Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA methylation changes induced by prenatal toxic metal exposure: An overview of epidemiological evidence

Abstract Accumulating evidence suggests that exposure to unfavorable conditions early in life can substantially contribute to the risk of chronic disorders later in life (‘developmental programming’ phenomenon). The mechanistic basis for this phenomenon remains poorly understood so far, although epigenetic mechanisms such as DNA methylation, histone modifications and microRNA-mediated gene regulation apparently play a crucial role. The key role of epigenetic modifications triggered by unfavorable environmental cues during sensitive developmental periods in linking adverse early-life events to later-life health outcomes is evident from a large body of studies, including methylome-wide association studies and research of candidate genes. Toxic metals (TMs), such as heavy metals, including lead, chromium, cadmium, arsenic, mercury, etc., are among environmental contaminants currently most significantly impacting human health status. Since TMs can cross the placental barrier and accumulate in fetal tissues, exposure to high doses of these xenobiotics early in development is considered to be among important factors contributing to the developmental programming of adult-life diseases in modern societies. In this mini-review, we summarize epidemiological findings indicating that prenatal TM exposure can induce epigenetic dysregulation, thereby potentially affecting adult health outcomes.
Blood Lactate AUC Is a Sensitive Test for Evaluating the Effect of Exercise Training on Functional Work Capacity in Patients with Chronic Heart Failure

Purpose Exercise training is an essential treatment option for patients with chronic heart failure (CHF). However, it remains controversial, which surrogate measures of functional work capacity are most reliable. The purpose of this paper was to compare functional capacity work measured as capillary lactate concentrations area under the curve (AUC) with standard cardiopulmonary exercise testing (CPET) with VO2peak and the 6-minute walk test (6 MWT). Methods Twenty-three patients in New York Heart Association (NYHA) class II/III with left ventricular ejection fraction (LVEF) <35% were randomised to home-based recommendation of regular exercise (RRE) (controls), moderate continuous training (MCT) or aerobic interval training (AIT). The MCT and AIT groups underwent 12 weeks of supervised exercise training. Exercise testing was performed as standard CPET treadmill test with analysis of VO2peak, the 6 MWT and a novel 30-minute submaximal treadmill test with capillary lactate AUC. Results All patients had statistically significant improvements in VO2peak, 6 MWT and lactate AUC after 12 weeks of exercise training: 6 MWT (p =0.035), VO2peak (p =0.049) and lactate AUC (p =0.002). Lactate AUC (p =0.046) and 6MWT (p =0.035), but not VO2peak revealed difference between the exercise modalities regarding functional work capacity. Conclusion 6-MWT and lactate AUC, but not VO2peak, were able to reveal a statistically significant improvement in functional capacity between different exercise modalities.
Reaction Time Decomposition as a Tool to Study Subcortical Ischemic Vascular Cognitive Impairment

Background: The study of reaction time (RT) and its intraindividual variability (IIV) in aging, cognitive impairment, and dementia typically fails to investigate the processing stages that contribute to an overall response. Applying “mental chronometry” techniques makes it possible to separately assess the role of processing components during environmental interaction. Objective: To determine whether RT and IIV-decomposition techniques can shed light on the nature of underlying deficits in subcortical ischemic vascular cognitive impairment (VCI). Using a novel iPad task, we examined whether VCI deficits occur during both initiation and movement phases of a response, and whether they are equally reflected in both RT and IIV. Methods: Touch cancellation RT and its IIV were measured in a group of younger adults (n = 22), cognitively healthy older adults (n = 21), and patients with VCI (n = 21) using an iPad task. Results: Whereas cognitively healthy aging affected the speed (RT) of response initiation and movement but not its variability (IIV), VCI resulted in both slowed RT and increased IIV for both response phases. Furthermore, there were group differences with respect to response phase. Conclusion: These results indicate that IIV can be more sensitive than absolute RT in separating VCI from normal aging. Furthermore, compared to cognitively healthy aging, VCI was characterized by significant deficits in planning/initiating action as well as performing movements. Such deficits have important implications for real life actions such as driving safety, employment, and falls risk.
Matrine ameliorates the inflammatory response and lipid metabolism in vascular smooth muscle cells through the NF-κB pathway

