Miracle-dz/UniFAR-FTUs huggingface dataset:
Hereditary spastic paraplegia SPG8 mutations impair CAV1-dependent, integrin-mediated cell adhesion

Hereditary spastic paraplegia–associated mutations in a WASH complex component impair integrin-mediated cell adhesion. Disease-associated mutations impair integrin recycling Hereditary spastic paraplegia (HSP) type SPG8 is an inherited neurologic disorder associated with mutations in WASHC5, which encodes strumpellin, a component of the WASH complex, which localizes to endosomes and plays a role in endosomal sorting. Lee et al. found that strumpellin interacted with the caveolar protein CAV1 and inhibited its degradation. Cultured cells lacking strumpellin or expressing SPG8-associated strumpellin mutants exhibited impaired endosomal tubulation, reduced CAV1 at intracellular vesicles, and reduced integrin-mediated cell adhesion. The actin nucleation activity of the WASH complex was required for inhibiting the degradation of CAV1 and integrin α5, and the interaction between strumpellin and CAV1 was required for proper recycling of integrin α5 and for integrin-mediated cell adhesion. These findings suggest that the axon defects that characterize HSP type SPG8 may be due to disruption of strumpellin- and CAV1-dependent, integrin-mediated cell adhesion. Mutations in WASHC5 (also known as KIAA0196) cause autosomal dominant hereditary spastic paraplegia (HSP) type SPG8. WASHC5, commonly called strumpellin, is a core component of the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex that activates actin nucleation at endosomes. Although various other cellular roles for strumpellin have also been described, none account for how SPG8-associated mutations lead to HSP. Here, we identified protein interactors of the WASH complex by immunoprecipitation and mass spectrometry and assessed the functions of strumpellin in cultured cells using both overexpression and RNA interference along with cell-spreading assays to investigate cell adhesion. We uncovered a decrease in CAV1 protein abundance as well as endosomal fission defects resulting from pathogenic SPG8 mutations. CAV1, a key component of caveolae, interacted with strumpellin in cells, and strumpellin inhibited the lysosomal degradation of CAV1. SPG8-associated missense mutations in strumpellin did not rescue endosomal tubulation defects, reduction in CAV1 protein abundance, or integrin-mediated cell adhesion in strumpellin-deficient cells. Mechanistically, we demonstrated that the WASH complex maintained CAV1 and integrin protein amounts by inhibiting their lysosomal degradation through its endosomal actin nucleation activity. In addition, the interaction of strumpellin with CAV1 stimulated integrin recycling, thereby promoting cell adhesion. These findings provide a molecular link between WASHC5 mutations and impairment of CAV1- and integrin-mediated cell adhesion, providing insights into the cellular pathogenesis of SPG8.
'There is anointing everywhere': An interpretative phenomenological analysis of the role of religion in the recovery of black African service users in England.

INTRODUCTION Religion is an important impetus for recovery. However, there has been little work examining the role of religion in recovery for black African service users (BASUs) in England. AIM The aim of this study is to explore how religion influences recovery from mental illness for BASUs in England. METHOD 12 black African service users were purposively selected and interviewed using face-to-face semi-structured interviews. Data was analysed using interpretative phenomenological analysis (IPA). RESULTS The study generates fascinating insights that BASUs views about mental illness and recovery are influenced by Pentecostalism and traditional African healing systems. DISCUSSION The participants' perceptions of their mental illness experiences and recovery which are characterised by the pragmatism of Pentecostalism and cultural beliefs are consistent with what is reported in the literature. IMPLICATIONS FOR PRACTICE The findings of the study show that broad changes are needed to accommodate the religious coping of BASUs in their recovery journey.
Mobile health app usability and quality rating scales: a systematic review

