Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic and outcome analysis of adult T-cell lymphoblastic lymphoma

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphoid neoplasm occurring predominantly in children and young adults. T-LBL is characterized by a proliferation of T lymphoblasts arrested at an early stage of maturation and accounts for less than 2% of all the non-Hodgkin lymphomas. Currently, the molecular pathogenetic mechanisms of T-LBL are largely unknown. Previous studies have identified recurring genetic alterations in NOTCH, PI3K/AKT and RAS signaling pathways in T-LBL patients; however, the genome-wide mutational landscape of T-LBL patients remains elusive. To address this question, we performed whole-exome sequencing in a cohort of 96 patients with T-LBL in the present study. All patients (nine pediatric and 87 adult T-LBL patients) were reviewed and interpreted independently by three experienced pathologists. Diagnoses were made according to the current World Health Organization classification criteria. The clinical characteristics of the patient cohort are summarized in the Online Supplementary Table S1, and the experimental design is depicted in the Online Supplementary Figure S1. The study was conducted in accordance with the Declaration of Helsinki and with the approval of the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University. Wholeexome sequencing was performed using DNA extracted from 96 T-LBL patient tumor samples and 41 paired normal tissue samples. Detailed descriptions of wholeexome sequencing and bioinformatics analysis are provided in the Online Supplementary Materials and Methods. The 41 patients with paired normal tissue were deemed a “discovery cohort,” and the remaining patients were considered a “validation cohort. ” In the discovery cohort, the mean sequencing depth was 217×, and a mean of 96.6% of the target sequence was covered to a depth of at least 50× after excluding the duplicates (Online Supplementary Table S2). A total of 1,599 nonsilent mutations (median 33, range 4-124) were identified (Online Supplementary Figure S2A and Table S3). We further evaluated the relationship between the somatic nonsilent mutation burden and the clinical features of T-LBL patients. The results showed that the somatic nonsilent mutation burden was associated with age (R=0.16, P=0.010; Online Supplementary Figure S2B) but not with other clinical features of these patients (sex, stage, or LDH). The predominant type of substitution was the C to T transition at NpCpG sites in T-LBL (Online Supplementary Figure S3A). Combined nonnegative matrix factorization clustering and correlation with the 30 curated mutational signatures defined by the Catalog of
MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21

CDK4/6 inhibition becomes effective in preclinical models of melanoma when combined with MDM2 antagonism. It takes two treatments to tango Inhibitors of cyclin-dependent kinases 4 and 6, proteins involved in cell proliferation, have shown promising results in breast cancer, but their application in other tumor types has been limited by the development of resistance. Vilgelm et al. used patient-derived xenografts in mice to study the mechanisms of this resistance in melanoma. The authors identified a shortage of p21, a protein that inhibits the cell cycle, in resistant tumors and demonstrated that it can be reversed using a pharmacological intervention. The combination therapy was effective in multiple models in vivo, suggesting that it may have clinical potential. Intrinsic resistance of unknown mechanism impedes the clinical utility of inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) in malignancies other than breast cancer. Here, we used melanoma patient-derived xenografts (PDXs) to study the mechanisms for CDK4/6i resistance in preclinical settings. We observed that melanoma PDXs resistant to CDK4/6i frequently displayed activation of the phosphatidylinositol 3-kinase (PI3K)–AKT pathway, and inhibition of this pathway improved CDK4/6i response in a p21-dependent manner. We showed that a target of p21, CDK2, was necessary for proliferation in CDK4/6i-treated cells. Upon treatment with CDK4/6i, melanoma cells up-regulated cyclin D1, which sequestered p21 and another CDK inhibitor, p27, leaving a shortage of p21 and p27 available to bind and inhibit CDK2. Therefore, we tested whether induction of p21 in resistant melanoma cells would render them responsive to CDK4/6i. Because p21 is transcriptionally driven by p53, we coadministered CDK4/6i with a murine double minute (MDM2) antagonist to stabilize p53, allowing p21 accumulation. This resulted in improved antitumor activity in PDXs and in murine melanoma. Furthermore, coadministration of CDK4/6 and MDM2 antagonists with standard of care therapy caused tumor regression. Notably, the molecular features associated with response to CDK4/6 and MDM2 inhibitors in PDXs were recapitulated by an ex vivo organotypic slice culture assay, which could potentially be adopted in the clinic for patient stratification. Our findings provide a rationale for cotargeting CDK4/6 and MDM2 in melanoma.
Hybrid foraging search in younger and older age.

