Miracle-dz/UniFAR-FTUs huggingface dataset:
High probability of follow-up termination among AYA survivors after allogeneic hematopoietic cell transplantation.

The need for long-term follow-up (LTFU) after allogeneic hematopoietic cell transplantation (HCT) has been increasingly recognized for managing late effects such as subsequent cancers and cardiovascular events. A substantial population, however, has already terminated LTFU at HCT centers. To better characterize follow-up termination, we analyzed the Japanese transplant registry database. The study cohort included 17 980 survivors beyond 2 years who underwent their first allogeneic HCT between 1974 and 2013. The median patient age at HCT was 34 years (range, 0-76 years). Follow-up at their HCT center was terminated in 4987 patients. The cumulative incidence of follow-up termination was 28% (95% confidence interval [CI], 27%-29%) at 10 years, increasing to 67% (95% CI, 65%-69%) at 25 years after HCT. Pediatric patients showed the lowest probability of follow-up termination for up to 16 years after HCT, whereas adolescent and young adult (AYA) patients showed the highest probability of follow-up termination throughout the period. Follow-up termination was most often made by physicians based on the patient's good physical condition. Multivariate analysis identified 6 factors associated with follow-up termination: AYA patients, female patients, standard-risk malignancy or nonmalignant disease, unrelated bone marrow transplantation, HCT between 2000 and 2005, and absence of chronic graft-versus-host disease. These results suggest the need for education of both physicians and patients about the importance of LTFU, even in survivors with good physical condition. The decreased risk for follow-up termination after 2005 may suggest the increasing focus on LTFU in recent years.
Interruptin B induces brown adipocyte differentiation and glucose consumption in adipose-derived stem cells

Interruptin B has been isolated from Cyclosorus terminans, however, its pharamcological effect has not been fully identified. In the present study, the effects of interruptin B, from C. terminans, on brown adipocyte differentiation and glucose uptake in adipose-derived stem cells (ASCs) were investigated. The results revealed that interruptin B dose-dependently enhanced the adipogenic differentiation of ASCs, with an induction in the mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. In addition, interruptin B efficiently increased the number and the membrane potential of mitochondria and upregulated the mRNA expression levels of uncoupling protein (UCP)-1 and cyclooxygenase (COX)-2, which are all predominantly expressed in brown adipocytes. Interruptin B increased glucose consumption in differentiated ASCs, accompanied by the upregulation in the mRNA expression levels of glucose transporter (GLUT)-1 and GLUT-4. The computational analysis of molecular docking, a luciferase reporter assay and surface plasmon resonance confirmed the marked binding affinity of interruptin B to PPAR-α and PPAR-γ (KD values of 5.32 and 0.10 µM, respectively). To the best of our knowledge, the present study is the first report to show the stimulatory effects of interruptin B on brown adipocyte differentiation and glucose uptake in ASCs, through its role as a dual PPAR-α and PPAR-γ ligand. Therefore, interruptin B could be further developed as a therapeutic agent for the treatment of diabetes.
Trends in Hospitalizations and Outcomes for Acute Cardiovascular Disease and Stroke, 1999–2011

Background— During the past decade, efforts focused intensely on improving the quality of care for people with, or at risk for, cardiovascular disease and stroke. We sought to quantify the changes in hospitalization rates and outcomes during this period. Methods and Results— We used national Medicare data to identify all Fee-for-Service patients ≥65 years of age who were hospitalized with unstable angina, myocardial infarction, heart failure, ischemic stroke, and all other conditions from 1999 through 2011 (2010 for 1-year mortality). For each condition, we examined trends in adjusted rates of hospitalization per patient-year and, for each hospitalization, rates of 30-day mortality, 30-day readmission, and 1-year mortality overall and by demographic subgroups and regions. Rates of adjusted hospitalization declined for cardiovascular conditions (38.0% for 2011 compared with 1999 [95% confidence interval (CI), 37.2–38.8] for myocardial infarction, 83.8% [95% CI, 83.3–84.4] for unstable angina, 30.5% [95% CI, 29.3–31.6] for heart failure, and 33.6% [95% CI, 32.9–34.4] for ischemic stroke compared with 10.2% [95% CI, 10.1–10.2] for all other conditions). Adjusted 30-day mortality rates declined 29.4% (95% CI, 28.1–30.6) for myocardial infarction, 13.1% (95% CI, 1.1–23.7) for unstable angina, 16.4% (95% CI, 15.1–17.7) for heart failure, and 4.7% (95% CI, 3.0–6.4) for ischemic stroke. There were also reductions in rates of 1-year mortality and 30-day readmission and consistency in declines among the demographic subgroups. Conclusions— Hospitalizations for acute cardiovascular disease and stroke from 1999 through 2011 declined more rapidly than for other conditions. For these conditions, mortality and readmission outcomes improved.
Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation

