Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of circularized E7 RNA, GLUT1, and PD-L1 in anal squamous cell carcinoma

Anal squamous cell carcinoma (ASCC) is a rare, potentially fatal malignancy primarily caused by high-risk human papillomaviruses (HPV). The prognostic implication of programmed death-ligand 1 (PD-L1) expression remains controversial, and glucose transporter 1 (GLUT1) expression has never been examined in ASCC. Covalently closed circular RNAs have recently been shown to be widespread in cancers and are proposed to be biomarkers. We discovered HPV16 expresses a circular E7 RNA (circE7) which has not been assessed as a potential biomarker. A retrospective, translational case series at UT Southwestern was conducted to analyze PD-L1, GLUT1, HPV-ISH, and HPV circE7 in relation to the clinical features and overall survival of patients with ASCC. Twenty-two (22) subjects were included in the study. Improved overall survival was predicted by basaloid histology ( p = 0.013), PD-L1 expression ( p = 0.08), and HPV-ISH positivity ( p & 0.001), but not GLUT1 expression. High levels of circE7 by quantitative RT-PCR predicted improved overall survival in ASCC ( p = 0.023) and analysis of The Cancer Genome Atlas sequencing from HPV-positive head and neck cancer and cervical cancer suggested high circE7 marked improved survival in 875 subjects ( p = 0.074). While our study suggests that circE7 levels correlate with improved survival in ASCC, larger, prospective studies are necessary to confirm the potential role of circE7 as a biomarker.
Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.

BACKGROUND Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML. METHODS In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission with full or partial hematologic recovery. Secondary end points included event-free survival (freedom from treatment failure [i.e., relapse or lack of remission] or death) and the percentage of patients who had complete remission. RESULTS Of 371 eligible patients, 247 were randomly assigned to the gilteritinib group and 124 to the salvage chemotherapy group. The median overall survival in the gilteritinib group was significantly longer than that in the chemotherapy group (9.3 months vs. 5.6 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P<0.001). The median event-free survival was 2.8 months in the gilteritinib group and 0.7 months in the chemotherapy group (hazard ratio for treatment failure or death, 0.79; 95% CI, 0.58 to 1.09). The percentage of patients who had complete remission with full or partial hematologic recovery was 34.0% in the gilteritinib group and 15.3% in the chemotherapy group (risk difference, 18.6 percentage points; 95% CI, 9.8 to 27.4); the percentages with complete remission were 21.1% and 10.5%, respectively (risk difference, 10.6 percentage points; 95% CI, 2.8 to 18.4). In an analysis that was adjusted for therapy duration, adverse events of grade 3 or higher and serious adverse events occurred less frequently in the gilteritinib group than in the chemotherapy group; the most common adverse events of grade 3 or higher in the gilteritinib group were febrile neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%). CONCLUSIONS Gilteritinib resulted in significantly longer survival and higher percentages of patients with remission than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated AML. (Funded by Astellas Pharma; ADMIRAL ClinicalTrials.gov number, NCT02421939.).
Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion

Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0. 5µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.
Interannual variation of terrestrial carbon cycle: Issues and perspectives

With accumulation of carbon cycle observations and model developments over the past decades, exploring interannual variation (IAV) of terrestrial carbon cycle offers the opportunity to better understand climate–carbon cycle relationships. However, despite growing research interest, uncertainties remain on some fundamental issues, such as the contributions of different regions, constituent fluxes and climatic factors to carbon cycle IAV. Here we overviewed the literature on carbon cycle IAV about current understanding of these issues. Observations and models of the carbon cycle unanimously show the dominance of tropical land ecosystems to the signal of global carbon cycle IAV, where tropical semiarid ecosystems contribute as much as the combination of all other tropical ecosystems. Vegetation photosynthesis contributes more than ecosystem respiration to IAV of the global net land carbon flux, but large uncertainties remain on the contribution of fires and other disturbance fluxes. Climatic variations are the major drivers to the IAV of net land carbon flux. Although debate remains on whether the dominant driver is temperature or moisture variability, their interaction,that is, the dependence of carbon cycle sensitivity to temperature on moisture conditions, is emerging as key regulators of the carbon cycle IAV. On timescales from the interannual to the centennial, global carbon cycle variability will be increasingly contributed by northern land ecosystems and oceans. Therefore, both improving Earth system models (ESMs) with the progressive understanding on the fast processes manifested at interannual timescale and expanding carbon cycle observations at broader spatial and longer temporal scales are critical to better prediction on evolution of the carbon–climate system.
Mentor and mentee perceptions of the importance and effectiveness of mentor support

