Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of Smokeless Tobacco Use in Pakistan: Insight from the Global Adult Tobacco Survey Pakistan (GATS Pakistan-2014).

OBJECTIVE Prevalence of tobacco consumption is increasing including both smoked and smokeless tobacco. The objective of this paper is to highlight the prevalence of smokeless tobacco use, its demographic trends as well as socioeconomic determinants based on Global Adult Tobacco Survey 2014 (GATS) -Pakistan. METHODS Secondary analysis of GATS data was done which was a nationally representative survey, conducted among non-institutionalized males and females aged 15 years and above. The survey included a total of 9,856 households which were selected using multistage stratified cluster sampling technique. RESULTS Secondary analysis of GATS data revealed that 8.6% of the Pakistani population was current users of smokeless tobacco; among them, 8.0% were daily users and 0.6% were less than daily users. Prevalence of SLT use was higher in males (13.7%) compared to females (3.9%) (p = 0.000). Mean age of male users was 39.96±14.43 years and of females was 47.71±16.21 (p=0.000). Males (3.959 95% CI = 3.291-4.764) and respondents with primary or less education (2.216 95%CI = 1.841-2.668) were at higher odds of SLT use prevalence. Among daily users, Naswar was the preferred (71.8%) SLT product in males, compared to females (p = 0.000). Whereas, in females, use of Paan with tobacco (26.4%) (P = 0.000) and Naas (20.9%) (P = 0.000) was more common compared to males. Among SLT users, 71.1% participants used to spend 1-100 Rs (0.0095-0.95USD) per week on purchase of SLT products. However 28.9% were spending more than one dollar on the purchase of SLT products including 19.1% who were spending Rs 101-200 (0.96-1.9USD) followed by 7.2% spending Rs 201-300 (1.91-2.85 USD) and 2.6% spending Rs. >300 (>2.85 USD). CONCLUSIONS Males and less educated individuals should be targeted with behavioral interventions for control of SLT use. Males started SLT use at an earlier age compared to females which can result in premature morbidity and mortality in males. SLT products are cheaper compared to cigarettes, therefore, taxes need to be levied on SLT products.
Lesion location impact on functional recovery of the hemiparetic upper limb

The effect of stroke topography on the recovery of hemiparetic upper limb (HUL) function is unclear due to limitations in previous studies–examination of lesion effects only in one point of time, or grouping together patients with left and right hemispheric damage (LHD, RHD), or disregard to different lesion impact on proximal and distal operations. Here we used voxel-based lesion symptom mapping (VLSM) to investigate the impact of stroke topography on HUL function taking into consideration the effects of (a) assessment time (subacute, chronic phases), (b) side of damaged hemisphere (left, right), (c) HUL part (proximal, distal). HUL function was examined in 3 groups of patients—Subacute (n = 130), Chronic (n = 66), and Delta (n = 49; patients examined both in the subacute and chronic phases)–using the proximal and distal sub-divisions of the Fugl-Meyer (FM) and the Box and Blocks (B&B) tests. HUL function following LHD tended to be affected in the subacute phase mainly by damage to white matter tracts, the putamen and the insula. In the chronic phase, a similar pattern was shown for B&B performance, whereas FM performance was affected by damage only to the white matter tracts. HUL function following RHD was affected in both phases, mainly by damage to the basal ganglia, white matter tracts and the insula, along with a restricted effect of damage to other cortical structures. In the chronic phase HUL function following RHD was affected also by damage to the thalamus. In the small Delta groups the following trends were found: In LHD patients, delayed motor recovery, captured by the B&B test, was affected by damage to the sensory-motor cortex, white matter association fibers and parts of the perisilvian cortex. In the RHD patients of the Delta group, delayed motor recovery was affected by damage to white matter projection fibers. Proximal and distal HUL functions examined in LHD patients (both in the subacute and chronic phases) tended to be affected by similar structures—mainly white matter projection tracts. In RHD patients, a distinction between proximal and distal HUL functions was found in the subacute but not in the chronic phase, with proximal and distal HUL functions affected by similar subcortical and cortical structures, except for an additional impact of damage to the superior temporal cortex and the retro-lenticular internal capsule only on proximal HUL function. The current study suggests the existence of important differences between the functional neuroanatomy underlying motor recovery following left and right hemisphere damage. A trend for different lesion effects was shown for residual proximal and distal HUL motor control. The study corroborates earlier findings showing an effect of the time after stroke onset (subacute, chronic) on the results of VLSM analyses. Further studies with larger sample size are required for the validation of these results.
The incidence of extra‐articular manifestations in southern Chinese patients with inflammatory joint diseases

