Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Smartphone Apps Versus Supervised Exercise on Physical Activity, Cardiorespiratory Fitness, and Body Composition Among Individuals With Mild-to-Moderate Mobility Disability: Randomized Controlled Trial

Background Adequate levels of physical activity (PA) and good cardiorespiratory fitness (CRF) are associated with profound health benefits for individuals with mobility disability (MD). Despite the vast amount of research published in the field of PA interventions, little attention has been given to individuals with MD. Objective The aim of this study was to examine the efficacy of an app-based versus a supervised exercise and health coaching program to support adults with MD to increase levels of PA, CRF, and improve body composition. Methods Participants with self-perceived MD, aged 18 to 45 years, were included in this 12-week parallel-group randomized controlled trial and allocated at random to an app-based intervention, using commercially available apps—the Swedish Military training app (FMTK), the Acupedo walking app, and the LogMyFood food photography app—or a supervised exercise and health coaching intervention, including 1 weekly supervised exercise session and healthy lifestyle coaching. The primary outcome was the level of moderate-to-vigorous PA (MVPA) measured with accelerometers. Secondary outcomes included CRF measured by a submaximal test performed on a stationary bicycle and body composition measured by bioelectrical impedance. All outcomes were measured at baseline, 6 weeks, and 12 weeks. Linear mixed-effect models were used to assess the between-group differences, as well as the within-group changes through time, in each intervention group. Results A total of 110 participants with MD were randomized to an app-based intervention (n=55) or a supervised exercise and health intervention (n=55). The mean age of participants was 34.9 years (SD 6.1), and 81.8% (90/110) of the participants were women. CRF showed a moderate increase in both groups after 12 weeks—1.07 (95% CI –0.14 to 2.27) mL/kg/min increase in the app-based group and 1.76 (95% CI 0.70 to 2.83) mLkg/min increase in the supervised exercise group. However, the intention-to-treat analysis showed no significant differences between the groups in MVPA or CRF after 12 weeks. Waist circumference was significantly lower in the app-based intervention group. Conclusions Commercially available apps increased levels of CRF and improved body composition over 12 weeks to the same extent as supervised exercise sessions, showing that both are equally effective. However, neither the app-based intervention nor the supervised exercise intervention increased MVPA. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 22387524; http://isrctn.com/ISRCTN22387524.
Validation of Deep Learning-Based Artifact Correction on Synthetic FLAIR Images in a Different Scanning Environment

We investigated the capability of a trained deep learning (DL) model with a convolutional neural network (CNN) in a different scanning environment in terms of ameliorating the quality of synthetic fluid-attenuated inversion recovery (FLAIR) images. The acquired data of 319 patients obtained from the retrospective review were used as test sets for the already trained DL model to correct the synthetic FLAIR images. Quantitative analyses were performed for native synthetic FLAIR and DL-FLAIR images against conventional FLAIR images. Two neuroradiologists assessed the quality and artifact degree of the native synthetic FLAIR and DL-FLAIR images. The quantitative parameters showed significant improvement on DL-FLAIR in all individual tissue segments and total intracranial tissues than on the native synthetic FLAIR (p < 0.0001). DL-FLAIR images showed improved image quality with fewer artifacts than the native synthetic FLAIR images (p < 0.0001). There was no significant difference in the preservation of the periventricular white matter hyperintensities and lesion conspicuity between the two FLAIR image sets (p = 0.217). The quality of synthetic FLAIR images was improved through artifact correction using the trained DL model on a different scan environment. DL-based correction can be a promising solution for ameliorating the quality of synthetic FLAIR images to broaden the clinical use of synthetic magnetic resonance imaging (MRI).
Early pubertal timing predicts onset and recurrence of depressive episodes in boys and girls.

BACKGROUND Recurrent depressive episodes during adolescence result in significant impairment and increased risk for subsequent adverse outcomes throughout the life span. Evidence suggests that early pubertal timing predicts the onset of depressive episodes (particularly for girls); however, it is not known if pubertal timing prospectively predicts recurrent depressive episodes in youth. METHODS At baseline, 603 youth (56% female, at baseline: Mage = 12.09, SD = 2.35) reported on their pubertal development. Youth and their parents completed a semistructured diagnostic interview to assess depressive episodes at baseline and then evaluated for onset repeatedly every 6 months for a period of 36 months. RESULTS Controlling for past history of depression, Cox proportional hazards models examined whether earlier pubertal timing predicted (a) days to first depressive episode from baseline and (b) days to a second (recurrent) depressive episode from the end of the first episode. Early pubertal timing predicted the onset of the first depressive episode after baseline (b = .19, Wald = 5.36, p = .02, HR = 1.21), as well as a recurrent episode during course of study follow-up episode (b = .32, Wald = 6.16, p = .01, HR = 1.38). CONCLUSIONS Findings reinforce the importance of considering the impact of early pubertal timing on depression risk. Investigation on how pubertal timing interacts with other risk factors to predict depression recurrence is needed.
Deletion of the mouse X‐linked Prame gene causes germ cell reduction in spermatogenesis

