Miracle-dz/UniFAR-FTUs huggingface dataset:
Study on the Impact of Psoriasis on Quality of Life: Psychological, Social and Financial Implications.

BACKGROUND Psoriasis is a chronic and stigmatising disease with significant and hard to meet clinical needs in patient management. Psoriasis is a relatively common disease, affecting up to 2% of the population. The impact of psoriasis on quality of life is significant given its chronicity and visibility. Psychological stress is a well-established systemic triggering factor in psoriasis. It has been associated with initial presentation of the disease as well as exacerbations of pre-existing psoriasis. The purpose of this study is to assess the psychological, social and financial implications of psoriasis. SUBJECTS AND METHODS 51 patients participated in this study. After dermatological examination and determination of Psoriasis Area and Severity Index score, patients were referred to a psychological consult. Assessment was done through questionnaires concerning quality of life, depression, anxiety, illness perception, financial domain and personal data. RESULTS Results of our study indicate that psoriasis has a strong impact on patients' life. It influences working habits, poses a significant financial burden, but most of all, significantly impairs their quality of life and psychological status. CONCLUSION Psoriasis poses a substantial threat to several dimensions in patient's quality of life. Patients feel that the current treatment, although often effective, does not provide a satisfactory long-term solution. Thus, long-term psychologic support for patients with psoriasis is desirable.
A CONTEXT-BASED APPROACH TO SCIENCE TEACHING

It has been traditional to educate students in school, especially secondary schools, through subject domains and within lessons named according to the domain. Today in most countries, science lessons are offered in the curriculum, specified as science, or one of its sub-components e.g. biology, chemistry, physics, or perhaps a combination of these e.g. physical science. It does not have to be this way, of course, as can be amplified by the concept of an integrated day, implemented at the primary level in a number of countries.
Tamibarotene inhibit the accumulation of fibrocyte and alleviate renal fibrosis by IL-17A

Abstract Renal fibrosis is a common pathological process in the progression of chronic kidney disease. Accumulating evidence suggests that interleukin-17A (IL‐17A) and fibrocytes play crucial roles in the pathogenesis of fibrosis. However, the role of IL-17A in the regulation of renal fibrocytes in renal fibrosis has rarely been reported. Here, we report that the plasma IL-17A level is increased in immunoglobulin A nephropathy (IgAN) patients and is correlated with clinical parameters. Using a mouse model of unilateral ureteral obstruction (UUO), we found that both IL-17A expression and fibrocyte infiltration were increased in the kidneys of UUO mice. Besides, IL-17A enhanced fibrosis and fibrocyte-associated chemokine and activator expression in vitro. Furthermore, inhibition of IL-17A using Am80 (Tamibarotene) decreased fibrocytes and fibrocyte-associated chemokine and activator expression and significantly attenuated renal fibrosis in the UUO mice. Our findings suggest that Am80, which inhibits the accumulation of fibrocytes and alleviates renal fibrosis mediated by IL-17A, maybe a novel therapeutic drug for renal fibrosis.
Characterising the Microstructure of an Additively Built Al-Cu-Li Alloy

Al-Cu-Li alloys are famous for their high strength, ductility and weight-saving properties, and have for many years been the aerospace alloy of choice. Depending on the alloy composition, this multi-phase system may give rise to several phases, including the major strengthening T1 (Al2CuLi) phase. Microstructure investigations have extensively been reported for conventionally processed alloys with little focus on their Additive Manufacturing (AM) characterised microstructures. In this work, the Laser Powder Bed Fusion (LPBF) built microstructures of an AA2099 Al-Cu-Li alloy are characterised in the as-built (no preheating) and preheat-treated (320 °C, 500 °C) conditions using various analytical techniques, including Synchrotron High-Energy X-ray Diffraction (S-HEXRD). The observed dislocations in the AM as-built condition with no detected T1 precipitates confirm the conventional view of the difficulty of T1 to nucleate on dislocations without appropriate heat treatments. Two main phases, T1 (Al2CuLi) and TB (Al7.5Cu4Li), were detected using S-HEXRD at both preheat-treated temperatures. Higher volume fraction of T1 measured in the 500 °C (75.2 HV0.1) sample resulted in a higher microhardness compared to the 320 °C (58.7 HV0.1) sample. Higher TB volume fraction measured in the 320 °C sample had a minimal strength effect.
Social Estrangement and Psychological Distress before and during the COVID-19 Pandemic: Patterns of Change in Canadian Workers

