a regional framework of the geology of the aUGGp before introducing visitors to the significance of the individual geosites, whose importance could be amplified if included in the geoevolutionary context of the Murge aUGGp.
Cancer Patients’ Satisfaction with In-Home Palliative Care and Its Impact on Disease Symptoms
Authors: Valero-Cantero Inmaculada , Casals Cristina , Espinar-Toledo Milagrosa , Barón-López Francisco Javier , Martínez-Valero Francisco Javier , Vázquez-Sánchez María Ángeles
Published: May 2023

The aim of the study was to determine whether the satisfaction of cancer patients with in-home palliative care is associated with the impact of disease symptoms and with self-perceived quality of life. This was a cross-sectional descriptive study, conducted in the primary health care sector in six clinical management units, where 72 patients were recruited over a period of six months. The severity of symptoms was determined by the Edmonton Symptom Assessment System (ESAS). Quality of life was evaluated with the EORTC QLQ-C30 (version 3) questionnaire, and patients’ satisfaction with the care received was evaluated by the Client Satisfaction Questionnaire (CSQ-8). The patients’ satisfaction with the health care received was represented by an average score of 6, on a scale of 1–10; thus, there is room for improvement in patient satisfaction. Moreover, it was found that more intense symptoms and lower quality of life are associated with lower satisfaction with health care received (p = 0.001). Similarly, when symptoms are more severe, the quality of life is lower (p < 0.001). The identification of fatigue, reduced well-being, pain, drowsiness, and depression as the symptoms experienced with the highest intensity by our patients provides valuable information for health care providers in developing individualized symptom management plans for patients with advanced cancer.
A Study of Factors Influencing the Volume of Responses to Posts in Physician Online Community
Authors: Liu Jingfang , Zeng Yu
Published: May 2023

Today’s diverse health needs place greater demands on physicians. However, individual doctors have limited capabilities and may encounter many unsolvable medical problems. The physician online community provides a platform for physicians to communicate with each other and help each other. Physicians can post for help about problems they encounter at work. The number of responses to physicians’ posts is critical to whether or not the problem is resolved. This study collected information on 13,226 posts from a well-known physician online community in China to analyze the factors that influence the number of post replies. In the analysis of the post content of the physician online community, this study innovatively introduces word usage features in the medical field. TextMind was used to extract the rate of several types of words in posts that frequently appear when describing medical information. Ultimately, we found that the rate of time words, visual words, auditory words, and physiological process words used in posts had a positive and significant effect on the number of post responses. A series of new post features has been found to have an impact on the number of post replies in physician online communities. This finding is beneficial for physicians to quickly obtain peer assistance through online platforms, increasing the likelihood of solving workplace challenges and improving physician care, as well as the success of physician online communities.
Cadmium, Lead, Chronic Physiological Stress and Endometrial Cancer: How Environmental Policy Can Alter the Exposure of At-Risk Women in the United States
Authors: Olarewaju Elizabeth , Obeng-Gyasi Emmanuel
Published: May 2023

The health and life outcomes of individuals are intertwined with the context in which they grow and live. The totality of exposures one experiences affects health in the short term and throughout the life course. Environmental exposure to multiple contaminants can increase stress levels in individuals and neighborhoods with psychosocial stressors such as crime, drug and alcohol misuse, and violence also taking a toll on individual and neighborhood wellbeing. In addition, the availability, organization, and quality of local institutions and infrastructure all affect health in the short and long term. The role of these factors in endometrial cancer will be explored in this paper. In addition, policy implications regarding lead, chronic physiological stress, and endometrial cancer will be explored to ascertain the impact of these factors on at-risk women.
Women’s Involvement in Steady Exercise (WISE): Study Protocol for a Randomized Controlled Trial
Authors: Ferrando-Terradez Irene , Dueñas Lirios , Parčina Ivana , Ćopić Nemanja , Petronijević Svetlana , Beltrami Gianfranco , Pezzoni Fabio , San Martín-Valenzuela Constanza , Gijssel Maarten , Moliterni Stefano , Papageorgiou Panagiotis , Rodríguez-Carrasco Yelko
Published: May 2023