Atherosclerosis is a chronic inflammatory disease associated with inflammatory responses and the uncontrolled proliferation and excessive apoptosis of vascular smooth muscle cells. However, the effects of matrine on the inflammatory response, abnormal lipid metabolism and cell proliferation and apoptosis marker proteins in human aortic vascular smooth muscle cells (HAVSMCs) have not been elucidated. Therefore, the present study aimed to investigate the effect of matrine on an in vitro model of atherosclerosis using HAVSMCs. The HAVSMCs were divided into normal, model and matrine groups. The model group was treated with oxidized low-density lipoprotein (oxLDL), the matrine group was treated with oxLDL and matrine and the normal group was treated with physiological saline. Total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) levels were measured in the cell supernatant. In addition, the relative mRNA levels of inflammatory factors were quantified using reverse transcription-quantitative PCR, and the cell proliferation and apoptosis rates were evaluated using Cell Counting Kit-8 and flow cytometry assays, respectively. The expression levels of proteins associated with proliferation and apoptosis were also determined using western blotting. The levels of TC, FC and CE and the mRNA levels of IL-1β, IL-6, and TNF-α in the matrine group were lower than those in the model group, but higher than those in the normal group. After 48 and 96 h of treatment, the cell proliferation and apoptotic rates were lower in the matrine group compared with the model group. The relative expression levels of Ki-67, proliferating cell nuclear antigen and Bax were decreased, while that of Bcl-2 was increased in the matrine group compared with the model group. In addition, the relative protein expression of nuclear factor κB (NF-κB) in the matrine group was lower than that in the model group, but higher than that in the normal group. In summary, matrine inhibited activation of the NF-κB pathway and reduced cell proliferation and apoptosis in the oxLDL-induced atherosclerosis model, and exhibited anti-inflammatory effects. These results suggest that matrine attenuated abnormal biological reactions in HAVSMCs through the NF-κB pathway.
The Use of Mobile Applications as Communication Aids for People with Dementia: Opportunities and Limitations

Background: Communication difficulties are one of the primary symptoms associated with dementia, and mobile applications have shown promise as tools for facilitating communication in patients with dementia (PwD). The literature regarding mobile health (mHealth) applications, especially communications-based mHealth applications, is limited. Objective: This review aims to compile the existing literature on communications-based mobile applications regarding dementia and assess their opportunities and limitations. A PICO framework was applied with a Population consisting of PwD, Interventions consisting of communication technology, focusing primarily on mobile applications, Comparisons between patient well-being with and without technological intervention, and Outcomes that vary but can include usability of technology, quality of communication, and user acceptance. Methods: Searches of PubMed, IEEE XPLORE, and ACM Digital Library databases were conducted to establish a comprehensive understanding of the current literature on dementia care as related to 1) mobile applications, 2) communication technology, and 3) communications-based mobile applications. Applying certain inclusion and exclusion criteria, yielded a set of articles (n = 11). Results: The literature suggests that mobile applications as tools for facilitating communication in PwD are promising. Mobile applications are not only feasible socially, logistically, and financially, but also produce meaningful communication improvements in PwD and their caregivers. However, the number of satisfactory communications-based mobile applications in the mHealth marketplace and their usability is still insufficient. Conclusion: Despite favorable outcomes, more research involving PwD using these applications are imperative to shed further light on their communication needs and on the role of mHealth.
Characteristics of new HIV diagnoses over 1995–2019: A clinic-based study in Montréal, Canada

Background Characterization of populations at risk of acquiring HIV is required to inform the public health response to HIV. To identify potential changing needs in HIV prevention and care cascade, we aim to describe how the demographic profiles and exposure categories of newly diagnosed HIV positive individuals attending a large sexual health clinic in Montréal (Canada) evolved since the beginning of the antiretroviral therapy era in the mid-1990s. Methods Using diagnosis data from participants of the Clinique médicale l’Actuel cohort of HIV-positive patients, we examined the distribution of exposure categories (sexual orientation, sexual behaviours, injection drug use, being born in an HIV-endemic country) by gender and year of diagnosis. Time trends in mean age and in the proportion of patients with late (CD4 <350 cells/μL) or advanced stage (CD4 <200 cells/μL) of HIV infection at diagnosis were assessed through meta-regressions. Results A total of 2,612 patients diagnosed with HIV between January 1st, 1995 and December 31st, 2019 were included. Overall, mean age was 35 years (standard deviation: 10 years) and remained stable over time. The proportion of patients with advanced stage of HIV infection decreased from 16% in 1995 to 4% in 2019. Although men who have sex with men (MSM) consistently accounted for the highest proportion of new diagnoses (77%, 2,022/2,612 overall), their proportion decreased since 2013. There was also a concomitant decrease in the proportion of people who inject drugs, with none of the newly diagnosed participants reporting injection drug use since 2017, and an important increase in the proportion of patients born in an HIV-endemic country (24%, 7/29 in 2019), especially among women. Compared to patients from non-endemic countries, those from HIV-endemic countries were characterized by higher proportions of heterosexuals (88% vs 17%) and of women (52% vs 7%), and were twice likely to get diagnosed at an advanced stage of HIV infection (32% vs 15%). Conclusions In absolute numbers, MSM continue to account for the largest exposure category. However, patients from HIV-endemic countries, who tend to be diagnosed at later stages of HIV infection, constitute an increasing proportion of newly diagnosed individuals. These persons could face distinct barriers to rapid diagnosis. Tailoring HIV testing strategies and other prevention interventions to the specific unmet prevention needs of these individuals is warranted.
Mathematics teachers’ reflective thinking: Level of understanding and implementation in their professional practices

