Miracle-dz/UniFAR-FTUs huggingface dataset:
Membrane Microdomains and Protease-Dependent Biased Agonism

P rotease-activated receptors (PARs) are G protein–coupled receptors (GPCRs) that transmit cellular responses begun by the actions of extracellular proteases. The activation of a PAR occurs by a unique mechanism whereby the extracellular N-terminal segment of the inactive receptor undergoes proteolytic cleavage, resulting in irreversible activation––unlike most GPCRs that are reversibly activated. PARs mediate cellular responses to coagulant proteases in various cell types localized within the vasculature. Additionally, PARs are expressed in other cell types and respond to a plethora of proteases. Recent studies have revealed that different proteases elicit distinct responses through the activation of the same PAR. This phenomenon appears to involve stabilization of distinct active PAR conformations that facilitates selectively coupling to different effectors and is localized to caveolae, a subtype of lipid rafts. of the cellular be evoked thrombin
Blood pressure and kidney outcomes in patients with severely decreased glomerular filtration rate: a nationwide observational cohort study

Objectives: To investigate the association between blood pressure (BP) and kidney outcomes in patients with estimated glomerular filtration rate less than 30 ml/min per 1.73 m2 and different degrees of albuminuria. Methods: National observational cohort study of 18 071 chronic kidney disease (CKD) stage 4–5 patients in routine nephrology care 2010–2017. The association between both baseline and repeated clinic office BP and eGFR slope and kidney replacement therapy (KRT) was explored using multivariable adjusted joint models. The analyses were stratified on albuminuria at baseline. Results: The adjusted yearly eGFR slope became increasingly steeper from −0,91 (95% CI −0.83 to −1.05) ml/min per 1.73 m2 per year in those with SBP less than 120 mmHg at baseline to −2.09 (−1.83 to −2.37) ml/min per 1.73 m2 in those with BP greater than 160 mmHg. Similarly, eGFR slope was steeper with higher DBP. Lower SBP and DBP was associated with slower eGFR decline in patients with albuminuria grade A3 (>30 mg/mmol) but not consistently in albuminuria A1–A2. Those with diabetes progressed faster and the association between BP and eGFR slope was stronger. In repeated BP measurement analyses, every 10 mmHg higher SBP over time was associated with 39% additional risk of KRT. Conclusion: In people with eGFR less than 30 ml/min per 1.73 m2, lower clinic office BP is associated with more favorable kidney outcomes. Our results support lower BP targets also in people with CKD stage 4–5.
User Experience and Usability of Neumorphism and Gamification User Interface Designs in an HIV Self-Test Referral Program for Men Who Have Sex With Men: Prospective Open-Label Parallel-Group Randomized Controlled Trial

Background Digital interventions have been applied for promoting HIV prevention and care among men who have sex with men (MSM). As user interface (UI) design plays a role in determining usability and user experience (UX), the intervention outcome could be affected. Objective In this study, we hypothesized that 2 UI design styles, namely gamification and neumorphism, could impact usability and be differentially preferred by distinct groups of MSM. Methods A prospective parallel-group open-label randomized controlled trial was conducted in Hong Kong. Eligible participants were adult MSM recruited by the research team or referred by enrolled participants, who followed instructions for performing an HIV self-test and promoted its use within their social network. Participants were randomized in a 1:1 ratio into either a gamification or neumorphism arm, with primarily visual differences in the UI only. The primary outcome was usability measured by the System Usability Scale (SUS) between the 2 arms. Distinct characteristics of promoters in the 2 arms who gave an SUS score of 80 or above were identified. Results Of 463 MSM registered in the study, 232 and 231 were randomized to the gamification and neumorphism arms, respectively. Excluding those who did not request a self-test kit, data from 218 and 216 participants in the gamification and neumorphism arms, respectively, were analyzed (totally 434 participants). With a median SUS score of 80 overall, participants in the neumorphism arm gave a higher score (P<.001), with a higher proportion giving a promoter-level SUS score (P=.002). Promoters used social media for sex networking (P=.02), used pre-exposure prophylaxis in the preceding year (P=.006), had higher satisfaction in UI design (P<.001), and had made a self-test referral (P=.04). In general, higher usability was recorded among participants who were confident in performing the HIV self-test (P<.001), and this was associated with a promoter-level SUS score in both arms. While no other personal characteristics were associated with promoters in the neumorphism arm, those in the gamification arm had higher HIV-related knowledge (P=.01), preferred a specific partner body image type (P=.03), and progressed toward peer referral by completing online training (P=.04). Conclusions Both gamified and neumorphic UI designs were well-accepted by MSM. UX and satisfaction of UI were both crucial in influencing the willingness of MSM to promote the application by referring their peers in the community to participate. The simplistic visual design of neumorphism conferred a more general acceptance in the community, whereas gamification was preferred in certain MSM subcommunities. Appropriate UI/UX design should be considered when developing digital interventions targeting the MSM community. Trial Registration ClinicalTrials.gov NCT04379206; https://clinicaltrials.gov/ct2/show/NCT04379206
Impact of Periodic Unsteadiness on Performance and Heat Load in Axial Flow Turbomachines