Significance Patterned spontaneous activity can modify the structure and function of neural circuits during development, such as retinal waves essential for establishing functional visual circuits. Retinal waves are initiated by presynaptic release, further inducing temporally synchronized oscillations of PKA activity. However, the PKA substrate regulating visual circuit refinement remains elusive. Here, we describe a biological mechanism in which PKA-mediated SN25 phosphorylation in presynaptic retinal neurons down-regulates synaptic strength and retinal waves during development. These changes in wave spatiotemporal patterns can further induce global effects on visual circuit refinement, i.e., the eye-specific segregation of retinogeniculate projection. Therefore, by switching the phosphorylation state by PKA, SN25 in wave-initiating neurons can regulate the plasticity of retinal circuit activity and sculpt developing visual circuits. Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.
Ophelimus mediterraneus sp. n. (Hymenoptera, Eulophidae): a new Eucalyptus gall wasp in the Mediterranean region

Abstract We report here for the first time the presence of Ophelimus mediterraneus sp. n. in Mediterranean Europe. This species appears to be closely related to Ophelimus maskelli, a well-known invasive pest of Eucalyptus. Based on molecular (cytochrome oxidase I, 28S), morphological (multivariate ratio analysis) and bio-ecological investigations, our study gives unambiguous relevant criteria that allow the discrimination between these two species. A full description of O. mediterraneus sp. n. is also provided. The geographic distribution of O. mediterraneus sp. n. as well as its impact on Eucalyptus species needs to be more widely assessed since its presence may have been confused with O. maskelli in their sympatric introduced areas. Further investigations of potential parasitoids in the native area may thus be welcomed to evaluate classical biological control achievability.
Influence of Electronic Devices on Sleep and Cognitive Performance During Athlete Training Camps

Supplemental Digital Content is Available in the Text. Abstract Jones, MJ, Dawson, B, Eastwood, PR, Halson, SL, Miller, J, Murray, K, Dunican, IC, Landers, GJ, and Peeling, P. Influence of electronic devices on sleep and cognitive performance during athlete training camps. J Strength Cond Res 35(6): 1620–1627, 2021—This study investigated the effects of removing athletes' electronic devices in the evening on sleep and performance during training camps. Water polo athletes (n = 26) attending a 7-night training camp (study 1) and triathletes (n = 23) attending a 4-night training camp (study 2) were randomly allocated to a no-device group (no electronic devices could be used after dinner or overnight; ND) or control group (unrestricted electronic device use; CON). Sleep was monitored through wrist actigraphy. The ND group completed a questionnaire measuring anxiety related to being unable to use electronic devices (“nomophobia”). Triathletes also completed a psychomotor vigilance test (PVT) at the start and end of camp. Water polo ND athletes went to bed earlier and spent longer time in bed than CON on the first night, but not on other nights. In triathletes, sleep quantity was not different between groups on any night. No statistically significant differences were observed for changes in nomophobia from the first to the last night of camp. No differences in PVT performance were observed between ND and CON triathletes. In conclusion, removal of evening electronic devices does not improve sleep quantity or cognitive performance in athletes during short-duration (4–7 nights) training camps.
Objective Morphological Classification of Neocortical Pyramidal Cells

Abstract A consensus on the number of morphologically different types of pyramidal cells (PCs) in the neocortex has not yet been reached, despite over a century of anatomical studies, due to the lack of agreement on the subjective classifications of neuron types, which is based on expert analyses of neuronal morphologies. Even for neurons that are visually distinguishable, there is no common ground to consistently define morphological types. The objective classification of PCs can be achieved with methods from algebraic topology, and the dendritic arborization is sufficient for the reliable identification of distinct types of cortical PCs. Therefore, we objectively identify 17 types of PCs in the rat somatosensory cortex. In addition, we provide a solution to the challenging problem of whether 2 similar neurons belong to different types or to a continuum of the same type. Our topological classification does not require expert input, is stable, and helps settle the long-standing debate on whether cell-types are discrete or continuous morphological variations of each other.
Trends and Perspectives in Immunosensors for Determination of Currently-Used Pesticides: The Case of Glyphosate, Organophosphates, and Neonicotinoids

Pesticides, due to their intensive use and their peculiar chemical features, can persist in the environment and enter the trophic chain, thus representing an environmental risk for the ecosystems and human health. Although there are several robust and reliable standard analytical techniques for their monitoring, the high frequency of contamination caused by pesticides requires methods for massive monitoring campaigns that are capable of rapidly detecting these compounds in many samples of different origin. Immunosensors represent a potential tool for simple, rapid, and sensitive monitoring of pesticides. Antibodies coupled to electrochemical or optical transducers have resulted in effective detection devices. In this review, the new trends in immunosensor development and the application of immunosensors for the detection of pesticides of environmental concern—such as glyphosate, organophosphates, and neonicotinoids—are described.
Exploring the structure of narcissism: Toward an integrated solution.

