Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of the asthma–chronic obstructive pulmonary disease syndrome on the stroke, Parkinson's disease, and dementia: a national cohort study

Background To evaluate the association of asthma–chronic obstructive pulmonary disease syndrome (ACOS) with neurodegenerative diseases (stroke, Parkinson's disease and dementia) and the role of the steroids in the neurodegenerative diseases among the ACOS cohort. Materials and Methods Comparison of the ACOS cohort (N = 10,260) with the non-ACOS cohort (n = 20,513) based on the patients aged ≧40 years in the National Health Insurance Research Database from January 1, 2000 to December 31, 2010. These patients follow up to diagnosis of neurodegenerative diseases or the December 31, 2011; using multivariable Cox proportional hazards models. Results After adjustment for potential confounders, the [adjusted hazard ratio (aHR), 95% confidence interval (CI)] in the ACOS cohort were [1.39, 1.28–1.50] [1.56, 1.34–1.81] and [1.43, 1.29–1.59] for stroke, Parkinson's disease, dementia; respectively. The [aHR, 95% CI] for ACOS cohort with (inhaler corticosteroids ≧0.13 gram/ oral steroids ≧0.08gram) were with less risk (all aHR<1, p values <0.05) for these 3 neurodegenerative diseases except Parkinson's disease with inhaler corticosteroids >0.43 gram. The risk of stroke and dementia were the lower in patients with < 250 μg/d of a fluticasone equivalent inhaler corticosteroids (aHR = 0.53, 95% CI = 0.35–0.79; aHR = 0.53, 95% CI = 0.31–0.90, respectively). Conclusions The ACOS cohort had a higher risk of the neurodegenerative diseases. The lower dose of the inhaler corticosteroids with cumulative dose ≧0.13 gram have the less risk of stroke and dementia.
Transition to Adult Mental Health Services for Young People With ADHD

Objective: To investigate the care management and continuity from child to adult mental health service for young adults with ADHD. Method: A questionnaire survey from 18 Regional ADHD Pediatric Centers (RAPC) in Lombardy, Italy, was used to collect data on transition protocols and population served, and to track the pathway of care of ADHD patients once they reached adulthood. Results: Twenty-eight percent of RAPC had transition protocols and 3% of the population annually served were potential referrals to adult service. Of 52 patients who turned 18 years, just over 70% were monitored by the general practitioner, of those 5 with RAPC support. One fifth of patients continued to use mental health services, the majority was still monitored by the RAPC, and only three by services for adult. Conclusion: Managing the process of transition to adult services in mental health care remains a need to be prioritized and better defined for ADHD patients.
Fungal Microbiota Profile in Newly Diagnosed Treatment-naïve Children with Crohn’s Disease

Background and Aims Although increasing evidence suggests a role for fungi in inflammatory bowel disease [IBD], data are scarce and mostly from adults. Our aim was to define the characteristics of fungal microbiota in newly diagnosed treatment-naïve children with Crohn's disease [CD]. Methods The children referred for colonoscopy were prospectively enrolled in the study at King Khalid University Hospital, King Saud University, and Al Mofarreh Polyclinics in Riyadh. Tissue and stool samples were collected and frozen till sequencing analysis. The children with confirmed CD diagnosis were designated as cases and the others as non- IBD controls; 78 samples were collected from 35 children [15 CD and 20 controls]. Statistical analysis was performed to investigate CD associations and diversity. Results CD-associated fungi varied with the level of phylogenetic tree. There was no significant difference in abundance between normal and inflamed mucosa. Significantly abundant CD-associated taxa included Psathyrellaceae [p = 0.01], Cortinariaceae [p = 0.04], Psathyrella [p = 0.003], and Gymnopilus [p = 0.03]. Monilinia was significantly depleted [p = 0.03], whereas other depleted taxa, although not statistically significant, included Leotiomycetes [p = 0.06], Helotiales [p = 0.08], and Sclerotiniaceae [p = 0.07]. There was no significant difference in fungal diversity between CD and controls. Conclusions We report highly significant fungal dysbiosis in newly diagnosed treatment-naïve CD children. Depleted and more abundant taxa suggest anti-inflammatory and pro-inflamatory potentials, respectively. Further studies with larger sample size and including functional analysis are needed to clarify the significance of the fungal community in the pathogenesis of CD.
Risk of Second Cancer in Hodgkin Lymphoma Survivors and Influence of Family History