Background: Physical inactivity is a serious public health problem for people of all ages and is currently the fourth highest global risk factor for mortality. The transition period from adolescence to adulthood coincides with a marked reduction in participation in physical activity, with more than 50% (and up to 80%) of young adults stopping physical activity. This decrease in physical activity is more evident in women than in men. Despite efforts, existing programs face challenges in effectively initiating and maintaining physical activity among individuals, particularly women, for extended durations. To address these limitations, the Women’s Involvement in Steady Exercise (WISE) randomized controlled trial (RCT) seeks to assess the efficacy of a digital high-intensity training intervention complemented by nutritional plans and other health-related advice. Methods: The study will be a three-center, randomized (1:1), controlled, parallel-group trial with a six-month intervention period. A total of 300 participants will be recruited at three study sites in Spain, Serbia and Italy. The participants will be randomized to one of the two groups and will follow a six-month program. The primary outcome of the study is the daily step count. Self-reported physical activity, the adherence to the exercise program, body composition, physical activity enjoyment, quality of sleep and physical capacities will also be evaluated.
Family Socioeconomic Status and Parental Involvement in Chinese Parents of Children with Autism Spectrum Disorder: A Moderated Mediation Model
Authors: Yan Tingrui , Hou Yujia , Liang Luyao
Published: May 2023

Parental involvement benefits children with autism spectrum disorder (ASD) in multiple developmental areas. We conducted the present study to examine the role of parenting stress and ASD symptom severity in the relationship between family socioeconomic status (SES) and parental involvement. A total of 165 Chinese parents of children with ASD participated in this study. Mediation analyses indicated that family SES was positively related to parental involvement; parenting stress partially mediated the relationship between family SES and parental involvement. The analyses also found that ASD symptom severity moderated the influence of parenting stress on parental involvement. Specifically, the decreased parenting stress improved parental involvement when ASD symptom severity was low. The findings enhanced our understanding of the mechanism underlying the relationship between family SES and parental involvement among parents facing considerable child-rearing challenges. Implications for devising evidenced-based interventions to promote parental involvement for low SES children with ASD are discussed.
Analysing Power Relations among Older Norwegian Patients and Spanish Migrant Nurses in Home Nursing Care: A Critical Discourse Analysis Approach from a Transcultural Perspective
Authors: Martínez-Angulo Pablo , Rich-Ruiz Manuel , Ventura-Puertos Pedro E. , López-Quero Salvador
Published: May 2023

Power relations in care are the link between patients and nurses regarding communication and the ability to act in this context. It can be affected when there is cultural interference between members, putting mutual understanding at risk in healthcare situations. This study analyses power relations in healthcare situations between older Norwegian patients and Spanish migrant nurses regarding active listening, shared decision-making, and patient participation. We performed a hermeneutical study endorsed in critical discourse studies framework from a transcultural perspective. A purposive sampling included older Norwegian patients living alone and Spanish migrant nurses working in Norway. Eleven face-to-face semi-structured interviews were conducted with older patients and four via videoconference with migrant nurses. The analysis followed hermeneutic considerations by Crist and Tanner, and linguistic analysis was performed. Shared decision-making and active listening situations sometimes showed a power imbalance that negatively influenced older Norwegian patients. However, Spanish migrant nurses were also conditioned by care organising institutions. This power triangle negatively affected the relationship between the older patients and migrant nurses, resulting in a lack of communication, personnel, time and trust. The migratory experience influenced the care provided by Spanish migrant nurses, shaping a series of cultural competencies acquired through the migratory process.
Psychosocial Factors Associated with Self-Management in Patients with Diabetes
Authors: León-Hernández Rodrigo , Rodríguez-Pérez Andrea C. , Pérez-González Yessica M. , de Córdova María I. P. , de León-Escobedo Raúl , Gómez-Gutiérrez Tranquilina , Toledano-Toledano Filiberto
Published: May 2023

