bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Machine Learning to Model Volume Load Effects on Changes in Jump Performance
Authors: Kipp Kristof , Krzyszkowski John , Kant-Hull Daniel
Published: May 2019

Purpose: To use an artificial neural network (ANN) to model the effect of 15 weeks of resistance training on changes in countermovement jump (CMJ) performance in male track-and-field athletes. Methods: Resistance training volume load (VL) of 21 male division I track-and-field athletes was monitored over the course of 15 weeks, which covered their indoor and outdoor competitive season. Weekly CMJ height was also measured and used to calculate the overall 15-week change in CMJ performance. A feed-forward ANN with 5 hidden layers was used to model how the VL from each of the 15 weeks was associated with the overall change in CMJ height. Results: Testing the performance of the developed ANN on 4 separate athletes showed that 15 weeks of VL data could predict individual changes in CMJ height with an average error between 0.21 and 1.47 cm, which suggested that the ANN adequately modeled the relationship between weekly VL and its effects on CMJ performance. In addition, analysis of the relative importance of each week in predicting changes in CMJ height indicated that the VLs during deload or taper weeks were the best predictors (10%–17%) of changes in CMJ performance. Conclusions: ANN can be used to effectively model the effects of weekly VL on changes in CMJ performance. In addition, ANN can be used to assess the relative importance of each week in predicting changes in CMJ height.
The Influence of Heat Acclimation and Hypohydration on Post-Weight-Loss Exercise Performance
Authors: Barley Oliver R. , Chapman Dale W. , Mavropalias Georgios , Abbiss Chris R.
Published: May 2019

Purpose: To examine the influence of fluid intake on heat acclimation and the subsequent effects on exercise performance following acute hypohydration. Methods: Participants were randomly assigned to 1 of 2 groups, either able to consume water ad libitum (n = 10; age 23 [3] y, height 1.81 [0.09] m, body mass 87 [13] kg; HAW) or not allowed fluid (n = 10; age 26 [5] y, height 1.76 [0.05] m, body mass 79 [10] kg; HANW) throughout 12 × 1.5-h passive heat-acclimation sessions. Experimental trials were completed on 2 occasions before (2 baseline trials) and 1 following the heat-acclimation sessions. These sessions involved 3 h of passive heating (45°C, 38% relative humidity) to induce hypohydration followed by 3 h of ad libitum food and fluid intake after which participants performed a repeat sled-push test to assess physical performance. Urine and blood samples were collected before, immediately, and 3 h following hypohydration to assess hydration status. Mood was also assessed at the same time points. Results: No meaningful differences in physiological or performance variables were observed between HANW and HAW at any time point. Using pooled data, mean sprint speed was significantly (P < .001) faster following heat acclimation (4.6 [0.7] s compared with 5.1 [0.8] s). Furthermore, heat acclimation appeared to improve mood following hypohydration. Conclusions: Results suggest that passive heat-acclimation protocols may be effective at improving short-duration repeat-effort performance following acute hypohydration.
The Association Between Noncontact Injuries and the Acute—Chronic Workload Ratio in Elite-Level Athletes: A Critically Appraised Topic
Authors: Myers Natalie L. , Mexicano Guadalupe , Aguilar Kristin V.
Published: May 2019

Clinical Scenario: Workload monitoring and management of an athlete is viewed by many as an essential training component to determine if an athlete is adapting to a training program and to minimize injury risk. Although training workload may be measured a variety of different ways, session rate of perceived exertion (sRPE) is often used in the literature due to its clinical ease. In recent years, sports scientists have been investigating sRPE as a measure of internal workload and its relationship to injury in elite-level athletes using a metric known as the acute:chronic workload ratio (ACWR). This critically appraised topic was conducted to determine if internal workload using the ACWR is associated with injury. Focused Clinical Question: In elite-level athletes, is there an association between the ACWR for sRPE and noncontact injuries? Summary of Search, Best Evidence Appraised, and Key Findings: The literature was searched for studies investigating the association between noncontact injuries and the sRPE ACWR in elite athletes. Three prospective cohort studies were included. Two studies found that high ACWR led to 2.0 to 4.5 times greater injury risk compared with a more balanced ACWR. One study found that low chronic workloads coupled with a low ACWR were associated with injury. Clinical Bottom Line: The majority of evidence suggests that when the acute workload exceeds the chronic workload, there is an increase in injury risk. The evidence also supports that a low chronic workload with a low ACWR should be considered as an injury risk factor. Strength of Recommendation: Based on the American Family Physician’s Strength of Recommendation Taxonomy, there is level A evidence to support the sRPE ACWR as a risk factor for noncontract injuries in elite athletes.
Ankle Sprains Risk Factors in a Sample of French Firefighters: A Preliminary Prospective Study
Authors: Vaulerin Jérôme , Chorin Frédéric , Emile Mélanie , d’Arripe-Longueville Fabienne , Colson Serge S.
Published: May 2019