Mathematics teachers must be able to engage in self-reflection and think constructively about their professional activities to instruct students effectively. This is also important for students’ ability to solve problems in class, as well as the challenges facing them and their societies in the future. This study aimed to examine in-service math teachers’ reflective thinking skills in the context of how they are applied to their understanding of their teaching practices. The sample included 322 mathematics teachers, who responded to a questionnaire designed to elucidate how they were thinking reflectively about their teaching practice. The findings revealed that the teachers’ practices concerning all the themes of reflective thinking addressed by the questionnaire, especially their ability to self-assess, fluctuated around the intermediate, and advanced levels. The implications of our findings are discussed in terms of extensive and continuous professional development centered on supporting ongoing growth in the reflective thinking skills of in-service math teachers.
Toughening hydrogels through force-triggered chemical reactions that lengthen polymer strands

Description Longer and stronger; stiff but not brittle Hydrogels are highly water-swollen, cross-linked polymers. Although they can be highly deformed, they tend to be weak, and methods to strengthen or toughen them tend to reduce stretchability. Two papers now report strategies to create tough but deformable hydrogels (see the Perspective by Bosnjak and Silberstein). Wang et al. introduced a toughening mechanism by storing releasable extra chain length in the stiff part of a double-network hydrogel. A high applied force triggered the opening of cycling strands that were only activated at high chain extension. Kim et al. synthesized acrylamide gels in which dense entanglements could be achieved by using unusually low amounts of water, cross-linker, and initiator during the synthesis. This approach improves the mechanical strength in solid form while also improving the wear resistance once swollen as a hydrogel. —MSL Polymer strands that react to grow longer upon stretching lead to improved extensibility and tear resistance in hydrogels. The utility and lifetime of materials made from polymer networks, including hydrogels, depend on their capacity to stretch and resist tearing. In gels and elastomers, those mechanical properties are often limited by the covalent chemical structure of the polymer strands between cross-links, which is typically fixed during the material synthesis. We report polymer networks in which the constituent strands lengthen through force-coupled reactions that are triggered as the strands reach their nominal breaking point. In comparison with networks made from analogous control strands, reactive strand extensions of up to 40% lead to hydrogels that stretch 40 to 50% further and exhibit tear energies that are twice as large. The enhancements are synergistic with those provided by double-network architectures and complement other existing toughening strategies.
Arboreality drives heat tolerance while elevation drives cold tolerance in tropical rainforest ants.

Determining how species thermal limits correlate with climate is important for understanding biogeographic patterns and assessing vulnerability to climate change. Such analyses need to consider thermal gradients at multiple spatial scales. Here we relate thermal traits of rainforest ants to microclimate conditions from ground to canopy (microgeographic scale) along an elevation gradient (mesogeographic scale) and calculate warming tolerance to assess climate change vulnerability in the Australian Wet Tropics Bioregion. We test the thermal adaptation and thermal niche asymmetry hypotheses to explain interspecific patterns of thermal tolerance at these two spatial scales. We tested cold tolerance (CTmin ), heat tolerance (CTmax ), and calculated thermal tolerance range (CTrange ), using ramping assays for 74 colonies of 40 ant species collected from terrestrial and arboreal habitats at lowland and upland elevation sites and recorded microclimatic conditions for one year. Within sites, arboreal ants were exposed to hotter microclimates and on average had a 4.2°C (95% CI: 2.7 - 5.6°C) higher CTmax and 5.3°C (95% CI: 3.5 - 7°C) broader CTrange than ground-dwelling ants. This pattern was consistent across the elevation gradient, whether it be the hotter lowlands or the cooler uplands. Across elevation, upland ants could tolerate significantly colder temperatures than lowland ants, whereas the change in CTmax was less pronounced, and CTrange did not change over elevation. Differential exposure to microclimates, due to localised niche preferences, drives divergence in CTmax while environmental temperatures along the elevation gradient drive divergence in CTmin . Our results suggest that both processes of thermal adaptation and thermal niche asymmetry are at play depending on the spatial scale of observation, and we discuss potential mechanisms underlying these patterns. Despite the broad thermal tolerance range of arboreal rainforest ants, lowland arboreal ants had the lowest warming tolerance and may be most vulnerable to climate change.
Recent Stressful Life Events and Suicidal Ideation in Schizophrenia

Supplemental digital content is available in the text. Abstract Half of patients with schizophrenia experience suicidal ideation. Only few studies have examined the effects of recent stress on both current and emergent suicidal ideation. A cohort of 85 patients with schizophrenia spectrum disorders was assessed. The study was divided into a cross-sectional and longitudinal arms to test the effect of recent stress on suicidal ideation. Analysis was done using logistic regression models. After correcting for covariates, recent stress had no significant effect on current suicidal ideation. However, increased total stress (odds ratio [OR] = 1.099 [1.032–1.170], p = 0.003) and health-related stress (OR = 1.331 [1.074–1.650], p = 0.009) at follow-up were predictive of emergent suicidal ideation. With this sample size, we were unable to draw firm conclusions regarding the effect of specific life events on suicidal ideation. Further studies involving larger samples that investigate the interplay between several risk factors are needed.
Immune-metabolic-inflammatory markers in Holstein cows exposed to a nutritional and environmental stressing challenge.