Preferentially expressed antigen in melanoma (PRAME) is cancer/testis antigen and a transcriptional repressor, inhibiting the signaling of retinoic acid through the retinoic acid receptor (RAR) for promoting cell proliferation and preventing cell apoptosis in cancer cells. The role of PRAME in testis and germline is unknown. We report here the generation and characterization of an X‐linked Prame conditional knockout (cKO) mouse. Although fertile, the testis size (p < .01) and sperm count (p < .05) of the Prame cKO mice were significantly reduced by 12% at 4 months of age compared with the Prame floxed mice. Histological, immunofluorescence with germ cell‐specific markers and terminal deoxynucleotidyl transferase dUTP nick end labeling analyses of testis cross‐sections at postnatal day 7 (P7), P14, P21, P35, P120, and P365 indicated a significant increase in apoptotic germ cells at P7 and P14 and an increase in abnormal seminiferous tubules at P21 and P35. Germ cells were gradually lost resulting in two different phenotypes in the Prame cKO testes: Sertoli‐cell‐only for some of the affected tubules in young mice (at P35) and germ cell arrest at spermatogonia stage for other affected tubules in mature mice. Both phenotypes were a consequence of disruption in RAR signaling pathway by the depletion of Prame at a different time point during the first and subsequent rounds of spermatogenesis. The results suggest that Prame plays a minor, but important role in spermatogenesis and different paralogs in the Prame gene family may be functionally and partially redundant.
Humanist chaplaincy according to Northwestern European humanist chaplains: towards a framework for understanding chaplaincy in secular societies

Abstract In this article, views on humanist chaplaincy of Northwestern European humanist chaplains are explored with a view to the question of how to understand chaplaincy in secular societies. Seventeen questionnaires were analyzed, filled in by humanist chaplains from Belgium, the UK, Ireland, and Denmark, who attended an international conference on humanist chaplaincy organized in 2015 in the Netherlands. In the Netherlands, humanist chaplaincy has a history of several decades and is meanwhile firmly integrated in public institutions; a brief overview over this history is presented. Using thematic analysis, respondents’ understandings of ‘humanist’ in humanist chaplaincy were explored, yielding 4 key themes: humanist chaplaincy as a calling, caring for all fellow human beings, belief in (inter)personal potential, and struggling with a non-supportive environment. On the basis of these themes, building blocks are proposed for a future-oriented perspective on chaplaincy that allows for open dialogue between all chaplains and identification of common ground.
Interplay between the tyrosine kinases Chk, Csk and phosphatase PTPRJ is critical for regulating platelets in mice.

The Src family kinases (SFKs) Src, Lyn and Fyn are essential for platelet activation and also involved in megakaryocyte (MK) development and platelet production. Platelet SFKs are inhibited by C-terminal Src kinase (Csk), which phosphorylates a conserved tyrosine in their C-terminal tail, and are activated by the receptor-type tyrosine phosphatase PTPRJ (CD148, DEP-1), which dephosphorylates the same residue. Deletion of Csk and PTPRJ in the MK lineage in mice results in increased SFK activity, but paradoxically hypoactive platelets due to negative feedback mechanisms, including upregulation of Csk homologous kinase (Chk) expression. Here, we investigate the role of Chk in platelets, functional redundancy with Csk and the physiological consequences of ablating Chk, Csk and PTPRJ in mice. Platelet count was normal in Chk knockout (KO) mice, reduced by 92% in Chk;Csk double KO (DKO) mice, and partially rescued in Chk;Csk;Ptprj triple KO (TKO) mice. Megakaryocyte numbers were significantly increased in both DKO and TKO mice. Phosphorylation of the inhibitory tyrosine of SFKs was almost completely abolished in DKO platelets, which was partially rescued in Src and Fyn in TKO platelets. This residual phosphorylation was abolished by Src inhibitors, revealing an unexpected mechanism in which SFKs auto-inhibit their activity by phosphorylating their C-terminal tyrosine residues. We demonstrate that reduced inhibitory phosphorylation of SFKs leads to thrombocytopenia with Csk being the dominant inhibitor in platelets, and Chk having an auxiliary role. PTPRJ deletion in addition to Chk and Csk ameliorates the extent of thrombocytopenia, suggesting targeting it may have therapeutic benefits in such conditions.
Representational Neural Mapping of Dexterous Grasping Before Lifting in Humans