vi Chapter 1: Introduction 1 Framework for the Study 3 Beginning Teachers and Induction Support 3 Sustained Professional Development for Beginning Teachers 4 Special Needs of Special Educators 5 Purpose and Rationale of Study 7 Research Questions 9 Significance of this Study 10 Scope and Study Limitations 11 Definitions of Significant Terminology 13 Chapter 2: Literature Review 15 Introduction 15 Key Legislation for Students with Special Needs 15 Significant Components of IDEA 16 Least Restrictive Environment 17 Individualized Education Plan 18 Due Process Safeguards 18 Nondiscriminatory Assessments 19 Related Services and Free and Appropriate Public Education 20
Burden and health state utility values of eating disorders: results from a population-based survey

Abstract Background There are no published estimates of the health state utility values (HSUVs) for a broad range of eating disorders (EDs). HSUVs are used in economic evaluations to determine quality-adjusted life years or as a measure of disorder burden. The main objective of the current study is to present HSUVs for a broad range of EDs based on DSM-5 diagnoses. Methods We used pooled data of two Health Omnibus Surveys (2015 and 2016) including representative samples of individuals aged 15 + years living in South Australia. HSUVs were derived from the SF-6D (based on the SF-12 health-related quality of life questionnaire) and analysed by ED classification, ED symptoms (frequency of binge-eating or distress associated to binge eating) and weight status. Multiple linear regression models, adjusted for socio-demographics, were used to test the differences of HSUVs across ED groups. Results Overall, 18% of the 5609 individuals met criteria for ED threshold and subthreshold. EDs were associated with HSUV decrements, especially if they were severe disorders (compared to non-ED), binge ED: −0.16 (95% CI −0.19 to −0.13), bulimia nervosa: −0.12, (95% CI −0.16 to −0.08). There was an inverse relationship between distress related binge eating and HSUVs. HSUVs were lower among people with overweight/obese compared to those with healthy weight regardless of ED diagnosis. Conclusions EDs were significantly associated with lower HSUVs compared to people without such disorders. This study, therefore, provides new insights into the burden of EDs. The derived HSUVs can also be used to populate future economic models.
The Easy Part of the Hard Problem: A Resonance Theory of Consciousness

Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a specific combination of gamma, beta and theta electrical synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and offers a possible solution to what we see as the “easy part” of the “Hard Problem” of consciousness, which is generally known as the “combination problem. ” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach, a meta-synthesis, as a (general) resonance theory of consciousness. We offer some suggestions for testing the theory.
Prevalence of growth hormone deficiency in middle-age adults recovering from stroke

ABSTRACT Objective: The prevalence of chronic growth hormone deficiency (GHD) and its association with other hormonal deficiencies was determined in middle-aged patients post-stroke with and without consideration of body mass index (BMI). Methods: Clinical records were reviewed to determine pituitary function at least 3 months post-stroke. Patients with a history of endocrine anomalies were excluded. GHD was determined by utilizing standard peak GH cutoffs following the glucagon stimulation test. A secondary analysis was conducted with stricter BMI-adjusted cutoffs. The accuracy of IGF-1 in predicting GHD was also examined. Results: GHD was diagnosed in 54% of patients (≥5.0 μg/L), with 32% falling into the severe (≤3 μg/L) category. Patients with GHD had lower levels of FSH, T3, LH, and SHBG. Analyzes of BMI-adjusted GH levels, revealed that 14% of patients were GHD. These patients had higher prolactin. IGF-1 values were not predictive of GHD. Latency to be admitted to post-acute rehabilitation was greater in patients with GHD. Conclusions: Evidence suggests patients with stroke may be at risk for developing GHD. GHD was associated with decreased levels of other hormones. Co-morbidities for stroke and neuroendocrine dysfunction overlap and may have implications for recovery following stroke.
Development of an In Vivo Sensor to Monitor the Effects of Vapour Pressure Deficit (VPD) Changes to Improve Water Productivity in Agriculture

Environment, biodiversity and ecosystem services are essential to ensure food security and nutrition. Managing natural resources and mainstreaming biodiversity across agriculture sectors are keys towards a sustainable agriculture focused on resource efficiency. Vapour Pressure Deficit (VPD) is considered the main driving force of water movements in the plant vascular system, however the tools available to monitor this parameter are usually based on environmental monitoring. The driving motif of this paper is the development of an in-vivo sensor to monitor the effects of VPD changes in the plant. We have used an in vivo sensor, termed “bioristor”, to continuously monitor the changes occurring in the sap ion’s status when plants experience different VPD conditions and we observed a specific R (sensor response) trend in response to VPD. The possibility to directly monitor the physiological changes occurring in the plant in different VPD conditions, can be used to increase efficiency of the water management in controlled conditions thus achieving a more sustainable use of natural resources.
Identification of Markers Associated With Development of Stroke in “Clinically Low‐Risk” Atrial Fibrillation Patients

