Miracle-dz/UniFAR-FTUs huggingface dataset:
Heating of metallic biliary stents during magnetic hyperthermia of patients with pancreatic ductal adenocarcinoma: an in silico study

Abstract Objective To investigate the eddy current heating that occurs in metallic biliary stents during magnetic hyperthermia treatments and to assess whether these implants should continue to be an exclusion criterion for potential patients. Methods Computer simulations were run on stent heating during the hyperthermia treatment of local pancreatic tumors (5–15 mT fields at 300 kHz for 30 min), considering factors such as wire diameter, type of stent alloy, and field orientation. Maxwell’s equations were solved numerically in a bile duct model, including the secondary field produced by the stents. The heat exchange problem was solved through a modified version of the Pennes’ bioheat equation assuming a temperature dependency of blood perfusion and metabolic heat. Results The choice of alloy has a large impact on the stent heating, preferring those having a lower electrical conductivity. Only for low field intensities (5 mT) and for some of the bile duct tissue layers the produced heating can be considered safe. The orientation of the applied field with respect to the stent wires can give rise to the onset of regions with different heating levels depending on the shape that the stent has finally adopted according to the body’s posture. Bile helps to partially dissipate the heat that is generated in the lumen of the bile duct, but not at a sufficient rate. Conclusion The safety of patients with pancreatic cancer wearing metallic biliary stents during magnetic hyperthermia treatments cannot be fully assured under the most common treatment parameters.
Temporal trend in mortality of cardiovascular diseases and its contribution to life expectancy increase in China, 2013 to 2018

Abstract Backgrounds: Cardiovascular disease (CVD) remains the leading cause of deaths nationwide. However, little is understood about its temporal trend and corresponding influence on longevity improvements. We aimed to describe the updated tendency in CVD mortality and to quantify its impact on life expectancy (LE) increase in China. Methods: All-cause mortality rates were calculated with population sizes from the National Bureau of Statistics and death counts from the National Health Commission. We estimated CVD mortality rates by allocating age- and sex-based mortality envelopes to each CVD subtype based on its proportion derived from the Disease Surveillance Points system. The probability of CVD premature deaths and LE were calculated with life tables and we adopted Arriaga's method to quantitate age- and cause-specific contributions to LE gains. Results: During 2013 to 2018, the age-standardized mortality rate of CVD decreased from 289.69 (95% confidence interval [CI]: 289.03, 290.35)/100,000 to 272.37 (95%CI: 271.81, 272.94)/100,000, along with a decline in probability of CVD premature deaths from 9.05% (95%CI: 9.02%, 9.09%) to 8.13% (95%CI: 8.10%, 8.16%). The gap in CVD mortality across sexes expanded with more remarkable declines in females, especially for those aged 15 to 64 years. Among major subtypes, the probability of premature deaths from hemorrhage stroke declined fastest, while improvements of ischemic stroke and ischemic heart disease were limited, and there was an increase in stroke sequelae. LE in China reached 77.04 (95%CI: 76.96, 77.12) years in 2018 with an increase of 1.38 years from 2013. Of the total LE gains, 21.15% (0.29 years) were attributed to reductions of CVD mortality in the overall population, mostly driven by those aged >65 years. Conclusions: The general process in reducing CVD mortality has contributed to longevity improvements in China. More attention should be paid to prevention and control of atherosclerotic CVD and stroke sequelae, especially for the elderly. Working-age males also deserve additional attention due to inadequate improvements.
Emerging roles of extracellular vesicles in normal and malignant hematopoiesis