Results of an analytical and experimental investigation, directed at the understanding of the impact of periodic unsteadiness on the time-averaged flows in axial flow turbomachines, are presented. Analysis of available experimental data, from a large-scale rotating rig (LSRR) (low speed rig), shows that in the time-averaged axisymmetric equations the magnitude of the terms representing the effect of periodic unsteadiness (deterministic stresses) are as large or larger than those due to random unsteadiness (turbulence). Numerical experiments, conducted to highlight physical mechanisms associated with the migration of combustor generated hot-streaks in turbine rotors, indicated that the effect can be simulated by accounting for deterministic stress like terms in the time-averaged mass and energy conservation equations. The experimental portion of this program shows that the aerodynamic loss for the second stator in a 1-1/2 stage turbine are influenced by the axial spacing between the second stator leading edge and the rotor trailing edge. However, the axial spacing has little impact on the heat transfer coefficient. These performance changes are believed to be associated with the change in deterministic stress at the inlet to the second stator. Data were also acquired to quantify the impact of indexing the first stator relative to the second stator. For the range of parameters examined, this effect was found to be of the same order as the effect of axial spacing.
“They treat you like a person, they ask you what you want”: a grounded theory study of quality paid disability support for adults with acquired neurological disability

Abstract Purpose Adults with acquired neurological disability often require paid disability support to live an ordinary life. However, little is known about what facilitates quality support. This study aims to explore the lived experience of people with acquired neurological disability to develop an understanding of the factors that influence the quality of support. Methods Guided by constructivist grounded theory, in-depth qualitative interviews were conducted with 12 adults with acquired neurological disability. Data analysis followed an iterative process to develop themes and subthemes and explore relations between themes to build a model of quality support. Results Nine key factors emerged in the dyadic space, with the support worker recognising the person as an individual as foundational to quality support. Beyond the dyadic space, three broader contextual factors were identified as influential on the quality of support by mechanism of facilitating or constraining the person with disability’s choice. Finally, the provision of quality support was characterised by the person feeling in control. Conclusions Findings support the rights of people with disability to quality, individualised support, and a need for interventions to better prepare the disability workforce to deliver support in line with the needs and preferences of people with acquired neurological disability. IMPLICATIONS FOR REHABILITATION To provide quality support, disability support workers need to recognise the person with disability as an individual and the expert in their support needs and preferences. The quality of paid disability support is primarily determined by the way the person with disability and support worker work together in the dyadic space. Ensuring people with acquired neurological disability have authentic choice over their support arrangements and daily living is critical to facilitate quality support, and in turn help the person with disability to feel in control.
Association of GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms with risk of age-related macular degeneration: a meta-analysis