Purpose Although advances in Hodgkin lymphoma (HL) treatment have led to improved disease-free survival, this has been accompanied by an increased risk of second cancers. We sought to quantify the second cancer risks and to investigate the impact of family history. Patients and Methods Using the Swedish Family-Cancer Project Database, we identified 9,522 individuals with primary HL diagnosed between 1965 and 2012. We calculated standardized incidence ratios and cumulative incidence of second cancer in HL survivors and compared the standardized incidence ratios of lung, breast, colorectal, and all second cancers in HL survivors with and without a site-specific family history of cancer. Interactions between family history of cancer and HL treatment were evaluated under additive and multiplicative models. Results Overall, the risk of a second cancer in HL survivors was increased 2.39-fold (95% CI, 2.29 to 2.53). The 30-year cumulative incidence of breast cancer in women diagnosed with HL at younger than 35 years of age was 13.8%. We observed no significant difference in cancer risk over successive time periods. The risk of all second cancers was 1.3-fold higher for HL survivors with a first-degree relative with cancer (P < .001), with 3.3-fold, 2.1-fold, and 1.8-fold differences shown for lung, colorectal, and breast cancers, respectively. Moreover, a greater than additive interaction between family history of lung cancer and HL treatment was shown (P = .03). Conclusion HL survivorship is associated with a substantive risk of a second cancer. Notably, the risk is higher in individuals with a family history of cancer. This information should be used to inform risk-adapted therapy and to assist in screening to reduce long-term morbidity and mortality in patients with HL.
Please hold on: Unobtrusive user authentication using smartphone's built-in sensors

Smartphones provide anytime-anywhere communications and are being increasingly used for a variety of purposes, e.g, sending email, performing online transactions, connecting with friends and acquaintances over social networks. As a result, a considerable amount of sensitive personal information is often generated and stored on smartphones. Thus, smartphone users may face financial as well as sentimental consequences if such information fall in the wrong hands. To address this problem all smartphones provide some form of user authentication, that is the process of verifying the user's identity. Existing authentication mechanisms, such as using 4-digit passcodes or graphical patterns, suffer from multiple limitations - they are neither highly secure nor easy to input. As a results, recent studies found that most smartphone's users do not use any authentication mechanism at all. In this paper, we present a fully unobtrusive user authentication scheme based on micro-movements of the user's hand(s) after the user unlocks her smartphone. The proposed scheme collects data from multiple 3-dimensional smartphone sensors in the background for a specific period of time and profiles a user based on the collected hand(s) movement patterns. Subsequently, the system matches the query pattern with the pre-stored patterns to authenticate the smartphone owner. Our system achieved a True Acceptance Rate (TAR) of 96% at an Equal Error Rate (EER) of 4%, on a dataset of 31 qualified volunteers (53, in total), using Random Forest (RF) classifier. Our scheme can be used as a primary authentication mechanism or can be used as a secondary authentication scheme in conjunction with any of the existing authentication schemes, e.g., passcodes, to improve their security.
Effectiveness of Community-Based Minigrants to Increase Physical Activity and Decrease Sedentary Time in Youth.

