Miracle-dz/UniFAR-FTUs huggingface dataset:
Teenage births in the United States: state trends, 1991-2000, an update.

OBJECTIVES This report provides State-specific birth rates for teenagers for 1991 and 2000, and the percent change between the time periods. METHODS Tabular and graphical description of trends in teenage birth rates by age group for each State and territory. RESULTS Birth rates for teenagers 15-19 years declined significantly in all States, the Virgin Islands and Guam, between 1991 and 2000. Declines by State ranged from 12 to 39 percent. Rates also fell significantly for teenage subgroups 15-17 and 18-19 years.
Impact of Ventilatory Modes on the Breathing Variability in Mechanically Ventilated Infants

Objectives: Reduction of breathing variability is associated with adverse outcome. During mechanical ventilation, the variability of ventilatory pressure is dependent on the ventilatory mode. During neurally adjusted ventilatory assist (NAVA), the support is proportional to electrical activity of the diaphragm (EAdi), which reflects the respiratory center output. The variability of EAdi is, therefore, translated into a similar variability in pressures. Contrastingly, conventional ventilatory modes deliver less variable pressures. The impact of the mode on the patient’s own respiratory drive is less clear. This study aims to compare the impact of NAVA, pressure-controlled ventilation (PCV), and pressure support ventilation (PSV) on the respiratory drive patterns in infants. We hypothesized that on NAVA, EAdi variability resembles most of the endogenous respiratory drive pattern seen in a control group. Methods: Electrical activity of the diaphragm was continuously recorded in 10 infants ventilated successively on NAVA (5 h), PCV (30 min), and PSV (30 min). During the last 10 min of each period, the EAdi variability pattern was assessed using non-rhythmic to rhythmic (NRR) index. These variability profiles were compared to the pattern of a control group of 11 spontaneously breathing and non-intubated infants. Results: In control infants, NRR was higher as compared to mechanically ventilated infants (p < 0.001), and NRR pattern was relatively stable over time. While the temporal stability of NRR was similar in NAVA and controls, the NRR profile was less stable during PCV. PSV exhibited an intermediary pattern. Perspectives: Mechanical ventilation impacts the breathing variability in infants. NAVA produces EAdi pattern resembling most that of control infants. NRR can be used to characterize respiratory variability in infants. Larger prospective studies are necessary to understand the differential impact of the ventilatory modes on the cardio-respiratory variability and to study their impact on clinical outcomes.
Enhancement of BDNF Expression and Memory by HDAC Inhibition Requires BET Bromodomain Reader Proteins

Histone deacetylase (HDAC) inhibitors may have therapeutic utility in multiple neurological and psychiatric disorders, but the underlying mechanisms remain unclear. Here, we identify BRD4, a BET bromodomain reader of acetyl-lysine histones, as an essential component involved in potentiated expression of brain-derived neurotrophic factor (BDNF) and memory following HDAC inhibition. In in vitro studies, we reveal that pharmacological inhibition of BRD4 reversed the increase in BDNF mRNA induced by the class I/IIb HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Knock-down of HDAC2 and HDAC3, but not other HDACs, increased BDNF mRNA expression, whereas knock-down of BRD4 blocked these effects. Using dCas9-BRD4, locus-specific targeting of BRD4 to the BDNF promoter increased BDNF mRNA. In additional studies, RGFP966, a pharmacological inhibitor of HDAC3, elevated BDNF expression and BRD4 binding to the BDNF promoter, effects that were abrogated by JQ1 (an inhibitor of BRD4). Examining known epigenetic targets of BRD4 and HDAC3, we show that H4K5ac and H4K8ac modifications and H4K5ac enrichment at the BDNF promoter were elevated following RGFP966 treatment. In electrophysiological studies, JQ1 reversed RGFP966-induced enhancement of LTP in hippocampal slice preparations. Last, in behavioral studies, RGFP966 increased subthreshold novel object recognition memory and cocaine place preference in male C57BL/6 mice, effects that were reversed by cotreatment with JQ1. Together, these data reveal that BRD4 plays a key role in HDAC3 inhibitor-induced potentiation of BDNF expression, neuroplasticity, and memory. SIGNIFICANCE STATEMENT Some histone deacetylase (HDAC) inhibitors are known to have neuroprotective and cognition-enhancing properties, but the underlying mechanisms have yet to be fully elucidated. In the current study, we reveal that BRD4, an epigenetic reader of histone acetylation marks, is necessary for enhancing brain-derived neurotrophic factor (BDNF) expression and improved memory following HDAC inhibition. Therefore, by identifying novel epigenetic regulators of BDNF expression, these data may lead to new therapeutic targets for the treatment of neuropsychiatric disorders.
Timing of combined antiretroviral treatment initiation in male and female migrants living with HIV in Western Europe