Context:Firefighters participating in mandatory physical exercise sessions are exposed to a high risk of ankle sprain injury. Although both physiological and psychological risk factors have been identified, few prospective studies considered the complex interaction of these factors in firefighters.Objective:To prospectively determine whether intrinsic physical risk factors and work-related environments predict ankle sprains occurring during on-duty physical exercise in firefighters during an 8-month follow-up period.Design:Prospective.Setting:Fire Department and Rescue Service.Participants:Thirty-nine firefighters were selected based on convenience sampling.Intervention:Participants performed physical tests and completed questionnaires.Main Outcome Measures:Lower Quarter Y-Balance Test, Weight-Bearing Lunge Test, anthropometric measures, postural stability, chronic ankle instability (Cumberland Ankle Instability Tool) scores, previous injuries, and perceived psychosocial work environment (Copenhagen Psychosocial Questionnaire [COPSOQ]).Results:During the follow-up, 9 firefighters sustained an injury. Lower Quarter Y-Balance Test and Weight-Bearing Lunge Test performances, Cumberland Ankle Instability Tool scores, history of previous ankle sprain, and specific dimensions of the COPSOQ significantly differed between injured and uninjured firefighters. Lower-limbs asymmetries of the Lower Quarter Y-Balance Test (ie, anterior, posteromedial, and posterolateral directions) and the Weight-Bearing Lunge Test were predictors of ankle sprains.Conclusions:These findings originally provide evidence that intrinsic factors mainly contribute to ankle sprains, although psychosocial work environment assessment could also characterize firefighters at risk.
Does an Accelerated Program Give Equivalent Results in Both Elite Athletes and Nonathletes?
Authors: Feyzioğlu Özlem , Öztürk Özgul , Sirmen Bilsen , Muğrabi Selim
Published: May 2019

Context: Although many researchers have investigated the functional outcomes of different accelerated rehabilitation programs after anterior cruciate ligament reconstruction (ACLR), the functional results of the same accelerated rehabilitation program following ACLR applied for both elite athletes and nonathletes have not yet been investigated. Objective: To examine the effects of the same accelerated anterior cruciate ligament rehabilitation program on pain and functionality of elite athletes and nonathletes. Design: Prospective preintervention–postintervention design. Setting: Physiotherapy department. Participants: Fifteen elite athletes and 15 nonathletes who underwent unilateral ACLR with autologous hamstring tendon graft. Intervention: All participants received the same protocol for 6 weeks (5 sessions in a week). Main Outcome Measures: Primary measurements were pain intensity, which was measured by visual analog scale, range of motion measurement using universal goniometer, and functionality, which was detected by Lysholm score. Secondary measurements were short form-36 and Beck Depression Inventory. Results: Higher Lysholm (P = .001) and Beck Depression Inventory (P = .03) scores were observed in the elite athlete group, and higher pain (P = .001) was observed in the nonathlete group at baseline assessments. Significant improvement detected for pain (P < .05), knee flexion range (P < .05), Lysholm score (P < .05), and Beck Depression Inventory (P < .05) compared with preintervention for both groups. Finally, after comparing the mean change values, the nonathlete group displayed greater decrease in pain level (P = .01) and participants in the elite athlete group further showed a greater decrease in depression level (P = .001). Conclusions: This study found that the same accelerated rehabilitation protocol provides significant improvements for pain, functionality, and depression in both elite athletes and nonathletes after ACLR. Clinicians should consider our results when applying an anterior cruciate ligament rehabilitation program for nonathlete groups.
Learning to Use Teaching for Personal and Social Responsibility Through Action Research
Authors: Gray Shirley , Wright Paul M. , Sievwright Richard , Robertson Stuart
Published: May 2019

Purpose: The purpose this investigation was to explore the learning experiences of two teachers from different secondary schools in Scotland as they engaged in their respective action research projects to learn to apply teaching personal and social responsibility in physical education.Method: Both teachers worked within a small community of practice and used qualitative methods to gather data to inform their inquiry. The teachers shared their findings with their coauthors and engaged in further, more focused analyses to explore and understand their learning experiences and the learning experiences of their pupils.Results: Both teachers found that their learning in context was much slower and more challenging than first expected. Over time, both teachers learned to set “new” learning objectives, applied “new” teaching strategies, talked more to their pupils, and reflected with others to evaluate their learning.Discussion/Conclusion: When teachers are committed to their own learning and when the subject of their learning aligns with their core values, professional needs, and the needs of their pupils, then pedagogical change is possible.
Development and Validation of a Scale Assessing Test Anxiety in Physical Education
Authors: Danthony Sarah , Mascret Nicolas , Cury François
Published: May 2019

Purpose: There is currently no scale assessing test anxiety in physical education (PE), despite the specificities of this class (e.g., body image, failure in front of peers). Accordingly, the aim of the present study was to develop a specific scale named the “Revised Test Anxiety and Regulatory Dimension of Anxiety in Physical Education” (RTAR-PE). Method: Self-report data were collected from 281 (Study 1) and 390 (Study 2) students in French schools (age range: 13–18 years). Results: Study 1 showed that the RTAR-PE scale has acceptable psychometric properties. Study 2 confirmed the results of Study 1 and showed the convergent, discriminant, and predictive validities of the scale. Gender differences were found, with girls showing higher PE test anxiety than boys. Discussion/Conclusion: The RTAR-PE is a newly available scale assessing the different facets of test anxiety in PE (worry, self-focus, bodily symptoms, somatic tension, and perceived control) considering the specificities of this class.
Exploring the Role of Physical Education Teachers’ Domain-Specific Innovativeness, Educational Background, and Perceived School Support in CSPAP Adoption
Authors: Webster Collin A. , Mindrila Diana , Moore Chanta , Stewart Gregory , Orendorff Karie , Taunton Sally
Published: May 2019

