Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Immuno-Oncologic Biomarkers Is Enriched in Colorectal Cancers and Other Solid Tumors Harboring the A59T Variant of KRAS

The molecular heterogeneity of KRAS is well established, with a pool of variants comprising >75% of all known mutations; this pool includes mutations in classic codons 12, 13, and 61, as well as 146 and 117. In addition, there are rare variants that are more frequently encountered clinically due to the advances in next-generation sequencing and more widespread implementation of All-RAS sequencing over the past five years. We have previously identified a missense variant of KRAS, A59T, in a patient with CRC that was associated with a response to an epidermal growth factor inhibitor when added to chemotherapy, supporting the hypothesis that distinct biochemical impacts of different KRAS mutations may produce varied responses to targeted therapy. In this study, we explored a large genomic database comprising 17,909 cases of CRC to determine the prevalence of the A59T mutation and characterized the concurrent genomic alterations associated with this variant in more detail, particularly in relation to the expanding set of potential predictive immuno-oncologic biomarkers. We identified 14 cases of A59 mutations in this dataset (0.08% prevalence). We evaluated the prevalence of high tumor mutation burden (TMB), positive PD-L1 expression, and microsatellite instability-high/mismatch repair-deficiency (MSI-H/dMMR) using both next generation sequencing (NGS) and immunohistochemistry (IHC). The genomic features of pertinent signaling pathways were also described, including RAS pathway, chromatin remodeling, DDR, hedgehog signaling, PI3K, receptor tyrosine kinases, signal transduction, TGF-beta, TP53, and WNT. We uncovered a high level of association of predictive markers of responsiveness to checkpoint inhibition and potentially other forms of immunotherapy, with nearly half of all cases harboring microsatellite instability as assessed using NGS. A59T was also detected in 11 additional cancer types, most prominently in cases of gynecologic or other gastrointestinal sites of origin. This study provides supportive evidence that A59T, and possibly other similarly rare KRAS variants, co-occur with predictive biomarkers of response to immunotherapy.
Tumor Recurrence and Graft Survival in Renal Transplant Recipients with a History of Pretransplant Malignancy: A Matched Pair Analysis

Organ scarcity demands critical decision-making regarding eligible transplant candidates and graft allocation to ensure best benefit from renal transplantation (RTx). Among the controversial relative contraindications is a history of pretransplant malignancy (PTM). While oncological outcomes of PTM-RTx recipients are well described, data on graft-specific outcome are scarce. A retrospective double case control matched pair analysis (60 months follow-up) was carried out and RTx-recipients were stratified for history of PTM. First, PTM-RTx recipients were matched according to age, sex and duration of immunosuppressive therapy. Next, PTM-RTx recipients were matched 1:1 for age, sex and cause of end-stage renal disease. Five-year patient and graft survival as well as oncological outcomes were analyzed. A total of 65 PTM-RTx recipients were identified. Post-RTx recurrence rate was 5%, while 20% developed second de novo malignancy, comparable to 14% in the control group. PTM-RTx recipients had a noticeable lower five-year death-censored as well as overall graft survival and Cox proportional hazard modeling showed a correlation between PTM and inferior graft survival. Although underlying reasons remain not fully understood, this study is the first to show inferior graft survival in PTM-RTx recipients and advocates necessity to focus on more meticulous graft monitoring in PTM recipients in addition to heightened surveillance for cancer recurrence.
A Novel Modified Super-Twisting Control Augmented Feedback Linearization for Wearable Robotic Systems Using Time Delay Estimation

