Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Three Hypopnea Scoring Criteria on OSA Prevalence and Associated Comorbidities in the General Population.

STUDY OBJECTIVES Apnea-hypopnea index (AHI) is the main polysomnographic measure to diagnose obstructive sleep apnea (OSA). We aimed to evaluate the effect of three standard hypopnea definitions on the prevalence of OSA and its association with cardiometabolic outcomes in the general population. METHODS We analyzed data from the HypnoLaus study (Lausanne, Switzerland), in which 2,162 participants (51% women, 57 ± 19 years) underwent in-home full polysomnography. AHI was calculated using three hypopnea definitions: AASM1999 (≥ 50% decrease in airflow or lower airflow reduction associated with oxygen desaturation ≥ 3% or an arousal), AASM2007 (≥ 30% airflow reduction associated with ≥ 4% oxygen desaturation), and AASM2012 (≥ 30% airflow reduction associated with ≥ 3% oxygen desaturation or an arousal). Participants underwent clinical assessment for hypertension, diabetes, and metabolic syndrome. RESULTS Median AHI of AASM1999, AASM2007 and AASM2012 criteria were 10.9, 4.4, and 10.1 events/h, respectively. OSA prevalence defined as AHI ≥ 5, ≥ 15, and ≥ 30 events/h was 74.5%, 39.3%, and 16.3% using AASM1999; 46.9%, 18.8%, and 6.8% using AASM2007; and 72.2%, 36.6%, and 14.9% using AASM2012. Different AHI thresholds derived from AASM1999, AASM2007, and AASM2012 criteria, respectively, were associated with hypertension (11.5, 4.8, 10.7 events/h), diabetes (15.7, 7.1, 14.4 events/h), and metabolic syndrome (12.8, 5.5, 11.8 events/h). CONCLUSIONS Hypopnea definition has a major effect on AHI and on OSA prevalence in the general population and, hence, important implications for public health policies. There is a twofold difference in the threshold above which an association with diabetes, hypertension, and metabolic syndrome is observed using AASM2007 compared to AASM1999 or AASM2012 criteria.
Hematological indices as simple, inexpensive and practical severity markers of obstructive sleep apnea syndrome: a meta-analysis.

Background Clinical detection of inflammatory markers is useful to assess the degree of nocturnal hypoxia and predict the presence of complications in obstructive sleep apnea syndrome (OSAS) patients. Nowadays, some researchers proposed that hematological parameters could be substituted for novel disease-specific biochemical markers (such as C-reactive protein) because they were comparatively cheap, simple and practical. But there was a contradiction whether the hematological parameters were positively correlated with the OSAS severity. Methods Medical databases were searched included PubMed, Web of Science, Scopus, Cochrane Library, Clinical Trial, Embase and Google Scholar (up to March 29, 2018). We used weighted mean differences (WMDs) with 95% confidence intervals (CIs) from random-effects model. Results Seventeen studies were included in this meta-analysis and results were presented by different hematological parameters. Pooled analysis showed that OSAS was associated with a high level of WBC (white blood cell, 11 studies, 2,206 subjects, WMD: 0.58; 95% CI: 0.31 to 0.85; P<0.0001), NLR (neutrophil-to-lymphocyte ratio, 5 studies, 1416 subjects, WMD: 0.46; 95% CI: 0.13 to 0.80; P=0.007), MPV (mean platelet volume, 8 studies, 1,854 subjects, WMD: 0.63; 95% CI: 0.29 to 0.98; P=0.0004), PDW (platelet distribution width, 6 studies, 1,911 subjects, WMD: 0.76; 95% CI: 0.47 to 1.06; P<0.00001), PLR (platelet-to-lymphocyte ratio, 3 studies, 998 subjects, WMD: 21.76; 95% CI: 8.54 to 34.99; P=0.001), RDW (red cell distribution width, 5 studies, 1,701 subjects, WMD: 0.31; 95% CI: 0.11 to 0.51; P=0.002) and HCT (hematocrit, 3 studies, 662 subjects, WMD: 1.58; 95% CI: 0.52 to 2.64; P=0.003). But OSAS was associated with a low level of LYM (lymphocyte, 5 studies, 1,285 subjects, WMD: -0.27; 95% CI: -0.49 to -0.06; P=0.01). There was a gradual rising trend from mild OSAS to severe OSAS existed in all subgroups. Conclusions Hematological indices are comparatively Simple, Inexpensive and Practical Severity Markers of OSAS including WBC, LYM, NLR, MPV, PDW, PLR, RDW and HCT.
Comparison of Apnea Detection Using Oronasal Thermal Airflow Sensor, Nasal Pressure Transducer, Respiratory Inductance Plethysmography and Tracheal Sound Sensor.

