Miracle-dz/UniFAR-FTUs huggingface dataset:
Respiratory and chronic

Objectives A cross-sectional study was conducted to evaluate the relationship between respiratory health and paraquat exposure. Methods The study population was selected from among workers at 15 Nicaraguan banana plantations which relied on paraquat for the control of weeds. All the workers were interviewed after they received their job assignment for the day of the survey, and all who reported never having applied paraquat and all who reported more than 2 years of cumulative exposure as applicators of paraquat with knapsack sprayers were invited for medical evaluation. One hundred and thirty-four exposed workers and 152 unexposed workers were administered a questionnaire interview asking about exposure and respiratory symptoms, and they underwent spirometric testing of forced expiratory volume in 1 s (FEV, ,) and forced vital capacity (FVC). Results In the exposed group 53% reported having experienced a skin rash or burn resulting from paraquat exposure, 25% reported epistaxis, 58% nail damage, and 42% paraquat splashed in the eyes. There was a consistent dose-response relationship between intensity of exposure (as indicated by a history of skin rash or burn) and the prevalence of dyspnea. This relationship was more marked for more severe dyspnea. There was a 3-fold increase in episodic wheezing accompanied by shortness of breath among the more intensely exposed workers. There was no relationship between exposure and FEV, , or FVC. COIICIUS~O~S The high prevalence of respiratory symptoms associated with exposure, in the absence of spirometric abnormalities associated with exposure, could be a result of unmeasured gas exchange abnormalities among workers with long-term exposure to paraquat.
An integral equation method for conformal mapping of doubly connected regions via the Kerzman-Stein and the Neumann Kernels

An integral equation method based on the Kerzman-Stein and the Neumann kernels for conformal mapping of doubly connected regions onto an annulus is presented. The theoretical development is based on the boundary integral equations for conformal mapping of doubly connected regions derived by Murid and Razali (1999). However, the integral equations are not in the form of Fredholm integral equation and no numerical experiments are reported. If some information on the zero and singularity of the mapping function is known, then the integral equations can be reduced to the numerically tractable Fredholm integral equations involving the unknown inner radius. For numerical experiments, discretizing the integral equations lead to a system of non-linear equations. The system obtained is solved simultaneously using Newton’s iterative method. Further modification of the integral equations of Murid and Razali (1999) has lead to an efficient and numerically tractable integral equations which involve the unknown inner radius. These integral equations are feasible for all doubly connected regions with smooth boundaries regardless of the information on the zeroes and singularities of the mapping functions. Discretizing the integral equations lead to an over determined system of non-linear equations which is solved using an optimization technique. Numerical implementations on some test regions are also presented.
Human age reversal: Fact or fiction?

Although chronological age correlates with various age‐related diseases and conditions, it does not adequately reflect an individual's functional capacity, well‐being, or mortality risk. In contrast, biological age provides information about overall health and indicates how rapidly or slowly a person is aging. Estimates of biological age are thought to be provided by aging clocks, which are computational models (e.g., elastic net) that use a set of inputs (e.g., DNA methylation sites) to make a prediction. In the past decade, aging clock studies have shown that several age‐related diseases, social variables, and mental health conditions associate with an increase in predicted biological age relative to chronological age. This phenomenon of age acceleration is linked to a higher risk of premature mortality. More recent research has demonstrated that predicted biological age is sensitive to specific interventions. Human trials have reported that caloric restriction, a plant‐based diet, lifestyle changes involving exercise, a drug regime including metformin, and vitamin D3 supplementation are all capable of slowing down or reversing an aging clock. Non‐interventional studies have connected high‐quality sleep, physical activity, a healthy diet, and other factors to age deceleration. Specific molecules have been associated with the reduction or reversal of predicted biological age, such as the antihypertensive drug doxazosin or the metabolite alpha‐ketoglutarate. Although rigorous clinical trials are needed to validate these initial findings, existing data suggest that aging clocks are malleable in humans. Additional research is warranted to better understand these computational models and the clinical significance of lowering or reversing their outputs.
A preliminary study exploring the mechanical properties of normal and Mgp-deficient mouse femurs during early growth

Matrix Gla protein (MGP) is mostly known to be a calcification inhibitor, as its absence leads to ectopic calcification of different tissues such as cartilage or arteries. MGP deficiency also leads to low bone mass and delayed bone growth. In the present contribution, we investigate the effect of MGP deficiency on the structural and material mechanical bone properties by focusing on the elastic response of femurs undergoing three-points bending. To this aim, biomechanical tests are performed on femurs issued from Mgp-deficient mice at 14, 21, 28, and 35 days of postnatal life and compared to healthy control femurs. µCT acquisitions enable to reconstruct bone geometries and are used to construct subject-specific finite element models avoiding some of the reported limitations concerning the use of beam-like assumptions for small bone samples. Our results indicate that MGP deficiency may be associated to differences in both structural and material properties of femurs during early stages of development. MGP deficiency appears to be related to a decrease in bone dimensions, compensated by higher material properties resulting in similar structural bone properties at P35. The search for a unique density-elasticity relationship based on calibrated bone mineral density (BMD) indicates that MGP deficiency may affect bone tissue in several ways, that may not be represented uniquely from the quantification of BMD. Despite of its limitation to elastic response, the present preliminary study reports for the very first time the mechanical skeletal properties of Mgp-deficient mice at early stages of development.
The future of telehealth in type 1 diabetes