Background: We evaluate differences in timing of cART (combined antiretroviral treatment) initiation by geographical origin in male and female HIV-positive patients in the Collaboration of Observational HIV Epidemiological Research Europe, a large European Collaboration of HIV Cohorts. Methods: We included individuals recruited in Western Europe between January 1997 and March 2013, with known geographical origin and at least 1 CD4+ cell count measurement while cART-naive. Timing of cART was assessed through modified time-to-event methods, in which a scale of CD4+ cell counts was used instead of time, with cART being the outcome. We estimated the median CD4+ cell count at cART initiation (estimated CD4+ levels at which the probability of having started cART is 50%) using Kaplan–Meier and adjusted hazard ratios of cART initiation using Cox regression. Results: Of 151 674 individuals, 110 592 (72.9%) were men. Median (95% confidence interval) CD4+ cell count falls far below 250 cells/&mgr;l in all groups and was lowest in sub-Saharan African [SSA: 161 (158–167)], Caribbean men [161 (150–174)] and in Asian women [Asian Continent and Oceania: 185 (165–197)]. Among men, the adjusted probability of cART initiation was lower in migrants compared with natives, but differences depended on initial CD4+ cell count. For example, in the group with more than 500 CD4+ at recruitment, they were 45% (36–53%), 30% (17–40%) and 25% (19–30%) lower for Caribbean, Eastern European and SSA men, respectively. In women, no meaningful differences were observed between natives and most migrant groups. However, SSA women had a 31% (24–38%) higher probability of cART initiation when recruited at a CD4+ more than 500 cells/&mgr;l and 9% (4–14%) lower when recruited at CD4+ less than 100 cells/&mgr;l. Conclusion: Most migrant men initiate cART at lower CD4+ cell count than natives, whereas this does not hold for migrant women.
Clinical outcomes of WBRT plus EGFR-TKIs versus WBRT or TKIs alone for the treatment of cerebral metastatic NSCLC patients: a meta-analysis

Whether WBRT plus EGFR-TKIs has a greater survival benefit than EGFR-TKIs alone or WBRT alone remains controversial in NSCLC patients with multiple brain metastases. To rectify this, we conducted a systematic meta-analysis based on 9 retrospective studies and 1 randomized controlled study published between 2012 and 2016, comprising 1041 patients. Five studies were included in the comparison of WBRT plus EGFR-TKIs and EGFR-TKIs alone. The combined HR for OS of patients with EGFR mutation was 1.25 [95% CI 0.98–2.15; P = 0.08] and for intracranial PFS was 1.30 [95% CI 1.03–1.65; P = 0.03], which revealed that EGFR-TKIs alone produced a superior intracranial PFS than WBRT plus EGFR-TKIs. Five studies were included in the comparison of WBRT plus EGFR-TKIs and WBRT alone. The combined HR for OS, intracranial PFS and extracranial PFS were 0.52 [95% CI 0.37–0.75; P = 0.0004], 0.36 [95% CI 0.24–0.53; P < 0.001] and 0.52 [95% CI 0.38–0.71; P < 0.001], respectively, which revealed a significant benefit of WBRT plus EGFR-TKIs compared with WBRT alone. The results indicated that EGFR-TKIs alone should be the first option for the treatment of NSCLC patients with multiple BM, especially with EGFR mutation, since it provides similar OS and extracranial PFS but superior intracranial PFS compared with WBRT plus EGFR-TKIs.
Measuring and Decomposing Socioeconomic Inequalities in Adult Obesity in Western Iran

