| 1. |
- Ababneh, Nidaa A., et al.
(författare)
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Identification of APTX disease-causing mutation in two unrelated Jordanian families with cerebellar ataxia and sensitivity to DNA damaging agents
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive cerebellar ataxia, caused by mutations in the APTX gene. The disease is characterized by early-onset cerebellar ataxia, oculomotor apraxia and severe axonal polyneuropathy. The aim of this study was to detect the disease-causing variants in two unrelated consanguineous Jordanian families with cerebellar ataxia using whole exome sequencing (WES), and to correlate the identified mutation(s) with the clinical and cellular phenotypes. METHODS: WES was performed in three affected individuals and segregation analysis of p.W279* APTX candidate variant was performed. Expression levels of APTX were measured in patients' skin fibroblasts and peripheral blood mononuclear cells, followed by western blot analysis in skin fibroblasts. Genotoxicity assay was performed to detect the sensitivity of APTX mutated cells to H2O2, MMC, MMS and etoposide. RESULTS: A recurrent homozygous nonsense variant in APTX gene (c.837G>A, p.W279*) was revealed in all affected individuals. qRT-PCR showed normal APTX levels in peripheral blood and lower levels in fibroblast cells. However, western blot showed the absence of APTX protein in patients' skin fibroblasts. Significant hypersensitivity to H2O2, MMC and etoposide and lack of sensitivity to MMS were noted. CONCLUSIONS: This is the first study to report the identification of a nonsense variant in the APTX gene (c.837G>A; p.W279*) in AOA1 patients within the Jordanian population. This study confirmed the need of WES to assist in the diagnosis of cerebellar ataxia and it emphasizes the importance of studying the pathophysiology of the APTX gene.
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| 2. |
- Abdullah Nasir, Ahmad, et al.
(författare)
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Ligand-specific regulation of transforming growth factor beta superfamily factors by leucine-rich repeats and immunoglobulin-like domains proteins
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- Leucine-rich repeats and immunoglobulin-like domains (LRIG) are transmembrane proteins shown to promote bone morphogenetic protein (BMP) signaling in Caenorhabditis elegans, Drosophila melanogaster, and mammals. BMPs comprise a subfamily of the transforming growth factor beta (TGFβ) superfamily, or TGFβ family, of ligands. In mammals, LRIG1 and LRIG3 promote BMP4 signaling. BMP6 signaling, but not BMP9 signaling, is also regulated by LRIG proteins, although the specific contributions of LRIG1, LRIG2, and LRIG3 have not been investigated, nor is it known whether other mammalian TGFβ family members are regulated by LRIG proteins. To address these questions, we took advantage of Lrig-null mouse embryonic fibroblasts (MEFs) with doxycycline-inducible LRIG1, LRIG2, and LRIG3 alleles, which were stimulated with ligands representing all the major TGFβ family subgroups. By analyzing the signal mediators pSmad1/5 and pSmad3, as well as the induction of Id1 expression, we showed that LRIG1 promoted BMP2, BMP4, and BMP6 signaling and suppressed GDF7 signaling; LRIG2 promoted BMP2 and BMP4 signaling; and LRIG3 promoted BMP2, BMP4, BMP6, and GDF7 signaling. BMP9 and BMP10 signaling was not regulated by individual LRIG proteins, however, it was enhanced in Lrig-null cells. LRIG proteins did not regulate TGFβ1-induced pSmad1/5 signaling, or GDF11- or TGFβ1-induced pSmad3 signaling. Taken together, our results show that some, but not all, TGFβ family ligands are regulated by LRIG proteins and that the three LRIG proteins display differential regulatory effects. LRIG proteins thereby provide regulatory means for the cell to further diversify the signaling outcomes generated by a limited number of TGFβ family ligands and receptors.
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| 3. |
- Abe, Takafumi, et al.
