Miracle-dz/UniFAR-FTUs huggingface dataset:
Organization of ATP-gated P2X1 receptor intracellular termini in apo and desensitized states

The human P2X1 receptor (hP2X1R) is a trimeric ligand-gated ion channel opened by extracellular ATP. The intracellular amino and carboxyl termini play significant roles in determining the time-course and regulation of channel gating—for example, the C terminus regulates recovery from the desensitized state following agonist washout. This suggests that the intracellular regions of the channel have distinct structural features. Studies on the hP2X3R have shown that the intracellular regions associate to form a cytoplasmic cap in the open state of the channel. However, intracellular features could not be resolved in the agonist-free apo and ATP-bound desensitized structures. Here we investigate the organization of the intracellular regions of hP2X1R in the apo and ATP-bound desensitized states following expression in HEK293 cells. We couple cysteine scanning mutagenesis of residues R25-G30 and H355-R360 with the use of bi-functional cysteine reactive cross-linking compounds of different lengths (MTS-2-MTS, BMB, and BM(PEG)2), which we use as molecular calipers. If two cysteine residues come into close proximity, we predict they will be cross-linked and result in ∼66% of the receptor subunits running on a Western blot as dimers. In the control construct (C349A) that removed the free cysteine C349, and some cysteine-containing mutants, cross-linker treatment does not result in dimerization. However, we detect efficient dimerization for R25C, G30C, P358C, K359C, and R360C. This selective pattern indicates that there is structural organization to these regions in the apo and desensitized states in a native membrane environment. The existence of such precap (apo) and postcap (desensitized) organization of the intracellular domains would facilitate efficient gating of the channel.
A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent

Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM.
The Potential for Cancer Immunotherapy in Targeting Surgery-Induced Natural Killer Cell Dysfunction

Natural Killer (NK) cells are granular lymphocytes of the innate immune system that are able to recognize and kill tumor cells without undergoing clonal selection. Discovered over 40 years ago, they have since been recognized to possess both cytotoxic and cytokine-producing effector functions. Following trauma, NK cells are suppressed and their effector functions are impaired. This is especially important for cancer patients undergoing the removal of solid tumors, as surgery has shown to contribute to the development of metastasis and cancer recurrence postoperatively. We have recently shown that NK cells are critical mediators in the formation of metastasis after surgery. While research into the mechanism(s) responsible for NK cell dysfunction is ongoing, knowledge of these mechanisms will pave the way for perioperative therapeutics with the potential to improve cancer outcomes by reversing NK cell dysfunction. This review will discuss mechanisms of suppression in the postoperative environment, including hypercoagulability, suppressive soluble factors, the expansion of suppressive cell populations, and how this affects NK cell biology, including modulation of cell surface receptors, the potential for anergy, and immunosuppressive NK cell functions. This review will also outline potential immunotherapies to reverse postoperative NK dysfunction, with the goal of preventing surgery-induced metastasis.
Effect of atorvastatin on oxidative stress and inflammation markers in myxomatous mitral valve disease in dogs: A comparison of subclinical and clinical stages

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disorder found in dogs. The disease process can lead to heart failure (HF) and has been found to be associated with oxidative stress and inflammation. Statins exert antioxidant and anti-inflammatory effects in human HF patients. However, the beneficial effects of statins in MMVD dogs are still unclear. Thirty MMVD dogs were enrolled in the study and were divided into two groups: MMVD without HF dogs (n = 15) and MMVD with HF dogs (n = 15). Atorvastatin (8 mg kg-1 day-1 ) was administered orally to all dogs for 4 weeks. All dogs underwent physical examination and cardiac examination at the beginning and end of the experiment, including baseline values for hematology, blood chemistry profile, lipid profile, N-terminal pro B-type natriuretic peptide, oxidative stress marker (8-isoprostane), and inflammatory marker (tumor necrosis factor alpha). The results showed that atorvastatin reduced plasma cholesterol levels in both groups. In addition, plasma concentrations of 8-isoprostane, tumor necrosis factor alpha, and N-terminal pro B-type natriuretic peptide were significantly lower after atorvastatin administration, but only in MMVD dogs in the HF group. Atorvastatin found to be associated with possible antioxidant and inflammatory effects in dogs with HF secondary to MMVD. The potential benefits of statins in dogs with HF merits further investigation in larger, placebo-controlled studies.
Improved Bioactivity of 3D Printed Porous Titanium Alloy Scaffold with Chitosan/Magnesium-Calcium Silicate Composite for Orthopaedic Applications