Abstract Purpose To review the rating scales used to evaluate usability and quality of mobile health applications, and to compare their purpose, content, and intended target users (i.e., patients, caregivers, or researchers). Material and Methods We conducted a systematic review of the literature in accordance with the PRISMA statement on Medline, CINAHL, PsycINFO, IEEE Explore databases, as well as a review of the grey literature to identify rating scales used to evaluate usability and quality of mobile health applications (m-health apps), between January 1, 2000 and July 31, 2018. Two researchers screened the titles and abstracts of articles that met inclusion criteria, and retrieved usability and quality rating scales from the articles. Results We identified 24 usability scales and 25 quality rating scales in 87 peer-reviewed articles. We identified only one quality rating scale designed for non-expert users (i.e., patients or caregivers). None of the studies used a theoretical framework for app evaluation to support the scales. The validity of existing quality rating scales is yet to be investigated. Conclusion Existing usability and quality rating scales are targeted at professionals, not end users who are patients or caregivers. Rating scales that are usable by all end-users would make mobile health apps accessible and meaningful to consumers. Implications for rehabilitation The number of mobile health applications on app stores that can be used for rehabilitation is increasing. Most healthcare providers lack the training to identify m-health apps with high quality to be used in rehabilitation. This study has reviewed the current rating scales that can help clinicians and care providers rate the quality of m-health apps and identify the ones that are most appropriate for their practice.
The Intergenerational Transmission of Discrimination: Children’s Experiences of Unfair Treatment and Their Mothers’ Health at Midlife

A growing body of research suggests that maternal exposure to discrimination helps to explain racial disparities in children’s health. However, no study has considered if the intergenerational health effects of unfair treatment operate in the opposite direction—from child to mother. To this end, we use data from mother–child pairs in the National Longitudinal Survey of Youth 1979 to determine whether adolescent and young adult children’s experiences of discrimination influence their mother’s health across midlife. We find that children who report more frequent instances of discrimination have mothers whose self-rated health declines more rapidly between ages 40 and 50 years. Furthermore, racial disparities in exposure to discrimination among children explains almost 10% of the black–white gap but little of the Hispanic–white gap in self-rated health among these mothers. We conclude that the negative health impacts of discrimination are likely to operate in a bidirectional fashion across key family relationships.
Middle managers' roles after a hospital merger.

PURPOSE Mergers are important and challenging elements in hospital reforms. The authors study the social aspects of management and the roles of middle managers in the aftermath of a hospital merger. Especially, the purpose of this paper is to investigate how professional staff and middle managers perceive their relationships with top managers several years after the merger. DESIGN/METHODOLOGY/APPROACH A survey was conducted among the professional staff in two merging hospitals' units six years after a merger. Based on the main findings from this survey, a follow-up interview study was done with a group of middle managers. FINDINGS The management practices were diagnostic with few interactive or communicative activities. The respondents expressed that mistrust developed between the staff and the top management, and a lack of involvement and interaction lead to decoupled and parallel organizations. Social controls, based on shared norms, had not been developed to create mutual commitment and engagement. PRACTICAL IMPLICATIONS Policy makers should be aware of the need in profound change processes not only to change the tangible elements, but to take care of changing the less tangible elements such as norms and values. Professionals in hospitals are in powerful positions, and changes in such organizations are dependent on trust-building, bottom-up initiatives and evolutionary pathways. ORIGINALITY/VALUE The paper addresses the need to understand the dynamics of the social aspect in managing hospitals as knowledge-intensive organizations when comprehensive restructuring processes are taking place over several years.
Web-ARM: A Web-Based Interface for the Automatic Construction of QM/MM Models of Rhodopsins