Objectives Obesity is a considerable and growing public health concern worldwide. The present study aimed to quantify socioeconomic inequalities in adult obesity in western Iran. Methods A total of 10 086 participants, aged 35-65 years, from the Ravansar Non-communicable Disease Cohort Study (2014-2016) were included in the study to examine socioeconomic inequalities in obesity. We defined obesity as a body mass index ≥30 kg/m2. The concentration index and concentration curve were used to illustrate and measure wealth-related inequality in obesity. Additionally, we decomposed the concentration index to identify factors that explained wealth-related inequality in obesity. Results Overall, the prevalence of obesity in the total sample was 26.7%. The concentration index of obesity was 0.04; indicating that obesity was more concentrated among the rich (p<0.001). Decomposition analysis indicated that wealth, place of residence, and marital status were the main contributors to the observed inequality in obesity. Conclusions Socioeconomic-related inequalities in obesity among adults warrant more attention. Policies should be designed to reduce both the prevalence of obesity and inequalities in obesity by focusing on those with higher socioeconomic status, urban residents, and married individuals.
Properdin homeostasis requires turnover of the alternative complement pathway

Properdin is a plasma protein and is also released from neutrophil granules following stimulation. At inflammatory sites it can bind bacteria and apoptotic bodies to trigger alternative pathway (AP) activation. Principles governing properdin homeostasis are unknown. We monitored properdin during AP activation and in complement-deficient mice. There was a >90% reduction of properdin in the Crry single-knockout mice (Crry SKO). These membrane complement regulatory protein-deficient mice feature accelerated AP turnover, leading to reduced C3 and fB. Injecting cobra venom factor into wild-type mice activated the AP and led to the consumption of C3, fB, and properdin. However, and unexpectedly, properdin was also deficient in C3−/−, fB−/−, and fD−/− mice. It was present in C1q−/−, C4−/−, and C5−/− mice. These findings implicate AP turnover in the maintenance of basal levels of properdin in the blood. To explore the mechanism, classical pathway-activating immune complexes were infused. Within 10 min, properdin was partially restored in fB−/− but not in C3−/− mice. Markedly reduced properdin in mice deficient in an AP component and its partial restoration by activating C3 suggest a requirement for continuous C3 activation via AP tickover to maintain properdin homeostasis. The mechanism underlying this C3-dependent process was not identified. Engagement of C3a and C5a receptors was ruled out. These findings represent an instructive example of how a positive regulator of an innate immune recognition and effector pathway is controlled. A rationale for such a means to supply properdin for immune reactions is proposed.
Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference.

RATIONALE Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited. OBJECTIVES To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF. METHODS The study population included all 1,156 randomized patients in two clinical trials of IFN-γ1b. FVC and other measures of functional status were measured at screening or baseline and 24-week intervals thereafter. Reliability was assessed based on two proximal measures of FVC, validity was assessed based on correlations between FVC and other measures of functional status, and responsiveness was assessed based on the relationship between 24-week changes in FVC and other measures of functional status. Distribution-based and anchor-based methods were used to estimate the MCID. MEASUREMENTS AND MAIN RESULTS Correlation of percent-predicted FVC between measurements (mean interval, 18 d) was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters were generally weak, with the strongest observed correlation between FVC and carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between change in FVC and changes in other parameters were slightly stronger (range, r = 0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold higher (P < 0.001) in patients with a 24-week decline in FVC between 5% and 10%. The estimated MCID was 2-6%. CONCLUSIONS FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference.
Variation in surgical-readmission rates and quality of hospital care.