Purpose of review Although telemedicine and telehealth services have been a part of type 1 diabetes (T1D) clinical care for several decades, the expansion of in-home telemedicine during the COVID-19 pandemic significantly increased interest in long-term use as part of routine care. This review highlights the current literature regarding telemedicine in T1D care as well as the benefits and barriers to use in a postpandemic world. Recent findings Telemedicine has increased patient contact with healthcare providers, allowing for more frequent insulin dose adjustments and improvements in glycemic outcomes. In addition to routine clinical care, T1D device training and mental healthcare have been successful through telemedicine. Significant barriers to continued telemedicine care exist, including patient access and technology knowledge, language, and loss of face-to-face interaction. Healthcare providers additionally face unpredictable reimbursement and loss of continuity across state lines, and lack of resources and training for device downloads and telemedicine software. Summary Telemedicine can be successfully used in T1D care and has the potential to significantly impact glycemic and long-term outcomes. Due to continued interest for in-person visits by people with T1D and providers, it is likely that long-term telemedicine use will include a hybrid format.
A Polygenic Risk Score for Hand Grip Strength Predicts Muscle Strength and Proximal and Distal Functional Outcomes among Older Women

ABSTRACT Purpose Hand grip strength (HGS) is a widely used indicator of overall muscle strength and general health. We computed a polygenic risk score (PRS) for HGS and examined whether it predicted muscle strength, functional capacity, and disability outcomes. Methods Genomewide association study summary statistics for HGS from the Pan-UK Biobank was used. PRS were calculated in the Finnish Twin Study on Aging (N = 429 women, 63–76 yr). Strength tests included HGS, isometric knee extension, and ankle plantarflexion strength. Functional capacity was examined with the Timed Up and Go, 6-min and 10-m walk tests, and dual-task tests. Disabilities in the basic activities of daily living (ADL) and instrumental ADL (IADL) were investigated with questionnaires. The proportion of variation in outcomes accounted for by PRS HGS was examined using linear mixed models and extended logistic regression. Results The measured HGS increased linearly over increasing PRS (β = 4.8, SE = 0.93, P < 0.001). PRS HGS independently accounted for 6.1% of the variation in the measured HGS (β = 14.2, SE = 3.1, P < 0.001), 5.4% of the variation in knee extension strength (β = 19.6, SE = 4.7, P < 0.001), 1.2% of the variation in ankle plantarflexion strength (β = 9.4, SE = 4.2, P = 0.027), and 0.1%–1.5% of the variation in functional capacity tests (P = 0.016–0.133). Further, participants with higher PRS HGS were less likely to have ADL/IADL disabilities (odds ratio = 0.74–0.76). Conclusions Older women with genetic risk for low muscle strength were significantly weaker than those with genetic susceptibility for high muscle strength. PRS HGS was also systematically associated with overall muscle strength and proximal and distal functional outcomes that require muscle strength.
Analysis of pattern dynamics for a nonlinear model of the human cortex via bifurcation theories