OBJECTIVE To determine the effectiveness of targeted grant funding for the implementation of multilevel community interventions to increase moderate to vigorous physical activity (MVPA) and decrease time spent sedentary among a large sample of youth in North Carolina. DESIGN A repeated, cross-sectional, group-randomized controlled trial design with a delayed treatment group. SETTING Twenty counties in North Carolina. PARTICIPANTS Analyses were conducted on 2138 youth, grades 4 to 8, who provided complete data across the 3 waves. INTERVENTION The North Carolina Eat Smart, Move More Community Grants program consisted of 20 separate community interventions implemented by grantees that targeted increasing physical activity and/or decreasing sedentary time in youth. County grantees were pair-matched and randomized to receive funding for implementation in year 1 (2010-2011) or year 2 (2011-2012). MVPA/sedentary time was assessed via accelerometer with demographics assessed via self-report in 3 waves of data collection (fall 2010, 2011, and 2012). MAIN OUTCOME MEASURE MVPA and sedentary time measured via accelerometry. RESULTS After adjusting for covariates, there was no difference in MVPA between counties implementing in year 1 (2010-2011) and those implementing in year 2 (2011-2012; ie, waitlist controls) comparing data collection wave 1 to wave 2 (fall 2010-2011). A significant increase of 2.32 minutes per day of MVPA was observed following the implementation year across all counties as compared with the baseline year. Differences were largely driven by increased MVPA in elementary school youth (fourth and fifth grades). No significant changes in sedentary time were observed. CONCLUSIONS Low-cost, high-reach mini-grants can have a small, but meaningful effect on children's MVPA, with greater effects seen in younger children. Future studies should examine characteristics of mini-grants projects that are associated with the greatest increases in MVPA among youth.
The Utilization of Gleason Grade as the Primary Criterion for Ordering Nuclear Bone Scan in Newly Diagnosed Prostate Cancer Patients

Utilization of nuclear bone scans for staging newly diagnosed prostate cancer has decreased dramatically due to PSA-driven stage migration. The current criteria for performing bone scans are based on limited historical data. This study evaluates serum PSA and Gleason grade in predicting positive scans in a contemporary large series of newly diagnosed prostate cancer patients. Eight hundred consecutive cases of newly diagnosed prostate cancer over a 64-month period underwent a staging nuclear scan. All subjects had histologically confirmed cancer. The relationship between PSA, Gleason grade, and bone scan was examined by calculating series of crude, stratified, and adjusted odds ratios with corresponding 95% confidence intervals. Four percent (32/800) of all bone scans were positive. This proportion was significantly lower in patients with Gleason score ≤7 (1.9%) vs. Gleason score ≥8 (18.8%, p < 0.001). Among patients with Gleason score ≤7, the rate of positive bones scans was 70-fold higher when the PSA was >30 ng/ml compared to ≤30 ng/ml (p < 0.001). For Gleason score ≥8, the rate was significantly higher (27.9 vs. 0%) when PSA was >10 ng/ml compared to ≤10 ng/ml (p = 0.002). The combination of Gleason score and PSA enhances predictability of bone scans in newly diagnosed prostate cancer patients. The PSA threshold for ordering bone scans should be adjusted according to Gleason score. For patients with Gleason scores ≤7, we recommend a bone scan if the PSA is >30 ng/ml. However, for patients with a high Gleason score (8–10), we recommend a bone scan if the PSA is >10 ng/ml.
Oxygen Desaturation Index Differs Significantly Between Types of Sleep Software.

STUDY OBJECTIVES The aim of this study was to compare the oxygen desaturation index (ODI) generated by two different sleep software systems. METHODS Participants undergoing diagnostic polysomnography for suspected obstructive sleep apnea underwent simultaneous oximetry recording using the ResMed ApneaLink Plus device (AL) and Compumedics Profusion PSG3 system (Comp). The ODI was calculated by the algorithms in the respective software of each system. To determine if differences were due to algorithm or recording devices, the Comp software was also used to generate ODI values using oximetry data from the AL. RESULTS In 106 participants, there was good correlation but poor agreement in the ODI generated by the two systems. AL ODI values tended to be higher than Comp ODI values, but with significant variability. For ODI4%, bias was 4.4 events/h (95% limits of agreement -5.8 to 14.6 events/h). There was excellent correlation and agreement when the same oximetry raw data was analyzed by both systems. For ODI4%, bias was 0.03 events/h (95% limits of agreement -2.7 to 2.8 events/h). Similar results were evident when the ODI3% was used. CONCLUSIONS There is a clinically significant difference in ODI values generated by the two systems, likely due to device signal processing, rather than difference in ODI calculation algorithms.
Physical properties of particles and their implications for the calculation of the human regional lung dose