Background Stroke and thromboembolic events may still occur in “clinically low‐risk” atrial fibrillation (AF) patients as categorized by CHA 2 DS 2‐VASc score. Our aim was to assess the proportion of “clinically low‐risk” patients using a nongender CHA 2 DS 2‐VASc (ie, CHA 2 DS 2‐VA) score of 0 to 1 among patients who experienced AF‐associated stroke and to identify markers associated with stroke in “clinically low‐risk” patients. Methods and Results We retrospectively recruited nonvalvular AF patients who experienced embolic stroke between 2013 and 2016 from 9 institutes in Korea. AF patients with CHA 2 DS 2‐VA score of 0 to 1 at the time of stroke were analyzed and compared with “clinically low‐risk” AF patients without stroke. A total of 3033 subjects with AF‐associated stroke were recruited. Of these, 583 patients (19.2%) had CHA 2 DS 2‐VA score of 0 to 1. On multivariate analysis, age (≥60 years), N‐terminal pro B‐type natriuretic peptide (≥300 pg/mL), creatinine clearance (<50 mL/min), and left atrial dimension (≥45 mm) were independently associated with stroke. With the combined application of these 4 factors (collectively, ABCD score) to the “clinically low‐risk” patients, the c‐index was 0.858 (95% CI 0.838–0.877; P<0.001). Conclusions The present study suggests a new insight into how additional use of markers can further refine stroke risk differentiation among AF patients initially classified as “clinically low‐risk. ” Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT03147911.
New species and record of phytoseiid mites (Acari: Mesostigmata: Phytoseiidae) from Myanmar

Abstract This paper is the first report of phytoseiid mites from Myanmar. By examining the specimens collected from two south-central cities, Mandalay and Mingun, five species were found in this survey, including four new species, Euseius mandalayensis sp. nov., E. dominativus sp. nov., E. longisaccatus sp. nov., and Phytoseius pseudoincisus sp. nov., and one new record E. ovalis. Herein, they are described and illustrated based on the current specimens.
Hereditary Sensory and Autonomic Neuropathy 2B Caused by a Novel RETREG1 Mutation (c.765dupT) and Paternal Uniparental Isodisomy of Chromosome 5

Hereditary sensory and autonomic neuropathy (HSAN) 2B is a rare disease and has been reported mostly in offspring of consanguineous parents. Here we report the case of a patient born to non-consanguineous parents who was diagnosed with HSAN 2B caused due to a novel frameshift mutation (NM_001034850.2: c.765dupT/p.Gly256TrpfsTer7) in the RETREG1 gene and paternal uniparental isodisomy of chromosome 5. Uniparental isodisomy of chromosome 5 is also a rare condition, and these two rare events lead to homozygous expression of a recessive mutation, as in the present case. Clinicians should be aware that autosomal recessive disorders due to homozygous variants can occur because of uniparental disomy in offspring of non-consanguineous parents.
Profile of nursing graduates: competencies and professional insertion*

Objective: evaluate the profile of the graduates of Nursing a public college from the perception of skills developed during graduation and the process of professional insertion. Method: quantitative, exploratory and descriptive study. The sample was composed of 216 graduates. The data was collected by a validated questionnaire and sent to a population of 470 egresses via electronic mail. For the analysis of the data, frequencies, mean and standard deviation were applied and, for the correlation, the chi-square test. Results: the majority of the participants were female (88%) and the mean age was 29.62 years. The majority (65%) had an employment relationship, 14% worked in a single institution and 48% started working six months after graduation. Regarding the form of work, 56% work in care, with an average of 4.5 minimum wages and a weekly workload between 37 and 44 hours. The majority reported competence acquisition to practice the profession, assisting the patient in his integrality with ethics and applying technical and scientific concepts in care. Conclusion: the study made it possible to describe the singularities of nurses’ education, their insertion in the world of work and the impact on the educational institution, as well as the presentation of specific competences from the perspective of the graduates themselves.
Parent-child coresidence: Who moves in with whom and for whose needs?