In hybrid foraging tasks, observers search visual displays, so called patches, for multiple instances of any of several types of targets with the goal of collecting targets as quickly as possible. Here, targets were photorealistic objects. Younger and older adults collected targets by mouse clicks. They could move to the next patch whenever they decided to do so. The number of targets held in memory varied between 8 and 64 objects, and the number of items (targets and distractors) in the patches varied between 60 and 105 objects. Older adults foraged somewhat less efficiently than younger adults due to a more exploitative search strategy. When target items became depleted in a patch and search slowed down, younger adults acted according to the optimal foraging theory and moved on to the next patch when the instantaneous rate of collection was close to their average rate of collection. Older adults, by contrast, were more likely to stay longer and spend time searching for the last few targets. Within a patch, both younger and older adults tended to collect the same type of target in "runs. " This behavior is more efficient than continual switching between target types. Furthermore, after correction for general age-related slowing, RT × set size functions revealed largely preserved attention and memory functions in older age. Hybrid foraging tasks share features with important real-world search tasks. Differences between younger and older observers on this task may therefore help to explain age differences in many complex search tasks of daily life. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Quantifying Activity Levels After Sport-Related Concussion Using Actigraph and Mobile (mHealth) Technologies.

CONTEXT Interest in identifying the effects of physical and mental activity on recovery after sport-related concussion is growing. Clinical studies of concussed athletes' activities require well-validated methods for tracking their intensity and timing. OBJECTIVE To develop and validate a novel multimodal approach to monitoring activity postconcussion using mobile (mHealth) technologies. DESIGN Cohort study. SETTING Translational research unit. PATIENTS OR OTHER PARTICIPANTS A total of 40 high school and collegiate football players were evaluated at preseason and followed longitudinally after either concussion (n = 25; age = 17.88 ± 1.74 years, height = 182.07 ± 8.08 cm, mass = 98.36 ± 21.70 kg) or selection as a nonconcussed control (n = 15; age = 18.27 ± 1.83 years, height = 180.01 ± 7.19 cm, mass = 93.83 ± 24.56 kg). MAIN OUTCOME MEASURE(S) Participants wore a commercial actigraph and completed a daily mobile survey for 2 weeks. Analyses focused on comparisons between groups for actigraph-based physical activity and self-reported physical and mental activity during the follow-up period. RESULTS For the first 2 days postinjury, objective measures showed fewer daily steps in concussed (6663 ± 2667 steps) than in control (11 148 ± 3381 steps) athletes (P < .001), and both objective and self-reported measures indicated less moderate to vigorous physical activity in concussed (27.6 ± 32.6 min/d and 25.0 ± 43.6 min/d, respectively) than in control (57.3 ± 38.6 min/d and 67.5 ± 40.1 min/d, respectively) athletes (both P < .05). Correlations between objective and self-reported measures of moderate to vigorous physical activity were moderate across select 1-week and 2-week averages. We observed no group differences in self-reported mental activities. CONCLUSIONS Physical activity after sport-related concussion varied widely across athletes but on average was reduced during the acute and early subacute postinjury periods for both objective and self-reported measures. The lack of differences in mental activities between groups may reflect limited change in mental exertion postconcussion or difficulty accurately measuring mental activities. Assessing concussed athletes' activities using actigraphy and self-reported scales may help monitor their compliance with activity recommendations and be useful in studies aimed at better understanding the effects of physical activity on concussion recovery.
Bioactive Compounds of Cooked Tomato Sauce Modulate Oxidative Stress and Arachidonic Acid Cascade Induced by Oxidized LDL in Macrophage Cultures

Sofrito is a mix of tomato, onion, garlic, and olive oil, which contains phenolic compounds and carotenoids. Consumption of tomato-based sofrito has been related to a lower risk of cardiovascular events, but the mechanisms behind such beneficial effects remain unclear. This study aimed to analyze the effects of representative sofrito compounds such as naringenin, hydroxytyrosol, lycopene, and β-carotene on mechanisms involved in the pathogenesis of atherosclerosis. We demonstrated that both phenolic compounds and both carotenoids studied were able to inhibit low density lipoproteins (LDL) oxidation, as well as oxidative stress and eicosanoid production induced by oxidized LDL (oxLDL) in macrophage cultures. These effects were not the consequences of disturbing oxLDL uptake by macrophages. Finally, we observed an additive effect of these sofrito compounds, as well as the activity of a main naringenin metabolite, naringenin 7-O-β-d-glucuronide on LDL oxidation and oxidative stress.
Validity and reliability of speed tests used in soccer: A systematic review