This study aims to investigate the physical properties of particles and their implications for source apportionment and health human exposure studies. A wide range of particle number size distribution (PNSD) measurements was conducted in selected environments using state-of-the-art high time resolution instruments. It is found that PNSD varied in different environments, depending on emission sources and atmospheric processes. A mass balance model was used to predict the penetration, infiltration factors, deposition and loss rates of indoor particles. The loss rates of indoor particles, which are mainly subject to deposition, coagulation and evaporation, were found to be a function of particle size and time. Moreover, HTDMA measurements were performed to study the hygroscopic properties of particles in outdoor and indoor environments, and from five major indoor sources. The particles emitted from indoor sources were mostly hydrophobic. An enhanced lung deposition model based on the ICRP and MPPD models was developed to predict the deposition fraction of particles in the human respiratory tract, with consideration of their hygroscopicity. Furthermore, a combination of lung deposition models and the PMF technique was applied to identify which sources are mostly responsible for deposited particles in the different regions of lung.
Antifungals discovery: an insight into new strategies to combat antifungal resistance

Undeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy.
Rare Variant Association Testing for Sequencing Data Using the Sequence Kernel Association Test ( SKAT )

*These authors contributed equally to this work. 1 Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA 2 Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA 3 Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA 4 Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Glucocorticoids induce differentiation of monocytes towards macrophages that share functional and phenotypical aspects with erythroblastic island macrophages

The classical central macrophage found in erythroblastic islands plays an important role in erythroblast differentiation, proliferation and enucleation in the bone marrow. Convenient human in vitro models to facilitate the study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance in vitro erythropoiesis by supporting hematopoietic stem and progenitor cell survival. Herein, we describe that these specific macrophages also support erythropoiesis. Human monocytes cultured in serum-free media supplemented with stem cell factor, erythropoietin, lipids and dexamethasone differentiate towards macrophages expressing CD16, CD163, CD169, CD206, CXCR4 and the phagocytic TAM-receptor family. Phenotypically, they resemble both human bone marrow and fetal liver resident macrophages. This differentiation is dependent on glucocorticoid receptor activation. Proteomic studies confirm that glucocorticoid receptor activation differentiates monocytes to anti-inflammatory tissue macrophages with a M2 phenotype, termed GC-macrophages. Proteins involved in migration, tissue residence and signal transduction/receptor activity are upregulated whilst lysosome and hydrolase activity GO-categories are downregulated. Functionally, we demonstrate that GC-macrophages are highly mobile and can interact to form clusters with erythroid cells of all differentiation stages and phagocytose the expelled nuclei, recapitulating aspects of erythroblastic islands. In conclusion, glucocorticoid-directed monocyte differentiation to macrophages represents a convenient model system to study erythroid-macrophage interactions.
Clinical and Technological Approaches to the Prehospital Diagnosis of Large Vessel Occlusion

