bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcitonin Gene-Related Peptide Antagonists for the Prevention of Migraine: Highlights From Pivotal Studies and the Clinical Relevance of This New Drug Class
Authors: Arca Karissa , Reynolds Jenna , Sands Kara A. , Shiue Harn J.
Published: February 2020

Objective: To review the new drug class of calcitonin gene-related peptide antagonists (monoclonal antibodies) and their clinical relevance in migraine prophylaxis. Data Sources: A literature search was performed in PubMed (January 2009 to November 2019) using the terms migraine, calcitonin gene-related peptide (CGRP), erenumab, fremanezumab, and galcanezumab for clinical trials and studies. Study Selection and Data Extraction: Reports from human studies in English were evaluated for clinical evidence supporting pharmacology, efficacy, and adverse events. Initial pharmacokinetic and preclinical studies were excluded. Data Synthesis: In chronic and episodic migraine, prophylaxis with injections of monoclonal antibodies antagonizing CGRP reduced monthly migraine days with minimal clinically significant adverse events. In addition, there is evidence supporting efficacy in refractory migraine despite optimal prophylaxis. Relevance to Patient Care and Clinical Practice: This is the first target-specific migraine prophylaxis treatment to show efficacy with minimal adverse effects. A higher drug cost is a barrier but is balanced by improved quality of life. Current therapies have limited efficacy and tolerability because of poor side effect profiles. CGRP antagonists represent a shift to more precise migraine treatments. Conclusions: Monoclonal antibodies inhibiting CGRP are effective in migraine prophylaxis with minimal adverse effects. Targeting CGRP is a novel clinical strategy in managing migraine.
lncRNA ROR Promotes Gastric Cancer Drug Resistance
Authors: Wang Shuai , Chen Wujun , Yu Hualong , Song Zhengming , Li Qian , Shen Xin , Wu Yudong , Zhu Lei , Ma Qingxia , Xing Dongming
Published: February 2020

Objective:

Gastric cancer is one of the most common malignant tumors worldwide, and for resectable tumors, the most effective treatment is surgery with chemotherapy in neoadjuvant or adjuvant setting. However, the majority of patients fail to achieve the ideal initial response and/or develop resistance to chemotherapy. It was reported that long noncoding RNA regulator of reprogramming (ROR) is highly associated with the progression of gastric cancer. However, the role ROR in multidrug resistance (MDR) remains unclear.

Methods:

The messenger RNA levels of 63 specimens of patients with gastric cancer were determined by real-time polymerase chain reaction analysis and were correlated with drug resistance and survival of patients. To determine the cellular functions of ROR, we generated gastric cancer MDR cells. The effect of ROR depletion on multidrug resistance-associated protein 1 (MRP1) expression and cell apoptosis were examined by immunoblotting analyses, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry.

Results:

We found that ROR expression levels are positively associated with increased MDR and poor prognosis of patients with gastric cancer. Regulator of reprogramming expression is increased in gastric cancer cells resistant to adriamycin (ADR) and vincristine (VCR). Depletion of ROR reduced MRP1 expression and increased apoptosis of drug-resistant gastric cancer cells in response to ADR and VCR treatment.

Conclusions:

We demonstrated that ROR expression promotes MRP1 expression and MDR of gastric cancer cells and is correlated with increased MDR and poor prognosis of patients with gastric cancer. Our finding highlighted the potential of targeting ROR to improve the efficacy of chemotherapy.
Fundamental solutions and analysis of an interfacial crack in a one-dimensional hexagonal quasicrystal bi-material
Authors: Fan CuiYing , Chen Shuai , Zhang QiaoYun , Zhao Ming Hao , Wang Bing Bing
Published: February 2020

Using the Stroh formalism, Green’s functions are obtained for phonon and phason dislocations and opening displacements on the interface of a one-dimensional hexagonal quasicrystal bi-material. The integro-differential equations governing the interfacial crack are then established, and the singularities of the phonon and phason displacements at the crack tip on the interface are analyzed. To eliminate the oscillating singularities, we represent the delta function in terms of the Gaussian distribution function in the Green’s functions and the integro-differential equations, which helps reduce these equations to the standard integral equations. Finally, a boundary element numerical approach is also proposed to solve the integral equation for the crack opening displacements, the asymptotic expressions of the extended intensity factors, and the energy release rate in terms of the crack opening displacements near the crack tip. In numerical examples, the effect of the Gaussian parameter on the numerical results is discussed, COMSOL software is used to validate the analytical solution, and the influence of the different phonon and phason loadings on the interfacial crack behaviors is further investigated.
Credibility by automation: Expectations of future knowledge production in social media analytics
Authors: Pääkkönen Juho , Laaksonen Salla-Maaria , Jauho Mikko
Published: February 2020

