Miracle-dz/UniFAR-FTUs huggingface dataset:
Voluntary suppression of associated activity decreases force steadiness in the active hand

Unilateral muscle contractions are often accompanied by the activation of the ipsilateral hemisphere, producing associated activity (AA) in the contralateral homologous muscles. However, the functional role of AA is not fully understood. We determined the effects of voluntary suppression of AA in the first dorsal interosseous (FDI), on force steadiness during a constant force isometric contraction of the contralateral FDI. Participants (n = 17, 25.5 years) performed two trials of isometric FDI contractions as steadily as possible. In Trial 1, they did not receive feedback or explicit instructions for suppressing the AA in the contralateral homologous FDI. In Trial 2, participants received feedback and were asked to voluntarily suppress the AA in the contralateral nontarget FDI. During both trials, corticospinal excitability and motor cortical inhibition were measured. The results show that participants effectively suppressed the AA in the nontarget contralateral FDI (−71%), which correlated with reductions in corticospinal excitability (−57%), and the suppression was also accompanied by increases in inhibition (27%) in the ipsilateral motor cortex. The suppression of AA impaired force steadiness, but the decrease in force steadiness did not correlate with the magnitude of suppression. The results show that voluntary suppression of AA decreases force steadiness in the active hand. However, due to the lack of association between suppression and decreased steadiness, we interpret these data to mean that specific elements of the ipsilateral brain activation producing AA in younger adults are neither contributing nor detrimental to unilateral motor control during a steady isometric contraction.
MuRF1 deficiency prevents age‐related fat weight gain, possibly through accumulation of PDK4 in skeletal muscle mitochondria in older mice

Recent studies show that muscle mass and metabolic function are interlinked. Muscle RING finger 1 (MuRF1) is a critical muscle‐specific ubiquitin ligase associated with muscle atrophy. Yet, the molecular target of MuRF1 in atrophy and aging remains unclear. We examined the role of MuRF1 in aging, using MuRF1‐deficient (MuRF1–/–) mice in vivo, and MuRF1‐overexpressing cell in vitro. MuRF1 deficiency partially prevents age‐induced skeletal muscle loss in mice. Interestingly, body weight and fat mass of more than 7‐month‐old MuRF1–/– mice were lower than in MuRF1+/+ mice. Serum and muscle metabolic parameters and results of indirect calorimetry suggest significantly higher energy expenditure and enhanced lipid metabolism in 3‐month‐old MuRF1–/– mice than in MuRF1+/+ mice, resulting in suppressed adipose tissue gain during aging. Pyruvate dehydrogenase kinase 4 (PDK4) is crucial for a switch from glucose to lipid metabolism, and the interaction between MuRF1 and PDK4 was examined. PDK4 protein levels were elevated in mitochondria from the skeletal muscle in MuRF1–/– mice. In vitro, MuRF1 interacted with PDK4 but did not induce degradation through ubiquitination. Instead, SUMO posttranscriptional modification (SUMOylation) of PDK4 was detected in MuRF1‐overexpressing cells, in contrast to cells without the RING domain of MuRF1. MuRF1 deficiency enhances lipid metabolism possibly by upregulating PDK4 localization into mitochondrial through prevention of SUMOylation. Inhibition of MuRF1‐mediated PDK4 SUMOylation is a potential therapeutic target for age‐related dysfunction of lipid metabolism and muscle atrophy.
Cytokeratin 5 and cytokeratin 20 inversely correlate with tumour grading in Ta non‐muscle‐invasive bladder cancer

Cytokeratin 5 is a marker of basal molecular subtypes of muscle‐invasive bladder cancer (MIBC), which correlates with worse overall survival compared to luminal subtypes. Our observations have not confirmed CK5 as a marker of high‐grade (HG) disease in Ta non‐muscle‐invasive bladder cancer (NMIBC). Therefore, to understand the basal‐luminal immunohistochemistry profile in Ta NMIBC, we performed immunohistochemistry for CK5, P40, P63 (basal), GATA3 and CK20 (luminal) and studied the correlation with HG and clinical outcome in 109 patients with Ta NMIBC. HG and low‐grade (LG) diseases were scored in each patient. Four different CK5 patterns were evaluated: absent (median 41.3%), normal (72.5%), rising (84.4%) and full thickness (23.9%). The median percentage of GATA3 was 100%. HG disease and CK5 expression and rising CK5 pattern had a significant inverse correlation, whereas HG disease and CK20 expression had a significant positive correlation. We also found a significant inverse correlation between CK5 expression and CK20 expression. Quantitative PCR confirmed that the presence of CK5 correlated with up‐regulation of CK5 RNA. None of the markers could differentiate patients with regard to clinical outcome. Our results suggest a role for CK5 and CK20 in differentiating between LG and HG disease in Ta NMIBC.
The effectiveness of weighted blankets on sleep and everyday activities – A retrospective follow-up study of children and adults with attention deficit hyperactivity disorder and/or autism spectrum disorder