Inflammatory joint diseases (IJDs) are chronic arthritis, but frequently present with co‐morbidities of other organs and systems, which is known as extra‐articular manifestations (EAMs). It is still unclear which clinical characteristics or bio‐markers can predict the development of EAMs. The aim of this study was to estimate the proportion of EAMs in southern Chinese patients with IJDs and to explore the risk factors.
Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry

Efavirenz (more specifically the S-enantiomer) is a cornerstone antiretroviral therapy for treatment of HIV infection. The major primary metabolite is S-8-hydroxyefavirenz, which does not have antiretroviral activity but is neurotoxic. Cytochrome P450 2B6 (CYP2B6) is the major enzyme catalyzing S-8-hydroxyefavirenz formation. CYP2B6 genetics and drug interactions are major determinants of clinical efavirenz disposition and dose adjustment. In addition, as a prototypic CYP2B6 substrate, S-efavirenz and analogs can inform on the structure, activity, catalytic mechanisms, and stereoselectivity of CYP2B6. Metabolism of R-efavirenz by CYP2B6 remains unexplored. This investigation assessed S-efavirenz metabolism by clinically relevant CYP2B6 genetic variants. This investigation also evaluated R-efavirenz hydroxylation by wild-type CYP2B6.1 and CYP2B6 variants. S-Efavirenz 8-hydroxylation by wild-type CYP2B6.1 and variants exhibited positive cooperativity and apparent cooperative substrate inhibition. On the basis of Clmax values, relative activities for S-efavirenz 8-hydroxylation were in the order CYP2B6.4 > CYP2B6.1 ≈ CYP2B6.5 ≈ CYP2B6.17 > CYP2B6.6 ≈ CYP2B6.7 ≈ CYP2B6.9 ≈ CYP2B6.19 ≈ CYP2B6.26; CYP2B6.16 and CYP2B6.18 showed minimal activity. Rates of R-efavirenz metabolism were approximately 1/10 those of S-efavirenz for wild-type CYP2B6.1 and variants. On the basis of Clmax values, there was 14-fold enantioselectivity (S > R-efavirenz) for wild-type CYP2B6.1, and 5- to 22-fold differences for other CYP2B6 variants. These results show that both CYP2B6 516G > T (CYP2B6*6 and CYP2B6*9) and 983T > C (CYP2B6*16 and CYP2B6*18) polymorphisms cause canonical diminishment or loss-of-function variants for S-efavirenz 8-hydroxylation, provide a mechanistic basis for known clinical pharmacogenetic differences in efavirenz disposition, and may predict additional clinically important variant alleles. Efavirenz is the most stereoselective CYP2B6 drug substrate yet identified and may be a useful probe for the CYP2B6 active site and catalytic mechanisms. SIGNIFICANCE STATEMENT Clinical disposition of the antiretroviral S-efavirenz is affected by CYP2B6 polymorphisms. Expressed CYP2B6 with 516G>T (CYP2B6*6 and CYP2B6*9), and 983T>C (CYP2B6*16 and CYP2B6*18) polymorphisms had a diminishment or loss of function for efavirenz 8-hydroxylation. This provides a mechanistic basis for efavirenz clinical pharmacogenetics and may predict additional clinically important variant alleles. Efavirenz metabolism showed both cooperativity and cooperative substrate inhibition. With greater than 10-fold enantioselectivity (S- vs. R- metabolism), efavirenz is the most stereoselective CYP2B6 drug substrate yet identified. These findings may provide mechanistic insights.
Methylene Blue Blocks and Reverses the Inhibitory Effect of Tau on PMCA Function