Social media analytics is a burgeoning new field associated with high promises of societal relevance and business value but also methodological and practical problems. In this article, we build on the sociology of expectations literature and research on expertise in the interaction between humans and machines to examine how analysts and clients make their expectations about social media analytics credible in the face of recognized problems. To investigate how this happens in different contexts, we draw on thematic interviews with 10 social media analytics and client companies. In our material, social media analytics appears as a field facing both hopes and skepticism – toward data, analysis methods, or the users of analytics – from both the clients and the analysts. In this setting, the idea of automated analysis through algorithmic methods emerges as a central notion that lends credibility to expectations about social media analytics. Automation is thought to, first, extend and make expert interpretation of messy social media data more rigorous; second, eliminate subjective judgments from measurement on social media; and, third, allow for coordination of knowledge management inside organizations. Thus, ideas of automation importantly work to uphold the expectations of the value of analytics. Simultaneously, they shape what kinds of expertise, tools, and practices come to be involved in the future of analytics as knowledge production.
Rasch calibration of the 25-item Connor-Davidson Resilience Scale
Authors: Papini Natalie , Kang Minsoo , Ryu Seungho , Griese Emily , Wingert Taylor , Herrmann Stephen
Published: February 2020

Rasch modeling was used to examine the 25-item Connor-Davidson Resilience Scale within adults ( n = 410) in a weight management program. Rasch analysis assessed model-data fit, item difficulty and person’s resilience level, an item-person map to evaluate relative distribution items and persons, and rating scale function. Four misfit items were identified and removed. Item difficulty ranged from 1.25 to 1.19 logits (higher logit values indicate more difficult items). Persons’ resilience level had wide distribution (resilience = 2.27 ± 1.56 logits). Item difficulty levels did not adequately assess higher resilience levels. An improved inventory that measures a wider range of resilient behaviors would improve measurement quality.
State variation in the drug felony lifetime ban on Temporary Assistance for Needy Families: Why the modified ban matters
Authors: Martin Brittany T , Shannon Sarah KS
Published: February 2020

The drug felony lifetime ban on Temporary Assistance for Needy Families (TANF) affects thousands of individuals with felony drug convictions in the United States. Federal law allows states to choose to opt out or modify the full ban. Prior research has treated the ban as a binary outcome, characterizing anything but a full ban as a sign of state reform of this harsh collateral consequence. We argue that modified versions of the ban, which simultaneously allow greater access to public aid while also monitoring and sanctioning recipient behavior, have been overlooked but pose important theoretical and empirical challenges to this narrative. To address this gap, we analyze state discretion in the implementation of the drug felony lifetime ban on TANF receipt between 1997 and 2010 utilizing a multilevel multinomial modeling strategy. Results reveal that distinct patterns of state-level factors are associated with each form of the ban, highlighting the need to treat modified bans as unique policy choices in their own right. Our study informs the understanding of state implementation of collateral consequences that straddle both the penal and welfare systems in the United States.
Challenges in uncovering non-invasive biomarkers of endometriosis
Authors: Hudson Quanah J , Perricos Alexandra , Wenzl Rene , Yotova Iveta
Published: February 2020

Endometriosis affects up to 10% of women of childbearing age, causing symptoms that can include chronic pelvic pain and reduced fertility. The symptoms are not specific to the disease and can be confused with other gynecological conditions or normal menstruation. Currently, the disease can be only definitively diagnosed by laparoscopy, as no clinically accepted biomarker exists. Biomarker discovery can either follow a hypothesis-driven approach selecting targets to be tested based on current knowledge of the disease, or take an unbiased high-throughput screening “omics” approach, such as transcriptomics or proteomics, to identify markers that are unique or elevated in accessible bodily fluids of patients with the disease. Numerous studies have been conducted using these approaches to try and identify endometriosis biomarkers, but variabilities in study design, cohort selection, and analysis, together with the fact that most studies were small-scale, have made independent validation of biomarker candidates difficult. Therefore, efforts are underway to standardize cohort selection, patient data, and sample collection to allow better cross-study comparisons. Large scale multi-center studies using this standardized approach are necessary to validate existing endometriosis biomarker candidates and uncover potential new markers. Given the complexity and heterogeneity of the disease, it is likely that a panel of biomarkers will be necessary to diagnose and categorize endometriosis.