STUDY OBJECTIVES Evaluation of apnea detection using a tracheal sound (TS) sensor during sleep in patients with obstructive sleep apnea. METHODS Polysomnographic recordings of 32 patients (25 male, mean age 66.7 ± 15.3 years, and mean body mass index 30.1 ± 4.5 kg/m2) were analyzed to compare the detection of apneas by four different methods of airflow signals: oronasal thermal airflow sensor (thermistor), nasal pressure transducer (NP), respiratory inductance plethysmography (RIPsum) and TS. The four used signals were scored randomly and independently from each other according to American Academy of Sleep Medicine rules. Results of apnea detection using NP, RIPsum and TS signals were compared to those obtained by thermistor as a reference signal. RESULTS The number of apneas detected by the thermistor was 4,167. The number of apneas detected using the NP was 5,416 (+29.97%), using the RIPsum was 2,959 (-29.71%) and using the TS was 5,019 (+20.45%). The kappa statistics (95% confidence interval) were 0.72 (0.71 to 0.74) for TS, 0.69 (0.67 to 0.70) for NP, and 0.57 (0.55 to 0.59) for RIPsum. The sensitivity/specificity (%) with respect to the thermistor were 99.23/69.27, 64.07/93.06 and 96.06/76.07 for the NP, RIPsum and TS respectively. CONCLUSIONS With the sensor placed properly on the suprasternal notch, tracheal sounds could help detecting apneas that are underscored by the RIPsum and identify apneas that may be overscored by the NP sensor due to mouth breathing. In the absence of thermistor, TS sensors can be used for apnea detection. CLINICAL TRIAL REGISTRATION Registry: German Clinical Trials Register (DRKS), Title: Using the tracheal sound probe of the polygraph CID102 to detect and differentiate obstructive, central, and mixed sleep apneas in patients with sleep disordered breathing, Identifier: DRKS00012795, URL: https://www.drks. de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00012795.
Bioinspired Fabrication of DNA–Inorganic Hybrid Composites Using Synthetic DNA

Nucleic acid nanostructures have attracted significant interest as potential therapeutic and diagnostic platforms due to their intrinsic biocompatibility and biodegradability, structural and functional diversity, and compatibility with various chemistries for modification and stabilization. Among the fabrication approaches for such structures, the rolling circle techniques have emerged as particularly promising, producing morphologically round, flower-shaped nucleic acid particles: typically hybrid composites of long nucleic acid strands and inorganic magnesium pyrophosphate (Mg2PPi). These constructs are known to form via anisotropic nucleic acid-driven crystallization in a sequence-independent manner, rendering monodisperse and densely packed RNA or DNA–inorganic composites. However, it still remains to fully explore how flexible polymer-like RNA or DNA strands (acting as biomolecular additives) mediate the crystallization process of Mg2PPi and affect the structure and properties of the product crystals. To address this, we closely examined nanoscale details to mesoscopic features of Mg2PPi/DNA hybrid composites fabricated by two approaches, namely rolling circle amplification (RCA)-based in situ synthesis and long synthetic DNA-mediated crystallization. Similar to the DNA constructs fabricated by RCA, the rapid crystallization of Mg2PPi was retarded on a short-range order when we precipitated the crystals in the presence of presynthesized long DNA, which resulted in effective incorporation of biomolecular additives such as DNA and enzymes. These findings further provide a more feasible way to encapsulate bioactive enzymes within DNA constructs compared to in situ RCA-mediated synthesis, i.e., by not only protecting them from possible denaturation under the reaction conditions but also preventing nonselective association of proteins arising from the RCA reaction mixtures.
Hydroxyethyl Starch-Based Nanoparticles Featured with Redox-Sensitivity and Chemo-Photothermal Therapy for Synergized Tumor Eradication