Methylene blue (MB) is a synthetic phenothiazine dye that, in the last years, has generated much debate about whether it could be a useful therapeutic drug for tau-related pathologies, such as Alzheimer’s disease (AD). However, the molecular mechanism of action is far from clear. Recently we reported that MB activates the plasma membrane Ca2+-ATPase (PMCA) in membranes from human and pig tissues and from cells cultures, and that it could protect against inactivation of PMCA by amyloid β-peptide (Aβ). The purpose of the present study is to further examine whether the MB could also modulate the inhibitory effect of tau, another key molecular marker of AD, on PMCA activity. By using kinetic assays in membranes from several tissues and cell cultures, we found that this phenothiazine was able to block and even to completely reverse the inhibitory effect of tau on PMCA. The results of this work point out that MB could mediate the toxic effect of tau related to the deregulation of calcium homeostasis by blocking the impairment of PMCA activity by tau. We then could conclude that MB could interfere with the toxic effects of tau by restoring the function of PMCA pump as a fine tuner of calcium homeostasis.
Central Nervous System Infection with Other Endemic Mycoses: Rare Manifestation of Blastomycosis, Paracoccidioidomycosis, Talaromycosis, and Sporotrichosis

The central nervous system (CNS) is not a major organ involved with infections caused by the endemic mycoses, with the possible exception of meningitis caused by Coccidioides species. When CNS infection does occur, the manifestations vary among the different endemic mycoses; mass-like lesions or diffuse meningeal involvement can occur, and isolated chronic meningitis, as well as widely disseminated acute infection that includes the CNS, are described. This review includes CNS infection caused by Blastomyces dermatitidis, Paracoccidioides brasiliensis, Talaromyces marneffei, and the Sporothrix species complex. The latter is not geographically restricted, in contrast to the classic endemic mycoses, but it is similar in that it is a dimorphic fungus. CNS infection with B. dermatitidis can present as isolated chronic meningitis or a space-occupying lesion usually in immunocompetent hosts, or as one manifestation of widespread disseminated infection in patients who are immunosuppressed. P. brasiliensis more frequently causes mass-like intracerebral lesions than meningitis, and most often CNS disease is part of disseminated infection found primarily in older patients with the chronic form of paracoccidioidomycosis. T. marneffei is the least likely of the endemic mycoses to cause CNS infection. Almost all reported cases have been in patients with advanced HIV infection and almost all have had widespread disseminated infection. Sporotrichosis is known to cause isolated chronic meningitis, primarily in immunocompetent individuals who do not have Sporothrix involvement of other organs. In contrast, CNS infection in patients with advanced HIV infection occurs as part of widespread disseminated infection.
Metabolomics of anoxia tolerance in D. melanogaster: evidence against substrate limitation and for roles of protective metabolites and paralytic hypometabolism.

Animals vary tremendously in their capacities to survive anoxia, and the mechanisms responsible are poorly understood. Adult Drosophila melanogaster are rapidly paralyzed and survive up to 12 h of anoxia, while larvae vigorously attempt escape but then die if anoxia exceeds 2 h. Here we use H-NMR methods to compare the metabolome of larvae and adult D. melanogaster under normoxic conditions and after various anoxic durations up to one hour. Glucose increased during anoxia in both larvae and adults, so anoxic death by carbohydrate limitation is unlikely for either stage. Lactate and alanine were the primary anaerobic end-products in both adults and larvae. During the first 30 min of anoxia, larvae accumulated anaerobic end-products (predominately lactate) at a higher rate, suggesting larvae may experience greater initial acid-base disruption during anoxic exposures. Adult Drosophila did not possess higher levels of putative protective metabolites; however, these increased during anoxia in adults and decreased in larvae. Metabolites that decreased during anoxia in larvae included mannitol, xylitol, glycerol, betaine, serine and tyrosine, perhaps due to use as fuels, antioxidants, or binding to denatured proteins. Adults showed significant increases in glycine, taurine and the polyols glycerol, mannitol and xylitol, suggesting that adult upregulate protective metabolites to prevent damage. Our results suggest that lower initial metabolic demand due to paralytic hypometabolism and capacities to upregulate protective metabolites may assist the better anoxia-tolerance of adult Drosophila.
Implication of alpha-Klotho as the predictive factor of stress

