Miracle-dz/UniFAR-FTUs huggingface dataset:
Perception and Motion in Real and Virtual Environments: A Narrative Review of Autism Spectrum Disorders

Atypical sensorimotor developmental trajectories greatly contribute to the profound heterogeneity that characterizes Autism Spectrum Disorders (ASD). Individuals with ASD manifest deviations in sensorimotor processing with early markers in the use of sensory information coming from both the external world and the body, as well as motor difficulties. The cascading effect of these impairments on the later development of higher-order abilities (e.g., executive functions and social communication) underlines the need for interventions that focus on the remediation of sensorimotor integration skills. One of the promising technologies for such stimulation is Immersive Virtual Reality (IVR). In particular, head-mounted displays (HMDs) have unique features that fully immerse the user in virtual realities which disintegrate and otherwise manipulate multimodal information. The contribution of each individual sensory input and of multisensory integration to perception and motion can be evaluated and addressed according to a user’s clinical needs. HMDs can therefore be used to create virtual environments aimed at improving people’s sensorimotor functioning, with strong potential for individualization for users. Here we provide a narrative review of the sensorimotor atypicalities evidenced by children and adults with ASD, alongside some specific relevant features of IVR technology. We discuss how individuals with ASD may interact differently with IVR versus real environments on the basis of their specific atypical sensorimotor profiles and describe the unique potential of HMD-delivered immersive virtual environments to this end.
Sex Differences in Exercise-Training-Related Functional and Morphological Adaptation of Rat Gracilis Muscle Arterioles

Background The cardiovascular effects of training have been widely investigated; however, few studies have addressed sex differences in arteriolar adaptation. In the current study, we examined the adaptation of the gracilis arterioles of male and female rats in response to intensive training. Methods Wistar rats were divided into four groups: male exercise (ME) and female exercise (FE) animals that underwent a 12-week intensive swim-training program (5 days/week, 200 min/day); and male control (MC) and female control (FC) animals that were placed in water for 5 min daily. Exercise-induced cardiac hypertrophy was confirmed by echocardiography. Following the training, the gracilis muscle arterioles were prepared, and their biomechanical properties and functional reactivity were tested, using pressure arteriography. Collagen and smooth muscle remodeling were observed in the histological sections. Results Left ventricular mass was elevated in both sexes in response to chronic training. In the gracilis arterioles, the inner radius and wall tension increased in female animals, and the wall thickness and elastic modulus were reduced in males. Myogenic tone was reduced in the ME group, whereas norepinephrine-induced vasoconstriction was elevated in the FE group. More pronounced collagen staining was observed in the ME group than in the MC group. Relative hypertrophy and tangential stress of the gracilis arterioles were higher in females than in males. The direct vasoconstriction induced by testosterone was lower in females and was reduced as an effect of exercise in males. Conclusion The gracilis muscle arteriole was remodeled as a result of swim training, and this adaptation was sex dependent.
Reactive T Cells in Convalescent COVID-19 Patients With Negative SARS-CoV-2 Antibody Serology

Despite RT-PCR confirmed COVID-19, specific antibodies to SARS-CoV-2 spike are undetectable in serum in approximately 10% of convalescent patients after mild disease course. This raises the question of induction and persistence of SARS-CoV-2-reactive T cells in these convalescent individuals. Using flow cytometry, we assessed specific SARS-CoV-2 and human endemic coronaviruses (HCoV-229E, -OC43) reactive T cells after stimulation with spike and nucleocapsid peptide pools and analyzed cytokine polyfunctionality (IFNγ, TNFα, and IL-2) in seropositive and seronegative convalescent COVID-19 patients as well as in unexposed healthy controls. Stimulation with SARS-CoV-2 spike and nucleocapsid (NCAP) as well as HCoV spike peptide pools elicited a similar T cell response in seropositive and seronegative post COVID-19 patients. Significantly higher frequencies of polyfunctional cytokine nucleocapsid reactive CD4+ T cells (triple positive for IFNγ, TNFα, and IL-2) were observed in both, seropositive (p = 0.008) and seronegative (p = 0.04), COVID-19 convalescent compared to healthy controls and were detectable up to day 162 post RT-PCR positivity in seronegative convalescents. Our data indicate an important role of NCAP-specific T cells for viral control.
Is There an Association Between Fixed Orthodontic Treatment and Initiation of Eating Disorders? A Review of Currently Available Evidence