Chemo-photothermal combination therapy could achieve synergistically enhanced efficiency against tumors. Nanocarriers with good safety and high efficiency for chemo- photothermal therapy are pressingly needed. A new type of hydroxyethyl starch (HES) based on nanoparticles (NPs) loaded with doxorubicin (DOX) and indocyanine green (ICG) was, thus, developed in this study. DOX-loaded HES conjugates with redox-sensitivity (HES-SS-DOX) were first synthesized and they were then combined with ICG to self-assemble into HES-SS-DOX@ICG NPs with controlled compositions and sizes via collaborative interactions. The optimal HES-SS-DOX@ICG NPs had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. They were able to fast release the loaded DOX in response to the redox stimulus and the applied laser irradiation. Based on the H22-tumor-bearing mouse model, these NPs were found to tendentiously accumulate inside tumors in comparison to other major organs. The HES-SS-DOX@ICG NPs together with dose-designated laser irradiation were able to fully eradicate tumors with only one injection and one single subsequent laser irradiation on the tumor site during a 14-day treatment period. In addition, they showed almost no impairment to the body. The presently developed HES-SS-DOX@ICG NPs have good in vivo safety and highly efficient anti-tumor capability. These NPs in conjugation with laser irradiation have promising potential for chemo-photothermal cancer therapy in the clinic.
The Role of Religion in Suicidal Behavior, Attitudes and Psychological Distress Among University Students: A Multinational Study

The purpose of this study was to determine the associations between religion, suicidal behavior, attitudes and psychological distress in 5572 students from 12 countries by means of a self-report questionnaire. Our results showed that an affiliation with Islam was associated with reduced risk for suicide ideation, however affiliating with Orthodox Christianity and no religion was related to increased risk for suicide ideation. While affiliating with Buddhism, Catholic religion and no religion was associated with lowered risk for attempting suicide, affiliation with Islam was related to heightened risk for attempting suicide. Affiliation with Hinduism, Orthodox Christianity, Catholicism, other religions and with no religion was associated with decreased risk for psychological distress but those reported affiliating with Islam evinced greater risk for psychological distress. The associations of the strength of religious belief to suicidal ideation and attempts were in the expected direction for most but had a positive relation in respondents affiliating with Catholicism and other religions. Students reporting affiliation with Islam, the Christian Orthodox religion and Buddhism were the least accepting of suicide but they displayed a more confronting interpersonal style to an imagined peer with a suicidal decision. It was concluded that the protective function of religion in educated segments of populations (university students) and in university students residing in Muslim countries where freedom from religion is restricted or religion is normative and/or compulsory is likely to be limited. Our findings suggest that public policies supporting religious freedom may augment the protective function of religion against suicide and psychological distress.
Neural circuit-wide analysis of gene expression during deafening-induced destabilization of birdsong

Sensory feedback is required for stable execution of learned motor skills, and its loss can severely disrupt motor performance. The neural mechanisms that mediate sensorimotor stability have been extensively studied at systems and physiological levels, yet relatively little is known about how disruptions to sensory input alter the molecular properties of associated motor systems. Songbird courtship song, a model for skilled behavior, is a learned and highly structured vocalization that is destabilized following deafening. Here, we sought to determine how the loss of auditory feedback modifies gene expression and its coordination across the birdsong sensorimotor circuit. To facilitate this system-wide analysis of transcriptional responses, we developed a gene expression profiling approach that enables the construction of hundreds of spatially-defined RNA-sequencing libraries. Using this method, we found that deafening preferentially alters gene expression across birdsong neural circuitry relative to surrounding areas, particularly in premotor and striatal regions. Genes with altered expression are associated with synaptic transmission, neuronal spines, and neuromodulation and show a bias toward expression in glutamatergic neurons and Pvalb/Sst-class GABAergic interneurons. We also found that connected song regions exhibit correlations in gene expression that were reduced in deafened birds relative to hearing birds, suggesting that song destabilization alters the inter-region coordination of transcriptional state. Finally, lesioning LMAN, a forebrain afferent of RA required for deafening-induced song plasticity, had the largest effect on groups of genes that were also most affected by deafening. Combined, this integrated transcriptomics analysis demonstrates that the loss of peripheral sensory input drives a distributed gene expression response throughout associated sensorimotor neural circuitry and identifies specific candidate molecular and cellular mechanisms that support stability and plasticity of learned motor skills.
Structural basis of ubiquitin recognition by the winged-helix domain of Cockayne syndrome group B protein

