Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidemiology of poisonings, fractures and burns among 0-24 year olds in England using linked health and mortality data.

BACKGROUND Understanding patterns of injury in England is challenging due to a lack of national injury surveillance data. Through recent linkage of a large primary care research database to hospitalization and mortality data, we describe the epidemiology of poisonings, fractures and burns over a 14-year period. METHODS We used linked English primary care, hospitalisation and mortality data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics between 1998 and 2011 to establish a cohort of 2,106,420 0-24 year olds. Incidence rates, per 10 000 person-years (PY) were estimated by age, sex, calendar year and socioeconomic status. Using Poisson regression we estimated incidence rate ratios, adjusting for age and sex. RESULTS Age patterns of injury incidence varied by injury type, with peaks at age 2 (74.3/10 000 PY) and 18 (74.7/10 000 PY) for poisonings, age 13 for fractures (305.1/10 000 PY) and age 1 for burns (116.8/10 000 PY). Over time, fracture incidence increased, whereas poisoning incidence increased only among 15-24 year olds and burns incidence reduced. Poisoning and burns incidence increased with deprivation, with the steepest socioeconomic gradient for poisonings among 20-24 year olds (IRR 2.63, 95% confidence interval 2.24-3.09). CONCLUSION Differing patterns according to age and injury type reflect differences in underlying injury mechanisms, highlighting the importance of developing tailored preventative interventions across the life course. Inequalities in injury occurrences support the targeting of preventative interventions to children and young people living in the most deprived areas.
Behavioral and psychological symptoms of dementia in older residents in long-term care facilities in Japan: a cross-sectional study

ABSTRACT Objective: To investigate the prevalence of the behavioral and psychological symptoms of dementia (BPSD) and associated factors in residents in long-term care (LTC) facilities. Method: We conducted a cross-sectional survey of older residents with dementia or similar symptoms (n = 312) using a questionnaire for care staff in 10 selected LTC facilities in Hokkaido, Japan. The questionnaire included sociodemographic characteristics, health conditions, living environments, and a brief questionnaire form of the Neuropsychiatric Inventory for assessing BPSD. Results: We revealed that the prevalence of BPSD in LTC facilities (percentage of people exhibiting at least one BPSD) in residents with dementia or similar symptoms was 64%. Having Alzheimer's disease, an imbalance between activities of daily living and cognitive function, poor relationships with other residents, and persistent requests in daily life were significantly associated with having BPSD. Conclusion: The prevalence of BPSD in LTC facilities was relatively low compared with other countries. The factors found to relate to BPSD may provide useful information for developing care methods to address BPSD in LTC residents.
Differential abilities of nitrogen dioxide and nitrite to nitrate proteins in thylakoid membranes isolated from Arabidopsis leaves

ABSTRACT Exposure of Arabidopsis leaves to nitrogen dioxide (NO2) results in nitration of specific chloroplast proteins. To determine whether NO2 itself and/or nitrite derived from NO2 can nitrate proteins, Arabidopsis thylakoid membranes were isolated and treated with NO2-bubbled or potassium nitrite (KNO2) buffer, followed by protein extraction, electrophoresis, and immunoblotting using an anti-3-nitrotyrosine (NT) antibody. NO2 concentrations in the NO2-bubbled buffer were calculated by numerically solving NO2 dissociation kinetic equations. The two buffers were adjusted to have identical nitrite concentrations. Both treatments yielded an NT-immunopositive band that LC/MS identified as PSBO1. The difference in the band intensity between the 2 treatments was designated nitration by NO2. Both NO2 and nitrite mediated nitration of proteins, and the nitration ability per unit NO2 concentration was ∼100-fold greater than that of nitrite.
Modeling event‐related heart period responses

Abstract Cardiac rhythm is generated locally in the sinoatrial node, but modulated by central neural input. This may provide a possibility to infer central processes from observed phasic heart period responses (HPR). Currently, operational methods are used for HPR analysis. These methods embody implicit assumptions on how central states influence heart period. Here, we build an explicit psychophysiological model (PsPM) for event‐related HPR. This phenomenological PsPM is based on three experiments involving white noise sounds, an auditory oddball task, and emotional picture viewing. The model is optimized with respect to predictive validity—the ability to separate experimental conditions from each other. To validate the PsPM, an independent sample of participants is presented with auditory stimuli of varying intensity and emotional pictures of negative and positive valence, at short intertrial intervals. Our model discriminates these experimental conditions from each other better than operational approaches. We conclude that our PsPM is more sensitive to distinguish experimental manipulations based on heart period data than operational methods, and furnishes a principled approach to analysis of HPR.
Single-stranded nucleic acid elasticity arises from internal electrostatic tension