Hematopoietic stem cells, regulated by their microenvironment (or “niche”), sustain the production of mature blood and immune cells. Leukemia cells remodel the microenvironment to enhance their survival, which is accompanied by the loss of support for normal hematopoiesis in hematologic malignancies. Extracellular vesicles (EVs) mediate intercellular communication in physiological and pathological conditions, and deciphering their functions in cell-cell interactions in the ecosystem can highlight potential therapeutic targets. In this Review, we illustrate the utility of EVs derived from various cell types, focusing on the biological molecules they contain and the behavioral alterations they can induce in recipient cells. We also discuss the potential for clinical application in hematologic malignancies, including EV-based therapeutic regimens, drug delivery via EVs, and the use of EVs (or their cargoes) as biomarkers.
Ten years of graduates: A cross-sectional study of the practice location of doctors trained at a socially accountable medical school

Introduction The study predicted practice location of doctors trained at a socially accountable medical school with education programs in over 90 communities. Methods A cross-sectional study examined practice location 10 years after the first class graduated from the Northern Ontario School of Medicine (NOSM), Canada. Exact tests and logistic regression models were used to assess practice location in northern Ontario; northern Canada; or other region; and rural (population <10,000) or urban community. Results There were 435 doctors with 334 (77%) practising as family doctors (FPs), 62 (14%) as generalist specialists and 39 (9%) as other medical or surgical specialists. Approximately 92% (128/139) of FPs who completed both UG and PG at NOSM practised in northern Ontario in 2019, compared with 63% (43/68) who completed only their PG at NOSM, and 24% (30/127) who completed only their UG at NOSM. Overall, 37% (23/62) of generalist specialists and 23% (9/39) of other specialists practised in northern Ontario. Approximately 28% (93/334) of FPs practised in rural Canada compared with 4% (4/101) of all other specialists. FP northern Ontario practice was predicted by completing UG and PG at NOSM (adjusted odds ratio = 46, 95% confidence interval = 20–103) or completing only PG at NOSM (15, 6.0–38) relative to completing only UG at NOSM, and having a northern Ontario hometown (5.3, 2.3–12). Rural Canada practice was predicted by rural hometown (2.3, 1.3–3.8), completing only a NOSM PG (2.0, 1.0–3.9), and age (1.4, 1.1–1.8). Conclusion This study uniquely demonstrated the interaction of two mechanisms by which medical schools can increase the proportion of doctors’ practices located in economically deprived regions: first, admit medical students who grow up in the region; and second, provide immersive UG and PG medical education in the region. Both mechanisms have enabled the majority of NOSM-trained doctors to practise in the underserved region of northern Ontario.
Evidence that heat acclimation training may alter sleep and incidental activity

ABSTRACT This randomized cross-over study tested the hypothesis that heat acclimation training would detrimentally affect sleep variables and alter incidental physical activity compared to a thermoneutral training control condition. Eight recreationally trained males (V̇O2peak 49±4.9 mL.kg-1.min-1) completed two separate interventions separated by at least 31 days: 5 consecutive day training blocks of moderate-intensity cycling (60 min·day-1 at 50% peak power output) in a hot (34.9±0.7 °C and 53±4 % relative humidity) and a temperate (22.2±2.6 °C; 65±8 % relative humidity) environment. Wrist-mounted accelerometers were worn continuously for the length of the training blocks and recorded physical activity, sleep quality and quantity. Data were analysed in a Bayesian framework, with the results presented as the posterior probability that a coefficient was greater or less than zero. Compared to the temperate training environment, heat acclimation impaired sleep efficiency (Pr β<0 = .979) and wake on sleep onset (Pr β>0 = .917). Daily sedentary time was, on average, 35 min longer (Pr β>0 = .973) and light physical activity time 18 min shorter (Pr β>0 = .960) during the heat acclimation period. No differences were observed between conditions in sleep duration, subjective sleep quality, or moderate or vigorous physical activity. These findings may suggest that athletes and coaches need to be cognisant that heat acclimation training may alter sleep quality and increase sedentary behaviour. Highlights Five consecutive days of heat training negatively affected some objective measures of sleep quality and incidental physical activity in recreationally trained athletes. Athletes and coaches need to be aware of the potential unintended consequences of using heat acclimation on sleep behaviours.
Proyecto Titi: Teaching children that cotton‐top tamarins (Saguinus oedipus) are not appropriate pets