This article introduces Web-ARM, a specialized, on-line available, tool designed to build quantum mechanical/molecular mechanical models of rhodopsins, a widely spread family of light-responsive proteins. Web-ARM allows to rapidly build models of rhodopsins with a documented quality and to predict trends in UV-Vis absorption maximum wavelengths, based on their excitation energies computed at the CASPT2//CASSCF/Amber level of theory. Web-ARM builds upon the recently reported, python-based a-ARM protocol [J. Chem. Theory Comput. , 2019, 15, 3134-3152], and as such necessitates only a crystallographic structure or a comparative model in PDB format and a very basic knowledge of the studied rhodopsin system. The user-friendly web interface uses such input to generate congruous, gas-phase models of rhodopsins and, if requested, their mutants. We present two possible applications of Web-ARM, which showcase how the interface can be employed to assist both research and educational activities in fields at the interface between chemistry and biology. The first application shows how, through Web-ARM, research projects (e.g., rhodopsin and rhodopsin mutant screening) can be carried out in significantly less time with respect to using the required computational photochemistry tools via a command line. The second application documents the use of Web-ARM in a real-life educational/training activity, through a hands-on experience illustrating the concepts of rhodopsin color tuning.
A genome‐wide linkage map for the house sparrow (Passer domesticus) provides insights into the evolutionary history of the avian genome

The house sparrow is an important model species for studying physiological, ecological and evolutionary processes in wild populations. Here, we present a medium density, genome wide linkage map for house sparrow (Passer domesticus) that has aided the assembly of the house sparrow reference genome, and that will provide an important resource for ongoing mapping of genes controlling important traits in the ecology and evolution of this species. Using a custom house sparrow 10 K iSelect Illumina SNP chip we have assigned 6,498 SNPs to 29 autosomal linkage groups, based on a mean of 430 informative meioses per SNP. The map was constructed by combining the information from linkage with that of the physical position of SNPs within scaffold sequences in an iterative process. Averaged between the sexes; the linkage map had a total length of 2,004 cM, with a longer map for females (2,240 cM) than males (1,801 cM). Additionally, recombination rates also varied along the chromosomes. Comparison of the linkage map to the reference genomes of zebra finch, collared flycatcher and chicken, showed a chromosome fusion of the two avian chromosomes 8 and 4A in house sparrow. Lastly, information from the linkage map was utilized to conduct analysis of linkage disequilibrium (LD) in eight populations with different effective population sizes (Ne) in order to quantify the background level LD. Together, these results aid the design of future association studies, facilitate the development of new genomic tools and support the body of research that describes the evolution of the avian genome.
Artificial Multiferroics and Enhanced Magnetoelectric Effect in van der Waals Heterostructures.

Multiferroic materials with coupled ferroelectric and ferromagnetic properties are important for multifunctional devices due to their potential ability of controlling magnetism via electric field, and vice versa. The recent discoveries of two-dimensional ferromagnetic and ferroelectric materials have ignited tremendous research interest and aroused hope to search for two-dimensional multiferroics. However, intrinsic two-dimensional multiferroic materials and, particularly, those with strong magnetoelectric couplings are still rare to date. In this paper, using first-principles simulations, we propose artificial two-dimensional multiferroics via a van der Waals heterostructure formed by ferromagnetic bilayer chromium triiodide (CrI3) and ferroelectric monolayer Sc2CO2. In addition to the coexistence of ferromagnetism and ferroelectricity, our calculations show that, by switching the electric polarization of Sc2CO2, we can tune the interlayer magnetic couplings of bilayer CrI3 between ferromagnetic and antiferromagnetic states. We further reveal that such a strong magnetoelectric effect is from a dramatic change of the band alignment induced by the strong build-in electric polarization in Sc2CO2 and the subsequent change of the interlayer magnetic coupling of bilayer CrI3. These artificial multiferroics and enhanced magnetoelectric effect give rise to realizing multifunctional nanoelectronics by van der Waals heterostructures.
One‐year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry

Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long‐term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS.
Reprogramming oxidative phosphorylation in cancer: A role for RNA binding proteins.