Significance Charged, flexible polymers, such as single-stranded nucleic acids (ssNAs), are ubiquitous in biology and technology. Quantitative description of their solution conformation has remained elusive due to the competing effects of polymer configurational freedom and salt-screened electrostatic repulsion between monomers. We investigate this by measuring the elastic response of single ssNA molecules over a range of salt concentrations. The data are well described by a model, inspired by a mean-field approach, in which intrapolymer electrostatic repulsion creates a salt-dependent internal tension whose interplay with the external force determines the elasticity. The internal tension can be related to the polymer’s charge spacing; thus, our results show how mesoscopic polymer conformation emerges from microscopic structure. Understanding of the conformational ensemble of flexible polyelectrolytes, such as single-stranded nucleic acids (ssNAs), is complicated by the interplay of chain backbone entropy and salt-dependent electrostatic repulsions. Molecular elasticity measurements are sensitive probes of the statistical conformation of polymers and have elucidated ssNA conformation at low force, where electrostatic repulsion leads to a strong excluded volume effect, and at high force, where details of the backbone structure become important. Here, we report measurements of ssDNA and ssRNA elasticity in the intermediate-force regime, corresponding to 5- to 100-pN forces and 50–85% extension. These data are explained by a modified wormlike chain model incorporating an internal electrostatic tension. Fits to the elastic data show that the internal tension decreases with salt, from >5 pN under 5 mM ionic strength to near zero at 1 M. This decrease is quantitatively described by an analytical model of electrostatic screening that ascribes to the polymer an effective charge density that is independent of force and salt. Our results thus connect microscopic chain physics to elasticity and structure at intermediate scales and provide a framework for understanding flexible polyelectrolyte elasticity across a broad range of relative extensions.
A Parallel Decomposition Method for Nonconvex Stochastic Multi-Agent Optimization Problems

This paper considers the problem of minimizing the expected value of a (possibly nonconvex) cost function parameterized by a random (vector) variable, when the expectation cannot be computed accurately (e.g., because the statistics of the random variables are unknown and/or the computational complexity is prohibitive). Classical stochastic gradient methods for solving this problem may suffer from slow convergence. In this paper, we propose a stochastic parallel Successive Convex Approximation-based (best-response) algorithm for general nonconvex stochastic sum-utility optimization problems, which arise naturally in the design of multi-agent networks. The proposed novel decomposition approach enables all users to update their optimization variables in parallel by solving a sequence of strongly convex subproblems, one for each user. Almost sure convergence to stationary points is proved. We then customize the algorithmic framework to solve the stochastic sum rate maximization problem over single-input-single-output (SISO) frequency-selective interference channels, multiple-input-multiple-output (MIMO) interference channels, and MIMO multiple-access channels. Numerical results corroborate that the proposed algorithms can converge faster than state-of-the-art stochastic gradient schemes while achieving the same (or better) sum-rates.
An improved cluster labeling method for support vector clustering

The support vector clustering (SVC) algorithm is a recently emerged unsupervised learning method inspired by support vector machines. One key step involved in the SVC algorithm is the cluster assignment of each data point. A new cluster labeling method for SVC is developed based on some invariant topological properties of a trained kernel radius function. Benchmark results show that the proposed method outperforms previously reported labeling techniques.
Preclinical PET imaging of glycoprotein non-metastatic melanoma B in triple negative breast cancer: feasibility of an antibody-based companion diagnostic agent