Stress is known as a risk factor for both mental and physical health problems. While stress is known as one of the major health problems in modern society, a biomarker of stress has not yet been well established. In the present study, we focused on the serum levels of α-Klotho (αKl) as a possible objective biomarker of stress. Subjects included apparently healthy individuals who underwent a health examination in the Osaka University Health and Counseling Center. Physical and biochemical parameters were obtained from all subjects. Information regarding the lifestyle of each individual was obtained via questionnaires. Among male subjects, serum levels of soluble αKl (sαKl) were significantly elevated in subjects who had poor stress management and unsatisfactory sleep, suggesting that stress management and sleeping conditions influenced the serum levels of sαKl. The total Kessler Screening Scale for Psychological Distress (K6) score was significantly increased in subjects who reported experiencing considerable stress, had poor stress management and unsatisfactory sleep. Since serum levels of sαKl showed the same tendency as the K6 score in terms of the relationship between stress management and sleeping conditions in male subjects, increased sαKl levels could be associated with considerable psychological stress in healthy men.
Femtosecond Laser Nano/Micro Textured Ti6Al4V Surfaces—Effect on Wetting and MG-63 Cell Adhesion

Nano- and microstructured titanium surfaces have recently attracted attention in the field of regenerative medicine because of the influence which surface characteristics such as roughness and wettability can have on cellular processes. This study focuses on the correlation of surface properties (wettability and nano/micro texture) of laser-structured Ti6Al4V samples with pronounced cell adhesion. Samples were structured with multiple laser parameters in order to create a range of surface properties. Surface characterization was performed by contact angle measurements 1 and 7 days after laser processing. The arithmetic mean roughness of the material surface in an area (Sa) was determined by means of confocal laser scanning microscopy (CLSM). Immediately after wettability tests of the laser-structured surfaces, in vitro experiments with human MG-63 osteoblasts were carried out. For this purpose, the cell morphology and actin cytoskeleton organization were analyzed using CLSM and scanning electron microscopy. On rough microstructures with deep cavities, the cell growth and spreading were inhibited. An improved cellular adhesion and growth on nanostructured and sinusoidal microstructured surfaces could be demonstrated, regardless of hydrophilicity of the surfaces.
Risk factors for CIDP: antecedent events, lifestyle and dietary habits. Data from the Italian CIDP database.

Background: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: We collected information about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly-selected controls with a 1:1 ratio between patients and controls. Results: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex–matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. Conclusions: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.
Effects of dry-season irrigation on leaf physiology and biomass allocation in tropical lianas and trees.

