Miracle-dz/UniFAR-FTUs huggingface dataset:
The signaling lipid sphingosine 1-phosphate regulates mechanical pain

Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli. These effects are mediated by fast-conducting A mechanonociceptors, which displayed a significant decrease in mechanosensitivity in S1PR3 mutant mice. We show that S1PR3 signaling tunes mechanonociceptor excitability via modulation of KCNQ2/3 channels. Our findings define a new role for S1PR3 in regulating neuronal excitability and establish the importance of S1P/S1PR3 signaling in the setting of mechanical pain thresholds.
The risk of cataract in relation to metal arc welding.

OBJECTIVES There are indications that solar ultraviolet radiation (UVR) increases the risk of cataract, but there is only circumstantial evidence that metal welding, an important occupational source of UVR exposure, is a risk factor. The objective of this study is to unravel if metal welding increases the risk of cataract. METHOD We compared the risk of being diagnosed with cataract from 1987-2012 in a historic cohort of 4288 male metal arc welders against a reference group comprised of Danish skilled and unskilled male workers with similar age distribution. For the welders' cohort, information on welding was collected from questionnaires and, for both cohorts, information about cataract diagnosis and operation was gathered from Danish national registers. Using Cox regression analysis, the hazard ratio (HR) for cataract diagnosis and/or operation was calculated in the follow-up period adjusted for baseline data regarding age, diabetes, and social group. RESULTS There were 266 welders and 29 007 referents with a diagnosis and/or operation for cataract. The unadjusted HR for cataract comparing ever-welders with referents was 1.07 [95% confidence interval (95% CI) 0.95-1.21] and the adjusted HR was 1.08 (95% CI 0.95-1.22). Age and diabetes were as expected strong risk factors. CONCLUSION We found no increased risk of developing cataract among Danish metal welders who worked with arc welding from 1950-1985. This may be attributed to the effectiveness of personal safety equipment.
APC/CCdh1-Rock2 pathway controls dendritic integrity and memory

Significance Disruption of neuronal dendrites causes cognitive impairment in Alzheimer’s disease (AD). Rock2, a kinase of the Rho family of proteins, is a dendrite destabilizer that accumulates in the AD brain. However, why Rock2 aberrantly aggregates, causing neuronal integrity loss, is unknown. Here, we show that Rock2 protein stability is controlled by the ubiquitin ligase APC/CCdh1. Accordingly, APC/CCdh1 loss of function in adult neurons increases Rock2 protein and activity, causing dendrite disruption in the cortex and hippocampus, along with memory loss and neurodegeneration, in mice. These effects are abolished by inhibition of Rock2 activity. Thus, the APC/CCdh1-Rock2 pathway may be a novel therapeutic target against neurodegeneration. Disruption of neuronal morphology contributes to the pathology of neurodegenerative disorders such as Alzheimer’s disease (AD). However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional knockout (cKO)], disrupts dendrite arborization and causes dendritic spine and synapse loss in the cortex and hippocampus, concomitant with memory impairment and neurodegeneration, in adult mice. We found that the dendrite destabilizer Rho protein kinase 2 (Rock2), which accumulates in the brain of AD patients, is an APC/CCdh1 substrate in vivo and that Rock2 protein and activity increased in the cortex and hippocampus of Cdh1 cKO mice. In these animals, inhibition of Rock activity, using the clinically approved drug fasudil, prevented dendritic network disorganization, memory loss, and neurodegeneration. Thus, APC/CCdh1-mediated degradation of Rock2 maintains the dendritic network, memory formation, and neuronal survival, suggesting that pharmacological inhibition of aberrantly accumulated Rock2 may be a suitable therapeutic strategy against neurodegeneration.
Comparison of Linezolid and Vancomycin for Methicillin‐Resistant Staphylococcus aureus Pneumonia: Institutional Implications

Recent studies suggesting clinical superiority of linezolid over vancomycin in the treatment of methicillin‐resistant Staphylococcus aureus (MRSA) pneumonia led to a change in our institution's clinical pathway/order form for hospital‐acquired pneumonia, positioning linezolid as the preferred agent. Our objective was to assess the impact of this change within our institution.
Social mixing in Fiji: Who-eats-with-whom contact patterns and the implications of age and ethnic heterogeneity for disease dynamics in the Pacific Islands