Abstract Cockayne syndrome group B (CSB, also known as ERCC6) protein is involved in many DNA repair processes and essential for transcription-coupled repair (TCR). The central region of CSB has the helicase motif, whereas the C-terminal region contains important regulatory elements for repair of UV- and oxidative stress-induced damages and double-strand breaks (DSBs). A previous study suggested that a small part (∼30 residues) within this region was responsible for binding to ubiquitin (Ub). Here, we show that the Ub-binding of CSB requires a larger part of CSB, which was previously identified as a winged-helix domain (WHD) and is involved in the recruitment of CSB to DSBs. We also present the crystal structure of CSB WHD in complex with Ub. CSB WHD folds as a single globular domain, defining a class of Ub-binding domains (UBDs) different from 23 UBD classes identified so far. The second α-helix and C-terminal extremity of CSB WHD interact with Ub. Together with structure-guided mutational analysis, we identified the residues critical for the binding to Ub. CSB mutants defective in the Ub binding reduced repair of UV-induced damage. This study supports the notion that DSB repair and TCR may be associated with the Ub-binding of CSB.
Laminin-511 Supplementation Enhances Stem Cell Localization With Suppression in the Decline of Cardiac Function in Acute Infarct Rats

Background. The extracellular matrix, in particular basement membrane components such as laminins (LMs), is essential for stem cell differentiation and self-renewal. LM511 and LM221 are the main extracellular matrix components of the epicardium, where stem cells were abundant. Here, we examined whether LMs affected the regeneration process by modulating stem cell activities. Methods. In vitro, adhesive, and proliferative activities of mesenchymal stem cells (MSCs) were evaluated on LM511 and LM221. To examine the effects of LMs in vivo, we established an acute myocardial infarction model by ligation of the proximal part of the left anterior descending artery at the height of the left atrial appendage and then placed atelocollagen sheets with or without LM511 and LM221 over the anterolateral surface of the left ventricular wall. Four or 8 weeks later, cardiac function, histology, and cytokine expressions were analyzed. Results. MSCs showed greater proliferation and adhesive properties on LM511 than on LM221. In vivo, at 4 weeks, isolectin B4–positive cells were significantly higher in the LM511-transplanted group than in the control group. Moreover, some isolectin B4–positive cells expressed both platelet-derived growth factor receptor &agr; and CD90, suggesting that LM511 enhanced MSC recruitment and attachment at the implanted site. After 8 weeks, these cells were more abundant than at 4 weeks. Transplantation with LM511-conjugated sheets increased the expression of cardioprotective and angiogenic factors. Conclusions. Transplantation with LM511-conjugated sheets enhanced MSC localization to the implantation site and modulated stem cells activities, leading to angiogenesis in acute myocardial infarction rat models.
Surgical Experience and Early Outcomes With a Slim Perimodiolar Electrode.

INTRODUCTION In 2016 the Cochlear CI532 received FDA approval and has since been the primary full-length electrode from this manufacturer implanted at our center. Our experience to date including surgical technique and early patient outcomes are reviewed here. METHODS Since 2016, this array was used as our standard full length Cochlear array, including children with normal anatomy, with 237 total implantations. Surgical experience and clinical outcomes including low frequency hearing preservation and speech perception on CNC words were analyzed in those with at least 6 months follow-up implanted through June 2017 (n = 94). RESULTS Speech perception scores are improving over clinical follow-up in accord with other electrode arrays. Hearing preservation is possible with a number of patients utilizing acoustic low frequency hearing in conjunction with electric stimulation from their CI. Tip fold overs were infrequent (4.6%) and always identified on intraoperative x-ray. No patients left the operating room with a tip fold over. CONCLUSIONS Speech perception outcomes with the CI532 slim periomodiolar array are similar to other full length arrays with the added potential for at least short term preservation of residual acoustic hearing. There is a learning curve to its use and intraoperative x-rays are valuable to ensure optimal placement.
Intra-Vesical Colistin for Pseudomonas aeruginosa Urinary Tract Infections.