Purpose: A comprehensive school physical activity program (CSPAP) is designed to help school-aged youth meet physical activity guidelines as well as develop the knowledge, skills, and dispositions that foster meaningful lifelong physical activity participation. In this study, we employed a “diffusion of innovations theory” perspective to examine the adoption of CSPAPs in relation to physical education teachers’ domain-specific innovativeness, educational background, demographics, and perceived school support. Methods: Physical education teachers (N = 407) responded to an electronic survey with validated measures for each of the above-mentioned variables. Results: Latent profile analysis classified teachers into three domain-specific innovativeness levels (high, average, and low). CSPAP-related professional training, knowledge, and perceived school support were found to be significant factors in domain-specific innovativeness and CSPAP adoption. Discussion/Conclusion: This study provides novel evidence to inform professional development initiatives so that they can be tailored to physical education teachers who may be less likely to adopt a CSPAP.
European Commission kills billion-euro flagship concept
Authors: Kupferschmidt Kai
Published: May 2019

Six candidate research proposals lost in limbo.
Facing Plan S, publishers may set papers free
Authors: Brainard Jeffrey
Published: May 2019

Journals consider offering "green" open access from the time of publication.
Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway
Authors: Lee Yu-Ru , Chen Ming , Lee Jonathan D. , Zhang Jinfang , Lin Shu-Yu , Fu Tian-Min , Chen Hao , Ishikawa Tomoki , Chiang Shang-Yin , Katon Jesse , Zhang Yang , Shulga Yulia V. , Bester Assaf C. , Fung Jacqueline , Monteleone Emanuele , Wan Lixin , Shen Chen , Hsu Chih-Hung , Papa Antonella , Clohessy John G. , Teruya-Feldstein Julie , Jain Suresh , Wu Hao , Matesic Lydia , Chen Ruey-Hwa , Wei Wenyi , Pandolfi Pier Paolo
Published: May 2019

Supporting tumor suppression

The protein PTEN is a phosphatase and tumor suppressor whose activity is often decreased in human cancers. Thus, reactivating such a protein could potentially be an effective therapy against cancer. Lee
et al.
identified a ubiquitin E3 ligase (WWP1) as a PTEN-interacting protein that modifies PTEN and inhibits its tumor suppressive activity (see the Perspective by Parsons). Depletion of WWP1 increased dimerization and membrane recruitment of PTEN. A natural compound found to be a pharmacological inhibitor of WWP1 inhibited tumor growth in a mouse model of prostate cancer. Thus, reactivation of the tumor suppressor PTEN may provide a strategy for battling tumors.

Science
, this issue p.
eaau0159
; see also p.
633
De novo design of tunable, pH-driven conformational changes
Authors: Boyken Scott E. , Benhaim Mark A. , Busch Florian , Jia Mengxuan , Bick Matthew J. , Choi Heejun , Klima Jason C. , Chen Zibo , Walkey Carl , Mileant Alexander , Sahasrabuddhe Aniruddha , Wei Kathy Y. , Hodge Edgar A. , Byron Sarah , Quijano-Rubio Alfredo , Sankaran Banumathi , King Neil P. , Lippincott-Schwartz Jennifer , Wysocki Vicki H. , Lee Kelly K. , Baker David
Published: May 2019

Designed to respond

Protein design has achieved success in finding sequences that fold to very stable target structures. Protein function, however, often requires conformational dynamics. Boyken
et al.
describe designed proteins that undergo conformational transitions in response to pH. They designed helical oligomers in which histidines are positioned in hydrogen-bond networks at the interfaces, with complimentary hydrophobic packing around the networks. Lowering the pH protonated the histidine, disrupting the oligomers. After endocytosis into low-pH compartments in cells, the designed proteins disrupted endosomal membranes.

Science
, this issue p.
658
Mechanism of allosteric modulation of P-glycoprotein by transport substrates and inhibitors
Authors: Dastvan Reza , Mishra Smriti , Peskova Yelena B. , Nakamoto Robert K. , Mchaourab Hassane S.
Published: May 2019

Transport control

The membrane protein P-glycoprotein protects cells by using energy from adenosine triphosphate (ATP) hydrolysis to expel chemical substances, including drugs. Inhibiting P-glycoprotein may thus ameliorate drug resistance. Structures of P-glycoprotein in the apo state and bound to substrate and inhibitor give insight into the transport mechanism, but a full picture requires access to substates in the transport cycle. Dastvan
et al.
used double electron electron resonance spectroscopy to show that substrates enhance transport by stabilizing an asymmetric post–ATP-hydrolysis state. By contrast, inhibitors stabilize a symmetric state that impairs transport.