Empirical data on contact patterns can inform dynamic models of infectious disease transmission. Such information has not been widely reported from Pacific islands, nor strongly multi-ethnic settings, and few attempts have been made to quantify contact patterns relevant for the spread of gastrointestinal infections. As part of enteric fever investigations, we conducted a cross-sectional survey of the general public in Fiji, finding that within the 9,650 mealtime contacts reported by 1,814 participants, there was strong like-with-like mixing by age and ethnicity, with higher contact rates amongst iTaukei than non-iTaukei Fijians. Extra-domiciliary lunchtime contacts follow these mixing patterns, indicating the overall data do not simply reflect household structures. Inter-ethnic mixing was most common amongst school-age children. Serological responses indicative of recent Salmonella Typhi infection were found to be associated, after adjusting for age, with increased contact rates between meal-sharing iTaukei, with no association observed for other contact groups. Animal ownership and travel within the geographical division were common. These are novel data that identify ethnicity as an important social mixing variable, and use retrospective mealtime contacts as a socially acceptable metric of relevance to enteric, contact and respiratory diseases that can be collected in a single visit to participants. Application of these data to other island settings will enable communicable disease models to incorporate locally relevant mixing patterns in parameterisation.
Timber-concrete composite slabs made of beech laminated veneer lumber with notched connection

This paper focuses on the structural behaviour of timber-concrete composite slabs made of beech laminated veneer lumber (LVL) plates with notched connection. In general, timber-concrete composite members are usually made of softwood, and are able to offer several advantages compared to reinforced concrete slabs and timber slabs. Beech LVL is an efficient structural material, but its use in structural engineering began in recent times. Although beech LVL plates are very performing and reliable structural elements, they have never been used in timber-concrete composites and no research exists about this topic. The structural system developed in this research project has high stiffness, load-carrying capacity, reliability, and is able to achieve ductility at failure level due to yielding of timber under compression within the notches. Because of the difference between the material properties of timber and concrete, local timber deformations within the notches may compromise the shear-carrying mechanism in concrete, leading to premature failure of the composite member. This problem can be solved by installing vertical reinforcements. To describe the interaction between timber, concrete and reinforcements, an analytical model was developed, which was validated by means of laboratory tests and allows a reliable design of the structure.
Mechanical Insufflation-Exsufflation Versus Conventional Chest Physiotherapy in Children With Cerebral Palsy

BACKGROUND: The cough mechanism is often impaired in children with quadriplegic spastic cerebral palsy, accounting for the high prevalence of pneumonia and atelectasis requiring prolonged hospitalization. Conventional chest physiotherapy (CPT) is a current technique recommended at the onset of lower-respiratory infections in cerebral palsy. Previous studies have demonstrated the usefulness of mechanical insufflation-exsufflation (MI-E) in children with neuromuscular disease. To date, there has been no study of MI-E in children with quadriplegic spastic cerebral palsy. The objective of the study is to compare the efficacy in reducing hospital stay and improvement of atelectasis between MI-E and CPT in children with quadriplegic spastic cerebral palsy with lower-respiratory infections. METHODS: This study is a randomized controlled trial. Children with quadriplegic spastic cerebral palsy, age 6 months to 18 y, admitted for lower-respiratory infections and/or atelectasis at King Chulalongkorn Memorial Hospital between June 1, 2014, and March 31, 2015, were recruited. Those with pneumothorax, severe pneumonia, active tuberculosis, and shock were excluded. Children were randomized into the MI-E or CPT group. The MI-E group received MI-E (3 therapies/d), and the CPT group received CPT (1 therapy/d). Vital signs per protocol and chest radiograph as needed were recorded. RESULTS: There were 22 children enrolled in the study, 11 in the MI-E and 11 in the CPT group. Demographic data were comparable in both groups. The length of hospital stay was similar in both groups (MI-E 4–24 d vs CPT 6–42 d, P = .15). There were 17 subjects with atelectasis (MI-E [n = 9] versus CPT [n = 8]). In this atelectasis subgroup, MI-E had shortened therapy time when compared with CPT (2.9 ± 0.8 d vs 3.9 ± 0.6 d, P = .01). No complications were observed. CONCLUSIONS: MI-E is proven to be beneficial in shortening the duration of airway clearance in children with quadriplegic spastic cerebral palsy presenting with lower-respiratory infections and atelectasis. MI-E is a safe and efficient intervention for airway clearance.
Accuracy comparison of guided surgery for dental implants according to the tissue of support: a systematic review and meta‐analysis