The ability of humans to reach and grasp objects in their environment has been the mainstay paradigm for characterizing the neural circuitry driving object-centric actions. Although much is known about hand shaping, a persistent question is how the brain orchestrates and integrates the grasp with lift forces of the fingers in a coordinated manner. The ability of humans to reach and grasp objects in their environment has been the mainstay paradigm for characterizing the neural circuitry driving object-centric actions. Although much is known about hand shaping, a persistent question is how the brain orchestrates and integrates the grasp with lift forces of the fingers in a coordinated manner. The objective of the current study was to investigate how the brain represents grasp configuration and lift force during a dexterous object-centric action in a large sample of male and female human subjects. BOLD activity was measured as subjects used a precision-grasp to lift an object with a center of mass (CoM) on the left or right with the goal of minimizing tilting the object. The extent to which grasp configuration and lift force varied between left and right CoM conditions was manipulated by grasping the object collinearly (requiring a non-collinear force distribution) or non-collinearly (requiring more symmetrical forces). Bayesian variational representational similarity analyses on fMRI data assessed the evidence that a set of cortical and cerebellar regions were sensitive to grasp configuration or lift force differences between CoM conditions at differing time points during a grasp to lift action. In doing so, we reveal strong evidence that grasping and lift force are not represented by spatially separate functionally specialized regions, but by the same regions at differing time points. The coordinated grasp to lift effort is shown to be under dorsolateral (PMv and AIP) more than dorsomedial control, and under SPL7, somatosensory PSC, ventral LOC and cerebellar control. SIGNIFICANCE STATEMENT Clumsy disasters such as spilling, dropping, and crushing during our daily interactions with objects are a rarity rather than the norm. These disasters are avoided in part as a result of our orchestrated anticipatory efforts to integrate and coordinate grasping and lifting of object interactions, all before the lift of an object even commences. How the brain orchestrates this integration process has been largely neglected by historical approaches independently and solely focusing on reaching and grasping and the neural principles that guide them. Here, we test the extent to which grasping and lifting are represented in a spatially or temporally distinct manner and identified strong evidence for the consecutive emergence of sensitivity to grasping, then lifting within the same region.
Social Support and Subclinical Coronary Artery Disease in Middle-Aged Men and Women: Findings from the Pilot of Swedish CArdioPulmonary bioImage Study

Social support has been associated with coronary artery disease (CAD), particularly in individuals who have sustained a cardiovascular event. This study investigated the relationship between social support and subclinical CAD among 1067 healthy middle-aged men and women. Social support was assessed with validated social integration and emotional attachment measures. Subclinical CAD was assessed as a coronary artery calcium score (CACS) using computed tomography. There was no association between social support and CACS in men. In women, low social support was strongly linked to cardiovascular risk factors, high levels of inflammatory markers, and CACS > 0. In a logistic regression model, after adjustment for 12 cardiovascular risk factors, the odds ratio (95% confidence intervals) for CACS > 0 in women with the lowest social integration, emotional attachment, and social support groups (reference: highest corresponding group) were 2.47 (1.23–5.12), 1.87 (0.93–3.59), and 4.28 (1.52–12.28), respectively. Using a machine learning approach (random forest), social integration was the fourth (out of 12) most important risk factor for CACS > 0 in women. Women with lower compared to higher or moderate social integration levels were about 14 years older in “vascular age”. This study showed an association between lack of social support and subclinical CAD in middle-aged women, but not in men. Lack of social support may affect the atherosclerotic process and identify individuals vulnerable to CAD events.
Inter- and intrabreed diversity of the major histocompatibility complex (MHC) in primitive and draft horse breeds

Background Polymorphism of major histocompatibility complex (MHC) genes ensures effective immune responses against a wide array of pathogens. However, artificial selection, as performed in the case of domestic animals, may influence MHC diversity. Here, we investigate and compare the MHC diversity of three populations of horses, for which different breeding policies were applied, to evaluate the impact of artificial selection and the environment on MHC polymorphism. Methods Samples of DNA were taken from 100 Polish draft horses, 38 stabled Konik Polski horses and 32 semiferal Konik Polski horses. MHC alleles and haplotype diversity within and between these populations of horses was estimated from 11 MHC microsatellite loci. Results MHC diversity measured based on allelic richness, observed heterozygosity, expected heterozygosity and polymorphism content was similar across the MHC microsatellite loci in all three populations. The highest expected heterozygosity was detected in semiferal primitive horses (He = 0.74), while the lowest was calculated for draft horses (He = 0.65). In total, 203 haplotypes were determined (111 in Polish draft horses, 43 in semiferal Konik Polski horses and 49 in stabled Konik Polski horses), and four haplotypes were shared between the two populations of Koniks. None of these haplotypes were present in any of the previously investigated horse breeds. Intra-MHC recombination events were detected in all three populations. However, the population of semiferal Konik horses showed the highest recombination frequency among the three horse populations. In addition, three recombination events were detected. Conclusions These results showed that despite the different breeding policies, the MHC allele and haplotype diversity was similarly high in all three horse populations. Nevertheless, the proportion of new haplotypes in the offspring was the highest in semiferal Konik Polski horses, which indicates the influence of the environment on MHC diversity in horses. Thus, we speculate that the genetic makeup of the domestic horse MHC might be more strongly influenced by the environment than by artificial selection. Moreover, intra-MHC conversion, insertion, and deletion and intra-MHC recombination may be proposed as mechanisms underlying the generation of new MHC haplotypes in horses.
Differential Depletion of Bone Marrow Resident B-ALL after Systemic Administration of Endosomal TLR Agonists