BACKGROUND Reducing hospital-readmission rates is a clinical and policy priority, but little is known about variation in rates of readmission after major surgery and whether these rates at a given hospital are related to other markers of the quality of surgical care. METHODS Using national Medicare data, we calculated 30-day readmission rates after hospitalization for coronary-artery bypass grafting, pulmonary lobectomy, endovascular repair of abdominal aortic aneurysm, open repair of abdominal aortic aneurysm, colectomy, and hip replacement. We used bivariate and multivariate techniques to assess the relationships between readmission rates and other measures of surgical quality, including adherence to surgical process measures, procedure volume, and mortality. RESULTS For the six index procedures, there were 479,471 discharges from 3004 hospitals. The median risk-adjusted composite readmission rate at 30 days was 13.1% (interquartile range, 9.9 to 17.1). In a multivariate model adjusting for hospital characteristics, we found that hospitals in the highest quartile for surgical volume had a significantly lower composite readmission rate than hospitals in the lowest quartile (12.7% vs. 16.8%, P<0.001), and hospitals with the lowest surgical mortality rates had a significantly lower readmission rate than hospitals with the highest mortality rates (13.3% vs. 14.2%, P<0.001). High adherence to reported surgical process measures was only marginally associated with reduced readmission rates (highest quartile vs. lowest quartile, 13.1% vs. 13.6%; P=0.02). Patterns were similar when each of the six major surgical procedures was examined individually. CONCLUSIONS Nearly one in seven patients hospitalized for a major surgical procedure is readmitted to the hospital within 30 days after discharge. Hospitals with high surgical volume and low surgical mortality have lower rates of surgical readmission than other hospitals.
Streptococcus gallolyticus, infective endocarditis, and colon carcinoma: new light on an intriguing coincidence.

In this issue of the Journal ,B oleij and colleagues [6] provide important data pointing to several virulence characteristics of SG that may play key roles in the pathogenesis of this remarkably adaptable organism. These investigators replicated the route of SG infection in vitro by using differentiated human epithelial colorectal adenocarcinoma cells (Caco-2) in a series of assays focusing on both bacterial and host cell responses. These studies focused on SG adhesion, invasion, translocation, biofilm formation, and ability to elicit an immune response in order to identify virulence characteristics that could provide an explanation for the link between SG IE and colon carcinoma. The results of this work suggest that this species of bacteria is uniquely able to translocate in a paracellular fashion across malignant intestinal epithelium without eliciting a significant immune response and then adhere to collagenrich surfaces and form biofilms. These data are exciting in that they address the key putative first steps in the dissemination of the bacteria from the gut environment to the bloodstream and ultimately to other locations more favorable for colonization, such as collagen-rich surfaces of cardiac valves. Future studies can now build on this work by focusing on specific virulence factors responsible for these specific characteristics observed for SG, but not for other related streptococci and other far more numerous bacterial species inhabiting the gut.
Physics and design for 20% and 25% efficiency nanowire array solar cells

Bottom-up fabricated single-junction III–V nanowire array solar cells have shown efficiency up to 15.3%, which is approximately half of the conventional Shockley–Queisser detailed balance efficiency limit of 33.6%. Here, based on numerical and analytical opto-electronics modeling and analysis, we give guidelines for (i) geometry that gives strong absorption as well as (ii) the design of efficient p–n junction and electrical contacts in the nanowires to reach 20% and 25% efficiency. We exemplify the impact of eight different optical and electrical loss mechanisms in a 15% and a 25% design. We also provide an analytical equation for estimating the efficiency drop due to resistive losses in the top contact layer for varying cell size.
In the Spotlight: Health Information Systems

Healthcare systems deal with only a part of the health continuum as they are organized to diagnose and treat patients. The Connected Health paradigm covers the continuum and includes the healthy and at risk individuals and chronically ill patients. The current system has been characterized as health profession centric; patients seek medical care which is delivered by healthcare professionals. In Connected Health, individuals are equal partners with healthcare professionals and take part in managing their health, wellness and care. Connected Health can be construed as being made up of one vertical layer providing privacy, security and interoperability services so that the users are able to use and trust the services and of five interacting horizontal layers as follows. The bottom layer houses the communications infrastructure, data stores (e.g. EHRs and PHRs) etc. The second layer health IT applications that enable and support the services on the third layer. The third layer is the one where health services are delivered. These cover the health continuum from end-to-end. The services span, e.g., wellness, self-management, retail clinics, policlinics, surgical operations and intensive care. The users see these as one integrated and accessible bundle. The fourth layer deals with reimbursement of health services. Providers can be paid on fee for service, capitation or pay for performance basis or a combination of these. The fifth layer sets the laws, regulations and policies that govern how health services are delivered and consumed. Health systems are already costly. Changes in demographics, our lifestyles and innovations in life sciences, medicine and technology are enabling new and improved care for all, which adds pressure to increase health expenditures.
Increasing Solar Absorption for Photocatalysis with Black Hydrogenated Titanium Dioxide Nanocrystals