Science
, this issue p.
689
RETRACTED: Insular cortex processes aversive somatosensory information and is crucial for threat learning
Authors: Berret Emmanuelle , Kintscher Michael , Palchaudhuri Shriya , Tang Wei , Osypenko Denys , Kochubey Olexiy , Schneggenburger Ralf
Published: May 2019

Fear behavior and the insular cortex

Threat learning is important to avoid dangers in the environment. The amygdala is a brain structure involved in the formation of threat memories. How unconditioned stimulus information reaches the amygdala remains unclear. Berret
et al.
found that independent subpopulations of neurons in the insular cortex project either to the lateral or the central amygdala and drive threat learning and fear-associated responses, respectively. Neurons in the posterior insula adapted their response patterns to conditioned stimulus presentation during fear conditioning and maintained this pattern at retrieval. Multisensory integration in the insula thus contributes to the storage and retrieval of threat memories.

Science
, this issue p.
eaaw0474
Constrained sialic acid donors enable selective synthesis of α-glycosides
Authors: Komura Naoko , Kato Keiichi , Udagawa Taro , Asano Sachi , Tanaka Hide-Nori , Imamura Akihiro , Ishida Hideharu , Kiso Makoto , Ando Hiromune
Published: May 2019

Sweet spot for making oligosaccharides

Sugars pose a challenge for chemists: how to string together functional group–rich building blocks that can adopt multiple conformations. Two papers in this issue used sugar building blocks constrained by a macrocyclic linker to encourage formation of a specific glycosidic linkage (see the Perspective by Pohl). Ikuta
et al.
used glucose building blocks containing a linker that changes the sugar conformation to synthesize cyclic oligomers with only three or four units. The linker changes the conformation of the glucose monomers, enabling them to come together despite the strain in the final structure. Komura
et al.
prepared sialic acid building blocks with a linker that allows for selective formation of the α-anomeric linkage with a range of nucleophiles. They synthesized dimers of sialic acid with many different linkages and a pentamer with four α(2,8) linkages. This method enabled chemical synthesis of components of mammalian glycans involved in brain development, cell adhesion, and immune response.

Science
, this issue p.
674
, p.
677
; see also p.
631
Probing and imaging spin interactions with a magnetic single-molecule sensor
Authors: Czap Gregory , Wagner Peter J. , Xue Feng , Gu Lei , Li Jie , Yao Jiang , Wu Ruqian , Ho W.
Published: May 2019

Visualizing superexchange interactions

The resolution that can be achieved in scanning probe microscopy can be greatly enhanced by absorbing a molecule such as CO on the probe tip. Czap
et al.
now show that this approach can be used to scan spin and magnetic properties of molecules on a surface. They adsorbed a magnetic molecule, Ni(cyclopentadienyl)
2
, on a silver surface and then transferred one of these molecules to a scanning tunnel microscope tip. They could then bring the tip toward the adsorbate-covered surface and map out the strength of superexchange interactions.

Science
, this issue p.
670
When science and politics collide: Enhancing the FDA
Authors: Adashi Eli Y. , Rajan Rohit S. , Cohen I. Glenn
Published: May 2019

Science-based decisions on drug safety are threatened by political interference
Environmental management for dengue control: a systematic review protocol
Authors: Mahmud Mohd Amierul Fikri , Abdul Mutalip Mohd Hatta , Lodz Noor Aliza , Muhammad Eida Nurhadzira , Yoep Norzawati , Hashim Mohd Hazrin , Paiwai Faizah , Rajarethinam Jayanthi , Aik Joel , Muhammad Nor Asiah
Published: May 2019

Introduction

Dengue is among the most important mosquito-borne diseases, with more than half of the world’s population at risk of infection in dengue endemic countries. Environmental management, which includes any activities that involve environmental modification, environmental manipulation and changes to human behaviour have been used to mitigate the risk of dengue transmission. In this protocol, we will integrate the data from various sources to assess the overall effect of environmental management on the incidence of dengue and other entomological indices.

Methods and analyses

We will conduct a systematic review of intervention that assess the effect of environmental management on the incidence of dengue and/or entomological indices. We will include any studies that include intervention through environmental management for dengue control, involving environmental modification, environmental manipulation and changes to human behaviour. A comprehensive search will be performed in electronic databases PUBMED, CENTRAL, SCOPUS, Web of Science and relevant research websites such as PROPSERO, WHO ICTRP and ClinicalTrials.gov to identify studies that meet our inclusion criteria. A systematic approach to searching, screening, reviewing and data extraction will be applied based on Preferred Reporting Items for Systematic reviews and Meta-Analysis. Titles, abstract, keywords for eligibility will be examined independently by researchers. The quality of the included studies will be assessed using quality assessment tool for studies with diverse design and Cochrane risk of bias tool. The characteristics of the selected articles will be described based on the study design, types of intervention and outcomes of the study in various countries. These include the types of environmental management intervention methods and the effectiveness of the intervention in reducing dengue cases or incidence and impact on entomological indices.

Ethics and dissemination

We will register this systematic review with the National Medical Research Register, Ministry of Health Malaysia. This protocol also had been registered with the PROSPERO. No ethical approval is necessary, as there will be no collection of primary data. The results will be disseminated though a peer-reviewed publication and conference presentation.

