Miracle-dz/UniFAR-FTUs huggingface dataset:
Does playing a musical instrument reduce the incidence of cognitive impairment and dementia? A systematic review and meta-analysis

Abstract Objectives: High levels of life course intellectually-stimulating activity are hypothesised to produce a cognitive reserve that mitigates against overt cognitive impairment in the face of neuropathology. Leisure-time musical instrument playing could be a viable source of that stimulation, but to date no systematic review has been undertaken to investigate the effect of musical instrument playing on the incidence of cognitive impairment and dementia. Methods: A systematic review and meta-analysis including any study with musical instrument playing as the exposure, and cognitive impairment and/or dementia as the outcome. Results: 1211 unduplicated articles were identified from literature searching, of which three articles were included: two cohort studies and one twin study. All studies were of good methodological quality, and reported large protective effects of musical instrument playing. The twin study reported that musicians were 64% less likely to develop mild cognitive impairment or dementia, after additionally adjusting for sex, education and physical activity. A meta-analysis of the cohort studies found a 59% reduction in the risk of developing dementia within the study follow up. The evidence base is limited by size, small sample sizes and the risk of reverse causality. Conclusion: The three identified studies that investigated the specific relationship of musical instrument playing and subsequent incidence of cognitive impairment and dementia all reported a large protective association. The results are encouraging but should be interpreted with caution. Larger, more focussed studies are required to further explore this association, with a particular need to consider the cumulative lifetime quantity of music playing.
Association of Biomarkers of Inflammation and Endothelial Dysfunction in Obese Type 2 Saudi Diabetic Patients

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of diabetes mellitus. The aim of the present study was to investigate the possible relationship between inflammation and endothelial dysfunction in obese type 2 Saudi diabetic patients. Forty obese type 2 diabetic patients (24 males and 21 females) with body mass index (BMI) ranged from 31 to 35 Kg/m2, non smokers, free from respiratory, kidney; liver, metabolic and neurological disorders were recorded in this study. Their age ranged from 35 to 55 years were included in this study as the first group (A). While a forty non-diabetic subjects (23 males and 22 females) not suffering of any disease, their age ranged from 30 to 45 years were included in this study as the second group (B) and considered as a control group. Findings of this study proved that elevated levels of BMI and HBA1c were associated with higher levels of CRP, TNF- , IL-6 and E-selectin levels in diabetic patients. There was a strong association between elevated biomarkers of inflammation and endothelial dysfunction type 2 diabetes among Saudi people.
Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus

Background: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. Methods: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. Results: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. Conclusion: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies.
Pyrrole derivatives as potential anti-cancer therapeutics: synthesis, mechanisms of action, safety

Abstract Pyrrole derivatives (PDs) chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one (D1) were synthesised as inhibitors of several protein kinases including EGFR and VEGFR. The aim of the study was to reveal the exact mechanisms of PDs’ action EGFR and VEGFR are involved in. We observed, that both PDs could bind with EGFR and VEGFR and form stable complexes. PDs entered into electrostatic interactions with polar groups of phospholipid heads in cell membrane, and the power of interaction depended on the nature of PD radical substituents (greater for MI-1 and smaller for D1). Partial intercalation of MI-1 into the membrane hydrophobic zone also occurred. PDs concentrations induced apoptosis in malignant cells but normal ones had different sensitivity to those. MI-1 and D1 acted like antioxidants in inflamed colonic tissue, as evidenced by reduce of lipid and protein peroxidation products (by 43–67%) and increase of superoxide dismutase activity (by 40 and 58%) with restoring these values to control ones. MI-1 restored reduced haemoglobin and normalised elevated platelets and monocytes in settings of colorectal cancer, whereas D1 normalised only platelets. Thus, MI-1 and D1 could be used as competitive inhibitors of EGFR and VEGFR and antioxidants, which might contribute to realisation of their anti-inflammatory, proapoptotic and antitumor activity.
Impact of Tailored Interventions on Receipt of a Preference-Concordant Colorectal Cancer Screening Test