This article argues that the COVID-19 pandemic and associated social distancing measures intended to slow the rate of transmission of the virus resulted in greater subjective isolation and community distrust, in turn adversely impacting psychological distress. To support this argument, we examine data from the Canadian Quality of Work and Economic Life Study, two national surveys of Canadian workers—one from late September 2019 (N = 2,477) and the second from mid-March 2020 (N = 2,446). Analyses show that subjective isolation and community distrust increased between the two surveys, which led to a substantial rise in psychological distress. Increases in subjective isolation were stronger in older respondents, resulting in a greater escalation in psychological distress. These findings support a Durkheimian perspective on the harm to social integration and mental health caused by periods of rapid social change but also illustrate how a life course context can differentiate individual vulnerability to disintegrative social forces.
Development and evaluation of a novel music-based therapeutic device for upper extremity movement training: A pre-clinical, single-arm trial

Restoration of upper limb motor function and patient functional independence are crucial treatment targets in neurological rehabilitation. Growing evidence indicates that music-based intervention is a promising therapeutic approach for the restoration of upper extremity functional abilities in neurologic conditions such as cerebral palsy, stroke, and Parkinson’s Disease. In this context, music technology may be particularly useful to increase the availability and accessibility of music-based therapy and assist therapists in the implementation and assessment of targeted therapeutic goals. In the present study, we conducted a pre-clinical, single-arm trial to evaluate a novel music-based therapeutic device (SONATA) for upper limb extremity movement training. The device consists of a graphical user interface generated by a single-board computer displayed on a 32” touchscreen with built-in speakers controlled wirelessly by a computer tablet. The system includes two operational modes that allow users to play musical melodies on a virtual keyboard or draw figures/shapes whereby every action input results in controllable sensory feedback. Four motor tasks involving hand/finger movement were performed with 21 healthy individuals (13 males, aged 26.4 ± 3.5 years) to evaluate the device’s operational modes and main features. The results of the functional tests suggest that the device is a reliable system to present pre-defined sequences of audiovisual stimuli and shapes and to record response and movement data. This preliminary study also suggests that the device is feasible and adequate for use with healthy individuals. These findings open new avenues for future clinical research to further investigate the feasibility and usability of the SONATA as a tool for upper extremity motor function training in neurological rehabilitation. Directions for future clinical research are discussed.
Canadian trends in testosterone therapy.

INTRODUCTION Rates of testosterone therapy (TT) prescribing dropped dramatically following the FDA and Health Canada warning regarding potential cardiovascular morbidity in 2014. Since then, prescription rates appear to be increasing in the U.S., however, data on TT use in Canada is lacking. Current database studies suffer from incomplete prescription capture, lack of information on continued use, and confounding from concurrent population growth. Nova Scotia (NS) is a Canadian province with minimal population growth over the past decade. NS tracks every testosterone prescription and refill through their prescription monitoring program (NSPMP). All testosterone prescriptions must be written on triplicate forms, allowing for comprehensive tracking. The purpose of this study is to describe the long-term prescription trends of testosterone in a mid-sized Canadian province, using a database that captures 100% of all TT prescriptions written and filled. METHODS Data were extracted from the NSPMP database on all prescriptions and prescription refills of androgens for men over 18 years of age from 2007-2019. Population statistics were gained using publicly available data from Statistics Canada. Analysis of patterns on individual years and over time were examined for number of patients, prescriptions, and prescribers, as well as formulation. RESULTS The male population of Nova Scotia remained relatively stable throughout the study period (2007: 455 064; 2019: 475 478; population increase of 4.3%). A total of 7883 men (1.7% of the male population) received a prescription for TT during the study period; 1673 men received only one prescription in the entire study period and 5446 men remained on TT for longer than six months. Of the 1730 men under 45 who were prescribed TT, 75% (n=1298) of them stayed on it for more than six months; 1856 men (24%) switched the type of testosterone they were on during the study period. The number of men receiving TT yearly increased by 98%, from 1235 in 2007 to 2448 in 2019. The number of men receiving TT plateaued in 2014, except for men under age 35, in whom it has steadily increased every year since 2007. Interestingly, primary care providers (PCPs) wrote 92% of all prescriptions on average (interquartile range 90-93). CONCLUSIONS In a mid-sized Canadian province with stable population growth, prescriptions of testosterone increased until 2014, and then either stabilized or decreased. TT prescriptions in young men have continued to increase yearly. Injectable and gel-based formulations have increased in popularity over the past decade. Future efforts to educate prescribers, especially surrounding the effects on fertility in young men, should be largely focused on PCPs.
Practice Patterns, Work Environments, and Job Outcomes of Rural and Urban Primary Care Nurse Practitioners