Impact statement

Endometriosis is a common disease affecting reproductive age women, which is associated with chronic pain and reduced fertility reducing the quality of life of many women. Definitive diagnosis requires invasive laparoscopic surgery creating a high barrier to diagnosis that can delay the onset of treatment significantly. Clinically approved biomarkers of endometriosis are currently lacking, making the discovery and validation of biomarkers that would lead to earlier diagnosis a priority for improving treatment of the disease.
Wireless sensor indoor positioning based on an improved particle filter algorithm
Authors: Feng Pan , Qin Danyang , Xu Guangchao , Guo Ruolin , Zhao Min
Published: February 2020

Positioning by wireless sensor network is one of its main functions and has been widely used in many fields. However, when signal propagation is hindered, serious errors, non-line-of-sight errors, occur. In order to solve this problem, this article proposes an improved particle filter algorithm, which introduces the idea of residual analysis to improve reliability. The algorithm assigns weights to the particles based on the residuals and selects the appropriate particles. In addition, the non-line-of-sight error parameter [Formula: see text] is introduced, and the second selection is made according to [Formula: see text], which considers the influence of non-line-of-sight error. The non-line-of-sight error is greatly reduced after two selections. The simulation is performed under several different non-line-of-sight errors, and results show that the algorithm is superior to Kalman filter and particle filter.
Experimental research and floating gait planning of crablike robot
Authors: Wang Hai-Long , Yan Xing-Ya , Wang Gang , Zhang Qi-Feng , Tian Qi-Yan , Fan Yun-Long
Published: February 2020

In order to improve the swimming performance of a paddle-propelled crablike robot, the sequence and parameters of swimming gait are planned according to the bionic swimming mechanism. Based on the bionic prototype of Portunus trituberculatus, the structure scheme of a leg–paddle hybrid driven robot is proposed with the functions of walking on land, crawling on seabed, and swimming underwater. By analyzing the underwater propulsion mechanism of single paddle and hydrodynamic performance of double paddles cooperatively propulsion, four direct swimming gaits are planned and the corresponding attitude changes are theoretically analyzed. Then, the numerical simulation and direct swimming experiments are carried out to verify the effectiveness of proposed gaits and correctness of force analysis. In alternate swimming gait of lift-based mode, the robot swims forward in a rolling attitude, with an advantage of the minimum water resistance and the optimum swimming velocity and efficiency. The influence of flapping frequency and relative phases of paddles on the swimming velocity shows the trend of raise first and then fall.
Towards social justice in highly complex schools in Catalonia, Spain
Authors: Silva Patricia , Antúnez Serafín , Slater Charles L
Published: February 2020

This study investigated social justice from the point of view of school directors, teachers, and parents. We chose two schools that were undergoing major demographic changes because of increased immigration into Catalonia, Spain. They were both classified as “schools of maximum complexity” because of their socio-economic characteristics. The research questions focused on how directors, teachers, and parents give meaning to social justice and what actions they take to achieve it. Teachers and principals adopted practices that have been described in leadership literature as transformational, such as building trust and challenging the process; they only occasionally showed transformative practices like those described by Santamaria (2014) as applied critical leadership (ACL). They were motivated by seeing the needs of migrant families and students with special needs. They seriously considered social cohesion and believed that all students should be given the same opportunities and treated fairly. While these principals wanted to guide teachers to see their work in new ways and develop practices to address the needs of a changing student population, they did not reflect on the connection between day-to-day problems and the larger social system. This critical perspective is essential to ACL.
Reconceptualizing intercultural communicative competence: A multinational perspective
Authors: Fantini Alvino E.
Published: February 2020

Given current trends in international education, many institutions of higher education in the United States and elsewhere seek to prepare students for life and careers in a globalized world. For many institutions, this means internationalizing curriculum and campus, increasing educational exchange opportunities (for both domestic and international students), and developing intercultural abilities in their students. In the process, several questions arise: (1) which strategies are effective, (2) what research gaps exist, (3) what standards measure quality, and (4) what factors determine the quality and effectiveness of their efforts while lacking evidence about competencies? This article explores a possible response to the questions posed drawing on half a century of experience in educational exchange and intercultural service, a review of the intercultural literature, plus two multinational research projects. These combined efforts led to an expansion and (re)conceptualization of the seminar theme of intercultural effectiveness. Despite more than 50 terms found in the literature (including “intercultural effectiveness”) (see, among others, Byram, 1997; Deardorff, 2004; Edelstein, 2014; Martin and Nakayama, 2000), to describe abilities needed for intercultural interaction, one term emerges as perhaps the most comprehensive and most accurate – intercultural communicative competence (ICC).
Cancer prevention and improving cancer outcomes
Authors: Marchant Rachael
Published: February 2020