Introduction Speed is an important prerequisite in soccer. Therefore, a large number of tests have been developed aiming to investigate several speed skills relevant to soccer. This systematic review aimed to examine the validity and reliability of speed tests used in adult soccer players. Methods A systematic search was performed according to the PRISMA guidelines. Studies were included if they investigated speed tests in adult soccer players and reported validity (construct and criterion) or reliability (intraday and interday) data. The tests were categorized into linear-sprint, repeated-sprint, change-of-direction sprint, agility, and tests incorporating combinations of these skills. Results In total, 90 studies covering 167 tests were included. Linear-sprint (n = 67) and change-of-direction sprint (n = 60) were studied most often, followed by combinations of the aforementioned (n = 21) and repeated-sprint tests (n = 15). Agility tests were examined fewest (n = 4). Mainly based on construct validity studies, acceptable validity was reported for the majority of the tests in all categories, except for agility tests, where no validity study was identified. Regarding intraday and interday reliability, ICCs>0.75 and CVs<3.0% were evident for most of the tests in all categories. These results applied for total and average times. In contrast, measures representing fatigue such as percent decrement scores indicated inconsistent validity findings. Regarding reliability, ICCs were 0.11–0.49 and CVs were 16.8–51.0%. Conclusion Except for agility tests, several tests for all categories with acceptable levels of validity and high levels of reliability for adult soccer players are available. Caution should be given when interpreting fatigue measures, e.g., percent decrement scores. Given the lack of accepted gold-standard tests for each category, researchers and practitioners may base their test selection on the broad database provided in this systematic review. Future research should pay attention to the criterion validity examining the relationship between test results and match parameters as well as to the development and evaluation of soccer-specific agility tests.
Increased Nonexudative Age-Related Macular Degeneration Diagnosis Among Medicare Beneficiaries With Rheumatoid Arthritis

Purpose AMD is the leading cause of blindness in the United States. The role of secondary inflammatory disease on AMD progression is largely unknown. Here we investigate the association between AMD and rheumatoid arthritis (RA), using MarketScan data for patients aged ≥65 years on Medicare. Methods Baseline data were extracted for subjects with at least two International Classification, Ninth Revision (ICD-9) diagnosis codes of RA and control subjects (no RA) and were matched at baseline by propensity score. Matched cohort data were extracted post-baseline time and examined up to 4.5 years of follow-up for ICD-9 diagnosis code AMD records. Multivariable regression models compared risk of an AMD diagnosis post-baseline for RA subjects and matched controls. Days until first AMD diagnosis between RA patients and controls was examined using survival analysis. Results Risk of new AMD diagnosis was elevated in RA patients (odds ratio [OR] 2.08; 95% confidence interval [CI] 1.98–2.18), with an increase in nonexudative AMD patients (P < 0.0001). Risk was elevated in female (n = 27,548) (OR 1.11; 95% CI 1.05–1.17) compared with male (n = 9704; P < 0.001) patients. The time to first AMD diagnosis was shorter for RA subjects than controls (P < 0.0001). Conclusions Our analysis provides support of association between RA diagnosis and increased nonexudative AMD diagnosis.
Endorsement of Feminist Beliefs, Openness, and Mindful Acceptance as Predictors of Decreased Transphobia

ABSTRACT The inclusion of transgender and gender nonconforming (TGNC) individuals in feminist theory, discourse, and activism is fraught with controversy. Given this historical tension within various feminism movements, the current study sought to understand the nature of the relationship between endorsement of feminist beliefs and transphobia, and whether the specific individual-level factors such as openness to experience and mindful acceptance, moderate such a relationship. Analyzing data from a sample of n = 211 participants recruited from the Amazon Mechanical Turk (MTurk) platform, the regression analyses indicate both endorsement of feminist beliefs and openness to experience are independent inverse predictors of transphobia, net of other variables in the regression models. However, openness to experience does not moderate the relationship between endorsement of feminist beliefs and transphobia. Further, mindful acceptance was not a significant predictor or moderating variable regarding transphobia. For the feminist community, this is an important contribution as it supports the idea that feminist attitudes may be inclusive of TGNC identities, along with the individual personality facet of openness to experience. Limitations and future directions are discussed.
M1 disruption delays motor processes but not deliberation about action choices

Decisions about actions typically involve a period of deliberation that ends with the commitment to a choice and the motor processes overtly expressing that choice. Previous studies have shown that neural activity in sensorimotor areas, including the primary motor cortex (M1), correlates with deliberation features during action selection. Yet, the causal contribution of these areas to the decision process remains unclear. Here, we investigated whether M1 determines choice commitment, or whether it simply reflects decision signals coming from upstream structures and instead mainly contributes to the motor processes that follow commitment. To do so, we tested the impact of a disruption of M1 activity, induced by continuous theta burst stimulation (cTBS), on the behavior of human subjects in (1) a simple reaction time (SRT) task allowing us to estimate the duration of the motor processes and (2) a modified version of the tokens task (Cisek et al., 2009), which allowed us to estimate subjects’ time of commitment as well as accuracy criterion. The efficiency of cTBS was attested by a reduction in motor evoked potential amplitudes following M1 disruption, as compared to those following a sham stimulation. Furthermore, M1 cTBS lengthened SRTs, indicating that motor processes were perturbed by the intervention. Critically, all of the behavioral results in the tokens task were similar following M1 disruption and sham stimulation, suggesting that the contribution of M1 to the deliberation process is negligible. Taken together, these findings indicate that M1 contribution is downstream of the decision process. News and noteworthy Decisions between actions are ubiquitous in the animal realm. Previous work indicates that deliberation during action choices entails changes in the activity of the sensorimotor areas controlling those actions, but the causal role of these areas has yet to be established. Using continuous theta burst stimulation, we show that disrupting the primary motor cortex delays the motor processes that follow instructed commitment but does not alter volitional deliberation, suggesting that the contribution of M1 is downstream of the decision process.
Tuberculosis among asylum seekers in Milan, Italy: epidemiological analysis and evaluation of interventions