Objectives: The aim was to review the available literature regarding the potential association between fixed orthodontic treatment (OT) and the onset of eating disorders (EDs). Method and Materials: Six indexed databases were searched until November 2020. The inclusion criteria were as follows: (a) patients undergoing fixed OT and (b) EDs in relation to fixed OT. Commentaries, letters to the Editor, reviews, and studies in patients with EDs not undergoing fixed OT were excluded. The pattern of the present review was customized to summarize the pertinent information. Results: Four out of 10,076 initially-identified studies were included, and all of them were case reports. All patients were females, and the EDs reported were either anorexia nervosa (AN) or bulimia nervosa (BN). In three case reports, patients developed EDs after the initiation of OT. Fixed OT was performed in all the studies, and a variety of oral complications such as sore mouth, gingivitis, tooth surface demineralization, and others were reported. Conclusion: Based upon the limited available evidence, the association between OT and the onset of EDs remains unclear. Further well-designed observational clinical studies are needed in this regard.
Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients

Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, NAT1 and NAT2 were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, NAT1 and NAT2 expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.
Attitudes of Different Age Groups Toward People With Intellectual Disability During the COVID-19 Pandemic

Background: The COVID-19 pandemic has been particularly risky for people with disabilities and severe medical conditions, not only because the virus may be a direct threat to their physical health but also because of social exclusion and negating their needs and rights. Objective: This study aimed to assess the attitudes of people from different age groups towards people with intellectual disability (ID). Methods: The study included 223 people (19–85 years old) and was conducted in May 2020–January 2021. Data was collected using the Multidimensional Attitudes Scale Towards Persons With Disabilities and a self-designed Questionnaire regarding the attitudes towards people with ID during the pandemic. Data analysis was performed using SPSS 24 (ANOVA). Results: The results of the study showed that the general attitudes were only slightly supportive and differed among people of different age groups: the youngest and the oldest generation expressed the most positive attitudes while the adults (35–60 y.o.) expressed the most negative ones. Conclusions: As the pandemic is spreading rapidly with no definitive solution, awareness to create more positive attitudes towards people with ID and recognizing their needs is essential.
Combating the COVID-19 Pandemic: Experiences of the First Wave From Nepal

Unprecedented and unforeseen highly infectious Coronavirus Disease 2019 (COVID-19) has become a significant public health concern for most of the countries worldwide, including Nepal, and it is spreading rapidly. Undoubtedly, every nation has taken maximum initiative measures to break the transmission chain of the virus. This review presents a retrospective analysis of the COVID-19 pandemic in Nepal, analyzing the actions taken by the Government of Nepal (GoN) to inform future decisions. Data used in this article were extracted from relevant reports and websites of the Ministry of Health and Population (MoHP) of Nepal and the WHO. As of January 22, 2021, the highest numbers of cases were reported in the megacity of the hilly region, Kathmandu district (population = 1,744,240), and Bagmati province. The cured and death rates of the disease among the tested population are ~98.00 and ~0.74%, respectively. Higher numbers of infected cases were observed in the age group 21–30, with an overall male to female death ratio of 2.33. With suggestions and recommendations from high-level coordination committees and experts, GoN has enacted several measures: promoting universal personal protection, physical distancing, localized lockdowns, travel restrictions, isolation, and selective quarantine. In addition, GoN formulated and distributed several guidelines/protocols for managing COVID-19 patients and vaccination programs. Despite robust preventive efforts by GoN, pandemic scenario in Nepal is, yet, to be controlled completely. This review could be helpful for the current and future effective outbreak preparedness, responses, and management of the pandemic situations and prepare necessary strategies, especially in countries with similar socio-cultural and economic status.
Mathematical Model of SARS-Cov-2 Propagation Versus ACE2 Fits COVID-19 Lethality Across Age and Sex and Predicts That of SARS