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. While frontline chemotherapy regimens are generally very effective, the prognosis for patients whose leukemia returns remains poor. The presence of measurable residual disease (MRD) in bone marrow at the completion of induction therapy is the strongest predictor of relapse, suggesting that strategies to eliminate the residual leukemic blasts from this niche could reduce the incidence of recurrence. We have previously reported that toll-like receptor (TLR) agonists achieve durable T cell-mediated protection in transplantable cell line-based models of B cell precursor leukemia (B-ALL). However, the successful application of TLR agonist therapy in an MRD setting would require the induction of anti-leukemic immune activity specifically in the bone marrow, a site of the chemotherapy-resistant leukemic blasts. In this study, we compare the organ-specific depletion of human and mouse primary B-ALL cells after systemic administration of endosomal TLR agonists. Despite comparable splenic responses, only the TLR9 agonist induced strong innate immune responses in the bone marrow and achieved a near-complete elimination of B-ALL cells. This pattern of response was associated with the most significantly prolonged disease-free survival. Overall, our findings identify innate immune activity in the bone marrow that is associated with durable TLR-induced protection against B-ALL outgrowth.
EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma

The transcription factor EVI1 plays an oncogenic role in several types of neoplasms by promoting aggressive cancer features. EVI1 contributes to epigenetic regulation and transcriptional control, and its overexpression has been associated with enhanced PI3K-AKT-mTOR signaling in some settings. These observations raise the possibility that EVI1 influences the prognosis and everolimus-based therapy outcome of clear cell renal cell carcinoma (ccRCC). Here, gene expression and protein immunohistochemical studies of ccRCC show that EVI1 overexpression is associated with advanced disease features and with poorer outcome—particularly in the CC-e.3 subtype defined by The Cancer Genome Atlas. Overexpression of an oncogenic EVI1 isoform in RCC cell lines confers substantial resistance to everolimus. The EVI1 rs1344555 genetic variant is associated with poorer survival and greater progression of metastatic ccRCC patients treated with everolimus. This study leads us to propose that evaluation of EVI1 protein or gene expression, and of EVI1 genetic variants may help improve estimates of prognosis and the benefit of everolimus-based therapy in ccRCC.
Modeling How Humans Judge Dot-Label Relations in Point Cloud Visualizations

When point clouds are labeled in information visualization applications, sophisticated guidelines as in cartography do not yet exist. Existing naive strategies may mislead as to which points belong to which label. To inform improved strategies, we studied factors influencing this phenomenon. We derived a class of labeled point cloud representations from existing applications and we defined different models predicting how humans interpret such complex representations, focusing on their geometric properties. We conducted an empirical study, in which participants had to relate dots to labels in order to evaluate how well our models predict. Our results indicate that presence of point clusters, label size, and angle to the label have an effect on participants’ judgment as well as that the distance measure types considered perform differently discouraging the use of label centers as reference points.
Cancer Prevention Using Machine Learning, Nudge Theory and Social Impact Bond

There have been prior attempts to utilize machine learning to address issues in the medical field, particularly in diagnoses using medical images and developing therapeutic regimens. However, few cases have demonstrated the usefulness of machine learning for enhancing health consciousness of patients or the public in general, which is necessary to cause behavioral changes. This paper describes a novel case wherein the uptake rate for colorectal cancer examinations has significantly increased due to the application of machine learning and nudge theory. The paper also discusses the effectiveness of social impact bonds (SIBs) as a scheme for realizing these applications. During a healthcare SIB project conducted in the city of Hachioji, Tokyo, machine learning, based on historical data obtained from designated periodical health examinations, digitalized medical insurance receipts, and medical examination records for colorectal cancer, was used to deduce segments for whom the examination was recommended. The result revealed that out of the 12,162 people for whom the examination was recommended, 3264 (26.8%) received it, which exceeded the upper expectation limit of the initial plan (19.0%). We conclude that this was a successful case that stimulated discussion on potential further applications of this approach to wider regions and more diseases.