In countries of the European Union, tuberculosis (TB) mainly affects marginalised people, including asylum seekers. Migratory flows from high-incidence countries to Italy have increased up to 2017, posing challenges to the national health system. This study sought to assess TB and latent TB infection (LTBI) prevalence among asylum seekers in Milan during the biennium 2016–2017 and to evaluate interventions in place. A two-level active surveillance and screening system was developed for both TB and LTBI. Asylum seekers underwent an initial screening with a tuberculin skin test (TST) and a questionnaire at the receiving sites. At the Regional TB Reference Centre, those with a positive result underwent chest radiography. People aged <35 years with negative chest radiography results underwent further testing by interferon-γ release assay. If results of the assay were positive, LTBI treatment was offered. TB and LTBI prevalence were compared with literature data. A total of 5324 asylum seekers, mostly young (10–39 years; 98%), male (84%) and from sub-Saharan Africa (69%), were enrolled in the study. 69 active TB cases were diagnosed and 863 LTBI-positive individuals were detected. TB prevalence was high (1236 per 100 000 population) and LTBI prevalence was 28%. Despite losses (41%) during the transition from initial screening sites and the diagnostic centre, a good TB cure rate (84%) and optimal LTBI treatment completion (94%) were achieved. Our study shows that TB incidence is high among asylum seekers in Milan and that well-coordinated screening measures are critical for early diagnosis and treatment. It also proves that rolling out successful at-scale interventions for both prophylaxis and disease management is feasible. Asylum seekers are vulnerable to TB owing to migration-related events and marginalisation in destination countries. Coordinated screening and surveillance programmes using well-informed datasets can reduce TB transmission, improve care and address LTBI. http://bit.ly/2SPp0uZ
The zebrafish subcortical social brain as a model for studying social behavior disorders

ABSTRACT Social behaviors are essential for the survival and reproduction of social species. Many, if not most, neuropsychiatric disorders in humans are either associated with underlying social deficits or are accompanied by social dysfunctions. Traditionally, rodent models have been used to model these behavioral impairments. However, rodent assays are often difficult to scale up and adapt to high-throughput formats, which severely limits their use for systems-level science. In recent years, an increasing number of studies have used zebrafish (Danio rerio) as a model system to study social behavior. These studies have demonstrated clear potential in overcoming some of the limitations of rodent models. In this Review, we explore the evolutionary conservation of a subcortical social brain between teleosts and mammals as the biological basis for using zebrafish to model human social behavior disorders, while summarizing relevant experimental tools and assays. We then discuss the recent advances gleaned from zebrafish social behavior assays, the applications of these assays to studying related disorders, and the opportunities and challenges that lie ahead. Summary: The zebrafish has become an increasingly attractive model for studying social behavior disorders. This Review summarizes relevant methods, established social deficit models, emerging technologies and the anatomical basis of sociality.
Sibling relationships in older adulthood: Links with loneliness and well-being.

Researchers have documented associations between family relationships and a variety of well-being outcomes. Yet, sibling relationships, the longest lasting relationships in most people's lives, have received very little research attention beyond young adulthood. The goals of the current study were to: provide descriptive information about sibling relationships in later adulthood, investigate predictors of individual differences in sibling relationship quality, and examine associations among sibling relationship quality, loneliness, and well-being in later adulthood. The sample included 608 older adults (329 men, 279 women) who were 64.6 years old (SD = 4.58) on average. Participants provided self-report data about their relationships and well-being. Results showed that older adults reported high levels of sibling warmth and low levels of sibling conflict and parental favoritism. Sister-sister pairs had warmer sibling relationships than other gender-compositions. Sibling conflict and parental favoritism were positively associated with symptoms of depression, anxiety, hostility, and loneliness. Sibling warmth was negatively associated with loneliness. Loneliness partially mediated the associations between sibling relationship quality and well-being. Results from this study highlight the importance of sibling relationships in older adults' health and well-being. (PsycINFO Database Record (c) 2019 APA, all rights reserved).