Treatments for cancer can be unpleasant and costly, both for patients and the health service. Preventing cancer is, therefore, beneficial to patients, their families, their communities and the economy. As the population ages, the incidence of cancer is increasing. It is, therefore, important to consider health strategies that combat this situation, including implementation of effective measures to prevent cancer. This article will discuss the preventable risk factors for different cancers and suggest practical, evidence-based ways of addressing risk factors within the time constraints of general practice consultations. In the UK, cancer screening programmes can detect early cancers and some, such as the cervical screening programme, also prevent cancer. It is important to be able to discuss screening with patients and explain the associated benefits and harms.
The All-Buryat Congress for the Spiritual Rebirth and Consolidation of the Nation: Siberian politics in the final year of the USSR
Authors: Chakars Melissa
Published: February 2020

This article examines the All-Buryat Congress for the Spiritual Rebirth and Consolidation of the Nation that was held in the Buryat Autonomous Soviet Socialist Republic in February 1991. The congress met to discuss the future of the Buryats, a Mongolian people who live in southeastern Siberia, and to decide on what actions should be taken for the revival, development, and maintenance of their culture. Widespread elections were carried out in the Buryat lands in advance of the congress and voters selected 592 delegates. Delegates also came from other parts of the Soviet Union, as well as from Mongolia and China. Government administrators, Communist Party officials, members of new political parties like the Buryat-Mongolian People’s Party, and non-affiliated individuals shared their ideas and political agendas. Although the congress came to some agreement on the general goals of promoting Buryat traditions, language, religions, and culture, there were disagreements about several of the political and territorial questions. For example, although some delegates hoped for the creation of a larger Buryat territory that would encompass all of Siberia’s Buryats within a future Russian state, others disagreed revealing the tension between the desire to promote ethnic identity and the practical need to consider economic and political issues.
Cannabis Use and Sport: A Systematic Review
Authors: Docter Shgufta , Khan Moin , Gohal Chetan , Ravi Bheeshma , Bhandari Mohit , Gandhi Rajiv , Leroux Timothy
Published: February 2020

Context:

Cannabis use has increased, in large part due to decriminalization. Despite this increase in usage, it remains unclear what proportion of athletes use cannabis and what effect it has on athletic performance and recovery.

Objective:

To systematically review cannabis use among athletes, including epidemiology, effect on performance and recovery, and regulations for use in sport.

Data Sources:

PubMed, MEDLINE, and EMBASE databases were queried from database inception through November 15, 2018. A hand search of policies, official documents, and media reports was performed for relevant information.

Study Selection:

All studies related to cannabis use in athletes, including impact on athletic performance or recovery, were included.

Study Design:

Systematic review.

Level of Evidence:

Level 4.

Data Extraction:

Demographic and descriptive data of included studies relating to epidemiology of cannabis use in athletes were extracted and presented in weighted means or percentages where applicable.

Results:

Overall, 37 studies were included, of which the majority were cross-sectional studies of elite and university athletes. Among 11 studies reporting use among athletes (n = 46,202), approximately 23.4% of respondents reported using cannabis in the past 12 months. Two studies found a negative impact on performance, while another 2 studies found no impact. There was no literature on the influence of cannabis on athletic recovery. Across athletic organizations and leagues, there is considerable variability in acceptable thresholds for urine tetrahydrocannabinol levels (>15 to 150 ng/mL) and penalties for athletes found to be above these accepted thresholds.

Conclusion:

Overall, these results suggest that approximately 1 in 4 athletes report using cannabis within the past year. Based on the available evidence, cannabis does not appear to positively affect performance, but the literature surrounding this is generally poor. Given the variability in regulation across different sport types and competition levels, as well as the growing number of states legalizing recreational cannabis use, there is a need to improve our understanding of the effects of cannabis use on the athlete and perhaps adopt a clearer and overarching policy for the use of cannabis by athletes in all sports and at all levels.
Pathophysiology of chronic peripheral ischemia: new perspectives
Authors: Signorelli Salvatore Santo , Vanella Luca , Abraham Nader G. , Scuto Salvatore , Marino Elisa , Rocic Petra
Published: February 2020

Peripheral arterial disease (PAD) affects individuals particularly over 65 years old in the more advanced countries. Hemodynamic, inflammatory, and oxidative mechanisms interact in the pathophysiological scenario of this chronic arterial disease. We discuss the hemodynamic, muscle tissue, and oxidative stress (OxS) conditions related to chronic ischemia of the peripheral arteries. This review summarizes the results of evaluating both metabolic and oxidative markers, and also therapy to counteract OxS. In conclusion, we believe different pathways should be highlighted to discover new drugs to treat patients suffering from PAD.
Reliability and validity of the self-reported frailty screening questionnaire in older adults
Authors: Zhang Yanhong , Zhang Yaxin , Li Yun , Chan Piu , Ma Lina
Published: February 2020

Background:

Frailty is one of the most important risk factors for adverse outcomes in older adults. Despite a high prevalence, there is still a lack of frailty screening instruments specific to Chinese older adults. We developed a simple frailty screening questionnaire (FSQ) that could predict long-term mortality. We aimed to explore the reliability and construct validity of this new measurement tool.