As nurse practitioners (NPs) are increasingly relied on to deliver primary care in rural communities, it is critical to understand the contexts in which they work and whether they are characterized by work environments and infrastructures that facilitate the provision of high-quality patient care. This study compares urban and rural NPs using data from a survey of 1,244 primary care NPs in Arizona, California, New Jersey, Pennsylvania, Texas, and Washington. While rural and urban NPs have a number of similarities in terms of demographic characteristics, practice patterns, and job outcomes, they also have noteworthy differences. Rural NPs report higher levels of independent practice, fewer structural capabilities that facilitate quality care, and poorer relationships with physicians. Health care organizations in rural communities may need to invest in work environments and infrastructures that facilitate high-quality care and autonomous practice for NPs.
The Differential Influence of Immune, Endocytotic, and Lipid Metabolism Genes on Amyloid Deposition and Neurodegeneration in Subjects at Risk of Alzheimer's Disease.

BACKGROUND Over 20 single-nucleotide polymorphisms (SNPs) are associated with increased risk of Alzheimer's disease (AD). We categorized these loci into immunity, lipid metabolism, and endocytosis pathways, and associated the polygenic risk scores (PRS) calculated, with AD biomarkers in mild cognitive impairment (MCI) subjects. OBJECTIVE The aim of this study was to identify associations between pathway-specific PRS and AD biomarkers in patients with MCI and healthy controls. METHODS AD biomarkers ([18F]Florbetapir-PET SUVR, FDG-PET SUVR, hippocampal volume, CSF tau and amyloid-β levels) and neurocognitive tests scores were obtained in 258 healthy controls and 451 MCI subjects from the ADNI dataset at baseline and at 24-month follow up. Pathway-related (immunity, lipid metabolism, and endocytosis) and total polygenic risk scores were calculated from 20 SNPs. Multiple linear regression analysis was used to test predictive value of the polygenic risk scores over longitudinal biomarker and cognitive changes. RESULTS Higher immune risk score was associated with worse cognitive measures and reduced glucose metabolism. Higher lipid risk score was associated with increased amyloid deposition and cortical hypometabolism. Total, immune, and lipid scores were associated with significant changes in cognitive measures, amyloid deposition, and brain metabolism. CONCLUSION Polygenic risk scores highlights the influence of specific genes on amyloid-dependent and independent pathways; and these pathways could be differentially influenced by lipid and immune scores respectively.
Development of a Larval Zebrafish Model for Acute Organophosphorus Nerve Agent and Pesticide Exposure and Therapeutic Evaluation