Abstract Background Attention deficit hyperactivity disorder (ADHD) and Autism Spectrum Disorder (ASD) are often accompanied by sleep problems influencing social, emotional and cognitive functioning in everyday activities. Aim The aim of this study was to investigate whether the use of a weighted blanket has a positive impact on sleep and everyday activities in individuals with ADHD and/or ASD. Material and methods The study included 85 individuals diagnosed with ADHD and/or ASD, 48 children aged ≤17 (57%) and 37 adults ≥18 years (44%), who were prescribed with a weighted blanket. The participants responded via a telephone interview. Results Findings demonstrated that a weighted blanket improved abilities related to falling asleep, sleeping the whole night, and relaxing during the day. Using a weighted blanket improved morning/evening daily routine, including preparing/going to sleep and waking up in the morning. Conclusions Weighted blankets showed positive impact on falling asleep, sleeping the whole night, and relaxing during the day, and they were used frequently by children and adults with ADHD and/or ASD. Findings indicate that a weighted blanket improved morning/evening routine, however this research area needs further investigation using both subjective and objective parameters.
Long-term assessment of airborne radiocesium after the Fukushima nuclearaccident: re-suspension from bare soil and forest ecosystems

Abstract. The long-term effect of 137Cs re-suspension from contaminated soil and forests due to the Fukushima nuclear accident has been quantitatively assessed by numerical simulation, a field experiment on dust emission flux in a contaminated area (town of Namie, Fukushima prefecture), and air concentration measurements inside (Namie) and outside (city of Tsukuba, Ibaraki prefecture) the contaminated area. In order to assess the long-term effect, the full year of 2013 was selected to study just after the start of the field experiments. The 137Cs concentrations at Namie and Tsukuba were approximately 10−1–1 and 10−2–10−1 mBq m−3, respectively. The observed monthly median concentration at Namie was 1 to 2 orders of magnitude larger than that at Tsukuba. This observed difference between the two sites was consistent with the simulated difference, indicating successful modeling of 137Cs re-suspension and atmospheric transport. The estimated re-suspension rate was approximately 10−6 day−1, which was significantly lower than the decreasing rate of the ambient gamma dose rate in Fukushima prefecture (10−4–10−3 day−1) as a result of radioactive decay, migration in the soil and biota, and decontamination. Consequently, re-suspension contributed negligibly in reducing ground radioactivity. The dust emission model could reproduce the air concentration of 137Cs in winter, whereas the summer air concentration was underestimated by 1 to 2 orders of magnitude. Re-suspension from forests at a constant rate of 10−7 h−1, multiplied by the green area fraction, could explain the air concentration of 137Cs at Namie and its seasonal variation. The simulated contribution of dust re-suspension to the air concentration was 0.7–0.9 in the cold season and 0.2–0.4 in the warm season at both sites; the remainder of the contribution was re-suspension from forest. The re-suspension mechanisms, especially through the forest ecosystems, remain unknown. This is the first study that provides a crude estimation of the long-term assessment of radiocesium re-suspension. Additional research activities should investigate the processes/mechanisms governing the re-suspension over the long term. This could be achieved through conducting additional field experiments and numerical simulations.
Entrustment Unpacked: Aligning Purposes, Stakes, and Processes to Enhance Learner Assessment

Educators use entrustment, a common framework in competency-based medical education, in multiple ways, including frontline assessment instruments, learner feedback tools, and group decision making within promotions or competence committees. Within these multiple contexts, entrustment decisions can vary in purpose (i.e., intended use), stakes (i.e., perceived risk or consequences), and process (i.e., how entrustment is rendered). Each of these characteristics can be conceptualized as having 2 distinct poles: (1) purpose has formative and summative, (2) stakes has low and high, and (3) process has ad hoc and structured. For each characteristic, entrustment decisions often do not fall squarely at one pole or the other, but rather lie somewhere along a spectrum. While distinct, these continua can, and sometimes should, influence one another, and can be manipulated to optimally integrate entrustment within a program of assessment. In this article, the authors describe each of these continua and depict how key alignments between them can help optimize value when using entrustment in programmatic assessment within competency-based medical education. As they think through these continua, the authors will begin and end with a case study to demonstrate the practical application as it might occur in the clinical learning environment.
Experiential avoidance in non-suicidal self-injury and suicide experiences: A systematic review and meta-analysis.