Methods:

A total of 205 individuals aged 65 years or older were recruited in this study. The FSQ and frailty phenotype were assessed. The FSQ included self-reported slowness, weakness, weight loss, inactivity, and exhaustion. A subgroup of 109 participants completed the FSQ a second time 2 weeks later for test–retest reliability. Frailty phenotype included slowness, exhaustion, weight loss, weakness, and inactivity.

Results:

The intraclass correlation coefficient for the FSQ, slowness, weakness, weight loss, inactivity and exhaustion were 0.937, 0.938, 0.934, 0.921, 0.826, and 0.832, respectively. Using a cut-off of 3, the sensitivity, specificity, and area under the curve of the receiver operating characteristic were 52.6%, 93.5%, and 0.883 ( p < 0.001), respectively. The kappa coefficient between the FSQ and frailty phenotype was 0.431 ( p < 0.001). FSQ score was negatively correlated with walking speed and grip strength, and positively correlated with age. Frailty defined by the FSQ was associated with older age, chronic diseases, and worse physical function.

Conclusions:

The FSQ is a potentially useful, reliable, and valid instrument in screening frailty in older adults, and can be recommended to identify frailty in clinical settings.
Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning
Authors: Pina Ana , Helgadottir Saga , Mancina Rosellina Margherita , Pavanello Chiara , Pirazzi Carlo , Montalcini Tiziana , Henriques Roberto , Calabresi Laura , Wiklund Olov , Macedo M Paula , Valenti Luca , Volpe Giovanni , Romeo Stefano
Published: February 2020

Aims

Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. The gold standard for FH diagnosis is genetic testing, available, however, only in selected university hospitals. Clinical scores – for example, the Dutch Lipid Score – are often employed as alternative, more accessible, albeit less accurate FH diagnostic tools. The aim of this study is to obtain a more reliable approach to FH diagnosis by a “virtual” genetic test using machine-learning approaches.

Methods and results

We used three machine-learning algorithms (a classification tree (CT), a gradient boosting machine (GBM), a neural network (NN)) to predict the presence of FH-causative genetic mutations in two independent FH cohorts: the FH Gothenburg cohort (split into training data ( N = 174) and internal test ( N = 74)) and the FH-CEGP Milan cohort (external test, N = 364). By evaluating their area under the receiver operating characteristic (AUROC) curves, we found that the three machine-learning algorithms performed better (AUROC 0.79 (CT), 0.83 (GBM), and 0.83 (NN) on the Gothenburg cohort, and 0.70 (CT), 0.78 (GBM), and 0.76 (NN) on the Milan cohort) than the clinical Dutch Lipid Score (AUROC 0.68 and 0.64 on the Gothenburg and Milan cohorts, respectively) in predicting carriers of FH-causative mutations.

Conclusion

In the diagnosis of FH-causative genetic mutations, all three machine-learning approaches we have tested outperform the Dutch Lipid Score, which is the clinical standard. We expect these machine-learning algorithms to provide the tools to implement a virtual genetic test of FH. These tools might prove particularly important for lipid clinics without access to genetic testing.
Early cardiovascular structural and functional abnormalities as a guide to future morbid events
Authors: Duprez Daniel A , Duval Sue , Hoke Lynn , Florea Natalia , Grandits Gregory , Carlson Claire , Lee Joy , Cohn Jay N
Published: February 2020

Aims

Our aim was to evaluate the predictive value of a battery of 10 non-invasive tests of cardiovascular structural and functional health on the future risk of cardiovascular morbid events.

Methods and Results

A total of 1900 asymptomatic adults concerned about their risk for cardiovascular disease underwent non-invasive assessment with 10 tests of vascular and cardiac structure and function. A disease score (DS) was calculated for each individual based on these 10 tests. Follow-up (mean 9.2 years) for cardiovascular morbidity and mortality was available for 1442 individuals (mean age 53.2 years, 48.2% women). Those in the lowest DS tertile (0–2) experienced 0.16 cardiovascular events per 100 patient-years (PY), those in the middle tertile (3–5) experienced 0.86 events per 100 PY, and those in the highest tertile (6+) experienced 1.3 events per 100 PY (p < .001). Sensitivity analysis, assuming a neutral effect of DS on projected events in subjects not followed, did not alter statistical significance. Risk assessment using the Framingham risk score (FRS) also predicted morbid events but the two methods differed in identifying individuals at high risk. The net reclassification index was improved by 0.11 (p = 0.01) when DS was added to FRS.