An amorphous surface layer on titantium dioxide nanoparticles creates electronic states that allow longer-wavelength photoexcitation. When used as a photocatalyst, titanium dioxide (TiO2) absorbs only ultraviolet light, and several approaches, including the use of dopants such as nitrogen, have been taken to narrow the band gap of TiO2. We demonstrated a conceptually different approach to enhancing solar absorption by introducing disorder in the surface layers of nanophase TiO2 through hydrogenation. We showed that disorder-engineered TiO2 nanocrystals exhibit substantial solar-driven photocatalytic activities, including the photo-oxidation of organic molecules in water and the production of hydrogen with the use of a sacrificial reagent.
The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial

Background and Purpose— Acute blood pressure (BP) reduction aimed at attenuation of intracerebral hemorrhage (ICH) expansion might also compromise cerebral blood flow (CBF). We tested the hypothesis that CBF in acute ICH patients is unaffected by BP reduction. Methods— Patients with spontaneous ICH <24 hours after onset and systolic BP > 150 mm Hg were randomly assigned to an intravenous antihypertensive treatment protocol targeting a systolic BP of <150 mm Hg (n=39) or <180 mm Hg (n=36). Patients underwent computed tomography perfusion imaging 2 hours postrandomization. The primary end point was perihematoma relative (relative CBF). Results— Treatment groups were balanced with respect to baseline systolic BP: 182±20 mm Hg (<150 mm Hg target group) versus 184±25 mm Hg (<180 mm Hg target group; P=0.60), and for hematoma volume: 25.6±30.8 versus 26.9±25.2 mL (P=0.66). Mean systolic BP 2 hours after randomization was significantly lower in the <150 mm Hg target group (140±19 vs 162±12 mm Hg; P<0.001). Perihematoma CBF (38.7±11.9 mL/100 g per minute) was lower than in contralateral homologous regions (44.1±11.1 mL/100 g per minute; P<0.001) in all patients. The primary end point of perihematoma relative CBF in the <150 mm Hg target group (0.86±0.12) was not significantly lower than that in the <180 mm Hg group (0.89±0.09; P=0.19; absolute difference, 0.03; 95% confidence interval −0.018 to 0.078). There was no relationship between the magnitude of BP change and perihematoma relative CBF in the <150 mm Hg (R=0.00005; 95% confidence interval, −0.001 to 0.001) or <180 mm Hg target groups (R=0.000; 95% confidence interval, −0.001 to 0.001). Conclusions— Rapid BP lowering after a moderate volume of ICH does not reduce perihematoma CBF. These physiological data indicate that acute BP reduction does not precipitate cerebral ischemia in ICH patients. Clinical Trial Registration Information— URL:http://clinicaltrials.gov. Unique Identifier: NCT00963976.
Multi-scale analysis of schizophrenia risk genes, brain structure, and clinical symptoms reveals integrative clues for subtyping schizophrenia patients

Abstract Analysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene expression, grey matter volume (GMV), and the positive and negative syndrome scale scores (PANSS) to explore the etiology of schizophrenia. With 72 drug-naive schizophrenic first episode patients (FEPs) and 73 matched heathy controls, we identified 108 genes, from schizophrenia risk genes, that correlated significantly with GMV, which are highly co-expressed in the brain during development. Among these 108 candidates, 19 distinct genes were found associated with 16 brain regions referred to as hot clusters (HCs), primarily in the frontal cortex, sensory-motor regions and temporal and parietal regions. The patients were subtyped into three groups with distinguishable PANSS scores by the GMV of the identified HCs. Furthermore, we found that HCs with common GMV among patient groups are related to genes that mostly mapped to pathways relevant to neural signaling, which are associated with the risk for schizophrenia. Our results provide an integrated view of how genetic variants may affect brain structures that lead to distinct disease phenotypes. The method of multi-scale analysis that was described in this research, may help to advance the understanding of the etiology of schizophrenia.