Cotton‐top tamarins (Saguinus oedipus) are a critically endangered species found only in Colombia. Their survival is threatened by extensive habitat destruction and the illegal pet trade. Because many people in Colombia have a low level of awareness of cotton‐top tamarins and even less understanding of the impacts that the illegal pet trade has on the species and its long‐term survival, Proyecto Tití has developed a series of programs for children in rural elementary schools that introduce children to cotton‐top tamarins. This study examines Proyecto Titi's efforts to reduce the desire to have a cotton‐top tamarin as a pet with outcomes focused specifically on (1) creating an emotional connection between people and cotton‐top tamarins, (2) identifying the feelings and understanding the challenges that cotton‐top tamarin face when they are kept as pets, and (3) empowering students to make positive choices to help cotton‐top tamarins. Both TITI KIDS and TITIRITIANDO programs helped students to (1) increase their knowledge of cotton‐top tamarins, (2) understand the damage that the pet trade has on individual animals and the long‐term survival of cotton‐top tamarins and (3) provide practical actions that they can engage in to protect cotton‐top tamarins for the future. Our hope is that students from our programs become advocates for conservation in their communities and assist in the long‐term conservation activities to protect cotton‐top tamarins in Colombia.
Hydrogels for localized drug delivery: A special emphasis on dermatologic applications

Skin disease treatment is a complex and time‐consuming process due to the complex etiology, numerous side effects of conventional therapies, and difficulties in determining primary causes of the disease. Superficial wounds are often easy to treat. However, treatment of severe wounds caused by burn is challenging for clinicians. Optimum therapeutic benefits are based on the site‐specific delivery of medicaments at the right time for a prolonged duration. Systemic toxicity and frequent dosing are the major challenges associated with the use of conventional therapeutics. Hydrogels are material of choice for drug delivery because of their high biocompatibility and ability to hold and release therapeutic agents. The number of hydrogels available for use in cosmetology and dermatology continues to grow during the past 1–2 decades. However, new hydrogel materials with high biocompatibility, antibacterial properties, and the ability to stimulate skin regeneration processes are in high demand. These are three‐dimensional networks, which absorb a large amount of biological fluids and water. Hydrogels can be used as a biosensor, carrier systems for cells, drug delivery carriers especially for topical applications and in contact lenses. Hydrogels are highly porous carriers containing about 90% water. Stimuli‐responsive hydrogels cause a change in network structure that is completely reversible in nature. The present review describes the applications of hydrogels in pharmaceutical formulations with a special emphasis on the treatment of dermatologic conditions such as acne, psoriasis, and mycosis.
Balance between breadth and depth in human many-alternative decisions

Many everyday life decisions require allocating finite resources, such as attention or time, to examine multiple available options, like choosing a food supplier online. In cases like these, resources can be spread across many options (breadth) or focused on a few of them (depth). Whilst theoretical work has described how finite resources should be allocated to maximize utility in these problems, evidence about how humans balance breadth and depth is currently lacking. We introduce a novel experimental paradigm where humans make a many-alternative decision under finite resources. In an imaginary scenario, participants allocate a finite budget to sample amongst multiple apricot suppliers in order to estimate the quality of their fruits, and ultimately choose the best one. We found that at low budget capacity participants sample as many suppliers as possible, and thus prefer breadth, whereas at high capacities participants sample just a few chosen alternatives in depth, and intentionally ignore the rest. The number of alternatives sampled increases with capacity following a power law with an exponent close to 3/4. In richer environments, where good outcomes are more likely, humans further favour depth. Participants deviate from optimality and tend to allocate capacity amongst the selected alternatives more homogeneously than it would be optimal, but the impact on the outcome is small. Overall, our results undercover a rich phenomenology of close-to-optimal behaviour and biases in complex choices.
Association of Accelerometer-Measured Physical Activity and Sedentary Time with Epigenetic Markers of Aging