AIM To systematically assess the current dental literature comparing the accuracy of computer-aided implant surgery when using different supporting tissues (tooth, mucosa, or bone). MATERIAL AND METHODS Two reviewers searched PubMed (1972 to January 2015) and the Cochrane Central Register of Controlled Trials (Central) (2002 to January 2015). For the assessment of accuracy, studies were included with the following outcome measures: (i) angle deviation, (ii) deviation at the entry point, and (iii) deviation at the apex. RESULTS Eight clinical studies from the 1602 articles initially identified met the inclusion criteria for the qualitative analysis. Four studies (n = 599 implants) were evaluated using meta-analysis. The bone-supported guides showed a statistically significant greater deviation in angle (P < 0.001), entry point (P = 0.01), and the apex (P = 0.001) when compared to the tooth-supported guides. Conversely, when only retrospective studies were analyzed, not significant differences are revealed in the deviation of the entry point and apex. The mucosa-supported guides indicated a statistically significant greater reduction in angle deviation (P = 0.02), deviation at the entry point (P = 0.002), and deviation at the apex (P = 0.04) when compared to the bone-supported guides. Between the mucosa- and tooth-supported guides, there were no statistically significant differences for any of the outcome measures. CONCLUSIONS It can be concluded that the tissue of the guide support influences the accuracy of computer-aided implant surgery.
Ordered Binary Decision Diagrams, Pigeonhole Formulas and Beyond

Groote and Zantema proved that a particular OBDD computation of the pigeonhole formula has exponential size, and that limited OBDD derivations cannot simulate resolution polynomially. Here we show that an arbitrary OBDD refutation of the pigeonhole formula has exponential size: we prove that for any order of computation at least one intermediate OBDD in the proof has size (1.14 n ). We also present a family of CNFs that show an exponential blow-up for all OBDD refutations compared to unrestricted resolution refutations.
The Effect of Monthly Medication on Mortality After a Coronary Event

Aim: The aim of this study was to analyze how the consumption of medication over time affects the survival rate in patients with a coronary event and whether there is a gender difference. Methods: The study included 804 patients admitted to 4 hospitals with a coronary event during 2007. Monitoring after coronary event was carried out during 2007 and every 6 months in the subsequent 2 years (2008 and 2009) throughout the review of the clinical history of the patient. The main outcome was the analysis of mortality after the coronary event. Kaplan-Meier survival curves were plotted to calculate the time to death, comparing women versus men for 4 medication groups: aspirin, statins, β-blockers, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs). A Cox regression model was used for the final mortality analysis. Results: During the follow-up time, 172 deaths were assessed. Each month of treatment with aspirin, statins, β-blockers, or ACEI/ARB was associated with a decrease in mortality between 13.0% and 0.5% (univariate analysis). The Kaplan-Meier method revealed a significant reduction in mortality after the coronary event for each month of treatment with aspirin (men), statins (men), and β-blockers (both men and women). No significant effect in survival was observed in either gender with ACEI/ARB treatment. The final multivariable model (Cox regression) showed that the taking of aspirin, statins, β-blockers, or ACEI/ARB is able to reduce mortality rates up to 7.0% (aspirin) throughout each month of treatment after a coronary event without any influence of gender. Conclusion: Aspirin, statins, β-blockers, and ACEI/ARB revealed a protective character with each month of treatment throughout the follow-up period, in terms of risk reduction of death. Aspirin and statins showed the maximum benefit, followed by ACEI/ARB and β-blockers.
The Effects of Thermal Ageing on Properties and Microstructure of Al-6063 Alloy

The effect of thermal ageing on the properties and microstructure of Al-Mg-Si alloy was investigated. In this work, an extruded Al-6063 alloy samples were used as the main materials. In order to study the effect of thermal ageing, the alloy samples were solution treated at 530 °C and then quenched into water before artificially aged at elevated temperatures between 120 and 250 °C. The ageing response and mechanical properties was monitored by Vickers hardness and tensile tests, respectively. The analysis of surface fracture and microstructure of peak aged alloy were carried out by means of scanning electron microscope (SEM) and transmission electron microscope (TEM), respectively. Result shows that the highest hardness value and tensile properties is gained by the alloy that aged at 120 °C. It is found that increasing in hardness and strength values of the alloy are due to precipitates formation during thermal ageing. Fracture analysis on peak-aged condition indicates that the alloy having more ductility after thermal ageing. The result shows that the higher ageing temperature will lead to the higher ductility of the Al-6063 alloy, as a results the alloy’s strength is reduced.
UPLC‐HRMS‐based untargeted metabolic profiling reveals changes in chickpea (Cicer arietinum) metabolome following long‐term drought stress