Using administrative data on all adult children living in The Netherlands age 30-40 and their parents (N = 1,999,700), we investigated the extent to which situations and events associated with the support needs and privacy needs of either generation determine intergenerational coresidence and the transition to coresidence. Logistic and multinomial logistic regression analyses showed that both generations' support needs increased the likelihood of coresidence and of a move of the generation in need into the other's home. Turning to privacy needs, we found that coresidence and the transition to coresidence was less likely when a partner or stepparent was present and more likely when the adult child was a never-married single parent.
Different Aspects of Emotional Awareness in Relation to Motor Cognition and Autism Traits

Emotion is inherently embodied, formulated through bodily sensation, as well as expressed and regulated through action. Both expressing one’s own emotions and understanding the emotional actions of others are common areas of difficulty in autism. Moreover, reduced emotional awareness is also thought to be problematic in autism, and such difficulties may be mediated by impaired motor cognition. We aimed to examine how intensity of emotional experience and ability to differentiate between one’s own emotions relates to motor empathy and autistic traits. We hypothesized that greater motor cognition would be associated with greater emotional intensity and more refined emotion differentiation. Participants from the general population (N = 160) completed the Actions and Feelings Questionnaire (AFQ), a self-report measure assessing motor cognition, alongside the Broad Autism Phenotype Questionnaire and an emotion elicitation task. Motor cognition was significantly associated with more intense emotional experiences but not with ability to differentiate between similar emotions. Autistic traits, particularly social aloofness, predicted less emotion differentiation and lower scores on the animation subscale of the AFQ. We suggest that whereas as intensity of experience may be dependent on sensorimotor representation of emotions, differentiation requires additional cognitive functions such as language understanding. A dissociation between awareness of intensity and differentiation may be critical for understanding emotional difficulties in autism.
Self-regulation mechanisms in health behavior change: a systematic meta-review of meta-analyses, 2006–2017

ABSTRACT Self-regulation is one primary mechanism in interventions for health behavior change and has been examined in numerous recent meta-analyses. This pre-registered meta-review (PROSPERO CRD42017074018) examined Mmeta-analyses of any intervention and health behavior/outcome were eligible if they quantitatively assessed self-regulation and appeared between January 2006 and August 2017. In total, 66 meta-analyses were ultimately eligible; 27% reported a protocol, 11% used GRADE; 58% focused on RCTs. Reviews satisfied only a moderate number of items on the AMSTAR 2 (M = 45.45%, SD = 29.57%). Only 6% of meta-analyses directly examined whether changes in self-regulation predicted the behavior change (i.e., self-efficacy and physical activity, l = 2; frequency of self-monitoring and goal attainment, l = 1; cognitive bias modification and addiction, l = 1). Meta-analyses more routinely assessed self-regulation by comparing the efficacy of intervention components (97%), such as those from behavior change taxonomies. Meta-analyses that focused on intervention components identified several as successful, including personalized feedback, goal setting, and self-monitoring; however, none were consistently successful in that each worked only for some health behaviors and with particular populations. Some components had inconclusive evidence, given that they were only examined in low- quality reviews. Future reviewers should utilize advanced methods to assess mechanisms, and study authors should report hypothesized mechanisms to facilitate synthesis.
Lung function and asthma control in school-age children managed in UK primary care: a cohort study

Background Spirometry and fraction of exhaled nitric oxide (FeNO) are commonly used in specialist centres to monitor children with asthma. The National Institute for Health and Care Excellence recommends spirometry for asthma monitoring from 5 years in all healthcare settings. There is little spirometry and FeNO data in children managed for asthma in UK primary care to support their use. Objectives To study the prevalence of abnormal spirometry and FeNO in children with asthma managed in primary care and to explore their relationship with asthma control and unplanned healthcare attendances (UHA). Methods Prospective observational cohort study in children aged 5–16 years with suspected or doctor-diagnosed asthma attending an asthma review in UK general practice. Spirometry, FeNO, asthma control test (ACT) scores and number of UHAs were studied. Results Of 612 children from 10 general practices, 23.5% had abnormal spirometry, 36.0% had raised FeNO ≥35 parts per billion and 41.8% reported poor control. Fifty-four per cent of children reporting good asthma control had abnormal spirometry and/or raised FeNO. At follow-up, the mean number of UHAs fell from 0.31/child in the 6 months preceding review to 0.20/child over the 6 months following review (p=0.0004). Median ACT scores improved from 20 to 22 (p=0.032), and children’s ACT from 21 to 23 (p<0.0001). Conclusions Abnormal lung function and FeNO are common in children attending for asthma review in primary care and relate poorly to symptom scores. A symptoms-based approach to asthma monitoring without objective testing is likely to miss children at high risk of future severe asthma attacks.