The fatality rate of Covid-19 escalates with age and is larger in men than women. I show that these variations correlate strongly with the level of the viral receptor protein ACE2 in rat lungs, which is consistent with the still limited data on human ACE2. Surprisingly, lower receptor levels correlate with higher fatality. I propose two possible explanations of this negative correlation: First, a previous mathematical model predicts that the velocity of viral progression in the organism as a function of the receptor level has a maximum and declines for abundant receptor. Secondly, degradation of ACE2 by the virus may cause the runaway inflammatory response that characterizes severe CoViD-19. I present here a mathematical model that predicts the lethality as a function of ACE2 protein level based on the two above hypothesis. The model fits Covid-19 fatality rate across age and sex in three countries with high accuracy ( r 2 > 0.9 ) under the hypothesis that the speed of viral progression in the infected organism is a decreasing function of the ACE2 level. Moreover, rescaling the fitted parameters by the ratio of the binding rates of the spike proteins of SARS-CoV and SARS-CoV-2 allows predicting the fatality rate of SARS-CoV across age and sex, thus linking the molecular and epidemiological levels.
Early and Next-Generation KIT/PDGFRA Kinase Inhibitors and the Future of Treatment for Advanced Gastrointestinal Stromal Tumor

The majority of gastrointestinal stromal tumors (GIST) harbor an activating mutation in either the KIT or PDGFRA receptor tyrosine kinases. Approval of imatinib, a KIT/PDGFRA tyrosine kinase inhibitor (TKI), meaningfully improved the treatment of advanced GIST. Other TKIs subsequently gained approval: sunitinib as a second-line therapy and regorafenib as a third-line therapy. However, resistance to each agent occurs in almost all patients over time, typically due to secondary kinase mutations. A major limitation of these 3 approved therapies is that they target the inactive conformation of KIT/PDGFRA; thus, their efficacy is blunted against secondary mutations in the kinase activation loop. Neither sunitinib nor regorafenib inhibit the full spectrum of KIT resistance mutations, and resistance is further complicated by extensive clonal heterogeneity, even within single patients. To combat these limitations, next-generation TKIs were developed and clinically tested, leading to 2 new USA FDA drug approvals in 2020. Ripretinib, a broad-spectrum KIT/PDGFRA inhibitor, was recently approved for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. Avapritinib, a type I kinase inhibitor that targets active conformation, was approved for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. In this review, we will discuss how resistance mutations have driven the need for newer treatment options for GIST and compare the original GIST TKIs with the next-generation KIT/PDGFRA kinase inhibitors, ripretinib and avapritinib, with a focus on their mechanisms of action.
The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis

Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the SPOP gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that SPOP mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation via mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the SPOP F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis.
The Association Between Exposure to Low Magnesium Blood Levels After Renal Transplantation and Cardiovascular Morbidity and Mortality

Background: Serum magnesium levels are associated with cardiovascular disease and all-cause mortality in the general population and chronic kidney disease patients, but the association between serum magnesium levels and cardiovascular risk after kidney transplantation is not established. We sought to evaluate whether exposure to low serum magnesium levels after renal transplantation is related to cardiovascular morbidity and mortality. Methods: We conducted a single center retrospective study that included all transplanted patients who had a functioning graft for at least 6 months after transplantation between January 2001 and December 2013. We calculated exposure to magnesium using time weighted average for serum magnesium levels, using all values available during the follow-up. Several statistical methods were used, including liner regression analysis, χ2 test, and multivariate Cox proportional hazard model. Results: Four hundred ninety-eight patients were included. Median follow-up was 5.26 years. High time weighted average of serum magnesium was associated with a hazard ratio of 1.94 for all-cause mortality and major cardiovascular outcome compared to low levels (95% CI 1.18–3.19, p = 0.009). The high quartile of time weighted average of serum magnesium was associated with death censored major cardiovascular outcome (hazard ratio 2.13, 95% CI 1.17–3.86, p = 0.013) in multivariate analysis. Conclusions: Exposure to low serum magnesium levels in renal transplant recipients was associated with a lower risk for all-cause mortality and major cardiovascular outcome. These findings contrast the higher risk found in the general population.
Electrical Conductivity and Diffusion of Oxygen Ions in Rare-Earth-Doped Ceria

An oxalate coprecipitation method was applied to produce rare-earth-doped ceria powders (Ce0.8R0.2O1.9, R=Yb, Y, Gd, Sm, Nd and La). The powders calcined at 600°C were isostatically compacted and sintered at 1600°C in air to reach a relative density exceeding 98%. The electrical conductivity of rare-earth-doped ceria ceramics was dominated by the migration of oxygen ions in the bulk and was in the range of 6.7 to 13.6S·m-1 at 800°C. The activation energies for diffusion of oxygen ions in the bulk ranged from 75.3 to 93.4kJ/mol. The lattice energy theory for the fluorite structure was applied to estimate the activation energy. The calculated activation energy was close to the measured value.
Pulmonary Vein Index Is Associated With Early Prognosis of Surgical Treatment for Tetralogy of Fallot