Despite the significant advances in research on diabetes, relatively few researchers have examined the theoretical and empirical usefulness of explanatory models that contribute to self-management of the disease. In response to the theoretical and empirical approaches related to this topic, the objective of this research was to assess a hypothetical model to explain self-management behavior in patients with type II diabetes through structural equation modeling in a population of users of the services of the State Health Department of Tamaulipas, Mexico. The study used a cross-sectional and explanatory design. The sample was intentional. A total of 183 patients with a diabetes diagnosis completed a sociodemographic data questionnaire, the Partners in Health Scale, the Duke-UNC-11, the Family Apgar, the Self-Efficacy Scale, the Personal Health Questionnaire and the Physical Activity Scale. The results indicated that the hypothetical model was improved by excluding the exercise variable. The appropriate model was used to determine the effects of depression, social support, self-efficacy, family functioning, years of formal education and years with a diagnosis on self-management. The goodness-of-fit indices (GFIs) were good, i.e., χ2/gl = 0.89 (p = 0.529), root mean square error of approximation (RMSEA) = 0.000, and comparative fit index (CFI) = 1.000, with an acceptable degree of parsimony (PNFI = 0.409 and PGFI = 317). The model explained 33.6% of the variance. Therefore, this model represents an important advance in knowledge concerning self-management and provides empirical and theoretical evidence, particularly for the Mexican or Latino population.
From Clinical Scenarios to the Management of Lower Urinary Tract Symptoms in Children: A Focus for the General Pediatrician
Authors: Palma Pier Luigi , Marzuillo Pierluigi , Di Sessa Anna , Guarino Stefano , Capalbo Daniela , Marrapodi Maria Maddalena , Buccella Giulia , Cameli Sabrina , Miraglia del Giudice Emanuele , Torella Marco , Colacurci Nicola , Capristo Carlo
Published: May 2023

Lower urinary tract symptoms (LUTS) are a relevant problem in the pediatric population, having a very high prevalence. Diurnal incontinence and nocturnal enuresis are surely the most frequent symptoms, presenting, respectively, in up to 30% of school-age children and up to 10% of children between 6 and 7 years. Stypsis is the most common comorbidity, and it must be considered in the management of LUTS; indeed, the treatment of constipation is curative in most cases for both incontinence and enuresis. The presence or absence of diurnal symptoms in nocturnal enuresis and urgency in diurnal incontinence helps in the differential diagnosis. Urotherapy is always the first-line treatment, while oxybutynin and desmopressin (where appropriate) may help if the first-line treatment is unsuccessful. It is essential to identify conditions that are potentially dangerous for kidney and urinary tract well-being, for which LUTS can be the first manifestation. Starting from a series of clinical scenarios, we will underline the diagnostic clues behind LUTS in children and we will summarize clinical and surgical approaches for the proper management of these conditions.
The Impact of the COVID-19 Pandemic on the Management of Mental Health Services for Hospitalized Patients in Sibiu County—Central Region, Romania
Authors: Băcilă Ciprian , Ștef Laura , Bucuță Mihaela , Anghel Claudia Elena , Neamțu Bogdan , Boicean Adrian , Mohor Cosmin , Ștețiu Andreea Angela , Roman Mihai
Published: May 2023

