Miracle-dz/UniFAR-FTUs huggingface dataset:
Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes-Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies.

RATIONALE Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking. OBJECTIVES To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry. METHODS The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry. MEASUREMENTS AND MAIN RESULTS A 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function. CONCLUSIONS Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.
Management of high risk pulmonary embolism - a single center experience.

BACKGROUND AND AIM Patients with acute pulmonary embolism (APE) associated with hemodynamic instability, i.e. high-risk APE (HR-APE), are at risk for early mortality and require urgent reperfusion therapy with thrombolysis or embolectomy. However, a considerable proportion of HR-APE subjects is not reperfused but only anticoagulated due to high bleeding risk. The aim of the present study was to assess the management of HR-APE in a single large-volume referral center. METHODS A single-center retrospective study of 32 HR-APE subjects identified among 823 consecutive patients hospitalized for symptomatic APE. RESULTS Out of 32 subjects with HR-APE (19 women, age 69 ± 19 years), 20 patients were unstable at admission and 12 subsequently deteriorated despite on-going anticoagulation. Thrombolysis was applied in 20 (62.5%) of HR-APE subjects, limited mainly by classical contraindications in the remainder. Percutaneous pulmonary embolectomy was performed in 4 patients. In-hospital PE-related mortality tended to be higher, albeit insignificantly, in the patients who developed hemodynamic collapse during the hospital course compared to those unstable at admission (67% vs. 40%, p = 0.14). Also, survival was slightly better in 22 patients treated with thrombolysis or percutaneous embolectomy in comparison to 10 subjects who received only anticoagulation (54% vs. 40%, p = 0.2). Major non-fatal bleedings occurred in 7 of 20 patients receiving thrombolysis (35%) and in 2 (17%) of the remaining non-thrombolysed 12 HR-APE subjects. CONCLUSIONS Hemodynamically instability, corresponding to the definition of HR-APE, affects about 4% of patients with APE, developing during the hospital course in approximately one-third of HR-APE subjects. As almost 40% of patients with HR-APE do not receive thrombolytic therapy for fear of bleeding, urgent percutaneous catheter-assisted embolectomy may increase the percentage of patients with HR-APE undergoing reperfusion therapy. Further studies are warranted for a proper identification of initially stable intermediate-risk APE subjects at risk of hemodynamic collapse despite appropriate anticoagulation.
Content validity of the SOS-WRIST questionnaire for timely identification of wrist overuse in young athletes

ABSTRACT Objectives: Young athletes do not always seek medical help for overuse wrist injuries, risking invalidating long-term consequences resulting from late diagnosis. This study aimed to develop a questionnaire to identify overuse wrist injuries in young athletes. Methods: According to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria, items were collected from literature and 6 focus groups of sports physicians and of young athletes with (previous) overuse wrist injuries. An expert panel and 40 Delphi study participants performed item reduction. Young athletes evaluated comprehensiveness during interviews and English translation was performed according to linguistic validation guidelines. Results: In total 323 items were generated and 110 were marked important by focus group participants. The resulting questionnaire consists of 18 multiple-choice questions about wrist pain during sports (e.g. pain during training, skipping training sessions/elements) and daily life activities (e.g. writing, turning a key), and other symptoms (e.g. reduced strength, swelling). Conclusion: The SOS-WRIST questionnaire for identification of overuse wrist injuries in young athletes has good content validity. It can be used to promote awareness and timely treatment of overuse wrist injuries in young athletes.
Impact of a novel oral health promotion program on routine oral hygiene among socioeconomically disadvantaged smokers: results from a randomized semi-pragmatic trial