OBJECTIVE Despite decades of work on narcissism, there remain many active areas of exploration and debate including a clear and consensual description of its underlying components. Understanding narcissism's factor structure is necessary for the precise measurement and investigation of specific psychological and behavioral processes. The aim of the current study was to explore the structure of narcissism by examining it at varying hierarchical levels. METHOD Participants recruited from Amazon's Mechanical Turk (N = 591) completed 303 narcissism items encompassing 46 narcissism scales and subscales. Criterion variables measuring the five-factor model, self-esteem, aggression, and externalizing behavior were also collected. RESULTS A series of factor analyses reveal the factor structure of narcissism at a range of specificities. No more than five meaningful factors (i.e., Grandiosity, Neuroticism, Antagonism, Distrustful Self-reliance, Attention-seeking) were identified and the most parsimonious model appears to be a three-factor structure. Narcissism scales that effectively capture each of the identified factors are identified. Factors diverged in their associations with criterion variables. CONCLUSIONS A three-factor model (i.e., Agentic Extraversion, Narcissistic Neuroticism, Self-centered Antagonism) seems to be the most parsimonious conceptualization. Larger factor solutions are discussed, but future research will be necessary to determine the value of these increasingly narrow factors.
Temperamental Anger and Positive Reactivity and the Development of Social Skills: Implications for Academic Competence During Preadolescence

ABSTRACT Research Findings: This study examines whether the development of social skills during childhood serves as a mechanism through which temperamental anger and positive reactivity in toddlerhood influence children’s academic competence during preadolescence (N = 406). Temperamental anger at age 2 was negatively associated with children’s social skills at age 7; in turn, children’s social skills at age 7 were positively associated with teacher reports of academic performance and negatively associated with child and teacher reports of school problems at age 10. All 3 indirect effects were significant, which suggests that children’s social skills at age 7 is one mechanism through which temperamental anger at age 2 is associated with age 10 child- and teacher-reported school problems. Temperamental positive reactivity was not associated with children’s social skills or academic competence. Practice or Policy: Results provide support for early entry points to teach toddlers, especially those high in anger reactivity, the skills to engage in socially appropriate interactions with classmates and teachers, which may lessen subsequent academic challenges.
Reporting elevated vancomycin minimum inhibitory concentration in methicillin-resistant Staphylococcus aureus: consensus by an International Working Group

Methicillin-resistant Staphylococcus aureus (MRSA) remains an important cause of serious infection, for which vancomycin is often recommended as the first-choice antibiotic treatment. Appropriate vancomycin prescribing requires accurate measurement of minimum inhibitory concentrations (MICs) to avoid treatment failure, and yet determination can be challenging due to methodological difficulties associated with susceptibility testing. An International Working Group of infectious disease specialists and clinical/medical microbiologists reached a consensus that empirical MRSA infection therapies should be chosen regardless of the suspected origin of the infecting strain (e.g., community or hospital) due to the complex intermingling epidemiology of MRSA clones in these settings. Also, if an elevated vancomycin MIC in the susceptible range is obtained in routine testing, an alternative second method should be used for confirmation and to aid antibiotic therapy recommendations. There is no absolutely dependable method for the accurate determination of vancomycin MIC, but broth microdilution appears to be the most reliable.
Public health responses to the opioid crisis in North America

The opioid overdose epidemic in North America remains among the most challenging public health issues of recent times. Sadly, all evidence points to a worsening of the epidemic,1 2 despite growing investment in responses that span policy and legislative changes, scale-up of evidence-based overdose interventions, and the implementation and evaluation of novel interventions. This has prompted concerns about what is and what is not being done to address this epidemic that has resulted in reductions in life expectancy in both the USA and Canada. Given the well-described problem of the overprescribing of opioids for pain, governments and medical bodies have sought to reduce opioid prescribing through guideline development, physician education and monitoring efforts. While the rate of prescribing in the USA dropped from a high of 81.3 per 100 persons in 2012 to 58.5 per 100 persons in 2017,3 the death rate attributable to opioids continues to rise, and prescription opioid misuse has remained fairly stable since 2010.3 While this result may seem unexpected, it is not entirely surprising given observed transitions from prescription opioid to heroin use in the USA, as well as evidence from Canada indicating that many individuals acquire heroin or diverted opioids from drug markets when denied opioids from physicians.4 These dynamics are consistent with evidence from a range of settings indicating that when access to one substance is restricted, most individuals will transition to using an alternative, which in many cases will be more dangerous than standardised doses of prescription opioids. While many have attributed the overdose crisis to opioid prescribing, this is an obvious oversimplification of this epidemic. There is now clear evidence of an increasing role of illicitly manufactured opioids, such as fentanyl and related analogues, in the continued rise in overdose deaths. In the USA, overdose deaths attributable to …
Occupational Risk Factors for COPD Phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