The research presents a novel controller designed for robotic systems subject to nonlinear uncertain dynamics and external disturbances. The control scheme is based on the modified super-twisting method, input/output feedback linearization, and time delay approach. In addition, to minimize the chattering phenomenon and ensure fast convergence to the selected sliding surface, a new reaching law has been integrated with the control law. The control scheme aims to provide high performance and enhanced accuracy via limiting the effects brought by the presence of uncertain dynamics. Stability analysis of the closed-loop system was conducted using a powerful Lyapunov function, showing finite time convergence of the system’s errors. Lastly, experiments shaping rehabilitation tasks, as performed by healthy subjects, demonstrated the controller’s efficiency given its uncertain nonlinear dynamics and the external disturbances involved.
Vitamin D: Current Challenges between the Laboratory and Clinical Practice

Vitamin D is a micronutrient with pleiotropic effects in humans. Due to sedentary lifestyles and increasing time spent indoors, a growing body of research is revealing that vitamin D deficiency is a global problem. Despite the routine measurement of vitamin D in clinical laboratories and many years of efforts, methods of vitamin D analysis have yet to be standardized and are burdened with significant difficulties. This review summarizes several key analytical and clinical challenges that accompany the current methods for measuring vitamin D. According to an external quality assessment, methods and laboratories still produce a high degree of variability. Structurally similar metabolites are a source of significant interference. Furthermore, there is still no consensus on the normal values of vitamin D in a healthy population. These and other problems discussed herein can be a source of inconsistency in the results of research studies.
Melatonin for Neonatal Encephalopathy: From Bench to Bedside

Neonatal encephalopathy is a leading cause of morbidity and mortality worldwide. Although therapeutic hypothermia (HT) is now standard practice in most neonatal intensive care units in high resource settings, some infants still develop long-term adverse neurological sequelae. In low resource settings, HT may not be safe or efficacious. Therefore, additional neuroprotective interventions are urgently needed. Melatonin’s diverse neuroprotective properties include antioxidant, anti-inflammatory, and anti-apoptotic effects. Its strong safety profile and compelling preclinical data suggests that melatonin is a promising agent to improve the outcomes of infants with NE. Over the past decade, the safety and efficacy of melatonin to augment HT has been studied in the neonatal piglet model of perinatal asphyxia. From this model, we have observed that the neuroprotective effects of melatonin are time-critical and dose dependent. Therapeutic melatonin levels are likely to be 15–30 mg/L and for optimal effect, these need to be achieved within the first 2–3 h after birth. This review summarises the neuroprotective properties of melatonin, the key findings from the piglet and other animal studies to date, and the challenges we face to translate melatonin from bench to bedside.
Nucleoporin TPR Affects C2C12 Myogenic Differentiation via Regulation of Myh4 Expression

The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of transcription; however, the role of TPR in gene expression and cell differentiation has not been described. Here we show that depletion of TPR results in an aberrant morphology of murine proliferating C2C12 myoblasts (MBs) and differentiated C2C12 myotubes (MTs). The ChIP-Seq data revealed that TPR binds to genes linked to muscle formation and function, such as myosin heavy chain (Myh4), myocyte enhancer factor 2C (Mef2C) and a majority of olfactory receptor (Olfr) genes. We further show that TPR, possibly via lysine-specific demethylase 1 (LSD1), promotes the expression of Myh4 and Olfr376, but not Mef2C. This provides a novel insight into the mechanism of myogenesis; however, more evidence is needed to fully elucidate the mechanism by which TPR affects specific myogenic genes.
Effect of You-Gui-Wan on House Dust Mite-Induced Mouse Allergic Asthma via Regulating Amino Acid Metabolic Disorder and Gut Dysbiosis