ABSTRACT Background This study determined to evaluate the association between glutathione S-transferase (GST) polymorphisms, namely, GSTM1 (rs1183423000, presence/absence), GSTT1 (rs1601993659, presence/absence), and GSTP1 Ile105Val (rs1695, A>G) polymorphisms, and AMD risk. Methods We searched PubMed, Embase, and Web of Science databases from January 2000 to June 2021. The odds ratio (OR) and 95% confidence interval (95% CI) were used as effect sizes. Heterogeneity was assessed using the heterogeneity metric I2. Results Five relevant studies involving 875 patients with AMD and 966 healthy controls were included in this meta-analysis, four studies concerning GSTM1 null polymorphism, four studies regarding GSTT1 null polymorphism, and four studies on GSTP1 Ile105Val polymorphism. The GSTM1 null polymorphism, GSTT1 null polymorphism and GSTP1 Ile105Val polymorphism were not significantly associated with AMD risk (OR 1.13, 95% CI 0.73–1.75, p = 0.59; OR 1.05, 95% CI 0.81–1.36, p = 0.69; OR 1.20, 95% CI 0.97–1.47, p = 0.09, respectively). There was no association between the combined GSTM1 null genotype and GSTT1 null genotype and AMD risk (OR 1.16, 95% CI 0.42–3.17, p = 0.77). Subgroup analyses revealed that the GSTM1 null genotype was associated with an increased risk of AMD in the Turkish population (OR 1.67, 95% CI 1.13–2.47, p = 0.01) and the GSTM1 null genotype was associated with a decreased incidence of non-exudative AMD (OR 0.72, 95% CI 0.52–0.99, p = 0.01). There was no obvious risk of publication bias found. Conclusions This meta-analysis indicated that there were no significant associations between GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms and AMD risk.
Assessing the Risk Factors For Diagnosed Symptomatic Dry Eye Using a Smartphone App: Cross-sectional Study

Background Dry eye (DE) is a chronic inflammatory disease of the ocular surface of the eye that affects millions of people throughout the world. Smartphone use as an effective health care tool has grown exponentially. The “Dry eye or not? ” app was created to evaluate the prevalence of symptomatic DE, screen for its occurrence, and provide feedback to users with symptomatic DE throughout Thailand. Objective The purpose of this study was to compare the prevalence of symptomatic dry eye (DE), blink rate, maximum blink interval (MBI), and best spectacle-corrected visual acuity (BSCVA) between people with and without symptomatic DE and to identify risk factors for symptomatic DE in Thailand. Methods This cross-sectional study sourced data from the “Dry eye or not? ” smartphone app between November 2019 and July 2020. This app collected demographic data, Ocular Surface Disease Index (OSDI) score, blink rate, MBI, BSCVA, and visual display terminal (VDT) use data. The criterion for symptomatic DE was OSDI score ≥13. Results The prevalence of symptomatic DE among individuals using this smartphone app in Thailand was 85.8% (8131/9482), with the Northeastern region of Thailand having the highest prevalence, followed by the Northern region. Worse BSCVA (median 0.20, IQR 0.40; P=.02), increased blink rate (median 18, IQR 16; P<.001), reduced MBI (median 8.90, IQR 10.80; P<.001), female sex (adjusted OR 1.83; 95% CI 1.59-2.09; P<.001), more than 6 hours of VDT use (adjusted OR 1.59; 95% CI 1.15-2.19; P=.004), and lower than bachelor’s degree (adjusted OR 1.30; 95% CI 1.03-1.64; P=.02) were significantly associated with symptomatic DE. An age over 50 years (adjusted OR 0.77; 95% CI 0.60-0.99) was significantly less associated with symptomatic DE (P=.04). Conclusions This smartphone DE app showed that the prevalence of symptomatic DE in Thailand was 85.8%. Signs and risk factors could be also evaluated with this smartphone DE app. Screening for DE by this app may allow for the development of strategic plans for health care systems in Thailand.
Numerical Study of Hubbard Model for Iron-based Superconductors