Background. Individuals at average risk for colorectal cancer (CRC) have multiple test options. Preference for a specific test modality may affect decision making about CRC screening. The current study examined 1) the sociodemographic and health belief characteristics of average-risk participants with a test preference for stool blood test (SBT) versus those with a preference of colonoscopy, and following receipt of a tailored CRC screening intervention, 2) the percentage of participants who completed a preference-concordant CRC screening test, and 3) the sociodemographic, health care experience, and health belief characteristics and intervention group(s) associated with completion of a preference-concordant screening test. Methods. Participants (N = 603) were female, aged 50 to 75 years, at average CRC risk, not currently up-to-date with CRC screening recommendations, had Internet access, and were randomized to receive 1 of 3 tailored CRC screening promotion interventions. Multivariable logistic regression analyses were conducted. Results. Most women (64%) preferred SBT, whereas 36% preferred colonoscopy. There were significant differences in test preference by age, stage of change for the specific tests, perceived benefits of CRC screening, perceived barriers to both tests, and self-efficacy for colonoscopy. Two hundred thirty participants completed CRC screening at 6 months post-intervention. Of those, most (84%) completed a test concordant with their preference. Multivariable analyses revealed that compared with participants completing a preference-discordant test, those completing a preference-concordant test were older (P = 0.01), had health insurance (P < 0.05), and were in the phone counseling–only group (P < 0.01). Conclusions. High levels of completion of preference-concordant CRC screening can be achieved by educating average-risk patients about the multiple screening test options, soliciting their preferences, and offering testing that is concordant with their preference.
An Analysis of the Decision-Making Process After “Decision not to Operate” in Acutely Unwell, High-Risk General Surgery Patients

Objectives: The purpose of this study was to analyze the decision-making process in emergency general surgery in an attempt to ascertain whether surgeons make the correct decision when decisions not to operate in high-risk acutely unwell surgical patients are taken. Background: A decision not to operate is sometimes associated with a certain degree of uncertainty as to the accuracy of the decision. Difficulty lies with the fact that the decisions are made on assumptions, and the tools available are not fool proof. Methods: We retrospectively evaluated “decisions not to operate” over a period of 32 months from April 2013 to August 2015 in a district general hospital in United Kingdom and compared with consecutive similar number of patients who had an operation as recorded in the National Emergency Laparotomy Audit (NELA) database (from January 2014 to August 2015). We looked at the demographics, American Society of Anesthesiologists grade, Portsmouth–Physiological and Operative Severity Score for enumeration of Mortality and Morbidity (P-POSSUM) score, functional status, and 30-day mortality. Results: Two groups (operated [n = 43] and conservative [n = 42]) had similar characteristics. Patients for conservative management had a higher P-POSSUM score (P < .001) and a poorer functional status (P < .001) at the time of decision-making compared to those who had surgery. Mortality at 30 days was significantly higher for patients decided for conservative management when compared with those who had surgery (76.2% and 18.6%, respectively). Conclusions: Elderly patients with poorer functional status and predicted risks more often drive multidisciplinary discussions on whether to operate. Within the limitations of not knowing the outcome otherwise, it appears surgeons take a reasonable approach when deciding not to operate.
Depletion of dietary phytoestrogens reduces hippocampal plasticity and contextual fear memory stability in adult male mouse

ABSTRACT Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modifying the levels of circulating sex hormones, phytoestrogens also exert direct effects on estrogen and androgen receptors in the brain and thus effectively modulate the neural circuit functions. Objective: The aim of this study was to investigate the long-term effects of low phytoestrogen intake (∼6 weeks) on the hippocampal plasticity and hippocampus-dependent memory formation in the adult C57BL/6 male mice. Methods and Results: In comparison to mice on a diet with normal phytoestrogen content, mice on low phytoestrogen diet showed a significant reduction in the phosphorylation of NR2B subunit, a molecular correlate of plasticity in the Schaffer collateral-CA1 synapse. We observed a profound decrease in long-term potentiation (LTP) in the ventral hippocampus, whereas no effect on plasticity was evident in its dorsal portion. Furthermore, we demonstrated that acute perfusion of slices with an estrogen analogue equol, an isoflovane metabolized from daidzein produced by the bacterial flora in the gut, was able to rescue the observed LTP deficit. Examining potential behavioral correlates of the plasticity attenuation, we found that mice on phytoestrogen-free diet display decreased contextual fear memory at remote but not at recent time points after training. Conclusions: Our data suggests that nutritional phytoestrogens have profound effects on the plasticity in the ventral hippocampus and ventral hippocampus-dependent memory.
First reported outbreak of Duck atadenovirus A tracheobronchitis in 3-week-old ducklings in Québec including whole genome sequence of the virus.