Objectives: To evaluate the predictive value of the pulmonary vein index (PVI) in the early prognosis of patients who received total tetralogy of Fallot (TOF) repair. Methods: We retrospectively reviewed 286 patients who underwent TOF repair in our institution between July 2013 and May 2020. The PVI, McGoon ratio, and Nakata index were measured and calculated. Logistic regression, linear stepwise regression, receiver operating characteristic (ROC) curve analysis, and Cox proportional hazards modeling were performed to evaluate the predictive value of PVI in the early prognosis after TOF repair surgery. Results: The median age and body weight were 1.23 (0.22–15.02) years and 9.00 (3.00–44.00) kg, respectively. There were five early deaths. The areas under the ROC curve for death were 0.89, 0.79, and 0.88 for the McGoon ratio, Nakata index, and PVI, respectively. A lower PVI better predicted prolonged postoperative hospital stay, cardiac intensive care unit stay, and ventilator time (Hazard Ratio, HR [95% Confidence intervals, CI]: 1.003 [1.002–1.004], p < 0.001; 1.002 [1.001–1.004], p < 0.001; 1.002 [1.001–1.003], p < 0.001, respectively) and was a significant risk factor for high 24 h max Vasoactive inotropic score (Crude Odds Ratio [OR] [95% CI]: −0.015 [−0.022, −0.007], p < 0.001), serous effusion (Crude OR [95% CI]: 0.996 [0.992–0.999], p = 0.020), delayed sternal closure (Crude OR [95% CI]: 0.983 [0.971–0.996], p = 0.010), and the need for peritoneal dialysis (Crude OR [95% CI]: 0.988 [0.980–0.996], p = 0.005). The area under the ROC curve of PVI for delayed postoperative recovery was 0.722 (p < 0.001), and the estimated cutoff point was 300.3 mm2/m2. Conclusion: PVI is a good predictor of early prognosis for surgical treatment of TOF patients.
Preliminary Scales for ICD-11 Personality Disorder: Self and Interpersonal Dysfunction Plus Five Personality Disorder Trait Domains

The ICD-11 personality disorder model is the first fully dimensional assessment of personality pathology. It consists of a personality disorder (PD) dysfunction-severity dimension, which encompasses both self- and interpersonal dysfunction, and six optional qualifiers for five prominent personality traits—Negative Affectivity (NA), Detachment (DET), Dissociality (DSL), Disinhibition (DSN), and Anankastia (ANK)—plus a borderline pattern that is defined by the criteria of DSM-IV borderline PD. This article reports on the development of a new self-report measure to assess self- and interpersonal dysfunction and the five trait qualifiers. It is the first comprehensive measure of the ICD-11 PD model in that (a) it is the only one to include both PD dysfunction-severity as well as trait scales and because (b) it is based on the Clinical Description and Diagnostic Guidelines, which are more detailed than the “statistical” model description that is currently on the ICD-11 website. The authors wrote 992 items and then reduced the pool to 300 items by eliminating redundancy and selecting the consensus best few items for each subconstruct. Data were collected using an online sample of 383 Prolific workers. Using exploratory factor analysis, seven domain scales were developed, each of which contained two to four scales assessing components of the domain. These preliminary scales’ psychometrics were excellent, as were the domains’ and their components’ convergent and discriminant validity, with a few generally minor exceptions. Structural analyses at the component level revealed a three-factor structure consisting of two moderately correlated Internalizing factors, one centered on Self Dysfunction with two NA components and a DSN component (Distractibility) and the other on Interpersonal Dysfunction with DET and ANK components; as well as an Externalizing factor with DSL and a DSN component (Reckless Impulsivity) that was uncorrelated with the other two factors. Two aspects of the results in particular are striking: (1) ANK was not the opposite end of a DSN dimension, but rather contributed to an Internalizing Interpersonal Dysfunction dimension and (2) DSN had both an Internalizing and an Externalizing component. Implications of the findings and study limitations are discussed.