(författare)
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Number of teeth and masticatory function are associated with sarcopenia and diabetes mellitus status among community-dwelling older adults : A Shimane CoHRE study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6 June
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We aimed to examine the number of teeth and masticatory function as oral health indices and clarify their roles in the pathogenesis of sarcopenia and diabetes mellitus in communitydwelling older adults. Subjects and methods: This cross-sectional study was conducted with 635 older adults in Ohnan, Shimane Prefecture, in rural Japan. The number of teeth and masticatory function (measured by the number of gummy jelly pieces collected after chewing) were evaluated by dental hygienists. Sarcopenia status was assessed using handgrip strength, skeletal muscle index, calf circumference, and a possible sarcopenia diagnosis based on the Asian Working Group for Sarcopenia 2019. Diabetes mellitus status was defined as a hemoglobin A1c level ≥6.5% or self-reported diabetes. A multivariable logistic regression model was used to analyze the association between oral health, sarcopenia, and diabetes mellitus after adjusting for confounders. Results: After adjusting for all confounders, logistic regression analysis showed that the number of remaining teeth was negatively associated with a low level of handgrip strength (odds ratio [OR], 0.961; 95% confidence interval [CI], 0.932-0.992) and possible sarcopenia (OR, 0.949; 95% CI, 0.907-0.992). Higher levels of masticatory function were also negatively associated with a low level of handgrip strength (OR, 0.965; 95% CI, 0.941-0.990) and possible sarcopenia (OR, 0.941; 95% CI, 0.904-0.979). Logistic regression analysis showed that the number of remaining teeth and a higher level of masticatory function were negatively associated with diabetes mellitus (OR, 0.978; 95% CI, 0.957-0.999; OR, 0.976; 95% CI, 0.960-0.992, respectively). Conclusion: Our findings suggest that improvement in oral health, including the maintenance of masticatory function and remaining teeth, may contribute to the prevention of sarcopenia and diabetes mellitus in older adults.
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| 4. |
- Abe, Takafumi, et al.
(författare)
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Social participation and physical prefrailty in older Japanese adults : The Shimane CoHRE study
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12 December
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Tidskriftsartikel (refereegranskat)abstract
- As older adults in an early stage (prefrailty) of frailty may return to a healthy state, it is necessary to examine the prevention of prefrailty. In this context, the number and types of social participation activities associated with physical prefrailty in community-dwelling older adults have remained relatively unexplored. This cross-sectional study investigates this issue by analyzing 616 participants living in Okinoshima, Shimane, a rural area of Japan, in 2019. Frailty was assessed using the 5-item frailty phenotype (unintentional weight loss, selfreported exhaustion, weakness, slow walking speed, and low physical activity). Data on social participation were obtained using a questionnaire based on participants' level of involvement with volunteer groups, sports clubs/groups, neighborhood associations, religious organizations/groups, and community elderly salons; their answers were categorized as "yes"if they answered "several times per year or more"and "no"if they answered "never."Binominal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prefrailty by the number or types of social participation activities, adjusted for gender, age, body mass index, smoking, medication-taking, educational attainment, working status, and living arrangement. Of the 616 participants, 273 (44.3%) and 28 (4.5%) had prefrailty and frailty, respectively. The analysis showed that the number of social participation activities was significantly associated with lower odds of prefrailty (OR = 0.83; 95% CI, 0.74-0.94). Regarding the types of social participation, sports clubs/groups were associated with lower odds of prefrailty (OR = 0.47; 95% CI, 0.31-0.73). Participation in neighborhood associations was associated with prefrailty/frailty (OR = 0.57; 95% CI, 0.37-0.86). These results suggest that increasing the number of social participation activities or involvement in sports clubs/groups and neighborhood associations may be important to prevent physical prefrailty in the older population.
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| 5. |
- Aboshady, Hadeer Moursy, et al.
(författare)
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Genomic variants from RNA-seq for goats resistant or susceptible to gastrointestinal nematode infection
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal nematodes (GIN) are an important constraint in small ruminant production. Genetic selection for resistant animals is a potential sustainable control strategy. Advances in molecular genetics have led to the identification of several molecular genetic markers associated with genes affecting economic relevant traits. In this study, the variants in the genome of Creole goats resistant or susceptible to GIN were discovered from RNA-sequencing. We identified SNPs, insertions and deletions that distinguish the two genotypes, resistant and susceptible and we characterized these variants through functional analysis. The T cell receptor signalling pathway was one of the top significant pathways that distinguish the resistant from the susceptible genotype with 78% of the genes involved in this pathway showing genomic variants. These genomic variants are expected to provide useful resources especially for molecular breeding for GIN resistance in goats.