D uck atadenovirus A, also known as Duck adenovirus 1 (DAdV-1), is a member of the genus Atadenovirus (1). This virus is also responsible for the Egg Drop Syndrome (EDS) of laying hens (2). This syndrome is listed as an immediately notifiable disease in Canada, because it is considered as an exotic disease for which there are no control or eradication programs (3). Although this virus has never been reported in commercial chicken production in Canada, DAdV-1 was identified in 2009 in 2 Muscovy duck farms in Ontario (4). An adenovirus was also isolated in goslings with respiratory clinical signs in Saskatchewan in 1992, but the adenovirus species was undetermined (5,6). Antibodies to DAdV-1 have been detected in numerous wild waterfowl in North America, up to 42% in sampled ducks, suggesting it is widespread on the continent and that these birds act as reservoirs (7). Overall, DAdV-1 seems weakly pathogenic for ducks and geese because most infections are asymptomatic, and the rare reports of clinical signs always imply very young (4 to 20 d of age) ducklings and goslings. When sick, these birds show gasping, dyspnea, coughing, and/or sneezing and mortality is moderate (2% to 7%) (4–6). DAdV-1 is substantially more pathogenic in chicken layers, in which it is associated with a severe drop in egg production that could last for 4 to 10 wk, and the laying of thin-shelled, soft-shelled, or shell-less eggs (2). The first clinical case of DAdV-1 in a commercial duck farm in Québec is described herein, with whole genome sequencing of the virus.
Cell Biology International

Apoptosis is an organised ATP‐dependent programmed cell death that organisms have evolved to maintain homoeostatic cell numbers and eliminate unnecessary or unhealthy cells from the system. Dysregulation of apoptosis can have serious manifestations culminating into various diseases, especially cancer. Accurate control of apoptosis requires regulation of a wide range of growth enhancing as well as anti‐oncogenic factors. Appropriate regulation of magnitude and temporal expression of key proteins is vital to maintain functional apoptotic signalling. Controlled protein turnover is thus critical to the unhindered operation of the apoptotic machinery, disruption of which can have severe consequences, foremost being oncogenic transformation of cells. The ubiquitin proteasome system (UPS) is one such major cellular pathway that maintains homoeostatic protein levels. Recent studies have found interesting links between these two fundamental cellular processes, wherein UPS depending on the cue can either inhibit or promote apoptosis. A diverse range of E3 ligases are involved in regulating the turnover of key proteins of the apoptotic pathway. This review summarises an overview of key E3 ubiquitin ligases involved in the regulation of the fundamental proteins involved in apoptosis, linking UPS to apoptosis and attempts to emphasize the significance of this relationship in context of cancer.
Sex-Based Differences in Cortical and Subcortical Development in 436 Individuals Aged 4-54 Years.

Sex-based differences in brain development have long been established in ex vivo studies. Recent in vivo studies using magnetic resonance imaging (MRI) have offered considerable insight into sex-based variations in brain maturation. However, reports of sex-based differences in cortical volumes and thickness are inconsistent. We examined brain maturation in a cross-sectional, single-site cohort of 436 individuals (201 [46%] males) aged 4-54 years (median = 16 years). Cortical thickness, cortical surface area, subcortical surface area, volumes of the cerebral cortex, white matter (WM), cortical and subcortical gray matter (GM), including the thalamic subnuclei, basal ganglia, and hippocampi were calculated using automatic segmentation pipelines. Subcortical structures demonstrated distinct curvilinear trajectories from the cortex, in both volumetric maturation and surface-area expansion in relation to age. Surface-area analysis indicated that dorsal regions of the thalamus, globus pallidus and striatum, regions demonstrating structural connectivity with frontoparietal cortices, exhibited extensive expansion with age, and were inversely related to changes seen in cortical maturation, which contracted with age. Furthermore, surface-area expansion was more robust in males in comparison to females. Age- and sex-related maturational changes may reflect alterations in dendritic and synaptic architecture known to occur during development from early childhood through to mid-adulthood.
Early experience and observations in endovascular dialysis fistula re-intervention

In recent years, new emerging technology has allowed the endovascular creation of dialysis fistulas in the proximal forearm without the need for open surgery. Two such systems currently exist, and evidence to date has demonstrated high rates of technical success in fistula creation, high rates of dialysis functionality, and low rates of re-intervention using both systems. Whilst early trial data has demonstrated lower rates of re-intervention to maintain patency compared to surgical fistulas, endovascular re-interventions are still required to maintain functionality. The endovascular fistula (endoAVF) typically exhibits a shared drainage pattern and is morphologically distinct from the surgical fistula and patterns of failure observed often differ to what has been traditionally encountered. A fresh approach and understanding is therefore required and here we share our observations and experience of endovascular re-intervention in endoAVF created with the Wavelinq system.
Quantitative Three-Dimensional Reconstructions of Excitatory Synaptic Boutons in the "Barrel Field" of the Adult "Reeler" Mouse Somatosensory Neocortex: A Comparative Fine-Scale Electron Microscopic Analysis with the Wild Type Mouse.