Conclusions

Assessing the biological disease process in the arteries and heart of asymptomatic adults provides a guide to the risk of a future cardiovascular morbid event. Larger and longer studies are needed to determine whether risk factor algorithms, the severity of the biological process or some combination is the optimal method for identifying individuals in need of intervention to delay morbid events.
LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial
Authors: Sever Peter , Gouni-Berthold Ioanna , Keech Anthony , Giugliano Robert , Pedersen Terje R , Im KyungAh , Wang Huei , Knusel Beat , Sabatine Marc S , O’Donoghue Michelle L
Published: February 2020

Aims

Some trials have reported diminished efficacy for statins in the elderly, and in women compared with men. We examined the efficacy and safety of evolocumab by patient age and sex in the FOURIER trial, the first major cardiovascular outcome trial of a PCSK9 inhibitor.

Methods and results

FOURIER was a randomised, double blind trial, comparing evolocumab with placebo in 27,564 patients with atherosclerotic cardiovascular disease receiving statin therapy (median follow-up 2.2 years). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina or coronary revascularisation. Cox proportional hazards models were used to assess the efficacy of evolocumab versus placebo stratified by quartiles of patient age and by sex. There were small variations in the cardiovascular event rate across the age range (for the primary endpoint, Kaplan–Meier at 3 years 15.6%, >69 years, vs. 15.1%, ≤56 years, P = 0.45); however, the relative efficacy of evolocumab was consistent regardless of patient age (for the primary endpoint (Q1 hazard ratio, 95% confidence interval) 0.83, 0.72–0.96, Q2 0.88, 0.76–1.01, Q3 0.82, 0.71–0.95, Q4 0.86, 0.74–1.00; Pinteraction = 0.91), and the key secondary endpoint (cardiovascular death, myocardial infarction, stroke) (Q1 0.74 (0.61–0.89), Q2 0.83 (0.69–1.00), Q3 0.78 (0.65–0.94), Q4 0.82 (0.69–0.98)); Pinteraction = 0.81). Women had a lower primary endpoint rate than men (Kaplan–Meier at 3 years 12.5 vs. 15.3%, respectively, P < 0.001). Relative risk reductions in the primary endpoint and key secondary endpoint were similar in women (0.81 (0.69–0.95) and 0.74 (0.61–0.90), respectively) compared with men (0.86 (0.80–0.94) and 0.81 (0.73–0.90), respectively), Pinteraction = 0.48 and 0.44, respectively. Adverse events were more common in women and with increasing age but, with the exception of injection site reactions, there were no important significant differences reported by those assigned evolocumab versus placebo.

Conclusions

The efficacy and safety of evolocumab are similar throughout a broad range of ages and in both men and women.
Health worker acceptability of an mHealth platform to facilitate the prevention of mother-to-child transmission of HIV in Tanzania
Authors: Thomas Deborah SK , Daly Kristen , Nyanza Elias C , Ngallaba Sospatro E , Bull Sheana
Published: February 2020

Objectives

Health workers (HWs) are increasingly using mobile health (mHealth) technologies in low-resource settings. Understanding HW acceptability of mHealth is critical to increasing the scale of mHealth solutions. We examined pre- and post-pilot clinical knowledge and acceptability of a tablet-based platform, the Tanzania Health Information System (T-HIT), targeting HWs delivering prevention of mother-to-child transmission (PMTCT) of HIV services in seven health facilities in Misungwi District, Tanzania.

Methods

We developed a survey based on the diffusion of innovation theory and administered it to 27 HWs before and after a 3-month pilot of T-HIT. Using a Wilcoxon signed-rank test, we analyzed changes in acceptability defined as attitudes towards and self-efficacy for system use comparing pre- and post-test assessment scores and changes in knowledge of clinical care. Using analysis of variance, we explored these changes, stratifying health facilities by level of care and by distance from the district hospital.

Results

Post-pilot scores showed statistically significant improvement from pre-test for the total survey ( Z = −2.67, p < 0.008) and for questions concerning system attitude ( Z = −2.63, p < 0.008). HWs in hospitals and health centers exhibited a lower initial level of system acceptability in attitude than those in dispensaries and a significant improvement in overall mean acceptability over the pilot (95% CI 0.004–0.0187). HWs working more than 20 km from the hospital had a lower initial level of both system knowledge and acceptability than their less remote counterparts, but demonstrated larger improvements in knowledge and acceptability over time, although this change was not statistically significant.