This thesis addresses the numerical and analytical study of the iron-based superconductors, mainly using the multi-orbital Hubbard model and Hartree-Fock approximation. The text starts with an introduction to the new iron-based superconductors, followed by a theoretical description of the multi-orbital Hubbard model and Hartree-Fock approximations. The numerical study of the Hubbard model in momentum space is described next, where the phase diagrams for threeand fiveorbital Hubbard models are provided. The physically “realistic” regime of couplings is highlighted, to guide future theoretical work into the proper region of parameters of Hubbard models for iron-based superconductors. What goes next is the numerical investigation of the two-orbital Hubbard model for the pnictides, using the real-space Hartree-Fock approximation on finite clusters. In this study, the charge stripes states are stabilized, upon electron doping. The observed patterns correspond to charge stripes oriented perpendicular to the direction of the spin stripes of the undoped magnetic ground state. After the iron pnictides, the numerical study of the magnetic state of K0.8Fe1. 6Se2 [potassium iron selenide] is presented, by applying the real-space Hartree-Fock approximation to the five-orbital Hubbard model. This study employed a 10×10 iron cluster with iron vacancies order. An insulating state with the same spin pattern as observed experimentally, involving 2×2 ferromagnetic plaquettes coupled with one another antiferromagnetically, is found to be stable in the phase diagram of the Hubbard model at intermediate Hubbard and Hund couplings. Another similar study of the magnetic state of the two-leg ladder selenide compound BaFe2Se3 [barium
Excessive platelet inhibition following Pipeline embolization of intracranial aneurysms

Background High levels of platelet inhibition have been associated with hemorrhagic complications following Pipeline embolization of intracranial aneurysms. We therefore titrate clopidogrel dosing to maintain a moderate level of platelet inhibition using the VerifyNow P2Y12 assay. However, many patients demonstrate dramatic increases in platelet inhibition following treatment despite being on a consistent antiplatelet regimen. We therefore elected to explore the incidence of this phenomenon and possible predisposing factors. Methods All successful Pipeline aneurysm treatments performed at our institution from 2011 to 2019 with moderate procedure-day platelet inhibition levels as indicated by a VerifyNow PRU of 60–235 were included. Patients who received glycoprotein IIb/IIIa inhibitors and those treated for ruptured/symptomatic lesions were excluded. The incidence of excessive platelet inhibition defined by a PRU<60 within 8 weeks of treatment was noted. Multivariable logistic regression was performed to determined independent predictors of the phenomenon. Results Some 190 treatments were performed in 178 qualifying patients. A post-procedure PRU <60 occurred following 79% of treatments, documented on average after 8.5 (range 1–47) days. A higher procedure day hematocrit level (P=0.003, OR 1.09, 95% CI 1.029 to 1.152) was an independent predictor of reaching a PRU <60, while intra-procedural midazolam exposure (P=0.044, OR 0.44, 95% CI 0.201 to 0.980) and a higher procedure-day PRU (P=0.047, OR 0.99, 95% CI 0.982 to 1.000) were associated with a reduced odds. Time-since-procedure and hematocrit levels were associated with excessive platelet inhibition when excluding patients who initially demonstrated hyperresponse. Conclusion Elevations in platelet inhibition were frequently observed following flow diversion with Pipeline.
Correspondence of Child Age and Gender Distribution in Child Sexual Exploitation Material and Other Child Content With Age and Gender of Child Sexual Assault Victims

Accessing child sexual exploitation material (CSEM; child pornography in legal statutes) can indicate sexual interest in children. It logically follows then that the age and gender of the depicted children may reflect specific interests in those age/gender groups, and if so, may correspond to age and gender of any known contact offending victims. We had data on CSEM characteristics and child victims for 71 men convicted of CSEM offenses who also had contact sexual offenses against children; some had also sexually solicited children online. Sixty-four men had 134 prior or concurrent child victims, and 14 men reoffended directly against 17 children during follow-up. There were significant, positive associations (with moderate to large effect sizes) between age and gender of children depicted in CSEM and age and gender of child contact or solicitation victims. Examining future offending, though with only 14 recidivists, all men who sexually reoffended against a girl had more girl CSEM content, and all men who sexually reoffended against a boy had more boy CSEM content. Our results suggest that CSEM characteristics can reflect child preferences. This information can be relevant in clinical settings, police investigations, and community risk management, though it does not rule out interest in, or offending against, victims of other ages or gender. We discuss these findings in the context of other evidence regarding victim cross-over, and suggest future research.
Pseudorabies Virus Infection Results in a Broad Inhibition of Host Gene Transcription