Abstract Introduction: The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation. Methods: We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45–84 year olds free of clinical cardiovascular disease at baseline. MESA ascertained the most recent job and employment, and the MESA Lung Study measured spirometry, and occupational exposures for 3686 participants. Associations between health outcomes (spirometry defined airflow limitation and Medical Research Council-defined chronic bronchitis) and occupational exposure [self-reported occupational exposure to vapor-gas, dust, or fumes (VGDF), severity of exposure, and a job-exposure matrix (JEM)-derived score] were evaluated using logistic regression models adjusted for non-occupational risk factors. Results: The prevalence of airflow limitation was associated with self-reported exposure to vapor-gas (OR 2.6, 95%CI 1.1–2.3), severity of VGDF exposure (P-trend < 0.01), and JEM dust exposure (OR 2.4, 95%CI 1.1–5.0), and with organic dust exposure in females; these associations were generally of greater magnitude among never smokers. The prevalence of chronic bronchitis and wheeze was associated with exposure to VGDF. The association between airflow limitation and the combined effect of smoking and VGDF exposure showed an increasing trend. Self-reported vapor-gas, dust, fumes, years and severity of exposure were associated with increased prevalence of chronic bronchitis and wheeze (P < 0.001). Conclusions: Airflow limitation was associated with self-reported VGDF exposure, its severity, and JEM-ascertained dust exposure in smokers and never-smokers in this multiethnic study.
Predictors for clinical benefit of immune checkpoint inhibitors in advanced non-small-cell lung cancer: a meta-analysis.

AIM In this meta-analysis, we evaluated several predictors of benefit to single-agent immune checkpoint inhibitors (ICIs) in metastatic non-small-cell lung cancer (NSCLC). PATIENTS & METHODS Using the random-effect model, we assessed the comparative efficacy of ICIs over chemotherapy according to age, gender, smoking history, PD-L1 status and CNS involvement. RESULTS Eight randomized trials were selected. In comparison to chemotherapy, ICIs demonstrated significant progression-free survival (PFS) superiority in ever-smoker, male and PD-L1 positive subgroups. Never-smoker was an unfavorable factor for ICIs. Female and PD-L1 nonexpressing patients demonstrated similar PFS between ICIs and chemotherapy. ICI's PFS benefit wasn't influenced by age or CNS involvement. The overall survival (OS) benefit of ICIs was consistent across all subgroups, except for never-smokers. CONCLUSION Male, ever-smoker and positive PD-L1 are indicative of benefit to ICIs in metastatic non-small-cell lung cancer.
Optimization of Methionyl tRNA-Synthetase Inhibitors for Treatment of Cryptosporidium Infection

Cryptosporidiosis is one of the leading causes of moderate to severe diarrhea in children in low-resource settings. The therapeutic options for cryptosporidiosis are limited to one drug, nitazoxanide, which unfortunately has poor activity in the most needy populations of malnourished children and HIV-infected persons. ABSTRACT Cryptosporidiosis is one of the leading causes of moderate to severe diarrhea in children in low-resource settings. The therapeutic options for cryptosporidiosis are limited to one drug, nitazoxanide, which unfortunately has poor activity in the most needy populations of malnourished children and HIV-infected persons. We describe here the discovery and early optimization of a class of imidazopyridine-containing compounds with potential for treating Cryptosporidium infections. The compounds target the Cryptosporidium methionyl-tRNA synthetase (MetRS), an enzyme that is essential for protein synthesis. The most potent compounds inhibited the enzyme with Ki values in the low picomolar range. Cryptosporidium cells in culture were potently inhibited with 50% effective concentrations as low as 7 nM and >1,000-fold selectivity over mammalian cells. A parasite persistence assay indicates that the compounds act by a parasiticidal mechanism. Several compounds were demonstrated to control infection in two murine models of cryptosporidiosis without evidence of toxicity. Pharmacological and physicochemical characteristics of compounds were investigated to determine properties that were associated with higher efficacy. The results indicate that MetRS inhibitors are excellent candidates for development for anticryptosporidiosis therapy.