This thesis examines the bifurcations, i.e., the emergent behaviours, for the Waikato cortical model under the influence of the gap-junction inhibitory diffusion D2 (identified as the Turing bifurcation parameter) and the time-to-peak for hyperpolarising GABA response γi (i.e., inhibitory rate-constant, identified as the Hopf bifurcation parameter). The cortical model simplifies the entire cortex to a cylindrical macrocolumn (∼ 1 mm) containing ∼ 10 neurons (85% excitatory, 15% inhibitory) communicating via both chemical and electrical (gap-junction) synapses. The linear stability analysis of the model equations predict the emergence of a Turing instability (in which separated areas of the cortex become activated) when gap-junction diffusivity is increased above a critical level. In addition, a Hopf bifurcation (oscillation) occurs when the inhibitory rate-constant is sufficiently small. Nonlinear interaction between these instabilities leads to spontaneous cortical patterns of neuronal activities evolving in space and time. Such model dynamics of delicately balanced interplay between Turing and Hopf instabilities may be of direct relevance to clinically observed brain dynamics such as epileptic seizure EEG spikes, deepsleep slow-wave oscillations and cognitive gamma-waves. The relationship between the modelled brain patterns and model equations can normally be inferred from the eigenvalue dispersion curve, i.e., linear stability analysis. Sometimes we experienced mismatches between the linear stability analysis and the formed cortical patterns, which hampers us in identifying the type of instability corresponding to the emergent patterns. In this thesis, I investigate the pattern-forming mechanism of the Waikato cortical model to better understand the model nonlinearities. I first study the pattern dynamics via analysis of a simple pattern-forming system, the Brusselator model, which has a similar model structure and bifurcation phenomena as the cortical model. I apply both linear and nonlinear perturbation methods to analyse the near-bifurcation behaviour of the Brusselator in order to precisely capture the dominant mode that contributes the most to the final formed-patterns. My nonlinear analysis of the Brusselator model yields Ginzburg-Landau type amplitude equations that describe the dynamics of the most unstable mode, i.e., the dominant mode, in the vicinity of a bifurcation point. The amplitude equations at a Turing point unfold three characteristic spatial structures: honeycomb Hπ, stripes, and reentrant honeycomb H0. A codimension-2 Turing–Hopf point (CTHP) predicts three mixed instabilities: stable Turing–Hopf (TH), chaotic TH,
Heterogeneity in mental health change during the COVID‐19 pandemic in Germany: The role of social factors

Abstract The COVID‐19 pandemic constitutes a prolonged global crisis, but its effects on mental health seem inconsistent. This inconsistency highlights the importance of considering the differential impact of the pandemic on individuals. There is some evidence that mental health trajectories are heterogeneous and that both sociodemographic and personal characteristics are associated with higher risk for mental health issues. By contrast, information on the role of social factors as potential determinants of initial reactions to the pandemic and on heterogeneous trajectories over time is lacking. We analysed seven assessments of a large‐scale (N = 2203) longitudinal study across 1.5 years, beginning in March 2020. Using self‐report data on mental health and life satisfaction, we applied latent change models to examine initial reactions and mean changes across the pandemic. In addition, we applied latent class growth analyses to investigate whether there were distinct groups with different patterns of change. Results showed that on average, levels of life satisfaction and anxiety decreased (d = −0.31 and d = −0.11, respectively), levels of depressive symptoms increased (d = 0.13), and stress levels remained unchanged (d = −0.01) during the first year of the pandemic. For each outcome, we identified four distinct mental health trajectories. Between 5% (for anxiety) and 11% (for life satisfaction) of the sample reported consistently high—and even increasing—impairments in mental health and well‐being. The trajectories of a sizeable number of people covaried with the course of the pandemic, such that people experienced better mental health when the number of COVID cases was low and when fewer restrictions were placed on public life. Low emotional support, high instrumental support, and the tendency to compare oneself with others were associated with more mental health issues. Findings show that whereas a substantial portion of people were largely unaffected by the pandemic, some individuals experienced consistently high levels of psychological distress. Social factors appear to play a crucial role in the maintenance of well‐being.
Population genetics of a recent range expansion and subsequent loss of migration in monarch butterflies

Range expansions—whether permanent or transient—strongly influence the distribution of genetic variation in space. Monarch butterflies are best known for long‐distance seasonal migration within North America but are also established as nonmigratory populations around the world, including on Pacific Islands. Previous research has highlighted stepwise expansion across the Pacific, though questions remain about expansion timing and the population genetic consequences of migration loss. Here, we present reduced‐representation sequencing data for 275 monarchs from North America (n = 85), 12 Pacific Islands (n = 136) and three locations in Australia (n = 54), with the goal of understanding (i) how the monarch's Pacific expansion has shaped patterns of population genetic variation and (ii) how loss of migration has influenced spatial patterns of differentiation. We find support for previously described stepwise dispersal across the Pacific and document an additional expansion from Hawaii into the Mariana Islands. Nonmigratory monarchs within the Mariana Islands show strong patterns of differentiation, despite their proximity; by contrast, migratory North American samples form a single genetically panmictic population across the continent. Estimates of Pacific establishment timing are highly uncertain (~100–1,000,000 years ago) but overlap with historical records that indicate a recent expansion. Our data support (i) a recent expansion across the Pacific whose timing overlaps with available historical records of establishment and (ii) a strong role for seasonal migration in determining patterns of spatial genetic variation. Our results are noteworthy because they demonstrate how the evolution of partial migration can drive population differentiation over contemporary timescales.
(−)-Epicatechin Reverses Glucose Intolerance in Rats Housed at Thermoneutrality