ABSTRACT Introduction/Purpose Physical activity may influence chronic disease risk, in part, through epigenetic mechanisms. Previous studies have demonstrated that an acute bout of physical activity can influence DNA methylation status. Few studies have explored the relationship between habitual, accelerometer-measured physical activity or sedentary time with epigenetic markers of aging. Methods We used linear regression to examine cross-sectional associations of accelerometer-measured physical activity and sedentary time with extrinsic and intrinsic epigenetic age acceleration (EEAA and IEAA) models and GrimAge measured from blood samples from Framingham Heart Study participants with accelerometry and DNA methylation data (n = 2435; mean age, 54.9 ± 14.3; 46.0% men). Residuals of Hannum-, Horvath-, and GrimAge-predicted epigenetic age were calculated by regressing epigenetic age on chronological age. We took into account blood cell composition for EEAA, IEAA, and AdjGrimAge. Moderate to vigorous physical activity was log-transformed to normalize its distribution. Adjustment models accounted for family structure, age, sex, smoking status, cohort–laboratory indicator, and accelerometer wear time. We additionally explored adjustment for body mass index (BMI). Results Walking 1500 more steps per day or spending 3 fewer hours sedentary was associated with >10 months lower GrimAge biological age (or ~1 month lower AdjGrimAge, after adjusting for blood cells, P < 0.05). Every 5 min·d−1 more moderate to vigorous physical activity was associated with 19–79 d of lower GrimAge (4–23 d lower using EEAA or AdjGrimAge, P < 0.01). Adjusting for BMI attenuated these results, but all statistically significant associations with AdjGrimAge remained. Conclusions Greater habitual physical activity and lower sedentary time were associated with lower epigenetic age, which was partially explained by BMI. Further research should explore whether changes in physical activity influence methylation status and whether those modifications influence chronic disease risk.
Widespread autogenous mRNA–protein interactions detected by CLIP-seq

Abstract Autogenous interactions between mRNAs and the proteins they encode are implicated in cellular feedback-loop regulation, but their extent and mechanistic foundation are unclear. It was recently hypothesized that such interactions may be common, reflecting the role of intrinsic nucleobase–amino acid affinities in shaping the genetic code's structure. Here we analyze a comprehensive set of CLIP-seq experiments involving multiple protocols and report on widespread autogenous interactions across different organisms. Specifically, 230 of 341 (67%) studied RNA-binding proteins (RBPs) interact with their own mRNAs, with a heavy enrichment among high-confidence hits and a preference for coding sequence binding. We account for different confounding variables, including physical (overexpression and proximity during translation), methodological (difference in CLIP protocols, peak callers and cell types) and statistical (treatment of null backgrounds). In particular, we demonstrate a high statistical significance of autogenous interactions by sampling null distributions of fixed-margin interaction matrices. Furthermore, we study the dependence of autogenous binding on the presence of RNA-binding motifs and structured domains in RBPs. Finally, we show that intrinsic nucleobase–amino acid affinities favor co-aligned binding between mRNA coding regions and the proteins they encode. Our results suggest a central role for autogenous interactions in RBP regulation and support the possibility of a fundamental connection between coding and binding.
Mortality rate, carbon emissions, renewable energy and per capita income nexus in Sub-Saharan Africa