Conclusions

The pilot demonstrates that HWs in PMTCT in Misungwi have a high acceptability of mHealth solutions. Using an mHealth solution can facilitate HW delivery of PMTCT care in rural and remote settings. Consideration of acceptability is important for fostering mHealth scale and program sustainability.
A Perspective on the Similarities and Differences Between Mindfulness and Relaxation
Authors: Luberto Christina M , Hall Daniel L , Park Elyse R , Haramati Aviad , Cotton Sian
Published: February 2020

Mind–body medicine is an evidence-based approach to health and healing that focuses on interactions between the mind, body, and behavior. It encompasses a wide range of interventions that are similar yet different in meaningful ways. Mindfulness and relaxation practices are 2 mind–body techniques that have similarities and differences; however, these techniques are often used or discussed interchangeably, such that the differences between them become obscured. A greater understanding of the unique facets of mindfulness and relaxation is needed for researchers and clinicians to make informed decisions when selecting an approach. The purpose of the current article is to offer an evidence-informed perspective on similarities and differences between mindfulness and relaxation. Specifically, mindfulness and relaxation practices are compared and contrasted in terms of theoretical foundation, intention, and psychological and physiological effects and mechanisms. Implications for clinical practice and suggestions for future research are discussed.
Return to Sport and Athletic Function in an Active Population After Primary Arthroscopic Labral Reconstruction of the Hip
Authors: Maldonado David R. , Chen Sarah L. , Yelton Mitchell J. , Rosinsky Philip J. , Walker-Santiago Rafael , Shapira Jacob , Lall Ajay C. , Domb Benjamin G.
Published: February 2020

Background:

Labral reconstruction has been advocated as an alternative to debridement for the treatment of irreparable labral tears, showing favorable short-term results. However, literature is scarce regarding outcomes and return to sport in the nonelite athletic population.

Purpose:

To report minimum 1-year clinical outcomes and the rate of return to sport in athletic patients who underwent primary hip arthroscopy with labral reconstruction in the setting of femoroacetabular impingement syndrome and irreparable labral tears.

Study Design:

Case series; Level of evidence, 4.

Methods:

Data were prospectively collected and retrospectively analyzed for patients who underwent an arthroscopic labral reconstruction between August 2012 and December 2017. Patients were included if they identified as an athlete (high school, college, recreational, or amateur); had follow-up on the following patient-reported outcomes (PROs): modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome Score–Sport Specific Subscale (HOS-SSS), and visual analog scale (VAS); and completed a return-to-sport survey at 1 year postoperatively. Patients were excluded if they underwent any previous ipsilateral hip surgery, had dysplasia, or had prior hip conditions. The proportions of patients who achieved the minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) for mHHS and HOS-SSS were calculated. Statistical significance was set at P = .05.

Results:

There were 32 (14 females) athletes who underwent primary arthroscopic labral reconstruction during the study period. The mean age and body mass index of the group were 40.3 years (range, 15.5-58.7 years) and 27.9 kg/m2 (range, 19.6-40.1 kg/m2), respectively. The mean follow-up was 26.4 months (range, 12-64.2 months). All patients demonstrated significant improvement in mHHS, NAHS, HOS-SSS, and VAS ( P < .001) at latest follow-up. Additionally, 84.4% achieved MCID and 81.3% achieved PASS for mHHS, and 87.5% achieved MCID and 75% achieved PASS for HOS-SSS. VAS pain scores decreased from 4.4 to 1.8, and the satisfaction with surgery was 7.9 out of 10. The rate of return to sport was 78%.

Conclusion:

At minimum 1-year follow-up, primary arthroscopic labral reconstruction, in the setting of femoroacetabular impingement syndrome and irreparable labral tears, was associated with significant improvement in PROs in athletic populations. Return to sport within 1 year of surgery was 78%.
Schistosomiasis-associated pulmonary arterial hypertension: a systematic review
Authors: Knafl Daniela , Gerges Christian , King Charles H. , Humbert Marc , Bustinduy Amaya L.
Published: February 2020

Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is a life-threatening complication of chronic hepatosplenic schistosomiasis. It is suggested to be the leading cause of pulmonary arterial hypertension (PAH) worldwide. However, pathophysiological data on Sch-PAH are scarce. We examined the hypothesis that there are pronounced similarities in pathophysiology, haemodynamics, and survival of Sch-PAH and idiopathic PAH (iPAH).

This systematic review and meta-analysis was registered in the PROSPERO database (identifier CRD42018104066). A systematic search and review of the literature was performed according to PRISMA guidelines for studies published between 01 January 1990 and 29 June 2018.