SIGNIFICANCE Cancer is a major disease imposing high personal and economic burdens draining large part of National Health Care and Research budgets worldwide. In the last decade, research in cancer has underscored the reprogramming of metabolism to an enhanced aerobic glycolysis as a major trait of the cancer phenotype with great potential for targeted therapy. Recent advances: Mitochondria are essential organelles in metabolic reprogramming by controlling the production of biological energy through oxidative phosphorylation (OXPHOS) and the supply of metabolic precursors that sustain proliferation. In addition, mitochondria are critical hubs that integrate different signaling pathways that control cellular metabolism and cell fate. The mitochondrial ATP synthase plays a fundamental role in OXPHOS and cellular signaling. CRITICAL ISSUES This review overviews mitochondrial metabolism and OXPHOS and the major changes reported in the expression and function of mitochondrial proteins of OXPHOS in oncogenesis and in cellular differentiation. We summarize the prominent role that RNA-binding proteins exert in the sorting and localized translation of nuclear-encoded mRNAs that help to define the mitochondrial cell-type specific phenotype. Moreover, we emphasize the mechanisms that contribute to restrain the activity and expression of the mitochondrial ATP synthase in carcinomas, and illustrate that the dysregulation of proteins that control energy metabolism correlates with patients' survival. FUTURE DIRECTIONS Future research should elucidate the mechanisms and RNA-binding proteins that promote the specific alterations of the mitochondrial phenotype in carcinomas arising in different tissues with the final aim of developing new therapeutic strategies to treat cancer.
Mining HPV Vaccine Knowledge Structures of Young Adults From Reddit Using Distributional Semantics and Pathfinder Networks

The human papillomavirus (HPV) vaccine protects adolescents and young adults from 9 high-risk HPV virus types that cause 90% of cervical and anal cancers and 70% of oropharyngeal cancers. This study extends our previous research analyzing online content concerning the HPV vaccination in social media platforms used by young adults, in which we used Pathfinder network scaling and methods of distributional semantics to characterize differences in knowledge organization reflected in consumer- and expert-generated online content. The current study extends this approach to evaluate HPV vaccine perceptions among young adults who populate Reddit, a major social media platform. We derived Pathfinder networks from estimates of semantic relatedness obtained by learning word embeddings from Reddit posts and compared these to networks derived from human expert estimation of the relationship between key concepts. Results revealed that users of Reddit, predominantly comprising young adults in the vaccine catch up age-group 18 through 26 years of age, perceived the HPV vaccine domain from a virus-framed perspective that could impact their lifestyle choices and that their awareness of the HPV vaccine for cancer prevention is also lacking. Further differences in knowledge structures were elucidated, with implications for future health communication initiatives.
Genome sequencing in persistently unsolved white matter disorders

Genetic white matter disorders have heterogeneous etiologies and overlapping clinical presentations. We performed a study of the diagnostic efficacy of genome sequencing in 41 unsolved cases with prior exome sequencing, resolving an additional 14 from an historical cohort (n = 191). Reanalysis in the context of novel disease‐associated genes and improved variant curation and annotation resolved 64% of cases. The remaining diagnoses were directly attributable to genome sequencing, including cases with small and large copy number variants (CNVs) and variants in deep intronic and technically difficult regions. Genome sequencing, in combination with other methodologies, achieved a diagnostic yield of 85% in this retrospective cohort.
Non‐additive effects of adjunct erythropoietin therapy with therapeutic hypothermia after global cerebral ischaemia in near‐term fetal sheep

Recombinant human erythropoietin (rEpo) is neuroprotective in immature animals, but it is unclear whether the combination of high‐dose rEpo therapy with therapeutic hypothermia can further improve outcomes. Hypothermia and rEpo independently improved neuronal survival, with greater improvement with hypothermia, and similarly reduced numbers of caspase‐3 positive cells and reactive microglia after 7 days recovery. Hypothermia, but not rEpo, was associated with markedly improved EEG power, whereas both interventions improved recovery of EEG frequency. There was no significant improvement in any outcome after combined rEpo and hypothermia compared with hypothermia alone, and of concern, the combination was associated with increased numbers of cortical caspase‐3‐positive cells compared with ischaemia‐hypothermia. These data suggest that the mechanisms of neuroprotection with hypothermia and rEpo overlap and, thus, high‐dose rEpo infusion does not appear to be an effective adjunct therapy for therapeutic hypothermia.
Network analysis of human muscle adaptation to aging and contraction