Abstract Smokers are at high risk of oral disease and report sub-optimal oral hygiene. Improving smokers’ oral hygiene could reduce their future disease risk. The purpose of this study is to assess the effects of a novel, multi-modal oral health promotion program (Oral Health 4 Life; OH4L) targeted to socioeconomically disadvantaged smokers and delivered through state-funded tobacco quitlines. Smokers (n = 718) were randomized to standard quitline care or standard care plus OH4L. OH4L recipients received a comprehensive behavioral intervention and were advised of the benefits of routine oral hygiene, encouraged to brush and floss daily (for better oral health and to manage cigarette cravings), and provided a toothbrush and floss. Participants were followed for 6 months to assess the intervention effects on routine oral hygiene (brushing and flossing) and changes in motivation and self-efficacy. Data were collected between 2015 and 2017. At 2-month follow-up, OH4L participants were more likely to meet the American Dental Association (ADA) recommendations for brushing twice daily (adjusted RR = 1.15 [1.04, 1.27], p = .006), flossing daily (adjusted RR = 1.20 [1.03, 1.39], p = .02), and for both brushing and flossing (adjusted RR = 1.33 [1.10, 1.61], p = .003). Daily flossing was more likely at 6-month follow-up (adjusted RR = 1.21 [1.04, 1.42], p = .02) among OH4L participants. The change in self-efficacy and motivation for daily flossing from baseline to 2 months was significantly greater among OH4L participants and mediated the intervention effect on flossing at 6 months. Integrating oral hygiene promotion with standard tobacco quitline services improved oral health self-care.
Similar relative decline in aerobic and anaerobic power with age in endurance and power master athletes of both sexes

Lower physical activity levels in old age are thought to contribute to the age‐related decline in peak aerobic and anaerobic power. Master athletes maintain high levels of physical activity with advancing age and endurance or power training may influence the extent to which these physical functions decline with advancing age. To investigate, 37‐90‐year‐old power (n = 20, 45% female) and endurance (n = 19, 58% female) master athletes were recruited. Maximal aerobic power was assessed when cycling two‐legged (VO2Peak2‐leg) and cycling one‐legged (VO2Peak1‐leg), while peak jumping (anaerobic) power was assessed by a countermovement jump. Men and women had a similar VO2Peak2‐leg (mL/kg/min, P = 0.138) and similar ratio of VO2Peak1‐leg to VO2Peak2‐leg (P = 0.959) and similar ratio of peak aerobic to anaerobic power (P = 0.261). The VO2Peak2‐leg (mL/kg/min) was 17% (P = 0.022) and the peak rate of fat oxidation (FATmax) during steady‐state cycling was 45% higher in endurance than power athletes (P = 0.001). The anaerobic power was 33% higher in power than endurance athletes (P = 0.022). The VO2Peak1‐leg:VO2Peak2‐leg ratio did not differ significantly between disciplines, but the aerobic to anaerobic power ratio was 40% higher in endurance than power athletes (P = 0.002). Anaerobic power, VO2Peak2‐leg, VO2Peak1‐leg, and power at FATmax decreased by around 7%‐14% per decade in male and female power and endurance athletes. The cross‐sectional data from 37‐90‐year‐old master athletes in the present study indicate that peak anaerobic and aerobic power decline by around 7%‐14% per decade and this does not differ between athletic disciplines or sexes.
Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity

Significance Regulatory T cells (Tregs) protect cancer cells from immune attack. Tregs express CD25 on their surface and can be killed by antibodies and immunoconjugates targeting CD25. These agents have not been effective in controlling tumor growth, probably because they also kill cytotoxic CD8 T cells expressing CD25 that are needed for antitumor activity. To overcome these deficiencies, we have directly injected tumors with a potent anti-CD25 immunotoxin, 2E4-PE38, that kills CD25-expressing Treg cells in the tumor, causes injected and distant tumors to regress, and induces antitumor immunity. Because 2E4-PE38 is present at very low concentrations in the blood, it does not kill CD25-expressing cells at distant sites. This strategy could be employed for treating tumors in people. The tumor microenvironment plays a critical role in controlling tumor progression and immune surveillance. We produced an immunotoxin (2E4-PE38) that kills mouse cells expressing CD25 by attaching the Fv portion of monoclonal antibody 2E4 (anti-mouse CD25) to a 38-kDa portion of Pseudomonas exotoxin A. We employed three mouse cancer tumor models (AB1 mesothelioma, 66c14 breast cancer, and CT26M colon cancer). Tumors were implanted at two sites on BALB/c mice. On days 5 and 9, one tumor was directly injected with 2E4-PE38, and the other was not treated; 2E4-PE38 produced complete regressions of 85% of injected AB1 tumors, 100% of 66c14 tumors, and 100% of CT26M tumors. It also produced complete regressions of 77% of uninjected AB1 tumors, 47% of 66c14 tumors, and 92% of CT26M tumors. Mice with complete regressions of 66c14 tumors were immune to rechallenge with 66c14 cells. Mice with complete regressions of AB1 or CT26M tumors developed cross-tumor immunity rejecting both tumor types. Injection of anti-CD25 antibody or a mutant inactive immunotoxin were generally ineffective. Tumors were analyzed 3 days after 2E4-PE38 injection. The number of regulatory T cells (Tregs) was significantly reduced in the injected tumor but not in the spleen. Injected tumors contained an increase in CD8 T cells expressing IFN-γ, the activation markers CD69 and CD25, and macrophages and conventional dendritic cells. Treatment with antibodies to CD8 abolished the antitumor effect. Selective depletion of Tregs in tumors facilitates the development of a CD8 T cell-dependent antitumor effect in three mouse models.
Effects of Ankaferd Hemostat on red blood cell aggregation: a hemorheological study

Background/aim Ankaferd hemostat (ABS; Ankaferd blood stopper, İstanbul, Turkey) is a prohemostatic agent affecting erythrocytes. The hemostatic action of ABS depends upon fibrinogen gamma chain, prothrombin, and red blood cells. The aim of this study was to assess the effects of ABS on erythrocyte aggregation via hemorheological analyses. Materials and methods To measure erythrocyte aggregation, blood samples were obtained from healthy, nonsmoker volunteers who had not taken any medication in the previous 10 days. One mL of blood was placed into the laser-assisted optical rotational cell analyzer (LORCA), into the chamber formed by the gap between two concentric glass cylinders. The solution prepared with ABS and saline was added to blood in incremental amounts of 10 µL, 20 µL, 30 µL, 40 µL, 50 µL, 60 µL, 70 µL, and 100 µL. Erythrocyte aggregation was determined by laser-assisted optical rotational cell analyzer at 37 °C. Results AMP was found to be 17.7 ± 2.1 au in the blood without ABS, whereas it was lower in the blood with ABS. AMP was 16.0 ± 3.3 in the ABS-added blood group. RBC aggregates did not form faster when cells contacted ABS. The t t½ value was 4.6 ± 2.6 in the ABS-added blood group and 1.9 ± 0.20 in the control group. Aggregation was faster in the control group (P = 0.03). AI, which is a combination of AMP and t½, was lowered in the ABS group (48.7 ± 12.3) compared to the control group (65.8 ± 1.6) (P = 0.02). It was notable that the γIsc max (sec-1) value of the control was higher (200 ± 106) than the ABS-added blood group (141 ± 51.0). Conclusion ABS has antierythroid aggregation effect. ABS inhibits pathological aggregation of red blood cells. Antithrombotic clinical effects of ABS may be ascribed to the antierythroid aggregan actions of the drug.
Androgen receptor nuclear localization correlates with AR-V7 mRNA expression in circulating tumor cells (CTCs) from metastatic castration resistance prostate cancer patients