Trial registration number

CRD42018092189.
Do hospital pressures change following rotavirus vaccine introduction? A retrospective database analysis in a large paediatric hospital in the UK
Authors: Heinsbroek Ellen , Hungerford Daniel , Cooke Richard P D , Chowdhury Margaret , Cargill James S , Bar-Zeev Naor , French Neil , Theodorou Eleni , Standaert Baudouin , Cunliffe Nigel A
Published: May 2019

Objective

Hospitals in the UK are under increasing clinical and financial pressures. Following introduction of childhood rotavirus vaccination in the UK in 2013, rotavirus gastroenteritis (RVGE) hospitalisations reduced significantly. We evaluated changes in ‘hospital pressures’ (demand on healthcare resources and staff) following rotavirus vaccine introduction in a paediatric setting in the UK.

Design

Retrospective hospital database analysis between July 2007 and June 2015.

Setting

A large paediatric hospital providing primary, secondary and tertiary care in Merseyside, UK.

Participants

Hospital admissions aged <15 years. Outcomes were calculated for four different patient groups identified through diagnosis coding (International Classification of Disease, 10th edition) and/or laboratory confirmation: all admissions; any infection, acute gastroenteritis and RVGE.

Methods

Hospital pressures were compared before and after rotavirus vaccine introduction: these included bed occupancy, hospital-acquired infection rate, unplanned readmission rate and outlier rate (medical patients admitted to surgical wards due to lack of medical beds). Interrupted time-series analysis was used to evaluate changes in bed occupancy.

Results

There were 116 871 admissions during the study period. Lower bed occupancy in the rotavirus season in the postvaccination period was observed for RVGE (−89%, 95% CI 73% to 95%), acute gastroenteritis (−63%, 95% CI 39% to 78%) and any infection (−23%, 95% CI 15% to 31%). No significant overall reduction in bed occupancy was observed (−4%, 95% CI −1% to 9%). No changes were observed for the other outcomes.

Conclusions

Rotavirus vaccine introduction was not associated with reduced hospital pressures. A reduction in RVGE hospitalisation without change in overall bed occupancy suggests that beds available were used for a different patient population, possibly reflecting a previously unmet need.

Trials registration number

NCT03271593
Physician-identified barriers to and facilitators of shared decision-making in the Emergency Department: an exploratory analysis
Authors: Schoenfeld Elizabeth M , Goff Sarah L , Elia Tala R , Khordipour Errel R , Poronsky Kye E , Nault Kelly A , Lindenauer Peter K , Mazor Kathleen M
Published: May 2019

Objectives

Shared decision-making (SDM) is receiving increasing attention in emergency medicine because of its potential to increase patient engagement and decrease unnecessary healthcare utilisation. This study sought to explore physician-identified barriers to and facilitators of SDM in the ED.

Methods

We conducted semistructured interviews with practising emergency physicians (EP) with the aim of understanding when and why EPs engage in SDM, and when and why they feel unable to engage in SDM. Interviews were transcribed verbatim and a three-member team coded all transcripts in an iterative fashion using a directed approach to qualitative content analysis. We identified emergent themes, and organised themes based on an integrative theoretical model that combined the theory of planned behaviour and social cognitive theory.

Results

Fifteen EPs practising in the New England region of the USA were interviewed. Physicians described the following barriers: time constraints, clinical uncertainty, fear of a bad outcome, certain patient characteristics, lack of follow-up and other emotional and logistical stressors. They noted that risk stratification methods, the perception that SDM decreased liability and their own improving clinical skills facilitated their use of SDM. They also noted that the culture of the institution could play a role in discouraging or promoting SDM, and that patients could encourage SDM by specifically asking about alternatives.

Conclusions

EPs face many barriers to using SDM. Some, such as lack of follow-up, are unique to the ED; others, such as the challenges of communicating uncertainty, may affect other providers. Many of the barriers to SDM are amenable to intervention, but may be of variable importance in different EDs. Further research should attempt to identify which barriers are most prevalent and most amenable to intervention, as well as capitalise on the facilitators noted.
IL23 induces IL23R recycling and amplifies innate receptor-induced signalling and cytokines in human macrophages, and the IBD-protective IL23R R381Q variant modulates these outcomes
Authors: Sun Rui , Hedl Matija , Abraham Clara
Published: May 2019

Objective

The interleukin (IL)23 pathway contributes to IBD pathogenesis and is being actively studied as a therapeutic target in patients with IBD. Unexpected outcomes in these therapeutic trials have highlighted the importance of understanding the cell types and mechanisms through which IL23 regulates immune outcomes. How IL23 regulates macrophage outcomes and the consequences of the IL23R R381Q IBD-protective variant on macrophages are not well defined; macrophages are key players in IBD pathogenesis and inflammation.

Design

We analysed protein and RNA expression, signalling and localisation in human monocyte-derived macrophages (MDMs) through western blot, ELISA, real-time PCR, flow cytometry, immunoprecipitation and microscopy.