Chinese herbal remedies have long been used for enhancing immunity and treating asthma. However, the evidence-based efficacy remains to be supported. This study aimed to explore the potential bio-signatures in allergic asthma and the effect of You-Gui-Wan (YGW), a traditional Chinese herbal prescription, on dust mite-induced mouse allergic asthma. Extract of Dermatophagoides pteronyssinus (Der p), a dust mite, was intratracheally administered to induce allergic asthma in mice. Serum metabolomic and 16S rRNA-based microbiome profiling were used to analyze untargeted metabolites with levels significantly changed and gut microbiota composition, respectively. Results indicated that 10 metabolites (acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine), mainly associated with branched-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism were markedly elevated after Der p treatment. YGW administration reversed the levels for 7 of the 10 identified metabolites, chiefly affecting BCAA metabolism. On 16S DNA sequencing, disordered Der p-induced gut microbiota was significantly alleviated by YGW. Multiple correlation analysis showed a good correlation between gut microbiota composition and levels of selected metabolites. Our study showed YGW administration effectively alleviated BCAA metabolic disorder and improved gut dysbiosis. This study provides support for YGW administration with benefits for allergic asthma.
Clinical Guideline-Guided Outcome Consistency for Surgically Resected Stage III Non-Small Cell Lung Cancer: A Retrospective Study

Simple Summary Evidence-based guidelines provide valuable management recommendations that can significantly improve patient treatment and outcome, thereby reducing clinical variability. Recent clinical trials demonstrated that personalised treatments based on genomic and immune profiles can contribute to the prognosis of non-small cell lung cancer (NSCLC). This retrospective study investigated whether guideline-consistency, including adjuvant treatments after surgical resection (ATSR) and guideline-matched first-line treatment for recurrence (GMT-R), could influence overall survival (OS). From 2006 to 2017, 308 patients with pathological stage III NSCLC were eligible, among whom 207 (67.2%) recurrence cases were identified. ATSR and GMT-R were allowed in 164 (53.2%) and 129 (62.3%) cases, respectively. The 5-year OS in guideline-consistent cases receiving ATSR and GMT-R was significantly better than that in guideline-inconsistent cases (p < 0.01). Subgroup analyses further revealed that the 5-year OS after propensity adjustment was significantly better in guideline-consistent than in guideline-inconsistent cases (p < 0.01). Hence, guideline-consistent treatment alternatives effectively contribute to better outcomes. Abstract Clinical guidelines can help reduce the use of inappropriate therapeutics due to localism and individual clinician perspectives. Nevertheless, despite the intention of clinical guidelines to achieve survival benefit or desirable outcomes, they cannot ensure a robust outcome. This retrospective study aimed to investigate whether guideline-consistency, including adjuvant treatments after surgical resection (ATSR) and guideline-matched first-line treatment for recurrence (GMT-R), according to the genomic profiles and immune status, could influence overall survival (OS). From 2006 to 2017, the clinical data of 308 patients with stage III non-small cell lung cancer (NSCLC) after surgical resection were evaluated. ATSR and GMT-R were allowed in 164 (53.2%) and 129 (62.3%) patients cases after surgical pulmonary resection, among which 207 (67.2%) recurrences were identified. The 5-year OS in guideline-consistent cases was significantly better than that in guideline-inconsistent cases (p < 0.01). Subgroup analyses further showed that the 5-year OS after propensity adjustment was significantly better in guideline-consistent than in guideline-inconsistent cases (p < 0.01), but not in either ATSR or GMT-R (p = 0.24). These data suggest that the guideline-consistent alternatives, which comprise ATSR or GMT-R, can contribute to survival benefits in pathological stage III NSCLC. However, only either ATSR or GMT-R has a potential survival benefit in these patients.
Left and Right Myocardial Functionality Assessed by Two-Dimensional Speckle-Tracking Echocardiography in Cats with Restrictive Cardiomyopathy