Recently, cases of bone defects have been increasing incrementally. Thus, repair or replacement of bone defects is gradually becoming a huge problem for orthopaedic surgeons. Three-dimensional (3D) scaffolds have since emerged as a potential candidate for bone replacement, of which titanium (Ti) alloys are one of the most promising candidates among the metal alloys due to their low cytotoxicity and mechanical properties. However, bioactivity remains a problem for metal alloys, which can be enhanced using simple immersion techniques to coat bioactive compounds onto the surface of Ti–6Al–4V scaffolds. In our study, we fabricated magnesium-calcium silicate (Mg–CS) and chitosan (CH) compounds onto Ti–6Al–4V scaffolds. Characterization of these surface-modified scaffolds involved an assessment of physicochemical properties as well as mechanical testing. Adhesion, proliferation, and growth of human Wharton’s Jelly mesenchymal stem cells (WJMSCs) were assessed in vitro. In addition, the cell attachment morphology was examined using scanning electron microscopy to assess adhesion qualities. Osteogenic and mineralization assays were conducted to assess osteogenic expression. In conclusion, the Mg–CS/CH coated Ti–6Al–4V scaffolds were able to exhibit and retain pore sizes and their original morphologies and architectures, which significantly affected subsequent hard tissue regeneration. In addition, the surface was shown to be hydrophilic after modification and showed mechanical strength comparable to natural bone. Not only were our modified scaffolds able to match the mechanical properties of natural bone, it was also found that such modifications enhanced cellular behavior such as adhesion, proliferation, and differentiation, which led to enhanced osteogenesis and mineralization downstream. In vivo results indicated that Mg–CS/CH coated Ti–6Al–4V enhances the bone regeneration and ingrowth at the critical size bone defects of rabbits. These results indicated that the proposed Mg–CS/CH coated Ti–6Al–4V scaffolds exhibited a favorable, inducive micro-environment that could serve as a promising modification for future bone tissue engineering scaffolds.
Age-Related Variations in Volar Cortical Angle of the Distal Radius

Background: The ideal volar locking plate for the treatment of distal radius fracture should anatomically fit the volar surface of the distal radius. The purpose of this study was to measure the volar cortical angle (VCA) of uninjured adult distal radii to determine how well the VCA matches that of modern volar locking plates and whether variations in the VCA are related to demographic factors. Methods: A retrospective radiographic analysis of 273 uninjured adult distal radii was performed. Patients were stratified into age quintiles: less than 27 years, 27 to 43 years, 44 to 51 years, 52 to 64 years, and 65 years or older. The VCA was measured on lateral wrist radiographs, and patient demographics, including age and sex, were collected. Multivariable linear regression analyses were performed to determine the relationship between VCA and demographic factors. Results: The VCA ranged from 23.2° to 42.6°, with a mean of 32.2° (SD = 3.79). Mean VCA was 32.8 (SD = 4.17) in the youngest cohort (<27 years) and 30.4 (SD = 3.63) in the oldest cohort (>65 years). Mean VCA decreased with age, approximately 0.04° per year after adjusting for sex. Men had a 1.6° greater VCA than women after adjusting for age. Conclusion: Mean VCA was greater than the VCA of modern volar locking plates. The VCA decreased with age in both men and women, and men had a greater VCA than women. Such differences must be taken into account to avoid malreduction, tendon irritation, or intra-articular screw placement using current volar plate designs.
Association Between Board Certification, Maintenance of Certification, and Surgical Complications in the United States

Physician credentialing processes aim to improve patient safety and quality, but little research has examined their direct relationship with surgical outcomes. Using national Medicare claims for 2009 to 2013, the authors studied the association between board certification and completion of Maintenance of Certification (MOC) requirements and surgeon rates of complications for 8 elective procedures. Exemplar surgeons were defined as those in the lowest decile of complication rates, and outlier surgeons were those in the highest decile. The analysis included 1.9 million procedures performed by 14 598 surgeons (64% orthopedics, 17% general surgery, 11% urology, 7% neurosurgery). Board-certified surgeons were less likely to be outliers (odds ratio 0.79 [0.66-0.94]). However, completion of MOC was not associated with differences in complication rates in orthopedic surgery or urology. Incorporating additional assessment methods into MOC, such as video evaluation of technical skills, retraining on state-of-the-art care, and peer review, may facilitate further improvements in surgical quality.
Correlates of Hearing Aid Use in UK Adults: Self-Reported Hearing Difficulties, Social Participation, Living Situation, Health, and Demographics.