Results

IL23R was critical for optimal levels of pattern-recognition receptor (PRR)-induced signalling and cytokines in human MDMs. In contrast to the coreceptor IL12Rβ1, IL23 induced dynamic IL23R cell surface regulation and this required clathrin and dynamin-mediated endocytosis and endocytic recycling-dependent pathways; these pathways were essential for IL23R-mediated outcomes. The IBD-protective IL23R R381Q variant showed distinct outcomes. Relative to IL23R R381, HeLa cells expressing IL23R Q381 showed decreased IL23R recycling and reduced assembly of IL23R Q381 with Janus kinase/signal transducer and activator of transcription pathway members. In MDMs from IL23R Q381 carriers, IL23R accumulated in late endosomes and lysosomes on IL23 treatment and cells demonstrated decreased IL23R- and PRR-induced signalling and cytokines relative to IL23R R381 MDMs.

Conclusion

Macrophage-mediated inflammatory pathways are key contributors to IBD pathogenesis, and we identify an autocrine/paracrine IL23 requirement in PRR-initiated human macrophage outcomes and in human intestinal myeloid cells, establish that IL23R undergoes ligand-induced recycling, define mechanisms regulating IL23R-induced signalling and determine how the IBD-protective IL23R R381Q variant modulates these processes.
CSF neurogranin as a neuronal damage marker in CJD: a comparative study with AD
Authors: Blennow Kaj , Diaz-Lucena Daniela , Zetterberg Henrik , Villar-Pique Anna , Karch Andre , Vidal Enric , Hermann Peter , Schmitz Matthias , Ferrer Abizanda Isidro , Zerr Inga , Llorens Franc
Published: May 2019

Objective

To investigate whether cerebrospinal fluid (CSF) neurogranin concentrations are altered in sporadic Creutzfeldt-Jakob disease (CJD), comparatively with Alzheimer’s disease (AD), and associated with neuronal degeneration in brain tissue.

Methods

CSF neurogranin, total tau, neurofilament light (NFL) and 14-3-3 protein were measured in neurological controls (NCs, n=64), AD (n=46) and CJD (n=81). The accuracy of neurogranin discriminating the three diagnostic groups was evaluated. Correlations between neurogranin and neurodegeneration biomarkers, demographic, genetic and clinical data were assessed. Additionally, neurogranin expression in postmortem brain tissue was studied.

Results

Compared with NC, CSF neurogranin concentrations were increased in CJD (4.75 times of NC; p<0.001, area under curve (AUC), 0.96 (95% CI 0.93 to 0.99) and AD (1.94 times of NC; p<0.01, AUC 0.73, 95% CI 0.62 to 0.82), and were able to differentiate CJD from AD (p<0.001, AUC 0.85, 95% CI 0.78 to 0.92). CSF tau was increased in CJD (41 times of NC) and in AD (3.1 times of NC), both at p<0.001. In CJD, neurogranin positively correlated with tau (r=0.55, p<0.001) and was higher in 14-3-3-positivity (p<0.05), but showed no association with NFL (r=0.08, p=0.46). CJD-MM1/MV1 cases displayed higher neurogranin levels than VV2 cases. Neurogranin was increased at early CJD disease stages and was a good prognostic marker of survival time in CJD. In brain tissue, neurogranin was detected in the cytoplasm, membrane and postsynaptic density fractions of neurons, with reduced levels in AD, and more significantly in CJD, where they correlated with synaptic and axonal markers.

Conclusions

Neurogranin is a new biomarker of prion pathogenesis with diagnostic and prognostic abilities, which reflects the degree of neuronal damage in brain tissue in a CJD subtype manner.
Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience
Authors: Lee Sarah , Heit Jeremy J , Albers Gregory W , Wintermark Max , Jiang Bin , Bernier Eric , Fischbein Nancy J , Mlynash Michael , Marks Michael P , Do Huy M , Dodd Robert L
Published: May 2019

Background

The extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined.

Methods

We performed a retrospective cohort study of patients aged <18 years presenting within 24 hours of acute large vessel occlusion. Patient consent was waived by our institutional IRB. Patient data derived from our institutional stroke database was compared between patients with good and poor outcome using Fisher’s exact test, t-test, or Mann-Whitney U-test.

Results

Twelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10–14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4 s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes.

Conclusions

Perfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.
Characterization of a gold tailings with hypersaline pore fluid
Authors: Reid David , Fourie Andy , Moggach Stephen
Published: May 2019

A series of samples obtained from adjacent to piezocone penetration test (CPTu) locations within a gold tailings storage facility with hypersaline pore fluid was tested to compare the inferred state parameter Ψ from CPTu results to the in situ density and critical state line (CSL) from reconstituted samples, and to assess the effects of salt concentration in the sample pore fluid on mechanical behaviour of the material. Preparation of samples with similar salt concentrations to those measured in situ gave CSLs that compared favourably to estimates of Ψ from the CPTu, in light of measured in situ density. Tests prepared without salt did not tend towards the same CSL as the salt samples, generally being at higher densities both following consolidation and during subsequent shearing. These results are consistent with the observed effects of salt on mechanical behaviour in previous testing on clays. The implications and limitations of the testing program are outlined and the need for further investigation of these issues is emphasized owing to the importance of perimeter embankment stability for a tailings storage facility.
Relativistic mass due to a dilatant vacuum leads to a quantum reformulation of the relativistic kinetic energy
Authors: Fedi Marco
Published: May 2019