Simple Summary The endomyocardial form of restrictive cardiomyopathy, a primary disorder of the myocardium, is one of the diseases with poor prognosis in cats. While two-dimensional speckle-tracking echocardiography has been known to identify myocardial deformations, its function relative to cats with the endomyocardial form of restrictive cardiomyopathy has yet to be characterized. We hypothesized that both the left and right myocardial functional abnormalities may occur in cats with the endomyocardial form of restrictive cardiomyopathy, causing this disease pathophysiology and clinical status. In the current study, cats were assessed for layer-specific myocardial function (whole, endocardial, and epicardial) in the left ventricular longitudinal and circumferential directions, and right ventricular longitudinal direction, via two-dimensional speckle-tracking echocardiography. Our study indicated that cats with restrictive cardiomyopathy have reduced left ventricular myocardial function. Notably, left ventricular systolic circumferential endocardial strain and circumferential endocardial-to-epicardial strain ratio were lower in cats with restrictive cardiomyopathy. Furthermore, some right ventricular myocardial deformations were also differerent in cats with restrictive cardiomyopathy. Myocardial function assessed by two-dimensional speckle-tracking echocardiography could reveal left and right myocardial dysfunction. Abstract The endomyocardial form of restrictive cardiomyopathy (EMF-RCM), a primary disorder of the myocardium, is one of the diseases with poor prognosis in cats. We hypothesized that both the left and right myocardial functional abnormalities may occur in cats with EMF-RCM, causing this disease pathophysiology and clinical status. Out of the 25 animals included in this study, 10 were client-owned cats with EMF-RCM, and 15 were healthy cats. In this study, cats were assessed for layer-specific myocardial function (whole, endocardial, and epicardial) in the left ventricular longitudinal and circumferential directions, and right ventricular longitudinal direction, via two-dimensional speckle-tracking echocardiography (2D-STE). Cats with EMF-RCM had depressed left ventricular myocardial deformations both in systole (whole longitudinal strain, epicardial longitudinal strain, and endocardial circumferential strain) and diastole (early and late diastolic longitudinal strain rates, and late diastolic circumferential strain rate) compared to controls. Furthermore, some right ventricular myocardial deformations (systolic longitudinal strain in epicardial layers, and endocardial-to-epicardial strain ratio) were significantly differerent in cats with EMF-RCM. Myocardial function assessed by 2D-STE could reveal left and right myocardial dysfunction.
Differences in Workplace Risk Perception between Foreign-Born and First-Generation Mexican American Construction Workers

Risk perception is used to quantify risks in the industry and is influenced by different socio-demographic variables. This work aims to determine significant differences in the risk perception between Mexican American migrants and first-generation Mexican American construction workers. This study used a sample of 112 construction workers. A guided questionnaire was applied to collect socio-demographic information. For workplace risk behaviors, we used a 21-item questionnaire adapted from the previous instrument. Each question asked the participant’s perception of the frequency with which they carried out risky activities during routine work activities and the severity of the possible injuries, using a five-level Likert scale. Then, an inferential analysis was carried out using analysis of variance (ANOVA). The main results highlight that time of residence in the United States had a significant influence (p = 0.012) on risk perception in the surveyed construction workers. On the other hand, the age and time they have been working for the organization did not significantly influence risk perception. Finally, risk perception can vary in construction workers according to different variables. It is essential to investigate the factors that influence it, to prevent risky behaviors that can lead to accidents.
Nutrition Knowledge of Collegiate Athletes in the United States and the Impact of Sports Dietitians on Related Outcomes: A Narrative Review

In the last decade, the number of full-time registered dietitians (RDs) serving intercollegiate athletes in the United States has more than quadrupled. However, many student athletes may be at increased risk of nutrition-related problems that impact physical and academic performance, which include inadequate macronutrients, inadequate micronutrients, and excessive macronutrients. This narrative review reports the current literature to date on nutrition-related knowledge in collegiate athletes and the impact of sports RDs on student athletes’ nutrition knowledge and behaviors. To date, only observational and quasi-experimental studies have been published with regard to changes in nutrition knowledge and behaviors in NCAA athletes. While these studies report benefits of the RD as a member of the interdisciplinary student athlete support team, more well-designed randomized control trials are warranted to determine benefits related to health outcomes and sport-specific performance outcomes.
Multi-Scale Organization of the Drosophila melanogaster Genome