Abstract Genetic improvement for drought tolerance in chickpea requires a solid understanding of biochemical processes involved with different physiological mechanisms. The objective of this study is to demonstrate genetic variations in altered metabolic levels in chickpea varieties (tolerant and sensitive) grown under contrasting water regimes through ultrahigh‐performance liquid chromatography/high‐resolution mass spectrometry‐based untargeted metabolomic profiling. Chickpea plants were exposed to drought stress at the 3‐leaf stage for 25 days, and the leaves were harvested at 14 and 25 days after the imposition of drought stress. Stress produced significant reduction in chlorophyll content, F v/F m, relative water content, and shoot and root dry weight. Twenty known metabolites were identified as most important by 2 different methods including significant analysis of metabolites and partial least squares discriminant analysis. The most pronounced increase in accumulation due to drought stress was demonstrated for allantoin, l‐proline, l‐arginine, l‐histidine, l‐isoleucine, and tryptophan. Metabolites that showed a decreased level of accumulation under drought conditions were choline, phenylalanine, gamma‐aminobutyric acid, alanine, phenylalanine, tyrosine, glucosamine, guanine, and aspartic acid. Aminoacyl‐tRNA and plant secondary metabolite biosynthesis and amino acid metabolism or synthesis pathways were involved in producing genetic variation under drought conditions. Metabolic changes in light of drought conditions highlighted pools of metabolites that affect the metabolic and physiological adjustment in chickpea that reduced drought impacts.
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a rare disease characterized by progressive fibrofatty replacement of the myocardium, primarily involving the right ventricle (RV). The structural changes in the ventricular myocardium form a substrate for ventricular arrhythmia ranging from premature ventricular complexes to ventricular tachycardia typically of RV origin and may result in RV failure and progress to congestive heart failure at a later stage. ARVC/D is a recognized cause of sudden cardiac death in young people, but it may occur at any age. With the discovery of underlying pathogenic mutations involved in the disease development and insight from long‐term follow‐up of ARVC/D patients, ARVC/D is an inherited cardiomyopathy. Mutations in at least eight genes have been involved in ARVC/D genesis in 30–50% of patients. Most of these genes are involved in the function of desmosomes, which are structures that attach heart muscle cells to one another. Desmosomes provide strength to the myocardium and play a role in signaling between neighboring cells. Mutations in the genes responsible for ARVC/D often impair the normal desmosomal function. There has been significant advancement in the diagnosis and management of ARVC/D in the past few decades. This chapter provides an overview of ARVC/D pathophysiology, clinical presentations, diagnosis, and manage‐ ment.
Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men

Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation in thyroid hormones within the euthyroid range modulates bone health, particularly among older men. We assessed whether thyroid stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone turnover markers (BTMs) and predict hip fracture risk in community‐dwelling older men without known thyroid disease.
A phase 3 trial of IV immunoglobulin for Alzheimer disease

Objective: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. Results: No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Conclusions: Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. Clinicaltrials.gov identifier: NCT00818662. Classification of evidence: This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.
Two dimensional kicked quantum Ising model: dynamical phase transitions

Using an efficient one and two qubit gate simulator operating on graphical processing units, we investigate ergodic properties of a quantum Ising spin 1 / 2 ? > model on a two-dimensional lattice, which is periodically driven by a δ-pulsed transverse magnetic field. We consider three different dynamical properties: (i) level density, (ii) level spacing distribution of the Floquet quasienergy spectrum, and (iii) time-averaged autocorrelation function of magnetization components. Varying the parameters of the model, we found transitions between ordered (non-ergodic) and quantum chaotic (ergodic) phases, but the transitions between flat and non-flat spectral density do not correspond to transitions between ergodic and non-ergodic local observables. Even more surprisingly, we found good agreement of level spacing distribution with the Wigner surmise of random matrix theory for almost all values of parameters except where the model is essentially non-interacting, even in regions where local observables are not ergodic or where spectral density is non-flat. These findings question the versatility of the interpretation of level spacing distribution in many-body systems and stress the importance of the concept of locality.