Introduction: The COVID-19 pandemic brought a burden and represented a challenge for the Romanian medical system. This study explored the consequences that COVID epidemiological measures had on the quality of the mental health care provided to hospitalized patients in a regional psychiatric hospital in Romania. Materials and methods: Both patient-level and hospital-level indicators were considered for this comparative retrospective study. On the one hand, we extracted patient-level indicators, such as sociodemographics, diagnosis, admission, and discharge dates for 7026 hospitalized patients (3701 women, average age = 55.14) from hospital records. On the other hand, for the hospital-level indicators, we included indicators referring to the aggregated concept of mental health services, such as case mix index, length of stay, bed occupancy rate and patients’ degree of satisfaction. Data extracted covered a period of two years (1 March 2019–28 February 2021) before and during the first year of the COVID-19 pandemic. Results: We found that, compared to the pre-pandemic period, the pandemic period was marked by a drastic decrease in hospitalized patient admissions, coupled with an increase in emergency-based admissions. Other management indicators, such as the case mix index, the number of cases contracted/performed, and the degree of patient satisfaction, decreased. In contrast, the average length of stay and bed occupancy rate increased. Conclusions: The COVID-19 pandemic, especially in the first year, raised multiple difficult issues for the management of psychiatric hospitals. It imposed an application of strict measures designed to face these new and unprecedented challenges. Our findings offer a detailed snapshot of the first year of the COVID-19 pandemic in terms of its impact on mental health services and suggest some future directions. Implications for hospital management are discussed.Keywords: hospital management; COVID-19 pandemic; hospitalized patients; psychiatric hospital; mental health services.
Structural Origins of Poor Health Outcomes in Documented Temporary Foreign Workers and Refugees in High-Income Countries: A Review
Authors: Yang Borum , Kelly Clara , Shamputa Isdore Chola , Barker Kimberley , Thi Kim Nguyen Duyen
Published: May 2023

Despite growing evidence of racial and institutional discrimination on minoritized communities and its negative effect on health, there are still gaps in the current literature identifying health disparities among minoritized communities. This review aims to identify health barriers faced by relatively less studied migrant subgroups including documented temporary foreign workers and refugees residing in high-income Organisation for Economic Co-operation and Development (OECD) countries focusing on the structural origins of differential health outcomes. We searched Medline, CINAHL, and Embase databases for papers describing health barriers for these groups published in English between 1 January 2011 and 30 July 2021. Two independent reviewers conducted a title, abstract, and full text screening with any discrepancies resolved by consensus or a third reviewer. Extracted data were analyzed using an inductive thematic analysis. Of the 381 articles that underwent full-text review, 27 articles were included in this review. We identified housing conditions, immigration policies, structural discrimination, and exploitative labour practices as the four major emerging themes that impacted the health and the access to healthcare services of our study populations. Our findings highlight the multidimensional nature of health inequities among migrant populations and a need to examine how the broader context of these factors influence their daily experiences.
Person-Centeredness in Digital Primary Healthcare Services—A Scoping Review
Authors: Leonardsen Ann-Chatrin Linqvist , Bååth Carina , Helgesen Ann Karin , Grøndahl Vigdis Abrahamsen , Hardeland Camilla
Published: May 2023

Background: Transformation toward digital services offers unique opportunities to meet the challenges of responding to changing public healthcare needs and health workforce shortages. There is a knowledge gap regarding digital health and person or patient-centered care. Aim: The aim of the current scoping review was to obtain an overview of existing research on person or patient centeredness in digital primary healthcare services. Design: A scoping review following the five stages by Arksey and O’Malley. Methods: Literature searches were conducted in the databases PubMed, Scopus (Elsevier), APA PsychInfo (Ovid), Embase (Ovid), Cinahl (Ovid) and Cochrane Library in June 2022. The Preferred Reporting Items for Systematic reviews and Meta-Analyzes extension for Scoping Reviews (PRISMA-ScR) Checklist was followed. Results: The electronic database searches identified 782 references. A total of 116 references were assessed in full text against the inclusion and exclusion criteria. Finally, a total of 12 references were included. The included papers represent research from 2015 to 2021 and were conducted in eight different countries, within a variety of populations, settings and digital solutions. Four themes providing knowledge about current research on patient or person centeredness and digital primary health care were identified: ‘Accessibility’, ‘Self-management’, ‘Digitalization at odds with patient centeredness’ and ‘Situation awareness’. The review underlines the need for further research on these issues.
Public–Private Partnership: Participants’ Experiences of the Web-Based Registration-and-Management System for Patients with Hypertension and Diabetes Mellitus
Authors: Lee Seonah , Song Nanyoung , Kim Suhyun
Published: May 2023