Relativistic mass change with speed is considered here as the effect of a viscous, dilatant vacuum, whose apparent viscosity is related to the Lorentz factor. Transient solid-like vacuum due to shear stress is presented as the reason why vacuum prevents the speed of massive objects from being indefinitely increased. Such a vacuum – that in a previous study allowed to exactly calculate the Pioneer anomaly, Mercury’s perihelion precession, and was shown to be compatible with stable planetary orbits – leads here to a quantum formula for the relativistic kinetic energy. A formula which distinguishes between the case of accelerated charges in a vacuum, for which a Stokes–Einstein radius comes into play, and the case of accelerated macroscopic bodies, for which the quantum potential term vanishes. In this way, incidentally, one obtains again correct results for the Pioneer 10, confirming the role of vacuum’s viscous force. This description of a quantum mechanism underlying the relativistic kinetic energy may be also helpful in constructing a theory of quantum relativity and may even tell us more about the interactions of matter with the Higgs field and the dark sector: two issues which can be themselves linked to a dilatant vacuum.
Found, forgotten, and found again: systematics and distribution of Cooper’s Rocky Mountain snail (Oreohelix cooperi) on a sky island in the Canadian Prairies
Authors: Dempsey Z.W. , Burg T.M. , Goater C.P.
Published: May 2019

The results of phylogeographic and biogeographic studies of organisms residing in isolated habitats provide key insights into processes of population differentiation, speciation, and endemicity. Several of the approximately 70 species of land snail in the genus Oreohelix Pilsbry, 1904 occur only on isolated sky islands on the North American Great Plains. The restricted distributions of these snails have led to concerns regarding their conservation status, particularly in western Canada where their systematics and distributions are poorly known. Cooper’s Rocky Mountain snail (Oreohelix cooperi (Binney, 1858)) has been reported from several sky islands in the northern United States. We evaluated morphological characteristics and sequence data for samples of putative O. cooperi collected from a sky island in the Cypress Hills area of southeastern Alberta and southwestern Saskatchewan. COI sequences matched O. cooperi from snails collected on sky islands in South Dakota and Wyoming and morphological analyses of shell shape and male genitalia were consistent with published descriptions of this species. COI and ITS2 sequences and morphological characteristics of these snails did not match other Oreohelix spp. found in the Cypress Hills and in the adjacent Rocky Mountains. Our results extend the distribution of O. cooperi into southern Canada and confirm its endemicity within sky islands of western North America.
Protecting biodiversity in British Columbia: Recommendations for developing species at risk legislation
Authors: Westwood Alana R. , Otto Sarah P. , Mooers Arne , Darimont Chris , Hodges Karen E. , Johnson Chris , Starzomski Brian M. , Burton Cole , Chan Kai M.A. , Festa-Bianchet Marco , Fluker Shaun , Gulati Sumeet , Jacob Aerin L. , Kraus Dan , Martin Tara G. , Palen Wendy J. , Reynolds John D. , Whitton Jeannette
Published: May 2019

British Columbia has the greatest biological diversity of any province or territory in Canada. Yet increasing numbers of species in British Columbia are threatened with extinction. The current patchwork of provincial laws and regulations has not effectively prevented species declines. Recently, the Provincial Government has committed to enacting an endangered species law. Drawing upon our scientific and legal expertise, we offer recommendations for key features of endangered species legislation that build upon strengths and avoid weaknesses observed elsewhere. We recommend striking an independent Oversight Committee to provide recommendations about listing species, organize Recovery Teams, and monitor the efficacy of actions taken. Recovery Teams would evaluate and prioritize potential actions for individual species or groups of species that face common threats or live in a common area, based on best available evidence (including natural and social science and Indigenous Knowledge). Our recommendations focus on implementing an adaptive approach, with ongoing and transparent monitoring and reporting, to reduce delays between determining when a species is at risk and taking effective actions to save it. We urge lawmakers to include this strong evidentiary basis for species recovery as they tackle the scientific and socioeconomic challenges of building an effective species at risk Act.
Proliferation and Migration of Lung Cancer Could be Inhibited by Oxymatrine through the Regulation for miR-520/VEGF
Authors: Zhou Wen , Wu Yunshan , Pan Miao , Liu Daojun , Liu Bo
Published: May 2019