Androgen receptor (AR) signaling drives prostate cancer (PC) progression and remains active upon transition to castration resistant prostate cancer (CRPC). Active AR signaling is achieved through the nuclear accumulation of AR following ligand binding and through expression of ligand-independent, constitutively active AR splice variants, such as AR-V7, which is the most commonly expressed variant in metastatic CRPC (mCRPC) patients. Most currently approved PC therapies aim to abrogate AR signaling and activity by inhibiting this ligand-mediated nuclear translocation. In a prospective multi-institutional clinical study, we recently showed that taxane based chemotherapy is also capable of impairing AR nuclear localization (ARNL) in circulating tumor cells (CTCs) from CRPC patients, whereas taxane induced decreases in ARNL were associated with response. Thus, quantitative assessment of ARNL in CTCs can be used to monitor therapeutic response in patients and help guide clinical decisions. Here, we describe the development and implementation of quantitative high throughput (QHT) image analysis algorithms to aid in CTC identification and quantitative assessment of percent ARNL (%ARNL). We applied this algorithm to fifteen CRPC patients at the start of taxane chemotherapy, quantified %ARNL in CTCs, and correlated with expression of AR-V7 mRNA (from CTCs enriched via negative, CD45+ depletion of peripheral blood) and with biochemical (prostate specific antigen; PSA) response to taxane chemotherapy. We found that CTCs from AR-V7 positive patients had higher baseline %ARNL compared to CTCs from AR-V7 negative patients, consistent with the constitutive nuclear localization of AR-V7. In addition, lower %ARNL in CTCs at baseline was associated with biochemical response to taxane chemotherapy. High inter- and intra-patient heterogeneity was also observed. As ARNL is required for active AR signaling, the QHT algorithms described herein can provide prognostic and/or predictive value in future clinical studies.
Type I interferon protects neurons from prions in in vivo models

Using cell culture and animal models of prion diseases, Ishibashi et al. show that type I interferon signalling interferes with prion infection in mammals. A selective type I interferon receptor agonist inhibits prion invasion and prolongs survival of prion-infected mice, suggesting potential clinical applications.
DNA crookedness regulates DNA mechanical properties at short length scales

Sequence-dependent DNA conformation and flexibility play a fundamental role in specificity of DNA-protein interactions. Here we quantify the DNA crookedness: a sequence-dependent deformation of DNA that consists on periodic bends of the base pair centers chain. Using molecular dynamics simulations, we found that DNA crookedness and its associated flexibility are bijective: unveiling a one-to-one relation between DNA structure and dynamics. This allowed us to build a predictive model to compute DNA stretching stiffness from solely its structure. Sequences with very little crookedness show extremely high stiffness and have been previously shown to form unstable nucleosomes and promote gene expression. Interestingly, the crookedness can be tailored by epigenetic modifications, known to affect gene expression. Our results rationalize the idea that the DNA sequence is not only a chemical code, but also a physical one that allows to finely regulate its mechanical properties and, possibly, its 3D arrangement inside the cell.
Evidence-Based Policy Making: Assessment of the American Heart Association’s Strategic Policy Portfolio A Policy Statement From the American Heart Association

Background— American Heart Association (AHA) public policy advocacy strategies are based on its Strategic Impact Goals. The writing group appraised the evidence behind AHA’s policies to determine how well they address the association’s 2020 cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management indicators and identified research needed to fill gaps in policy and support further policy development. Methods and Results— The AHA policy research department first identified current AHA policies specific to each CVH metric and CVD management indicator and the evidence underlying each policy. Writing group members then reviewed each policy and the related metrics and indicators. The results of each review were summarized, and topic-specific priorities and overarching themes for future policy research were proposed. There was generally close alignment between current AHA policies and the 2020 CVH metrics and CVD management indicators; however, certain specific policies still lack a robust evidence base. For CVH metrics, the distinction between policies for adults (age ≥20 years) and children (<20 years) was often not considered, although policy approaches may differ importantly by age. Inclusion of all those <20 years of age as a single group also ignores important differences in policy needs for infants, children, adolescents, and young adults. For CVD management indicators, specific quantitative targets analogous to criteria for ideal, intermediate, and poor CVH are lacking but needed to assess progress toward the 2020 goal to reduce deaths from CVDs and stroke. New research in support of current policies needs to focus on the evaluation of their translation and implementation through expanded application of implementation science. Focused basic, clinical, and population research is required to expand and strengthen the evidence base for the development of new policies. Evaluation of the impact of targeted improvements in population health through strengthened surveillance of CVD and stroke events, determination of the cost-effectiveness of policy interventions, and measurement of the extent to which vulnerable populations are reached must be assessed for all policies. Additional attention should be paid to the social determinants of health outcomes. Conclusions— AHA’s public policies are generally robust and well aligned with its 2020 CVH metrics and CVD indicators. Areas for further policy development to fill gaps, overarching research strategies, and topic-specific priority areas are proposed.
Inactivity induces resistance to the metabolic benefits following acute exercise.