Hypertension and diabetes mellitus, which induce cardiovascular and cerebrovascular diseases, require government intervention. In South Korea, the web-based registration-and-management system for patients with hypertension and diabetes mellitus was operated as a pilot program. This study explored the experiences of the 71 participating medical centers in G city, South Korea, of using the web-based registration-and-management system for preventing and managing hypertension and diabetes mellitus. After the survey, 40 physicians participated in interviews, and the recorded interviews were analyzed and classified into three categories: participation motivation, participation experiences, and suggestions. The study participants participated in a national pilot project with different expectations. Similar to the survey results on participation experiences, the satisfaction from a patient-care perspective was high, but there was an excessive burden of administrative work from the perspective of primary-medical-center operations. In addition, the suggestions included strengthening systematic education, continuous maintenance, broad project application, and improvements to the system. The system needs to be unified and simplified, the project continuity needs to be secured, and the application of the system to other regions and medical centers needs to be considered to induce public–private cooperation to reduce the amount of administrative work, which is currently excessive.
Investigating Students’ Perceptions towards Artificial Intelligence in Medical Education
Authors: Buabbas Ali Jasem , Miskin Brouj , Alnaqi Amar Ali , Ayed Adel K. , Shehab Abrar Abdulmohsen , Syed-Abdul Shabbir , Uddin Mohy
Published: May 2023

Implementing a reform in medical education requires students’ awareness regarding the importance of artificial intelligence (AI) in modern medical practice. The objective of this study was to investigate students’ perceptions of AI in medical education. A cross-sectional survey was conducted from June 2021 to November 2021 using an online questionnaire to collect data from medical students in the Faculty of Medicine at Kuwait University, Kuwait. The response rate for the survey was 51%, with a sample size of 352. Most students (349 (99.1%)) agreed that AI would play an important role in healthcare. More than half of the students (213 (60.5%)) understood the basic principles of AI, and (329 (93.4%)) students showed comfort with AI terminology. Many students (329 (83.5%)) believed that learning about AI would benefit their careers, and (289 (82.1%)) believed that medical students should receive AI teaching or training. The study revealed that most students had positive perceptions of AI. Undoubtedly, the role of AI in the future of medicine will be significant, and AI-based medical practice is required. There was a strong consensus that AI will not replace doctors but will drastically transform healthcare practices.
CoastFLOOD: A High-Resolution Model for the Simulation of Coastal Inundation Due to Storm Surges
Authors: Makris Christos , Mallios Zisis , Androulidakis Yannis , Krestenitis Yannis
Published: May 2023

Storm surges due to severe weather events threaten low-land littoral areas by increasing the risk of seawater inundation of coastal floodplains. In this paper, we present recent developments of a numerical modelling system for coastal inundation induced by sea level elevation due to storm surges enhanced by astronomical tides. The proposed numerical code (CoastFLOOD) performs high-resolution (5 m × 5 m) raster-based, storage-cell modelling of coastal inundation by Manning-type equations in decoupled 2-D formulation at local-scale (20 km × 20 km) lowland littoral floodplains. It is fed either by outputs of either regional-scale storm surge simulations or satellite altimetry data for the sea level anomaly. The presented case studies refer to model applications at 10 selected coastal sites of the Ionian Sea (east-central Mediterranean Sea). The implemented regular Cartesian grids (up to 5 m) are based on Digital Elevation/Surface Models (DEM/DSM) of the Hellenic Cadastre. New updated features of the model are discussed herein concerning the detailed surveying of terrain roughness and bottom friction, the expansion of Dirichlet boundary conditions for coastal currents (besides sea level), and the enhancement of wet/dry cell techniques for flood front propagation over steep water slopes. Verification of the model is performed by comparisons against satellite ocean color observations (Sentinel-2 images) and estimated flooded areas by the Normalized Difference Water Index (NDWI). The qualitative comparisons are acceptable, i.e., the modelled flooded areas contain all wet area estimations by NDWI. CoastFLOOD results are also compared to a simplified, static level, “bathtub” inundation approach with hydraulic connectivity revealing very good agreement (goodness-of-fit > 0.95). Furthermore, we show that proper treatment of bottom roughness referring to realistic Land Cover datasets provides more realistic estimations of the maximum flood extent timeframe.
Riluzole-Loaded Nanostructured Lipid Carriers for Hyperproliferative Skin Diseases
Authors: Llorente Xavier , Esteruelas Gerard , Bonilla Lorena , Agudelo Mariana Garnica , Filgaira Ingrid , Lopez-Ramajo Daniel , Gong Ruoyi C , Soler Concepció , Espina Marta , García Maria Luisa , Manils Joan , Pujol Montserrat , Sánchez-López Elena
Published: May 2023

Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions.
Investigation into the Potential Role of Propionibacterium freudenreichii in Prevention of Colorectal Cancer and Its Effects on the Diversity of Gut Microbiota in Rats
Authors: Dikeocha Ifeoma Julieth , Al-Kabsi Abdelkodose Mohammed , Ahmeda Ahmad Faheem , Mathai Michael , Alshawsh Mohammed Abdullah
Published: May 2023

Colorectal cancer (CRC) accounts for 10% of all cancer diagnoses and cancer-related deaths worldwide. Over the past two decades, several studies have demonstrated the clinical benefits of probiotic supplementation and some studies have shown that certain probiotics can modulate immunity and strengthen gut microbiota diversity. This study aims to assess the impact of the Propionibacterium freudenreichii (PF) probiotic against CRC induced by azoxymethane (AOM), and to investigate its effects on gut microbiota diversity in rats, as well as to evaluate the anti-proliferative activities of PF in HCT116 CRC cells. This experiment was performed using four groups of SD rats: normal control, AOM group, PF group (1 × 109 CFU/mL), and standard drug control (5-fluorouracil, 35 mg/kg). Methylene blue staining of colon tissues showed that the administration of PF significantly reduced the formation of colonic aberrant crypt foci (ACF) compared to the AOM control group. In addition, treated rats had lower levels of malondialdehyde in their colon tissue homogenates, indicating that lipid peroxidation was suppressed by PF supplementation. Furthermore, 16S rRNA gene analysis revealed that probiotic treatment enhanced the diversity of gut microbiota in rats. In vitro study showed that the viability of HCT116 cells was inhibited by the probiotic cell-free supernatant with an IC50 value of 13.3 ± 0.133. In conclusion, these results reveal that consuming PF as probiotic supplements modulates gut microbiota, inhibits the carcinogenic effects of AOM, and exerts anti-proliferative activity against CRC cells. Further studies are required to elucidate the role of PF on the immune response during the development and growth of CRC.
Effect of RONS-Induced Intracellular Redox Homeostasis in 6-NBDG/Glucose Uptake in C2C12 Myotubes and Single Isolated Skeletal Muscle Fibres
Authors: Fernández-Puente Escarlata , Martín-Prieto Eva , Márquez Carlos Manuel , Palomero Jesús
Published: May 2023

The glucose uptake in skeletal muscle is essential to produce energy through ATP, which is needed by this organ to maintain vital functions. The impairment of glucose uptake compromises the metabolism and function of skeletal muscle and other organs and is a feature of diabetes, obesity, and ageing. There is a need for research to uncover the mechanisms involved in the impairment of glucose uptake in skeletal muscle. In this study, we adapted, developed, optimised, and validated a methodology based on the fluorescence glucose analogue 6-NBDG, combined with a quantitative fluorescence microscopy image analysis, to determine the glucose uptake in two models of skeletal muscle cells: C2C12 myotubes and single fibres isolated from muscle. It was proposed that reactive oxygen and nitrogen species (RONS) and redox homeostasis play an important role in the modulation of intracellular redox signalling pathways associated with glucose uptake. In this study, we prove that the prooxidative intracellular redox environment under oxidative eustress produced by RONS such as hydrogen peroxide and nitric oxide improves glucose uptake in skeletal muscle cells. However, when oxidation is excessive, oxidative distress occurs, and cellular viability is compromised, although there might be an increase in the glucose uptake. Based on the results of this study, the determination of 6-NBDG/glucose uptake in myotubes and skeletal muscle cells is feasible, validated, and will contribute to improve future research.
AI-Driven De Novo Design and Molecular Modeling for Discovery of Small-Molecule Compounds as Potential Drug Candidates Targeting SARS-CoV-2 Main Protease
Authors: Andrianov Alexander M. , Shuldau Mikita A. , Furs Konstantin V. , Yushkevich Artsemi M. , Tuzikov Alexander V.
Published: May 2023