INTRODUCTION This systematic review and meta-analysis aimed to (i) examine the associations between experiential avoidance (EA), non-suicidal self-injury (NSSI), and suicide experiences, and (ii) identify sample- and methodological-related variables affecting the strength of these associations. METHOD Medline, Embase, PsychINFO, Web of Science, and CINAHL were searched until April 2020. Random-effect meta-analyses were applied. The I2 statistic and the Egger's test assessed heterogeneity and publication bias. Meta-regression analyses were used to evaluate the impact of moderator variables on the strength of these associations. RESULTS Data from 19 independent studies based on n = 9900 participants were pooled. The analyses demonstrated a weak but significant association between EA and NSSI. None of the examined moderator variables influenced the strength of this relationship. There was an indication of publication bias, suggesting that this association may have been inflated. The associations between EA, and suicide ideation and behaviors were moderate to strong. DISCUSSION The current study concluded that (i) the EA model for NSSI should be revised by incorporating new evidence implicating feelings of relief in NSSI, and (ii) future studies should examine interactive factors between EA and key psychological components in the pathways to suicide experiences because these findings have direct clinical implications.
Fusobacterium nucleatum secretes amyloid‐like FadA to enhance pathogenicity

Fusobacterium nucleatum (Fn) is a Gram‐negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2‐like autotransporter to enhance its virulence. The extracellular FadA binds Congo Red, Thioflavin‐T, and antibodies raised against human amyloid β42. Fn produces amyloid‐like FadA under stress and disease conditions, but not in healthy sites or tissues. It functions as a scaffold for biofilm formation, confers acid tolerance, and mediates Fn binding to host cells. Furthermore, amyloid‐like FadA induces periodontal bone loss and promotes CRC progression in mice, with virulence attenuated by amyloid‐binding compounds. The uncleaved signal peptide of FadA is required for the formation and stability of mature amyloid FadA fibrils. We propose a model in which hydrophobic signal peptides serve as “hooks” to crosslink neighboring FadA filaments to form a stable amyloid‐like structure. Our study provides a potential mechanistic link between periodontal disease and CRC and suggests anti‐amyloid therapies as possible interventions for Fn‐mediated disease processes.
Don’t be STUMPed: description and management of uncommon pathologies encountered on specimens from benign gynecologic surgery

Purpose of review In this review, we aim to describe uncommon pathologies that gynecologic surgeons may reasonably encounter on surgical specimens following benign gynecologic surgery. Recent findings Herein, we describe uncommon pathologic findings of the uterus (e.g. squamous morular metaplasia, fibroid variants, stromal tumor of uncertain malignant potential), peritoneum and adnexa (e.g. endosalpingiosis, serous tubal intraepithelial carcinoma), endometriosis (e.g. stromal endometriosis, atypical endometriosis), and findings of particular interest in postmenopausal women (e.g. ovarian cortical stromal hyperplasia, tubal metaplasia). The majority of pathologic findings presented in this article are inherently benign, although they can present diagnostic challenges. If properly classified, additional treatment and/or extended follow-up is often not required; exceptions are highlighted. Summary The gynecologic surgeon may encounter uncommon pathologies during a career. Inherent diagnostic difficulties, as well as nonstandardized or outdated terminology, can introduce further uncertainty. Whenever such a situation arises, the surgeon and pathologist should discuss the diagnosis to ensure appropriate treatment options.
Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells

How cells count and regulate organelle number is a fundamental question in cell biology. For example, most cells restrict centrioles to two in number and assemble one cilium; however, multiciliated cells (MCCs) synthesize hundreds of centrioles to assemble multiple cilia. Aberration in centriole/cilia number impairs MCC function and can lead to pathological outcomes. Yet how MCCs control centriole number remains unknown. Using Xenopus, we demonstrate that centriole number scales with apical area over a remarkable 40-fold change in size. We find that tensile forces that shape the apical area also trigger centriole amplification based on both cell stretching experiments and disruption of embryonic elongation. Unexpectedly, Piezo1, a mechanosensitive ion channel, localizes near each centriole suggesting a potential role in centriole amplification. Indeed, depletion of Piezo1 affects centriole amplification and disrupts its correlation with the apical area in a tension-dependent manner. Thus, mechanical forces calibrate cilia/centriole number to the MCC apical area via Piezo1. Our results provide new perspectives to study organelle number control essential for optimal cell function.
Male and Female Conceptualizations of Sexual Harassment in Tanzania: The Role of Consent, Male Power, and Social Norms