High levels of expression of glycoprotein non-metastatic B (gpNMB) in triple negative breast cancer (TNBC) and its association with metastasis and recurrence make it an attractive target for therapy with the antibody drug conjugate, glembatumumab vedotin (CDX-011). This report describes the development of a companion PET-based diagnostic imaging agent using 89Zr-labeled glembatumumab ([89Zr]DFO-CR011) to potentially aid in the selection of patients most likely to respond to targeted treatment with CDX-011. [89Zr]DFO-CR011 was characterized for its pharmacologic properties in TNBC cell lines. Preclinical studies determined that [89Zr]DFO-CR011 binds specifically to gpNMB with high affinity (Kd = 25 ± 5 nM), immunoreactivity of 2.2-fold less than the native CR011, and its cellular uptake correlates with gpNMB expression (r = 0.95). In PET studies at the optimal imaging timepoint of 7 days p.i. , the [89Zr]DFO-CR011 tumor uptake in gpNMB-expressing MDA-MB-468 xenografts had a mean SUV of 2.9, while significantly lower in gpNMB-negative MDA-MB-231 tumors with a mean SUV of 1.9. [89Zr]DFO-CR011 was also evaluated in patient-derived xenograft models of TNBC, where tumor uptake in vivo had a positive correlation with total gpNMB protein expression via ELISA (r = 0.79), despite the heterogeneity of gpNMB expression within the same group of PDX mice. Lastly, the radiation dosimetry calculated from biodistribution studies in MDA-MB-468 xenografts determined the effective dose for human use would be 0.54 mSv/MBq. Overall, these studies demonstrate that [89Zr]DFO-CR011 is a potential companion diagnostic imaging agent for CDX-011 which targets gpNMB, an emerging biomarker for TNBC.
ILDR1 is important for paracellular water transport and urine concentration mechanism

Significance The role of tight junction in water homeostasis is an important but understudied area. Here, we reveal a paracellular water permeation pathway made by the tricellular tight junction and regulated by its integral protein, known as Ildr1. The importance of paracellular water permeation is demonstrated here with emphasis of its potential role in causing urinary concentrating defects in the kidney. Ildr1 and its related proteins, Ildr2 and Ildr3, may play broader physiologic roles to establish the water homeostasis in other organs, such as the skin, the lung, and the intestine. Whether the tight junction is permeable to water remains highly controversial. Here, we provide evidence that the tricellular tight junction is important for paracellular water permeation and that Ig-like domain containing receptor 1 (ILDR1) regulates its permeability. In the mouse kidney, ILDR1 is localized to tricellular tight junctions of the distal tubules. Genetic knockout of Ildr1 in the mouse kidney causes polyuria and polydipsia due to renal concentrating defects. Microperfusion of live renal distal tubules reveals that they are impermeable to water in normal animals but become highly permeable to water in Ildr1 knockout animals whereas paracellular ionic permeabilities in the Ildr1 knockout mouse renal tubules are not affected. Vasopressin cannot correct paracellular water loss in Ildr1 knockout animals despite normal effects on the transcellular aquaporin-2–dependent pathway. In cultured renal epithelial cells normally lacking the expression of Ildr1, overexpression of Ildr1 significantly reduces the paracellular water permeability. Together, our study provides a mechanism of how cells transport water and shows how such a mechanism may be exploited as a therapeutic approach to maintain water homeostasis.
Relationships between autism spectrum disorder and intolerance of uncertainty

Intolerance of uncertainty (IU) is a dispositional risk factor involving maladaptive responding under conditions of uncertainty. Recent data indicate that IU is likely elevated in youth with autism spectrum disorder (ASD) and is positively correlated with anxiety. This study examined whether IU may be associated with ASD independent of anxiety. Relationships between anxiety, ASD, and IU were examined in 57 children with ASD without co‐occurring intellectual disability and 32 control participants, ages 7–16 years. Hierarchal linear regressions were run to examine whether ASD variables, including emotion dysregulation, were predictive of IU when controlling for anxiety. Severity of social communication deficits, repetitive behaviors, and emotion dysregulation were each related to IU when controlling for the effects of anxiety. When these variables were entered into the regression model together, emotion dysregulation was the only significant predictor of IU. These findings suggest that IU is directly related to features of ASD possibly due to shared genetic, neurological, or psychological underpinnings. Autism Res 2018, 11: 636–644. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
Werner Syndrome Protein Phosphorylation by Abl Tyrosine Kinase Regulates Its Activity and Distribution