Over the past three years, significant progress has been made in the development of novel promising drug candidates against COVID-19. However, SARS-CoV-2 mutations resulting in the emergence of new viral strains that can be resistant to the drugs used currently in the clinic necessitate the development of novel potent and broad therapeutic agents targeting different vulnerable spots of the viral proteins. In this study, two deep learning generative models were developed and used in combination with molecular modeling tools for de novo design of small molecule compounds that can inhibit the catalytic activity of SARS-CoV-2 main protease (Mpro), an enzyme critically important for mediating viral replication and transcription. As a result, the seven best scoring compounds that exhibited low values of binding free energy comparable with those calculated for two potent inhibitors of Mpro, via the same computational protocol, were selected as the most probable inhibitors of the enzyme catalytic site. In light of the data obtained, the identified compounds are assumed to present promising scaffolds for the development of new potent and broad-spectrum drugs inhibiting SARS-CoV-2 Mpro, an attractive therapeutic target for anti-COVID-19 agents.
PIMT Controls Insulin Synthesis and Secretion through PDX1
Authors: Sharma Rahul , Maity Sujay K. , Chakrabarti Partha , Katika Madhumohan R. , Kapettu Satyamoorthy , Parsa Kishore V. L. , Misra Parimal
Published: May 2023

Pancreatic beta cell function is an important component of glucose homeostasis. Here, we investigated the function of PIMT (PRIP-interacting protein with methyl transferase domain), a transcriptional co-activator binding protein, in the pancreatic beta cells. We observed that the protein levels of PIMT, along with key beta cell markers such as PDX1 (pancreatic and duodenal homeobox 1) and MafA (MAF bZIP transcription factor A), were reduced in the beta cells exposed to hyperglycemic and hyperlipidemic conditions. Consistently, PIMT levels were reduced in the pancreatic islets isolated from high fat diet (HFD)-fed mice. The RNA sequencing analysis of PIMT knockdown beta cells identified that the expression of key genes involved in insulin secretory pathway, Ins1 (insulin 1), Ins2 (insulin 2), Kcnj11 (potassium inwardly-rectifying channel, subfamily J, member 11), Kcnn1 (potassium calcium-activated channel subfamily N member 1), Rab3a (member RAS oncogene family), Gnas (GNAS complex locus), Syt13 (synaptotagmin 13), Pax6 (paired box 6), Klf11 (Kruppel-Like Factor 11), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1) was attenuated due to PIMT depletion. PIMT ablation in the pancreatic beta cells and in the rat pancreatic islets led to decreased protein levels of PDX1 and MafA, resulting in the reduction in glucose-stimulated insulin secretion (GSIS). The results from the immunoprecipitation and ChIP experiments revealed the interaction of PIMT with PDX1 and MafA, and its recruitment to the insulin promoter, respectively. Importantly, PIMT ablation in beta cells resulted in the nuclear translocation of insulin. Surprisingly, forced expression of PIMT in beta cells abrogated GSIS, while Ins1 and Ins2 transcript levels were subtly enhanced. On the other hand, the expression of genes, PRIP/Asc2/Ncoa6 (nuclear receptor coactivator 6), Pax6, Kcnj11, Syt13, Stxbp1 (syntaxin binding protein 1), and Snap25 (synaptosome associated protein 25) associated with insulin secretion, was significantly reduced, providing an explanation for the decreased GSIS upon PIMT overexpression. Our findings highlight the importance of PIMT in the regulation of insulin synthesis and secretion in beta cells.