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| 6. |
- Abraham, Katharina, et al.
(författare)
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Benefits of a digital health technology for older nursing home residents. A de-novo cost-effectiveness model for digital health technologies to aid in the assessment of toileting and containment care needs
- 2024
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Ingår i: PLOS ONE. - 1932-6203. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was first, to introduce a comprehensive, de-novo health economic (HE) model incorporating the full range of activities involved in toileting and containment care (T&CC) for people with incontinence, capturing all the potential benefits and costs of existing and future Digital Health Technologies (DHT) aimed at improving continence care, for both residential care and home care. Second, to use this novel model to evaluate the cost-effectiveness of the DHT TENA SmartCare Identifi in the implementation of person-centred continence care (PCCC), compared with conventional continence care for Canadian nursing home residents. The de-novo HE model was designed to evaluate technologies across different care settings from the perspective of several stakeholders. Health states were based on six care need profiles with increasing need for toileting assistance, three care stages with varying degrees of toileting success, and five levels of skin health. The main outcomes were incremental costs and quality-adjusted life years. The effectiveness of the TENA SmartCare Identifi was based primarily on trial data combined with literature and expert opinion where necessary. Costs were reported in CAD 2020. After 2 years, 21% of residents in the DHT group received mainly toileting as their continence care strategy compared with 12% in the conventional care group. Conversely, with the DHT 15% of residents rely mainly on absorbent products for incontinence care, compared with 40% with conventional care. On average, residents lived for 2.34 years, during which the DHT resulted in a small gain in quality-adjusted life years of 0.015 and overall cost-savings of $1,467 per resident compared with conventional care. Most cost-savings were achieved through reduced costs for absorbent products. Since most, if not all, stakeholders gain from use of the DHT-assisted PCCC, widespread use in Canadian residential care facilities should be considered, and similar assessments for other countries encouraged.
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| 7. |
- Abu Hatab, Assem, et al.
(författare)
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COVID-19 risk perception and public compliance with preventive measures : Evidence from a multi-wave household survey in the MENA region
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:7
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the association between individuals’ concern about contracting COVID-19 and their compliance with recommended preventive and mitigation measures, namely wearing face masks, maintaining social distancing and handwashing, in the context of the Middle East and North Africa (MENA) region. The empirical analysis is based on a panel dataset from the Combined COVID-19 MENA Monitor Household Survey, which was carried out in Jordan, Morocco, Sudan, Tunisia and Egypt. Applying a probit estimation technique, a positive and statistically significant association was found between the level of COVID-19 worries and individuals’ compliance with the mitigation measures. Notably, the results revealed that this association followed a “first-up-then-down” trend, showing that compliance with the three mitigation measures rose as individuals’ worries about contracting the virus increased, and then markedly decreased after they had been infected. Socio-demographic characteristics contributing to lower levels of compliance included being male, being over 60, having lower levels of education and having a lower household income. A cross-country analysis revealed remarkable differences between the five countries, with the strongest association between COVID-19 concerns and adherence to mitigation measures observed in Tunisia and Sudan, and the weakest association seen in Jordan and Morocco. Policy implications are outlined for effective risk communication and management during disease outbreaks and public health emergencies to encourage appropriate public health behaviours.
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| 8. |
- Aburawi, Elhadi H., et al.