Organophosphorus compound exposure remains a present threat through agricultural accidents, warfare, or terrorist activity. The primary mechanism of organophosphorus toxicity is through inhibition of the enzyme acetylcholinesterase, with current emergency treatment including anticholinergics, benzodiazepines, and oxime reactivators. However, a need for more effective and broadly acting countermeasures remains. This study aimed to develop larval zebrafish as a high-throughput model for evaluating novel therapeutics against acute organophosphorus exposure. Larval zebrafish at six days post-fertilization were exposed to acute concentrations of seven organophosphorus compounds and treated with one of three oximes. Lethality studies indicated similar relative toxicity to that seen in the established rodent model, with chemical warfare agents proving more lethal than organophosphorus pesticides. Additionally, the organophosphorus-specific response for oxime reactivation of acetylcholinesterase was comparable to what has been previously reported. Behavioral studies measuring the visual motor response demonstrated greater efficacy for centrally acting oxime compounds than for those that are contained to the peripheral tissue. Overall, these results support the use of this larval zebrafish model as a high-throughput screening platform for evaluating novel treatments following acute organophosphorus exposure.
Predictive Performance of Exposome Score for Schizophrenia in the General Population

Abstract Previously, we established an estimated exposome score for schizophrenia (ES-SCZ) as a cumulative measure of environmental liability for schizophrenia to use in gene–environment interaction studies and for risk stratification in population cohorts. Hereby, we examined the discriminative function of ES-SCZ for identifying individuals diagnosed with schizophrenia spectrum disorder in the general population by measuring the area under the receiver operating characteristic curve (AUC). Furthermore, we compared this ES-SCZ method to an environmental sum score (Esum-SCZ) and an aggregate environmental score weighted by the meta-analytical estimates (Emet-SCZ). We also estimated ORs and Nagelkerke’s R2 for ES-SCZ in association with psychiatric diagnoses and other medical outcomes. ES-SCZ showed a good discriminative function (AUC = 0.84) and statistically significantly performed better than both Esum-SCZ (AUC = 0.80) and Emet-SCZ (AUC = 0.80). At optimal cut point, ES-SCZ showed similar performance in ruling out (LR− = 0.20) and ruling in (LR+ = 3.86) schizophrenia. ES-SCZ at optimal cut point showed also a progressively greater magnitude of association with increasing psychosis risk strata. Among all clinical outcomes, ES-SCZ was associated with schizophrenia diagnosis with the highest OR (2.76, P < .001) and greatest explained variance (R2 = 14.03%), followed by bipolar disorder (OR = 2.61, P < .001, R2 = 13.01%) and suicide plan (OR = 2.44, P < .001, R2 = 12.44%). Our findings from an epidemiologically representative general population cohort demonstrate that an aggregate environmental exposure score for schizophrenia constructed using a predictive modeling approach—ES-SCZ—has the potential to improve risk prediction and stratification for research purposes and may help gain insight into the multicausal etiology of psychopathology.
Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis

Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15–50 mg) and three dose cohorts of eight patients with IPF (5:3 TD139:placebo ratio) with once-daily doses of TD139 (0.3–10 mg) for 14 days. Inhaled TD139 was well tolerated with no significant treatment-related side-effects. TD139 was rapidly absorbed, with mean time taken to reach maximum plasma concentration (Cmax) values ranging from 0.6 to 3 h and a plasma half-life (T1/2) of 8 h. The concentration of TD139 in the lung was >567-fold higher than in the blood, with systemic exposure predicting exposure in the target compartment. Gal-3 expression on alveolar macrophages was reduced in the 3 and 10 mg dose groups compared with placebo, with a concentration-dependent inhibition demonstrated. Inhibition of Gal-3 expression in the lung was associated with reductions in plasma biomarkers centrally relevant to IPF pathobiology (platelet-derived growth factor-BB, plasminogen activator inhibitor-1, Gal-3, CCL18 and YKL-40). TD139 is safe and well tolerated in healthy subjects and IPF patients. It was shown to suppress Gal-3 expression on bronchoalveolar lavage macrophages and, in a concerted fashion, decrease plasma biomarkers associated with IPF progression. TD139 is a potent inhibitor of galectin-3, a key driver of fibrosis in the lung. In this phase 1/2a clinical study, inhaled TD139 was safe, well tolerated, and demonstrated target engagement and decreased plasma biomarkers associated with IPF progression. https://bit.ly/2JREKx6
Sex Differences in Time-Domain and Frequency-Domain Heart Rate Variability Measures of Fatigued Drivers