The numbers of multiple drug-resistant Gram-negative bacterial infections are rising worldwide. The threat is increased by the lack of new antibiotics, so clinicians are turning to older drugs previously abandoned due to their recognized toxicity, such as colistin. However, the need to avoid kidney toxicity from colistin has led to its topical use. We present the case of a patient with type I cardiorenal syndrome with cystitis due to multiple drug-resistant Pseudomonas aeruginosa who was successfully treated with intravesical instillation of colistin. LEARNING POINTS The case report is one of the few in the literature on the intravesical instillation of colistin to address lower urinary tract infection.Isolated intravesical colistin instillation was effective in a patient with anuria.
Population Pharmacokinetics of Doravirine and Exposure-Response Analysis in Individuals with HIV-1

Doravirine is a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus 1 (HIV-1) infection. A population pharmacokinetic (PK) model was developed for doravirine using pooled data from densely sampled phase 1 trials and from sparsely sampled phase 2b and phase 3 trials evaluating doravirine administered orally as a single entity or as part of a fixed-dose combination of doravirine-lamivudine-tenofovir disoproxil fumarate. ABSTRACT Doravirine is a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus 1 (HIV-1) infection. A population pharmacokinetic (PK) model was developed for doravirine using pooled data from densely sampled phase 1 trials and from sparsely sampled phase 2b and phase 3 trials evaluating doravirine administered orally as a single entity or as part of a fixed-dose combination of doravirine-lamivudine-tenofovir disoproxil fumarate. A one-compartment model with linear clearance from the central compartment adequately described the clinical PK of doravirine. While weight, age, and healthy versus HIV-1 status were identified as statistically significant covariates affecting doravirine PK, the magnitude of their effects was not clinically meaningful. Other intrinsic factors (gender, body mass index, race, ethnicity, and renal function) did not have statistically significant or clinically meaningful effects on doravirine PK. Individual exposure estimates for individuals in the phase 2b and 3 trials obtained from the final model were used for subsequent exposure-response analyses for virologic response (proportion of individuals achieving <50 copies/ml) and virologic failure. The exposure-response relationships between these efficacy endpoints and doravirine PK were generally flat over the range of exposures achieved for the 100 mg once-daily regimen in the phase 3 trials, with a minimal decrease in efficacy in individuals in the lowest 10th percentile of steady-state doravirine concentration at 24 h values. These findings support 100 mg once daily as the selected dose of doravirine, with no dose adjustment warranted for the studied intrinsic factors.
Prevalence, Patterns, and Predictors: A Statewide Longitudinal Study of Childhood Obesity.

BACKGROUND We examined prevalence, incidence, and trajectory of obesity from kindergarten through grade 8 in one of the first states to implement annual surveillance. METHODS Participants included 16,414 children enrolled in kindergarten in Arkansas in 2004 with complete body mass index (BMI) measurements in kindergarten and eighth grade. Repeated measures of weight status were entered in multiple linear and logistic regression models with demographics and family poverty status. RESULTS The prevalence of obesity (BMI ≥ 95th percentile) was lowest in kindergarten (14.9%), with subsequent incidence rates consistent at 4%. Prevalence and incidence peaked in eighth grade (24.5% and 4.9%, respectively), with 33.8% of children measuring obese at least once by eighth grade. Kindergarten obesity was a significant predictor of eighth grade obesity (odds ratio, 17.5; 95% confidence interval, 15.8-19.3). We found statistically significant 3-way interactions for sex, race, and time, suggesting unique patterns for Hispanic boys and black girls. CONCLUSIONS Our study documents unique longitudinal patterns of obesity from kindergarten through eighth grade that expand our understanding of risk. It demonstrates the value of public school health systems that collect routine administrative data about student BMI that is integrated with education records to foster program and policy discussions.