Resistance exercise (RE) remains a primary approach for minimising aging muscle decline. Understanding muscle adaptation to individual contractile components of RE (eccentric, concentric) might optimise RE-based intervention strategies. Herein, we employed a network-driven pipeline to identify putative molecular drivers of muscle aging and contraction mode responses. RNA-sequencing data was generated from young (21±1 y) and older (70±1 y) human skeletal muscle before and following acute unilateral concentric and contralateral eccentric contractions. Application of weighted gene co-expression network analysis identified 33 distinct gene clusters (‘modules’) with an expression profile regulated by aging, contraction and/or linked to muscle strength. These included two contraction ‘responsive’ modules (related to ‘cell adhesion’ and ‘transcription factor’ processes) that also correlated with the magnitude of post-exercise muscle strength decline. Module searches for ‘hub’ genes and enriched transcription factor binding sites established a refined set of candidate module-regulatory molecules (536 hub genes and 60 transcription factors) as possible contributors to muscle aging and/or contraction responses. Thus, network-driven analysis can identify new molecular candidates of functional relevance to muscle aging and contraction mode adaptations.
Influence of keratinized mucosa on the surgical therapeutical outcomes of peri-implantitis.

AIM To assess the impact of keratinized mucosa (KM) width around dental implants on surgical therapeutic outcomes when treating peri-implantitis. MATERIAL AND METHODS Surgically treated peri-implantitis implants were divided into two groups(KM width < 2 mm and ≥ 2mm). Retrospective data was obtained after implant placement (T0) and the day of peri-implantitis surgical treatment (T1). Patients were later recruited (≥1 year after T1) for clinical and radiographic examination (T2). Outcomes were analyzed using generalized estimating equation (GEE) models. RESULTS 40 patients (68 implants) (average follow-up: 52.4 ± 30.5 months) were included in this study. From T0-T1, no differences were found between KM groups in terms of peri-implant probing depths (PPD)and bleeding on probing (BOP). However, sites with < 2mm KM exhibited singnificantly higher suppuration (SUP) and lower marginal bone level (MBL) (p > .01). Between T1-T2, no major differences were noted on PPD reduction, BOP and MBL changes between the two groups. GEE modelling demonstrated that MBL severity prior to surgical therapy was a better predictor for implant survival than KM width. CONCLUSION Surgical outcome in treating peri-implantitis was influenced by the severity of bone loss present at the time of treatment and not by the presence of keratinized mucosa at the time of treatment.
Glaucocalyxin A inhibits hydrogen peroxide‐induced oxidative stress and inflammatory response in coronary artery smooth muscle cells

Atherosclerosis is a complex chronic inflammatory disease that remains one of the leading causes of death and disability worldwide. A previous study reported that glaucocalyxin A (GLA), a natural ent‐Kaurane diterpenoid triptolide, exhibits anti‐atherosclerotic activity. However, the underlying molecular mechanism has not yet been explored. In the present study, we evaluated the anti‐atherosclerotic effect of GLA and the underlying mechanism in vitro. Human coronary artery smooth muscle cells (HCASMCs) were stimulated by hydrogen peroxide (H2O2) to induce oxidative stress and inflammation. The results showed that GLA pretreatment improved the viability of H2O2‐induced HCASMCs. The increased reactive oxygen species production and decreased superoxide dismutase and glutathione peroxidase activities in H2O2‐induced HCASMCs were reversed by GLA pretreatment. In addition, GLA treatment suppressed the H2O2‐induced expression of inducible nitric oxide synthase, NADPH oxidase (NOX) 2, and NOX4 in HCASMCs. Moreover, treatment with GLA reduced the production of several inflammatory cytokines, including tumour necrosis factor‐alpha, interleukin (IL)‐6, and IL‐1β in H2O2‐induced HCASMCs. Furthermore, GLA treatment suppressed the phosphorylation of p38, as well as inactivating the NF‐κB signalling pathway. These findings suggested that GLA protected against H2O2‐induced oxidative stress and inflammation via inhibition of p38 phosphorylation and NF‐κB activation in HCASMCs.