Abstract Diabetes is a life-threatening and debilitating disease with pathological hallmarks, including glucose intolerance and insulin resistance. Plant compounds are a source of novel and effective therapeutics, and the flavonoid (−)-epicatechin, common to popular foods worldwide, has been shown to improve carbohydrate metabolism in both clinical studies and preclinical models. We hypothesized that (−)-epicatechin would alleviate thermoneutral housing-induced glucose intolerance. Male rats were housed at either thermoneutral (30 °C) or room temperature (24 °C) for 16 weeks and gavaged with either 1 mg/kg body weight or vehicle for the last 15 days before sacrifice. Rats housed at thermoneutrality had a significantly elevated serum glucose area under the curve (p < 0.05) and reduced glucose-mediated insulin secretion. In contrast, rats at thermoneutrality treated with (−)-epicatechin had improved glucose tolerance and increased insulin secretion (p < 0.05). Insulin tolerance tests revealed no differences in insulin sensitivity in any of the four groups. Pancreatic immunohistochemistry staining showed significantly greater islet insulin positive cells in animals housed at thermoneutrality. In conclusion, (−)-epicatechin improved carbohydrate tolerance via increased insulin secretion in response to glucose challenge without a change in insulin sensitivity.
Warthog Genomes Resolve an Evolutionary Conundrum and Reveal Introgression of Disease Resistance Genes

Abstract African wild pigs have a contentious evolutionary and biogeographic history. Until recently, desert warthog (Phacochoerus aethiopicus) and common warthog (P. africanus) were considered a single species. Molecular evidence surprisingly suggested they diverged at least 4.4 million years ago, and possibly outside of Africa. We sequenced the first whole-genomes of four desert warthogs and 35 common warthogs from throughout their range. We show that these two species diverged much later than previously estimated, 400,000–1,700,000 years ago depending on assumptions of gene flow. This brings it into agreement with the paleontological record. We found that the common warthog originated in western Africa and subsequently colonized eastern and southern Africa. During this range expansion, the common warthog interbred with the desert warthog, presumably in eastern Africa, underlining this region’s importance in African biogeography. We found that immune system–related genes may have adaptively introgressed into common warthogs, indicating that resistance to novel diseases was one of the most potent drivers of evolution as common warthogs expanded their range. Hence, we solve some of the key controversies surrounding warthog evolution and reveal a complex evolutionary history involving range expansion, introgression, and adaptation to new diseases.
Prediction of Whole Body Discomfort on the basis of Hand Position and External Load

○cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective: The purpose of this study is to develop linear models for predicting whole body discomfort and a new external load classification scheme depending upon hand position and external load.
Plasma carnitine concentrations in Medium‐chain acyl‐CoA dehydrogenase deficiency: lessons from an observational cohort study

Our aim was to study the effect of secondary carnitine deficiency (SCD) and carnitine supplementation on important outcome measures for persons with medium‐chain Acyl–CoA dehydrogenase deficiency (MCADD). We performed a large retrospective observational study using all recorded visits of persons with MCADD in the University Medical Center Groningen, the Netherlands, between October 1994 and October 2019. Frequency and duration of acute unscheduled preventive hospital visits, exercise tolerance, fatigue, and muscle pain were considered important clinical outcomes and were studied in relation to (acyl)carnitine profile and carnitine supplementation status. The study encompassed 1228 visits of 93 persons with MCADD. >60% had SCD during follow‐up. This included only persons with severe MCADD. Carnitine supplementation and SCD were unrelated to the frequency and duration of the acute unscheduled preventive hospital visits (P > 0.05). The relative risk for fatigue, muscle ache, or exercise intolerance was equal between persons with and without SCD (RR 1.6, 95% CI 0.48–5.10, P = 0.4662). No episodes of metabolic crisis were recorded in non‐carnitine‐supplemented persons with MCADD and SCD. In some persons with MCADD, SCD resolved without carnitine supplementation. There is absence of real‐world evidence in favor of routine carnitine analysis and carnitine supplementation in the follow‐up of persons with MCADD.
A Deep Learning Method for Breast Cancer Classification in the Pathology Images

Objective: Breast cancer is the most common female cancer in the world, and it poses a huge threat to women's health. There is currently promising research concerning its early diagnosis using deep learning methodologies. However, some commonly used Convolutional Neural Network (CNN) and their variations, such as AlexNet, VGGNet, GoogleNet and so on, are prone to overfitting in breast cancer classification, due to both small-scale breast pathology image datasets and overconfident softmax-cross-entropy loss. To alleviate the overfitting issue for better classification accuracy, we propose a novel framework for breast pathology classification, called the AlexNet-BC model. The model is pre-trained using the ImageNet dataset and fine-tuned using an augmented dataset. We also devise an improved cross-entropy loss function to penalize overconfident low-entropy output distributions and make the predictions suitable for uniform distributions. The proposed approach is then validated through a series of comparative experiments on BreaKHis, IDC and UCSB datasets. The experimental results show that the proposed method outperforms the state-of-the-art methods at different magnifications. Its strong robustness and generalization capabilities make it suitable for histopathology clinical computer-aided diagnosis systems.