Herpesviruses are highly successful pathogens that cause lifelong persistent infections of their host. Modulation of the intracellular environment of infected cells is imperative for the success of virus infections. ABSTRACT Pseudorabies virus (PRV) is a porcine alphaherpesvirus that belongs to the Herpesviridae family. We showed earlier that infection of porcine epithelial cells with PRV triggers activation of the nuclear factor κB (NF-κB) pathway, a pivotal signaling axis in the early immune response. However, PRV-induced NF-κB activation does not lead to NF-κB-dependent gene expression. Here, using electrophoretic mobility shift assays (EMSAs), we show that PRV does not disrupt the ability of NF-κB to interact with its κB target sites. Assessing basal cellular transcriptional activity in PRV-infected cells by quantitation of prespliced transcripts of constitutively expressed genes uncovered a broad suppression of cellular transcription by PRV, which also affects the inducible expression of NF-κB target genes. Host cell transcription inhibition was rescued when viral genome replication was blocked using phosphonoacetic acid (PAA). Remarkably, we found that host gene expression shutoff in PRV-infected cells correlated with a substantial retention of the NF-κB subunit p65, the TATA box binding protein, and RNA polymerase II—essential factors required for (NF-κB-dependent) gene transcription—in expanding PRV replication centers in the nucleus and thereby away from the host chromatin. This study reveals a potent mechanism used by the alphaherpesvirus PRV to steer the protein production capacity of infected cells to viral proteins by preventing expression of host genes, including inducible genes involved in mounting antiviral responses. IMPORTANCE Herpesviruses are highly successful pathogens that cause lifelong persistent infections of their host. Modulation of the intracellular environment of infected cells is imperative for the success of virus infections. We reported earlier that a DNA damage response in epithelial cells infected with the alphaherpesvirus pseudorabies virus (PRV) results in activation of the hallmark proinflammatory NF-κB signaling axis but, remarkably, that this activation does not lead to NF-κB-induced (proinflammatory) gene expression. Here, we report that PRV-mediated inhibition of host gene expression stretches beyond NF-κB-dependent gene expression and in fact reflects a broad inhibition of host gene transcription, which correlates with a substantial recruitment of essential host transcription factors in viral replication compartments in the nucleus, away from the host chromatin. These data uncover a potent alphaherpesvirus mechanism to interfere with production of host proteins, including proteins involved in antiviral responses.
Socioeconomic status largely explains integrase inhibitors-related body composition differences in chronically infected men living with HIV

Background Substantial body composition alterations have been reported after starting combined antiretroviral therapy (cART). We characterized a cohort of chronically infected and virologically suppressed (VL < 50 copies/ml) men (≥50 years old) living with HIV (MLWH) who were switched to integrase inhibitors (INSTI), and compared their body composition parameters and proinflammatory/endocrine profiles to age-matched MLWH on integrase inhibitor free (non-INSTI) regimens, taking into account neighborhood-level measures of socioeconomic status (SES). In addition, we used previously published HIV-seronegative men of the same age as controls. Methods We used dual energy X-ray absorptiometry to quantify body composition parameters, and measured plasma proinflammatory/endocrine markers in 56 MLWH. We compared body composition to a publicly available dataset of 450 HIV-seronegative men of similar age. Within the MLWH group, body composition and plasma proinflammatory/endocrine markers were compared between individuals on INSTI and non-INSTI regimens, accounting for SES. Results Men living with HIV tended to have a greater android/gynoid ratio compared to HIV-seronegative men (p < 0.001). INSTI usage in MLWH was associated with lower adiposity measures when compared to non-INSTI, although these differences largely disappeared after controlling for SES. Proinflammatory/endocrine markers were similar for INSTI and non-INSTI MLWH. Conclusions Among cART-experienced MLWH, those receiving INSTI-containing regimens had modestly lower adiposity compared to non-INSTI MLWH, although these differences were explained by SES. Future studies examining the relationship between INSTI use and body composition should consider the impact of SES.