Endovascular thrombectomy is highly effective for the treatment of acute ischemic stroke because of proximal large vessel occlusion,1 but the treatment effect falls rapidly with time.2 Almost all patients with severe stroke are transported by an emergency medical service (EMS), which is independently associated with reduced time to treatment.3 Nevertheless, delays are frequent in patients arriving for endovascular thrombectomy via secondary transport from another facility.1 To reduce time to treatment, some jurisdictions are exploring redirect policies, whereby patients bypass a closer primary stroke center and are instead transported directly to endovascular-capable facilities.4 Instituting a pathway for hospital bypass is a complex undertaking that involves the coordination of diverse stakeholders.4 Core components include patient selection criteria, interfacility agreements (eg, transfer and repatriation), paramedic training, and outcome evaluation. Approaches to patient selection have drawn recent interest, particularly in the use of simplified standardized clinical examinations for the diagnosis of proximal large vessel occlusion. In this review, we review current clinical and technological approaches to patient selection and discuss implementation in the context of jurisdictional features. The database search terms for this review article are provided in the online-only Data Supplement. Proximal large vessel occlusion is the substrate for endovascular thrombectomy—field diagnosis of large vessel occlusion is the sine qua non for hospital bypass. In this section, we discuss important caveats in prehospital diagnosis and follow with a review of specific clinical and technological approaches. ### Caveats Three caveats apply to the interpretation of studies of diagnostic tests for transport decision making: First, diagnosis is primarily a means to support transport decision making, not an end. If 2 diagnoses share the same transport destination, then it might not be so important to distinguish between them. For example, distinguishing between intracerebral hemorrhage (ICH) and large vessel occlusion may be …
Mitochondria control store‐operated Ca2+ entry through Na+ and redox signals

Mitochondria exert important control over plasma membrane (PM) Orai1 channels mediating store‐operated Ca2+ entry (SOCE). Although the sensing of endoplasmic reticulum (ER) Ca2+ stores by STIM proteins and coupling to Orai1 channels is well understood, how mitochondria communicate with Orai1 channels to regulate SOCE activation remains elusive. Here, we reveal that SOCE is accompanied by a rise in cytosolic Na+ that is critical in activating the mitochondrial Na+/Ca2+ exchanger (NCLX) causing enhanced mitochondrial Na+ uptake and Ca2+ efflux. Omission of extracellular Na+ prevents the cytosolic Na+ rise, inhibits NCLX activity, and impairs SOCE and Orai1 channel current. We show further that SOCE activates a mitochondrial redox transient which is dependent on NCLX and is required for preventing Orai1 inactivation through oxidation of a critical cysteine (Cys195) in the third transmembrane helix of Orai1. We show that mitochondrial targeting of catalase is sufficient to rescue redox transients, SOCE, and Orai1 currents in NCLX‐deficient cells. Our findings identify a hitherto unknown NCLX‐mediated pathway that coordinates Na+ and Ca2+ signals to effect mitochondrial redox control over SOCE.
Lipidomic Profiling Links the Fanconi Anemia Pathway to Glycosphingolipid Metabolism in Head and Neck Cancer Cells

Purpose: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC), and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway–dependent lipid metabolism and to extract lipid-based signatures and effectors of invasion in FA-deficient cells. Experimental Design: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells. Cellular invasion assays were carried out in the presence and absence of N-butyldeoxynojirimycin (NB-DNJ), a biosynthetic inhibitor of the newly identified class of gangliosides, to investigate the requirement of ganglioside upregulation in FA-deficient HNSCC cells. Results: The most notable element of the lipid profiling results was a consistent elevation of glycosphingolipids, and particularly the accumulation of gangliosides. Conversely, repression of this same class of lipids was observed upon genetic correction of FA patient–derived HNSCC cells. Functional studies demonstrate that ganglioside upregulation is required for HNSCC cell invasion driven by FA pathway loss. The motility of nontransformed keratinocytes in response to FA loss displayed a similar dependence, thus supporting early and late roles for the FA pathway in controlling keratinocyte invasion through lipid regulation. Conclusions: Elevation of glycosphingolipids including the ganglioside GM3 in response to FA loss stimulates invasive characteristics of immortalized and transformed keratinocytes. An inhibitor of glycosphingolipid biosynthesis NB-DNJ attenuates invasive characteristics of FA-deficient HNSCC cells. Clin Cancer Res; 24(11); 2700–9. ©2018 AACR.