OBJECTIVES Hearing impairment is ranked fifth globally for years lived with disability, yet hearing aid use is low among individuals with a hearing impairment. Identifying correlates of hearing aid use would be helpful in developing interventions to promote use. To date, however, no studies have investigated a wide range of variables, this has limited intervention development. The aim of the present study was to identify correlates of hearing aid use in adults in the United Kingdom with a hearing impairment. To address limitations in previous studies, we used a cross-sectional analysis to model a wide range of potential correlates simultaneously to provide better evidence to aid intervention development. DESIGN The research was conducted using the UK Biobank Resource. A cross-sectional analysis of hearing aid use was conducted on 18,730 participants aged 40 to 69 years old with poor hearing, based on performance on the Digit Triplet test. RESULTS Nine percent of adults with poor hearing in the cross-sectional sample reported using a hearing aid. The strongest correlate of hearing aid use was self-reported hearing difficulties (odds ratio [OR] = 110.69 [95% confidence interval {CI} = 65.12 to 188.16]). Individuals who were older were more likely to use a hearing aid: for each additional year of age, individuals were 5% more likely to use a hearing aid (95% CI = 1.04 to 1.06). People with tinnitus (OR = 1.43 [95% CI = 1.26 to 1.63]) and people with a chronic illness (OR = 1.97 [95% CI = 1.71 to 2.28]) were more likely to use a hearing aid. Those who reported an ethnic minority background (OR = 0.53 [95% CI = 0.39 to 0.72]) and those who lived alone (OR = 0.80 [95% CI = 0.68 to 0.94]) were less likely to use a hearing aid. CONCLUSIONS Interventions to promote hearing aid use need to focus on addressing reasons for the perception of hearing difficulties and how to promote hearing aid use. Interventions to promote hearing aid use may need to target demographic groups that are particularly unlikely to use hearing aids, including younger adults, those who live alone and those from ethnic minority backgrounds.
Further Evidence for Embedded Performance Validity Tests in Children within the Conners’ Continuous Performance Test – Second Edition

ABSTRACT Objective: To replicate previous research on Conners’ Continuous Performance Test – Second Edition subscales as performance validity tests (PVTs) in children. Method: Classification accuracy for the Omissions (OMI), Hit Reaction Time (HRT), and Perseverations (PER) subscales was computed for 414 children and adolescents. Results: Overall, OMI, HRT, and PER demonstrated good specificity but low and variable sensitivity across cutoffs. Conclusions: Results suggest that OMI, HRT, and PER can function as embedded PVTs in mixed clinical samples of children, although their clinical utility is limited by their low sensitivity. Implications for the use of these PVTs in the context of attention-deficit/hyperactivity disorder evaluations, medication-seeking patients, and sports concussion clinics are discussed.
Differential Impact According to Mission’s Operational Intensity on Psychoactive Substance Use: A Retrospective Cohort of French Male Army Service Members

Abstract Background: Stressful deployments in combat areas are known to increase the risk of substance abuse in military personnel. Objectives: The aim of the study was to compare deployment on stressful, high-intensity missions (HIMs) to deployment on low-intensity missions (LIMs) in order to understand factors associated with substance use variations across the mission. Methods: A retrospective cohort study based on a one-shot self-questionnaire was performed four months after their return on two samples of male French Army service members: one returning from an HIM and one from an LIM. The questionnaire focused on tobacco, alcohol, cannabis, cocaine, and psychoactive medication use at three times: before, during, and after the mission. Results: During an HIM, the frequency of tobacco use increased, alcohol use remained stable – although 38% declared a decrease in consumption – and illicit drug use decreased. During an LIM, tobacco and alcohol use increased, cannabis use remained stable, and only cocaine and medication use decreased. After their return, use levels among both samples reverted to values similar to those reported before the mission, except for a decrease in tobacco use observed at return from an HIM. The main factors perceived as related to variations were stress in an HIM and low cost in an LIM. Conclusions/importance: The study suggests a differential impact of deployment on substance use according to the operational intensity of the mission. Variations in use are predominant during the mission with a washout effect after returning home.
Factors influencing success of radiant exposure in light-curing posterior dental composite in the clinical setting.