Sexual harassment is pervasive worldwide, yet there is a lack of clarity on its conceptualization in many settings, especially in low-income countries. Context-specific conceptualization of sexual harassment is vital to develop effective measurement tools, estimate its magnitude, and the design of interventions to address it. We explored how different population groups in Mwanza, Tanzania, understood, conceptualized, and experienced sexual harassment. This study employed a qualitative research design involving 74 in-depth interviews and 13 focus group discussions with participants from educational, workplace, and public settings in Mwanza, Tanzania. Participants were adolescent girls and boys, adult women and men. We explored individual-level perceptions and experiences of sexual harassment, and community norms and expectations around sexual harassment. We analyzed the data using a thematic approach. Participants’ perceptions of sexual harassment emphasized the critical role of consent, the expression of male power, and social norms with regard to sexual harassment. Sexual harassment was understood to be a result of men being in positions of power and in charge of material resources, school grades, or employment opportunities. These in turn enabled them to take advantage of girls and women. Social norms around male and female interactions, courtship and seduction, expressions of sexual interest were crucial in delineating what was and what was not considered sexual harassment. Sexual harassment is a fluid concept, and its definition is highly dependent on contextual factors. Consent underpins the conceptualization of sexual harassment and is a fundamental feature in the definition and measurement of sexual harassment in Tanzania. Consent is largely determined by sexual norms around male and female interactions and gendered power. There is a need for consensus in schools, workplaces, and communities about what constitutes sexual harassment in order to measure and address it appropriately.
Standardizing the Development of Serious Games for Physical Rehabilitation: Conceptual Framework Proposal

Background Serious games have been used as supportive therapy for traditional rehabilitation. However, most are designed without a systematic process to guide their development from the phases of requirement identification, planning, design, construction, and evaluation, which reflect the lack of adaptation of rehabilitation requirements and thus the patient’s needs. Objective The aim of this study was to propose a conceptual framework with standardized elements for the development of information systems by using a flexible and an adaptable process centered on the patient’s needs and focused on the creation of serious games for physical rehabilitation. Methods The conceptual framework is based on 3 fundamental concepts: (1) user-centered design, which is an iterative design process focused on users and their needs at each phase of the process, (2) generic structural activities of software engineering, which guides the independent development process regardless of the complexity or size of the problem, and (3) gamification elements, which allow the transformation of obstacles into positive and fun reinforcements, thereby encouraging patients in their rehabilitation process. Results We propose a conceptual framework to guide the development of serious games through a systematic process by using an iterative and incremental process applying the phases of context identification, user requirements, planning, design, construction of the interaction devices and video game, and evaluation. Conclusions This proposed framework will provide developers of serious games a systematic process with standardized elements for the development of flexible and adaptable software with a high level of patient commitment, which will effectively contribute to their rehabilitation process.
Allelic diversification after transposable element exaptation promoted gsdf as the master sex determining gene of sablefish

Concepts of evolutionary biology suggest that morphological change may occur by rare punctual but rather large changes, or by more steady and gradual transformations. It can therefore be asked whether genetic changes underlying morphological, physiological, and/or behavioral innovations during evolution occur in a punctual manner, whereby a single mutational event has prominent phenotypic consequences, or if many consecutive alterations in the DNA over longer time periods lead to phenotypic divergence. In the marine teleost, sablefish (Anoplopoma fimbria), complementary genomic and genetic studies led to the identification of a sex locus on the Y Chromosome. Further characterization of this locus resulted in identification of the transforming growth factor, beta receptor 1a (tgfbr1a) gene, gonadal somatic cell derived factor (gsdf), as the main candidate for fulfilling the master sex determining (MSD) function. The presence of different X and Y Chromosome copies of this gene indicated that the male heterogametic (XY) system of sex determination in sablefish arose by allelic diversification. The gsdfY gene has a spatio-temporal expression profile characteristic of a male MSD gene. We provide experimental evidence demonstrating a pivotal role of a transposable element (TE) for the divergent function of gsdfY. By insertion within the gsdfY promoter region, this TE generated allelic diversification by bringing cis-regulatory modules that led to transcriptional rewiring and thus creation of a new MSD gene. This points out, for the first time in the scenario of MSD gene evolution by allelic diversification, a single, punctual molecular event in the appearance of a new trigger for male development.
Contributions of the international plant science community to the fight against infectious diseases in humans—part 2: Affordable drugs in edible plants for endemic and re‐emerging diseases

Summary The fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded health systems and often requiring international interventions. The provision of vaccines and other biologics is hampered not only by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, but also by challenges caused by distribution and storage, particularly in regions without a complete cold chain. In this review article, we consider the potential of molecular farming to address the challenges of endemic and re‐emerging diseases, focusing on edible plants for the development of oral drugs. Key recent developments in this field include successful clinical trials based on orally delivered dried leaves of Artemisia annua against malarial parasite strains resistant to artemisinin combination therapy, the ability to produce clinical‐grade protein drugs in leaves to treat infectious diseases and the long‐term storage of protein drugs in dried leaves at ambient temperatures. Recent FDA approval of the first orally delivered protein drug encapsulated in plant cells to treat peanut allergy has opened the door for the development of affordable oral drugs that can be manufactured and distributed in remote areas without cold storage infrastructure and that eliminate the need for expensive purification steps and sterile delivery by injection.