Interphase chromatin, despite its appearance, is a highly organized framework of loops and bends. Chromosomes are folded into topologically associating domains, or TADs, and each chromosome and its homolog occupy a distinct territory within the nucleus. In Drosophila, genome organization is exceptional because homologous chromosome pairing is in both germline and somatic tissues, which promote interhomolog interactions such as transvection that can affect gene expression in trans. In this review, we focus on what is known about genome organization in Drosophila and discuss it from TADs to territory. We start by examining intrachromosomal organization at the sub-chromosome level into TADs, followed by a comprehensive analysis of the known proteins that play a key role in TAD formation and boundary establishment. We then zoom out to examine interhomolog interactions such as pairing and transvection that are abundant in Drosophila but rare in other model systems. Finally, we discuss chromosome territories that form within the nucleus, resulting in a complete picture of the multi-scale organization of the Drosophila genome.
Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations

Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million. MG is considered a classic example of antibody-mediated autoimmune disease. Most patients with MG have autoantibodies against the acetylcholine receptors (AChRs). Less commonly identified autoantibodies include those targeted to muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (Lrp4), and agrin. These autoantibodies disrupt cholinergic transmission between nerve terminals and muscle fibers by causing downregulation, destruction, functional blocking of AChRs, or disrupting the clustering of AChRs in the postsynaptic membrane. The core clinical manifestation of MG is fatigable muscle weakness, which may affect ocular, bulbar, respiratory and limb muscles. Clinical manifestations vary according to the type of autoantibody, and whether a thymoma is present.
Picky Eating Is Associated with Lower Nutrient Intakes from Children’s Home-Packed School Lunches

The objective was to assess the relationship between children’s picky eating (PE) status and nutrient intake from home-packed school lunches. The lunches of 321 students, aged 7–10 years, were quantified via cross-sectional direct observation. Children were classified as having PE (n = 155) or not (non-PE; n = 166) based on food neophobia scores and parental perceptions of PE. The PE group consumed significantly less protein, folate, magnesium, potassium, zinc, and vitamins B1, B2, B3, B6, D, and E than the non-PE group; however, both groups consumed amounts exceeding Dietary Reference Intakes (DRIs) for protein, carbohydrates, sugar, sodium, iron, and vitamins B1, B2, B3, B6, B12, and C. Conversely, both groups consumed amounts significantly lower than DRIs for calcium, fibre, folate, magnesium, potassium, zinc, and vitamins A, D, E, and K. The PE group ate significantly less meat and alternatives, vegetables and fruit, and fruit than the non-PE group, and did not meet any of Canada’s Food Guide (2007) recommendations. The non-PE group met recommendations for meat and alternatives only. PE impacts the dietary intake of children’s home-packed lunches; however, many packed lunches were of low nutritional quality. Focus should be placed on provision of nutritionally complete school lunches for all children.
EEG Correlates of Old/New Discrimination Performance Involving Abstract Figures and Non-Words

The processing of pre-experimentally unfamiliar stimuli such as abstract figures and non-words is poorly understood. Here, we considered the role of memory strength in the discrimination process of such stimuli using a three-phase old/new recognition memory paradigm. Memory strength was manipulated as a function of the levels of processing (deep vs. shallow) and repetition. Behavioral results were matched to brain responses using EEG. We found that correct identification of the new abstract figures and non-words was superior to old item recognition when they were merely studied without repetition, but not when they were semantically processed or drawn. EEG results indicated that successful new item identification was marked by a combination of the absence of familiarity (N400) and recollection (P600) for the studied figures. For both the abstract figures and the non-words, the parietal P600 was found to differentiate between the old and new items (late old/new effects). The present study extends current knowledge on the processing of pre-experimentally unfamiliar figurative and verbal stimuli by showing that their discrimination depends on experimentally induced memory strength and that the underlying brain processes differ. Nevertheless, the P600, similar to pre-experimentally familiar figures and words, likely reflects improved recognition memory of meaningless pictorial and verbal items.