Recent evidence suggests that Oxymatrine (OMT) has excellent effects in anticancer. The mechanism, however, remains unclear. In the present study, we investigated the potential mechanism of OMT against cancer. The differential expression of miRNA was screened by miRNA array. The expression of miRNA-520 and VEGF in lung cancer was assayed by real-time PCR, Western blot and immunohistochemistry, respectively. The direct interaction between miRNA-520 and VEGF was assayed by luciferase activity assay and their roles in lung cancer proliferation, invasion and migration were analyzed in vivo and in vitro. We found that miR-520 was markedly down-regulated and VEGF was markedly up-regulated in lung cancer tissues compared with adjacent normal tissues, which had significant negative correlation. Dual-luciferase assays confirmed that miR-520 directly targeting VEGF by binding to its upstream promoter region. Through in vitro and in vivo experiments, we found that different doses of OMT could up-regulate miR-520, selectively inhibit VEGF and thus inhibit the proliferation and migration of lung cancer. Our findings indicate that OMT inhibited cancer progression and metastasis by upregulation of miR-520 and downregulation of VEGF, which provide new support for OMT may be as a novel anticancer drug for the treatment of lung cancer in the future.
Lorentz violation with an invariant minimum speed as foundation of the uncertainty principle in Minkowski, dS and AdS spaces
Authors: Nassif da Cruz Cláudio
Published: May 2019

This research aims to provide the geometrical foundation of the uncertainty principle within a new causal structure of spacetime so-called Symmetrical Special Relativity (SSR), where there emerges a Lorentz violation due to the presence of an invariant minimum speed [Formula: see text] related to the vacuum energy. SSR predicts that a dS scenario occurs only for a certain regime of speeds [Formula: see text], where [Formula: see text], which represents the negative gravitational potentials ([Formula: see text]) connected to the cosmological parameter [Formula: see text]. For [Formula: see text], Minkowski (pseudo-Euclidean) space is recovered for representing the flat space ([Formula: see text]), and for [Formula: see text] ([Formula: see text]), Anti-de Sitter (AdS) scenario prevails ([Formula: see text]). The fact that the current universe is flat as its average density of matter distribution ([Formula: see text] given for a slightly negative curvature [Formula: see text]) coincides with its vacuum energy density ([Formula: see text] given for a slightly positive curvature [Formula: see text]), i.e. the cosmic coincidence problem, is now addressed by SSR. SSR provides its energy–momentum tensor of perfect fluid, leading to the EOS of vacuum ([Formula: see text]). Einstein equation for vacuum given by such SSR approach allows us to obtain [Formula: see text] associated with a scalar curvature [Formula: see text], whereas the solution of Einstein equation only in the presence of a homogeneous distribution of matter [Formula: see text] for the whole universe presents a scalar curvature [Formula: see text], in such a way that the presence of the background field [Formula: see text] opposes the Riemannian curvature [Formula: see text], thus leading to a current effective curvature [Formula: see text] according to observations. This corrects the notion of gravity as being only of Riemannian origin as the flat space has connection with a background gravity. In view of the current dS scenario with a quasi-zero [Formula: see text] slightly larger than [Formula: see text], we will just obtain a Generalized Uncertainty Principle (GUP) given in the cases of weak gravity and anti-gravity.
Neutrino mass matrix in a gauge group SU(2)L × U(1)e × U(1)μ × U(1)τ
Authors: Fayyazuddin
Published: May 2019

The electroweak unification group [Formula: see text] in which each fermion multiplet has its own [Formula: see text] factor was proposed in 1986 to get the neutrino mass matrix. In this paper, the gauge group [Formula: see text] is restricted to lepton section only, leaving quark multiplets as in the Standard Model. In addition to lepton multiplets [Formula: see text], [Formula: see text] and [Formula: see text], there are three [Formula: see text] singlet right-handed neutrinos [Formula: see text]’s. With the breaking of [Formula: see text] to [Formula: see text], the right-handed neutrinos acquire heavy Majorana masses. Three heavy right-handed neutrinos [Formula: see text]’s are available to generate a [Formula: see text] nondiagonal neutrino mass matrix in terms of three Yukawa couplings [Formula: see text], [Formula: see text], [Formula: see text] of the Higgs scalar doublet to [Formula: see text], [Formula: see text], [Formula: see text] with [Formula: see text], [Formula: see text] and [Formula: see text], respectively. Three Yukawa couplings can be arranged and expressed in terms of masses [Formula: see text], [Formula: see text], [Formula: see text] in three different ways to obtain the results of interest for Case 1: [Formula: see text]; Case 2: [Formula: see text]; Case 3: [Formula: see text]. The results obtained for the three cases are compared with the experimental data from neutrino oscillations. Cases 1 and 2 are relevant for solar neutrino oscillations whereas Case 3 is relevant for atmospheric neutrino oscillations.
Efficient and Adaptive Tone Mapping Algorithm Based on Guided Image Filter
Authors: Jia Yuan , Zhang Wenting
Published: May 2019

The recognition rate of computer vision algorithms is highly dependent on the image quality. To enhance the visual quality of the images captured under high-dynamic range (HDR) scenes, we propose an efficient and adaptive tone mapping algorithm based on guided image filter (GIF). The HDR image is compressed adaptively according to its average luminance. Then we decompose it into a base layer and a detail layer using the guided image filter. We improve the base layer and enhance the detail layer simultaneously, and combine the two layers to get the final low-dynamic range (LDR) image. Since the parameters are linked with image statistics, they adaptively fit to various kinds of images. The objective evaluation results on HDR image sets demonstrate the superiority of our proposed algorithm. Meanwhile, the result of our algorithm can reduce the halo artifacts and preserve more detail by subjective observation.