PURPOSE (1) To conduct a comprehensive review of the literature on factors influencing the radiant exposure of resin-based composite (RBC) restorations and (2) To fully understand the appropriate way of using the light curing units (LCUs) to perform restorations with optimal mechanical/physical properties. METHODS A PubMed search identified recent publications in English that addressed the factors affecting the longevity of the RBC restorations and the optimal usage of LCUs. RESULTS RBCs require light-induced polymerization of methacrylate monomers present in its composition to reach acceptable mechanical and physical properties. Complete polymerization of the RBC is never reached, and the maximum degree of conversion (DC) varies from 40 to 80%. The amount of radiant exposure (Joules/cm²) required for the commencement of polymerization becomes a core driver for the quality of the RBCs. Insufficient radiant exposure may lead to low strength behavior and susceptibility to degradation, thereby shortening the lifespan of restorations inside the mouth. This suggests that there are factors affecting the radiant exposure during clinical procedures; these factors can be categorized as material-related, LCU-related and operator-related factors. CLINICAL SIGNIFICANCE Proper light-curing techniques are critical for delivering an adequate amount of radiant exposure to RBCs. Adequate light curing decreases the number of underexposed RBC restorations, improves their mechanical and physical properties and accordingly, increases their clinical longevity.
Associations of Smoke‐Free Policies in Restaurants, Bars, and Workplaces With Blood Pressure Changes in the CARDIA Study

Background Smoke‐free legislation has been associated with reductions in secondhand smoke exposure and cardiovascular disease. However, it remains unknown whether smoke‐free policies are associated with reductions in blood pressure (BP). Methods and Results Longitudinal data from 2606 nonsmoking adult participants of the CARDIA (Coronary Artery Risk Development in Young Adults) Study (1995–2011) were linked to state, county, and local‐level 100% smoke‐free policies in bars, restaurants, and/or nonhospitality workplaces based on participants’ census tract of residence. Mixed‐effects models estimated associations of policies with BP and hypertension trajectories over 15 years of follow‐up. Fixed‐effects regression estimated associations of smoke‐free policies with within‐person changes in systolic and diastolic BP and hypertension. Models were adjusted for sociodemographic, health‐related, and policy/geographic covariates. Smoke‐free policies were associated with between‐person differences and within‐person changes in systolic BP. Participants living in areas with smoke‐free policies had lower systolic BP on average at the end of follow‐up compared with those in areas without policies (adjusted predicted mean differences [in mm Hg]: restaurant: −1.14 [95% confidence interval: −2.15, −0.12]; bar: −1.52 [−2.48, −0.57]; workplace: −1.41 [−2.32, −0.50]). Smoke‐free policies in restaurants and bars were associated with mean within‐person reductions in systolic BP of −0.85 (−1.61, −0.09) and −1.08 (−1.82, −0.34), respectively. Only restaurant policies were associated with a significant within‐person reduction in diastolic BP, of −0.58 (−1.15, −0.01). Conclusions While the magnitude of associations was small at the individual level, results suggest a potential mechanism through which reductions in secondhand smoke because of smoke‐free policies may improve population‐level cardiovascular health.
Understanding users’ continuance intention toward smartphone augmented reality applications

In spite of high expectations for augmented reality (AR) technology, many smartphone AR applications have failed and terminated their services in Korea because of low usage rates. As failures of smartphone AR applications have increased, investigating factors that influence users’ continuance intention to use the AR applications become an important topic. This study develops a theoretical model that explains continuance intention of users based on AR and motivation theories, and empirically examines the influencing factors with collected data from smartphone AR application users. The results showed that information quality was the most influencing factor for AR continuance intention among AR factors, while perceived enjoyment was not a significant antecedent. The implications of this study provide additional insights for smartphone AR researchers and developers.
Compliance with Standard Precautions among Clinical Nurses: Validity and Reliability of the Italian Version of the Compliance with Standard Precautions Scale (CSPS-It)

Background: The compliance with Standard Precautions (SPs) guidelines, as a primary strategy for the prevention of healthcare associated infections, is still suboptimal among healthcare providers. However, no instrument measuring nurses’ compliance with SPs is available in Italian. This study aims to assess the validity and reliability of the Compliance with Standard Precaution Scale–Italian version (CSPS-It) among clinical nurses. Methods: The study consisted of two phases: (1) translation and cross-cultural adaptation of the CSPS; (2) validity and reliability evaluation of the CSPS-It. Confirmatory factor analysis (CFA) and hypothesis testing were performed to evaluate the construct validity. Cronbach’s alpha, intra-class correlation coefficient of test-retest scores, and item-total correlations were computed to establish reliability. Results: The CSPS-It showed a sound validity and reliability. The unidimensional model tested at CFA yielded acceptable fit indices. The hypothesis testing supported better nurses’ compliance based on participation in at least one training course on SPs. Conclusions: The CSPS-It is a valid and reliable instrument for measuring the compliance with SPs among clinical nurses. This version will allow for the conduction of further studies in favor of progress in this specific field of research. Managers should pay greater attention in monitoring compliance with SPs among clinical nurses.