The effects of fatigue on a driver’s autonomic nervous system (ANS) were investigated through heart rate variability (HRV) measures considering the difference of sex. Electrocardiogram (ECG) data from 18 drivers were recorded during a simulator-based driving experiment. Thirteen short-term HRV measures were extracted through time-domain and frequency-domain methods. First, differences in HRV measures related to mental state (alert or fatigued) were analyzed in all subjects. Then, sex-specific changes between alert and fatigued states were investigated. Finally, sex differences between alert and fatigued states were compared. For all subjects, ten measures showed significant differences (Mann-Whitney U test, p < 0.01) between different mental states. In male and female drivers, eight and four measures, respectively, showed significant differences between different mental states. Six measures showed significant differences between males and females in an alert state, while ten measures showed significant sex differences in a fatigued state. In conclusion, fatigue impacts drivers’ ANS activity, and this impact differs by sex; more differences exist between male and female drivers’ ANS activity in a fatigued state than in an alert state.
Gender differences in the associations of early onset poly tobacco and drug use prior to age 18 with the prevalence of adult bronchitis in the United States

Abstract Purpose We investigated the associations of early onset polysubstance use prior to age 18 with the prevalence of bronchitis among U.S. adults and tested whether the associations differ by gender. Methods A total of 77,950 adults, of them 2,653 with bronchitis in the past year, were from the combined 2013 and 2014 National Survey on Drug Use and Health data. The variable cluster analysis was used to classify nine variables about substance use prior to age 18 (cigarettes, cigars, smokeless tobacco, marijuana, cocaine, heroin, methamphetamines, ecstasy, and phencyclidine). Weighted multivariate logistic regression analysis (MLR) was used to examine the associations with bronchitis. Results Nine variables were divided into two clusters: early onset poly tobacco use (three tobacco use variables) and early onset poly drug use (six drug use variables). The overall prevalence of bronchitis was 3.8% (5.1% for females and 2.3% for males). MLR analysis showed that being female, elderly (ages 65 and above), obese, and early onset poly tobacco use were associated with increased odds of bronchitis (p < 0.05). Gender-stratified analyses showed that early-onset poly tobacco use was significantly associated with bronchitis only in males, whereas early onset poly drug use was associated with bronchitis only in females. Moreover, obesity and tobacco use in the past year revealed associations with bronchitis regardless of gender. Conclusions Obesity, early onset poly tobacco use prior to age 18, and tobacco use in the past year were positively associated with bronchitis; furthermore, the associations of early onset polysubstance use with bronchitis differed by gender, which indicated that gender differences should be considered in developing effective prevention strategies.
The impact of childhood trauma on thalamic functional connectivity in patients with obsessive–compulsive disorder

Abstract Background Childhood trauma is a vulnerability factor for the development of obsessive–compulsive disorder (OCD). Empirical findings suggest that trauma-related alterations in brain networks, especially in thalamus-related regions, have been observed in OCD patients. However, the relationship between childhood trauma and thalamic connectivity in patients with OCD remains unclear. The present study aimed to examine the impact of childhood trauma on thalamic functional connectivity in OCD patients. Methods Magnetic resonance imaging resting-state scans were acquired in 79 patients with OCD, including 22 patients with a high level of childhood trauma (OCD_HCT), 57 patients with a low level of childhood trauma (OCD_LCT) and 47 healthy controls. Seven thalamic subdivisions were chosen as regions of interest (ROIs) to examine the group difference in thalamic ROIs and whole-brain resting-state functional connectivity (rsFC). Results We found significantly decreased caudate-thalamic rsFC in OCD patients as a whole group and also in OCD_LCT patients, compared with healthy controls. However, OCD_HCT patients exhibited increased thalamic rsFC with the prefrontal cortex when compared with both OCD_LCT patients and healthy controls. Conclusions Taken together, OCD patients with high and low levels of childhood trauma exhibit different pathological alterations in thalamic rsFC, suggesting that childhood trauma may be a predisposing factor for some OCD patients.