Acute exercise improves postprandial lipemia, glucose tolerance, and insulin sensitivity, all of which are risk factors for cardiovascular disease. However, recent research suggests that prolonged sedentary behavior might abolish these healthy metabolic benefits. Accordingly, this study aimed to elucidate the impact of an acute bout of exercise on postprandial plasma triglyceride, glucose, and insulin concentrations after 4 days of prolonged sitting (~13.5 h/day). Ten untrained to recreationally active men (n = 5) and women (n = 5) completed a counterbalanced, crossover study. Four days of prolonged sitting without exercise (SIT) were compared with 4 days of prolonged sitting with a 1-h bout of treadmill exercise (SIT + EX; 63.1 ± 5.2% V̇o2max) on the evening of the fourth day. The following morning, participants completed a high-fat/glucose tolerance test (HFGTT), during which plasma was collected over a 6-h period and analyzed for triglycerides, glucose, and insulin. No differences between trials (P > 0.05) were found in the overall plasma triglyceride, glucose, or insulin responses during the HFGTT. This lack of difference between trials comes with similarly low physical activity (~3,500-4,000 steps/day) on each day except for the 1-h bout of exercise during SIT + EX the day before the HFGTT. These data indicate that physical inactivity (e.g., sitting ~13.5 h/day and <4,000 steps/day) creates a condition whereby people become "resistant" to the metabolic improvements that are typically derived from an acute bout of aerobic exercise (i.e., exercise resistance). NEW & NOTEWORTHY In people who are physically inactive and sitting for a majority of the day, a 1-h bout of vigorous exercise failed to improve lipid, glucose, and insulin metabolism measured the next day. It seems that something inherent to inactivity and/or prolonged sitting makes the body resistant to the 1 h of exercise preventing the normally derived metabolic improvements following exercise.
Reply to Alizadeh's Letter to the Editor on 'Dietary patterns and endometrial cancer: a meta-analysis'.

First, we are grateful to Alizadeh for alerting us on the methodological limitations in our articles. We value the feedback on the methodological limitations in this metaanalysis. Thus, in this reply, we have endeavored to respond to the point highlighted by Alizadeh. As Alizadeh reports, there are only five studies (McCann et al., 2001; Dalvi et al., 2007; Biel et al., 2011; Bravi et al., 2015; Canchola et al., 2015) reporting the associations between dietary patterns and EC risk. However, we cannot ignore the effect of food groups on the risk of EC, although they do not represent whole diet. To our knowledge, the association of diet with the risk of EC has been inconclusive. Besides, although some studies have reported the decreased risk of EC associated with fruits and vegetables, an international panel of experts concluded that the evidence for the association of vegetable and fruit consumption with EC risk is limited and inconsistent. Thus, to minimize error, the authors ensured that the defined dietary patterns were similar with regard to the main factor, loadings of foods, which are consumed within those whole diets. For example, the first pattern, named as healthy pattern, is characterized to have high loadings of foods such as fresh vegetables and fruit, whole grain, fish, soy, and antioxidants (e.g. vitamins C and E, flavonoids, and carotenoids), and low fat dairy. The second pattern was named as ‘western-style’ dietary pattern, which is characterized to have high consumption of – for example, red and/or processed meat, refined grains, sweets, high-fat dairy products, butter, potatoes and high-fat gravy, and low intakes of fruits and vegetables. Higher intake of meat may reflect a western dietary behavior and lifestyle. Thus, we considered meat intake in the studies by Genkinger et al. (2012), Shu et al. (1993), and Arem et al. (2013) as a western dietary pattern.