Synapses are key structural determinants for information processing and computations in the normal and pathologically altered brain. Here, the quantitative morphology of excitatory synaptic boutons in the "reeler" mutant, a model system for various neurological disorders, was investigated and compared with wild-type (WT) mice using high-resolution, fine-scale electron microscopy (EM) and quantitative three-dimensional (3D) models of synaptic boutons. Beside their overall geometry, the shape and size of presynaptic active zones (PreAZs) and postsynaptic densities (PSDs) forming the active zones and the three pools of synaptic vesicles (SVs), namely the readily releasable pool (RRP), the recycling pool (RP), and the resting pool, were quantified. Although the reeler mouse neocortex is severely disturbed, no significant differences were found in most of the structural parameters investigated: the size of boutons (~3 μm2), size of the PreAZs and PSDs (~0.17 μm2), total number of SVs, and SVs within a perimeter (p) of 10 nm and p20 nm RRP; the p60 nm, p100 nm, and p60-p200 nm RP; and the resting pool, except the synaptic cleft width. Taken together, the synaptic organization and structural composition of synaptic boutons in the reeler neocortex remain comparably "normal" and may thus contribute to a "correct" wiring of neurons within the reeler cortical network.
Interfacial Engineering through Chloride-Functionalized Self-Assembled Monolayer for High-Performance Perovskite Solar Cells.

The family of organic-inorganic hybrid perovskite (OIHPs) materials is one of the most promising for very high efficiency photovoltaic solar cells application. In the present work, the effect of a series of self-assembled monolayers placed at the TiO2-perovskite junction, on the functioning of triple cation perovskite solar cells has been investigated. We show that employing 4-chlorobenzoic acid leads to the marked boosting of the solar cells performances. The starting pristine cell had a 20.3% power conversion efficiency (PCE) and the chemical engineering permitted to reach a PCE up to 21.35%. Our experimental study completed by density functional theory (DFT) calculations and modelling show that this improvement is due to the reduction of interfacial states, to the improvement of the quality of the OIHP material and to the structural continuity between TiO2 and the OIHP. Especially, we demonstrate that the interfacial chemical interactions are important to consider in the design of highly efficient devices.
Temporal Trends and Site Variation in High‐Risk Coronary Intervention and the Use of Mechanical Circulatory Support: Insights From the Veterans Affairs Clinical Assessment Reporting and Tracking (CART) Program

Background Patients undergoing percutaneous coronary intervention (PCI) are older with greater medical comorbidities and anatomical complexity than ever before, resulting in an increased frequency of nonemergent high‐risk PCI (HR‐PCI). We thus sought to evaluate the temporal trends in performance of HR‐PCI and utilization of mechanical circulatory support in the largest integrated healthcare system in the United States. Methods and Results A cohort of high‐risk adult patients that underwent nonemergent PCI in the Veterans Affairs Healthcare System between January 2008 and June 2018 were identified by objective clinical, hemodynamic, and anatomic criteria. Temporal trends in the performance of HR‐PCI, utilization of mechanical circulatory support, and site‐level variation were assessed. Of 111 548 patients assessed during the study period, 554 met 3 high‐risk criteria whereas 4414 met at least 2 criteria for HR‐PCI. There was a significant linear increase in the proportion of interventions that met 3 (P<0.001) or at least 2 (P<0.001) high‐risk criteria over time, with rates approaching 1.9% and 11.2% in the last full calendar year analyzed. A minority of patients who met all high‐risk criteria received PCI with mechanical support (15.7%) without a significant increase over time (P=0.193). However, there was significant site‐level variation in the probability of performing HR‐PCI (4.0‐fold higher likelihood) and utilizing mechanical circulatory support (1.9‐fold higher likelihood) between high and low utilization sites. Conclusions The proportion of cases categorized as HR‐PCI has increased over time, with significant site‐level variation in performance. The majority of HR‐PCI cases did not utilize mechanical support, highlighting a discrepancy between current recommendations and clinical practice in an integrated healthcare system.