Lianas are more abundant in seasonal forests than in wetter forests and are thought to perform better than trees when light is abundant and water is limited. We tested the hypothesis that lianas perform better than trees during seasonal drought using a common garden experiment with 12 taxonomically diverse species (6 liana and 6 tree species) in 12 replicated plots. We irrigated six of the plots during the dry season for four years, while the remaining 6 control plots received only ambient rainfall. In year 5, we measured stem diameters for all individuals and harvested above- and belowground biomass for a subset of individuals to quantify absolute growth and biomass allocation to roots, stems, and leaves, as well as total root length and maximum rooting depth. We also measured rate of photosynthesis, intrinsic water use efficiency (iWUE), pre-dawn and midday water potential, and a set of functional and hydraulic traits. During the peak of the dry season, lianas in control plots had 54% higher predawn leaf water potentials (ΨPD ), and 45% higher photosynthetic rates than trees in control plots. By contrast, during the peak of the wet season, these physiological differences between lianas and trees become less pronounced and, in some cases, even disappeared. Trees had higher specific leaf area (SLA) than lianas; however, no other functional trait differed between growth forms. Trees responded to the irrigation treatment with 15% larger diameters and 119% greater biomass than trees in control plots. Liana growth, however, did not respond to irrigation; liana diameter and biomass were similar in control and irrigation plots, suggesting that lianas were far less limited by soil moisture than were trees. Contrary to previous hypotheses, lianas did not have deeper roots than trees; however, lianas had longer roots per stem diameter than did trees. Our results support the hypothesis that lianas perform better and experience less physiological stress than trees during seasonal drought, suggesting clear differences between growth forms in response to altered rainfall regimes. Ultimately, better dry-season performance may explain why liana abundance peaks in seasonal forests compared to trees, which peak in abundance in less seasonal, wetter forests. This article is protected by copyright. All rights reserved.
Early roots of sexual-orientation health disparities: associations between sexual attraction, health and well-being in a national sample of Australian adolescents

Background Research documents substantial adolescent health disparities by sexual orientation, but studies are confined to a small number of countries—chiefly the USA. We provide first-time evidence of associations between sexual orientation and adolescent health/well-being in a new country—Australia. We also add to knowledge by examining health/well-being outcomes not previously analysed in national samples, considering adolescents reporting no sexual attractions, and rank-ordering sexual-orientation health disparities by magnitude. Methods Data from an Australian national probability sample of 14/15 years old (Longitudinal Study of Australian Children, n=3318) and regression models adjusted for confounding and for multiple comparisons were used to examine the associations between sexual attraction and 30 outcomes spanning multiple domains of health/well-being—including socio-emotional functioning, health-related quality of life, depressive symptoms, health-related behaviours, social support, self-harm, suicidality, victimisation, self-concept, school belonging and global health/well-being assessments. Results Lesbian, gay, bisexual and questioning adolescents displayed significantly worse health/well-being than their heterosexual peers in all outcomes (p<0.05). The magnitude of the disparities ranged between 0.13 and 0.75 SD, and was largest in the domains of self-harm, suicidality, peer problems and emotional problems. There were fewer differences between the heterosexual and no-attraction groups. Worse outcomes were observed among both-sex-attracted adolescents compared with same-sex-attracted adolescents, and sexual-minority girls compared with sexual-minority boys. Conclusions Consistent with the minority stress model and recent international scholarship, sexual-minority status is an important risk factor for poor adolescent health/well-being across domains in Australia. Interventions aimed at addressing sexual-orientation health disparities within Australian adolescent populations are urgently required.
The Mechanism for the Energy Buildup Driving Solar Eruptive Events

The underlying origin of solar eruptive events (SEEs), ranging from giant coronal mass ejections to small coronal-hole jets, is that the lowest-lying magnetic flux in the Sun’s corona undergoes continual buildup of stress and free energy. This magnetic stress has long been observed as the phenomenon of “filament channels:” strongly sheared magnetic field localized around photospheric polarity inversion lines. However, the mechanism for the stress buildup—the formation of filament channels—is still debated. We present magnetohydrodynamic simulations of a coronal volume that is driven by transient, cellular boundary flows designed to model the processes by which the photosphere drives the corona. The key feature of our simulations is that they accurately preserve magnetic helicity, the topological quantity that is conserved even in the presence of ubiquitous magnetic reconnection. Although small-scale random stress is injected everywhere at the photosphere, driving stochastic reconnection throughout the corona, the net result of the magnetic evolution is a coherent shearing of the lowest-lying field lines. This highly counterintuitive result—magnetic stress builds up locally rather than spreading out to attain a minimum energy state—explains the formation of filament channels and is the fundamental mechanism underlying SEEs. Furthermore, this process is likely to be relevant to other astrophysical and laboratory plasmas.