ABSTRACT The Werner syndrome protein (WRN) is a caretaker of the human genome, and the Abl kinase is a regulator of the DNA damage response. Aberrant DNA repair has been linked to the development of cancer. Here, we have identified a direct binding between WRN and c-Abl in vitro via the N-terminal and central regions of WRN and the Src homology domain 3 of c-Abl. After bleomycin treatment in culture, WRN and c-Abl are dissociated and followed by an Abl kinase-dependent WRN relocalization to the nucleoplasm. WRN is a substrate of c-Abl in vitro and in vivo. WRN is tyrosine phosphorylated either transiently by treatment of HeLa cells with bleomycin or constitutively in cells from chronic myeloid leukemia (CML) patients, and these phosphorylations are prevented by treatment with the Abl kinase inhibitor STI-571. Tyrosine phosphorylation of WRN results in inhibition of both WRN exonuclease and helicase activities. Furthermore, anti-WRN immunoprecipitates from CML cells treated with STI-571 show increased 3′→5′ exonuclease activity. These findings suggest a novel signaling pathway by which c-Abl mediates WRN nuclear localization and catalytic activities in response to DNA damage.
Social-cognitive antecedents of hand washing: Action control bridges the planning–behaviour gap

Objectives. To examine motivational and volitional factors for hand washing in young adults, using the Health Action Process Approach (HAPA) as a theoretical framework. Design. In a longitudinal design with two measurement points, six weeks apart, university students (N = 440) completed paper-based questionnaires. Main outcome measures. Prior hand washing frequency, self-efficacy, outcome expectancies, intention and action planning were measured at baseline, and coping planning, action control and hand washing frequency were measured at follow-up. Results. A theory-based structural equation model was specified. In line with the HAPA, the motivational factors of self-efficacy and outcome expectancies predicted intention, whereas the volitional factors of planning and action control mediated between intention and changes in hand washing frequency. Action control was confirmed as the most proximal factor on hand washing behaviour, thus representing a bridge of the planning–behaviour gap. Conclusions. Both motivational and volitional processes are important to consider in the improvement of hand hygiene practices. Moreover, the statistically significant effects for planning and action control illustrate the importance of these key self-regulatory factors in the prediction of hand hygiene. The current study highlights the importance of adopting models that account for motivational and volitional factors to better understand hand washing behaviour.
Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection

ABSTRACT Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly (P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system.
Psychopathology of terrorists

Terrorist behavior represents a subtype of human aggression probably determined by a combination of biological, psychological, and social factors, as well as by peculiar environmental influences and group dynamics. As regards terrorists’ psychological characteristics, the available studies (mostly carried out with no sound scientific design) have failed to identify the common or typical pathological personality traits of modern terrorists. The popular opinion that terrorists must be insane or psychopathic is still widespread; however, no evidence exists that terrorist behavior may be caused either by prior or current psychiatric disorders or psychopathy. Not surprisingly, some theories have proposed social factors and non-pathological psychological traits as predisposing elements for terrorist acts, but they generally lack of empirical validation. Moreover, most of these theories do not explain why, even if so many people are exposed to the same social factors or show the same psychological traits, only a tiny minority of them join a terrorist group. Therefore, it is mandatory that systematic and scientific investigations be carried out in order to understand the possible bases for terrorist aggression, including the early detection of possibly associated psychopathology, and to design an appropriate counterterrorism prevention policy.
Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells

Significance The upper respiratory tract (URT) is the first contact site for inhaled pathogens and intranasal vaccines, and is serviced by a network of lymphoid-tissues, including draining lymph nodes and nasal-associated lymphoid tissues (NALTs). Whether these lymphoid structures have distinct roles in facilitating T-cell immunity to inhaled antigens is unclear. We show, following antigen delivery into the URT, NALTs failed to support naïve T-cell priming; however, they supported the recall expansion of memory T cells. Although antigen delivery to the URT may not induce effective T-cell priming, it would be an effective means of boosting responses in the context of preexisting T-cell immunity. These results have significant implications for intranasal vaccines that deliver antigen to NALTs and aim to elicit protective T-cell immunity. The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8+ T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine. Whereas NALTs served as the induction site for the recall expansion of memory CD8+ T cells following influenza virus infection or vaccination, they failed to support activation of naïve CD8+ T cells. Strikingly, NALTs, unlike other lymphoid tissues, were not routinely surveyed during the steady state by circulating T cells. The selective recruitment of memory T cells into these lymphoid structures occurred in response to infection-induced elevation of the chemokine CXCL10, which attracted CXCR3+ memory CD8+ T cells. These results have significant implications for intranasal vaccines, which deliver antigen to mucosal-associated lymphoid tissue and aim to elicit protective CTL-mediated immunity.