This study exclusively contributes to the health-environment discourse by using mortality rates, carbon emissions (proxy for environmental degradation), renewable energy and real per capita income to investigate these intrinsic relationships. This study uses an unbalanced sample of 47 Sub-Saharan African countries from 2005–2019 to reveal that: (1) both carbon emissions and renewable energy are associated with higher mortality rates; (2) real per capita income is associated with reducing mortality rates; (3) per capita income attenuates the effect of renewable energy on mortality rates, (4) persistency in mortalities exist; and (5) the health-environment-energy-income dynamics differ across income groups. Additionally, this study submits that the interaction of renewable energy and real per capita income dampens the positive effect of renewable energy on mortality rates and supports the argument that income levels lessen the extent of mortalities. Besides, these results vividly show that real per capita income reduces the devastating effect of renewable energy on infant and under-5 mortality rates from 0.942% to 0.09%, 2.42% to 0.55%, 1.04% to 0.09% and 2.8% to 0.64% for high and middle-income countries, respectively. This is a novel and significant contribution to the health-environment literature. Hence, real per capita income is a crucial determinant of mortality rate. Policy recommendations are discussed.
Event boundaries structure the contents of long-term memory in younger and older adults

ABSTRACT Event boundaries impose structure on how events are stored in long-term memory. Research with young adults has shown that associations within events are stronger than those that cross event boundaries. Recently, this effect was observed in both young and old adults using movie stimuli (Davis, Chemnitz, et al., 2021). Here, we test whether this effect extends to written narratives. Young and old participants read a series of narratives that were interspersed with temporal shifts in the storyline meant to elicit the perception of an event boundary. Later, participants were cued with sentences and were asked to recall the sentence that immediately followed. We expected participants would have worse memory when a cue and correct answer flanked a boundary than when it did not. In Experiment 1, we found that despite older adults’ lower performance overall, both age groups had lower accuracy for cues that flanked a boundary, compared to cues that elicited a response from within the same event. Experiment 2 replicated the results from Experiment 1. Our results support past work that did not find age differences in event perception and demonstrate that older and younger adults may store events similarly in long-term memory.
Inverse Design of Mechanical Metamaterials with Target Nonlinear Response via a Neural Accelerated Evolution Strategy

Materials with target nonlinear mechanical response can support the design of innovative soft robots, wearable devices, footwear, and energy‐absorbing systems, yet it is challenging to realize them. Here, mechanical metamaterials based on hinged quadrilaterals are used as a platform to realize target nonlinear mechanical responses. It is first shown that by changing the shape of the quadrilaterals, the amount of internal rotations induced by the applied compression can be tuned, and a wide range of mechanical responses is achieved. Next, a neural network is introduced that provides a computationally inexpensive relationship between the parameters describing the geometry and the corresponding stress–strain response. Finally, it is shown that by combining the neural network with an evolution strategy, one can efficiently identify geometries resulting in a wide range of target nonlinear mechanical responses and design optimized energy‐absorbing systems, soft robots, and morphing structures.
miR-181a-5p is a potential candidate epigenetic biomarker in Multiple Sclerosis.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Abnormal expression of microRNAs (miRNA) plays an important role in MS pathology. In this cohort study, differential expression of the four miRNAs (hsa-miR-155-5p, hsa-miR-9-5p, hsa-miR-181a-5p, and hsa-miR-125b-5p) were investigated in 69 individuals, including 39 MS patients (relapsing-remitting MS (RRMS), n = 27; secondary progressive MS (SPMS), n = 12) and 30 healthy controls. In silico analyzes revealed possible genes and pathways specific to miRNAs. Peripheral blood miRNA expressions were detected by quantitative Real-Time PCR (qPCR). hsa-miR-181a-5p was downregulated and associated with increased MS risk (P = 0.012). The other three miRNAs were upregulated and not associated with MS (P < 0.05). The area under the curve (AUC) is 0.779. In silico analyzes showed that hsa-miR-181a-5p may participate in MS pathology by targeting MAP2K1, CREB1, ATXN1, and ATXN3 genes in inflammation and neurodegeneration pathways. The circulatory hsa-miR-181a-5p can regulate target genes, reversing the mechanisms involved in MS pathologies such as protein uptake and processing, cell proliferation and survival, inflammation, and neurodegeneration. Thus, this miRNA could be used as an epigenomic-guided diagnostic tool and therapeutic.