Dairy cows are exposed to multiple stressors during the productive cycle, such as metabolic challenges, overcrowding, grouping change, environmental stress and dietary errors. Thus, it is essential to study reliable markers able to detect stress conditions in dairy farms. This study evaluates dairy cows' immunologic and metabolic markers after the sudden and combined exposition to a high-grain diet (75% concentrates) and the abrupt change of the housing system (from free stall to tie stall). A group of twenty-four Holstein cows were enrolled in a challenge study of 28 days duration. Several immunological and metabolic blood markers were evaluated over the trial. Blood samples were taken at day 0 (normal value) and day 1, 3, 7, 14, 21, and 28 (challenge). Data were submitted to a mixed model for repeated measures, including time as fixed and cows as random effects. The nutritional and environmental challenge had heavy effects on animal welfare and cows responded with a dramatic rumination drop. Our results suggest that the most responsive markers after abiotic stressors in cows were as follows: Serum Amyloid A and ROM in the acute response; Ceruloplasmin and GGT in the mid acute and Albumin, Paroxonase and FRAP in the chronic phase. Serum Amyloid A, Ceruloplasmin, Paraoxonase, GGT and ROM resulted as positive phase proteins, while, Albumin and FRAP resulted as negative phase proteins. Preliminary obtained results could concur to develop strategies able to mitigate stressor effects; moreover, the proposed design can be used as a model to test stress nutritional modulators.
Grain boundary velocity and curvature are not correlated in Ni polycrystals

Description Revising grain growth Polycrystalline materials will often coarsen during annealing, a process that can modify the physical properties. A generally accepted theory ties the grain boundary curvature to the velocity at which grain boundaries migrate. Bhattacharya et al. measured this relationship for 52,000 grains in a nickel sample. They did not observe any relationship between curvature and velocity, suggesting that this accepted theory is not robust for polycrystalline samples. The observations require grain-coarsening models to be updated to more accurately predict the effects of annealing. —BG The growth of crystal grains during annealing may not be tied to the curvature of the grain boundary. Grain boundary velocity has been believed to be correlated to curvature, and this is an important relationship for modeling how polycrystalline materials coarsen during annealing. We determined the velocities and curvatures of approximately 52,000 grain boundaries in a nickel polycrystal using three-dimensional orientation maps measured by high-energy diffraction microscopy before and after annealing at 800°C. Unexpectedly, the grain boundary velocities and curvatures were uncorrelated. Instead, we found strong correlations between the boundary velocity and the five macroscopic parameters that specify grain boundary crystallography. The sensitivity of the velocity to grain boundary crystallography might be the result of defect-mediated grain boundary migration or the anisotropy of the grain boundary energy. The absence of a correlation between velocity and curvature likely results from the constraints imposed by the grain boundary network and implies the need for a new model for grain boundary migration.
Asymmetrical Thoracic Osteophytosis in Professional Golfers: Case Series and Literature Review

Introduction Golf-related injuries are reported by most professional golfers (85%) and by many amateur golfers (39%) (1,2). Spinal injuries are the most common type of injury, accounting for 55% of injuries in professionals and 35%of injuries in amateurs (3,4). The modern golf swingmaximizes thoracic rotation to store potential energy for the greatest release of power upon the impact of the club with the golf ball. During the downswing, the lateral translation of the hips (bending force on the trailing side) and the unwinding of the torso (axial rotation force) create a “reverse-C” in the thoracic spine (Fig. 1). These forces can be eight times the normal weight of a golfer, or as much as 7500N. This repetitive lateral bending and loading eventually results in asymmetric spinal degeneration on the trailing side (4,5). Lumbar spine injuries are the most common type of spinal injury in golfers, affecting 22% to 34%of all golfers (1). Although thoracic injuries account for only 8% of spinal injuries, they are the most debilitating. On average, a golfer loses 28 d to an injury, but the average for those with thoracic injuries is almost five times greater: 137 d of lost time (6). There is limited existing information in the sports medicine literature on the treatment of golf-related thoracic spine injuries and their outcomes. In this article, we describe two cases of asymmetrical thoracic osteophytosis (ATO) in professional golfers. To the best of our knowledge, this type of injury has not been reported previously.