(författare)
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Epigenetics of conotruncal congenital heart disease : Protocol for a systematic review and meta-analysis
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:4
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Conotruncal congenital heart defects (CTD) are a subset of congenital heart diseases (CHD) that involve structural anomalies of the right, left, or both cardiac outflow tracts. CHD is caused by multifactorial inheritance and changes in the genes or chromosomes. Recently, CHD was found to be due to epigenetic alterations, which are a combination of genetic and other environmental factors. Epigenetics is the study of how a gene's function changes as a result of environmental and behavioral influences. These causative factors can indirectly cause CHD by altering the DNA through epigenetic modifications. This is a protocol for a systematic review and meta-analysis that aims to explore whether the strength of association between various epigenetic changes and CTD types varies by race. Furthermore, to determine and compare the changes in gene expression of each mutation.METHODS: Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. A comprehensive pre-search has been developed in PubMed and PubMed's Medical Subject Headings (MeSH). The final search will be performed in June 2023 in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CIANHL, and PsycInfo, without restrictions on publication years. The Covidence systematic review software will be used for blinded screening and selection. Conflicts will be resolved by a third, independent reviewer. The risk of bias in selected studies will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The data to be extracted will cover basic information on the included studies, study sample size, number of patients with various types of epigenetic changes, number of patients with various CTD types, measures of association and their 95% confidence interval between each epigenetic change and each CTD. The protocol has been registered with the International Prospero Register of Systematic Review (PROSPERO) [CRD42023377597].DISCUSSION: To the best of our knowledge, this protocol outlines the first systematic review and meta-analysis of the epigenetics of CTD. There is a growing body of evidence on epigenetics and its indirect involvement in disease by altering the DNA through epigenetic modifications in the genes associated with the causative factors for CHD. We will conduct a comprehensive and systematic search for literature in the above-mentioned seven core biomedical databases. It is very important to identify population-specific risk factors for CHD, which will have significant creative, custom-made, and effective prevention programs for the future generation.
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| 9. |
- Acciai, C, et al.
(författare)
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Institution and gender-related differences in publication speed before and during COVID-19
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11, s. e0277011-
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic elicited a substantial hike in journal submissions and a global push to get medical evidence quickly through the review process. Editorial decisions and peer-assessments were made under intensified time constraints, which may have amplified social disparities in the outcomes of peer-reviewing, especially for COVID-19 related research. This study quantifies the differential impact of the pandemic on the duration of the peer-review process for women and men and for scientists at different strata of the institutional-prestige hierarchy. Using mixed-effects regression models with observations clustered at the journal level, we analysed newly available data on the submission and acceptance dates of 78,085 medical research articles published in 2019 and 2020. We found that institution-related disparities in the average time from manuscript submission to acceptance increased marginally in 2020, although half of the observed change was driven by speedy reviews of COVID-19 research. For COVID-19 papers, we found more substantial institution-related disparities in review times in favour of authors from highly-ranked institutions. Descriptive survival plots also indicated that scientists with prestigious affiliations benefitted more from fast-track peer reviewing than did colleagues from less reputed institutions. This difference was more pronounced for journals with a single-blind review procedure compared to journals with a double-blind review procedure. Gender-related changes in the duration of the peer-review process were small and inconsistent, although we observed a minor difference in the average review time of COVID-19 papers first authored by women and men.
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| 10. |
- Acuña Mora, Mariela, 1990, et al.
(författare)
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The longitudinal association between patient empowerment and patient-reported outcomes: What is the direction of effect?
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- Theoretical literature and cross-sectional studies suggest empowerment is associated with other patient-reported outcomes (PROs). However, it is not known if patient empowerment is leading to improvements in other PROs or vice versa.The present study aimed to examine the direction of effects between patient empowerment and PROs in young persons with congenital heart disease (CHD).As part of the STEPSTONES-CHD trial, adolescents with CHD from seven pediatric cardiology centers in Sweden were included in a longitudinal observational study (n = 132). Data were collected when patients were 16 (T0), 17 (T1) and 18 ½ years old (T2). The Gothenburg Young Persons Empowerment Scale (GYPES) was used to measure patient empowerment. Random intercepts cross-lagged panel models between patient empowerment and PROs (communication skills; patient-reported health; quality of life; and transition readiness) were undertaken.We found a significant cross-lagged effect of transition readiness over patient empowerment between T1 and T2, signifying that a higher level of transition readiness predicted a higher level of patient empowerment. No other significant cross-lagged relationships were found.Feeling confident before the transition to adult care is necessary before young persons with CHD can feel in control to manage their health and their lives. Clinicians interested in improving patient empowerment during the transitional period should consider targeting transition readiness.
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