For Sch-PAH, 18 studies evaluating pathophysiological mechanisms, eight studies on haemodynamics (n=277), and three studies on survival (n=191) were identified. 16 clinical registries reporting data on haemodynamics and survival including a total of 5792 patients with iPAH were included for comparison. Proinflammatory molecular pathways are involved in both Sch-PAH and iPAH. The transforming growth factor (TGF)-β signalling pathway is upregulated in Sch-PAH and iPAH. While there was no difference in mean pulmonary artery pressure (54±17 mmHgversus55±15 mmHg, p=0.29), cardiac output (4.4±1.3 L·min−1versus4.1±1.4 L·min−1, p=0.046), and cardiac index (2.6±0.7 L·min−1·m−2versus2.3±0.8 L·min−1·m−2, p<0.001) were significantly higher in Sch-PAH compared to iPAH, resulting in a lower pulmonary vascular resistance in Sch-PAH (10±6 Woods unitsversus13±7 Woods units, p<0.001). 1- and 3-year survival were significantly better in the Sch-PAH group (p<0.001).

Sch-PAH and iPAH share common pathophysiological mechanisms related to inflammation and the TGF-β signalling pathway. Patients with Sch-PAH show a significantly better haemodynamic profile and survival than patients with iPAH.
Multi-template matching: a versatile tool for object-localization in microscopy images
Authors: Thomas Laurent S. V. , Gehrig Jochen
Published: February 2020

Background

The localization of objects of interest is a key initial step in most image analysis workflows. For biomedical image data, classical image-segmentation methods like thresholding or edge detection are typically used. While those methods perform well for labelled objects, they are reaching a limit when samples are poorly contrasted with the background, or when only parts of larger structures should be detected. Furthermore, the development of such pipelines requires substantial engineering of analysis workflows and often results in case-specific solutions. Therefore, we propose a new straightforward and generic approach for object-localization by template matching that utilizes multiple template images to improve the detection capacity.

Results

We provide a new implementation of template matching that offers higher detection capacity than single template approach, by enabling the detection of multiple template images. To provide an easy-to-use method for the automatic localization of objects of interest in microscopy images, we implemented multi-template matching as a Fiji plugin, a KNIME workflow and a python package. We demonstrate its application for the localization of entire, partial and multiple biological objects in zebrafish and medaka high-content screening datasets. The Fiji plugin can be installed by activating the Multi-Template-Matching and IJ-OpenCV update sites. The KNIME workflow is available on nodepit and KNIME Hub. Source codes and documentations are available on GitHub (https://github.com/multi-template-matching).

Conclusion

The novel multi-template matching is a simple yet powerful object-localization algorithm, that requires no data-pre-processing or annotation. Our implementation can be used out-of-the-box by non-expert users for any type of 2D-image. It is compatible with a large variety of applications including, for instance, analysis of large-scale datasets originating from automated microscopy, detection and tracking of objects in time-lapse assays, or as a general image-analysis step in any custom processing pipelines. Using different templates corresponding to distinct object categories, the tool can also be used for classification of the detected regions.
Epidemic ribotypes of Clostridium (now Clostridioides) difficile are likely to be more virulent than non-epidemic ribotypes in animal models
Authors: Vitucci John C. , Pulse Mark , Tabor-Simecka Leslie , Simecka Jerry
Published: February 2020

Background

Clostridioides difficileinfections have become more frequently diagnosed and associated with greater disease severity, which has resulted in an increase burden on the healthcare system. These increases are attributed to the increased prevalence of hypervirulent strains encompassing select ribotypes. These epidemic ribotypes were characterized as hypervirulent due to higher in vitro spore and toxin production, as well as increased incidence, severity and mortality within patients. However, it is unclear whether epidemic ribotypes are truly more virulent than non-epidemic ribotypes in vivo.Furthermore, there is conflicting evidence about the ability of a strain’s in vitro phenotype to be predictive of their in vivo virulence. The goals of the current studies were to determine if epidemic ribotypes are more virulent than other ribotypes in animal models, and whether the in vitro virulence phenotype of an isolate or ribotype predict in vivo virulence.

Results

To determine if epidemic strains were truly more virulent than other non-epidemic strains, the in vivo virulence of 13C. difficileisolates (7 non-epidemic and 6 epidemic ribotype isolates) were determined in murine and hamster models of CDI. The isolates of epidemic ribotype ofC. difficilewere found to be more virulent in both the murine and hamster models than non-epidemic isolates. In particular, the group of epidemic ribotypes ofC. difficilehad lower LD50values in hamsters. The increased severity of disease was associated with higher levels of Toxin A and Toxin B production found in fecal samples, but not numbers of organisms recovered. The isolates were further characterized for their in vitro virulence phenotypes, e.g. toxin production, growth rates, spore formation and adherence of spores to intestinal epithelial cell lines. Although there were higher levels of toxins produced and greater adherence for the group of epidemic ribotypes, the in vitro profiles of individual isolates were not always predictive of their in vivo virulence.

Conclusions

Overall, the group of epidemic ribotypes ofC. difficilewere more virulent in vivo despite individual isolates having similar phenotypes to the non-epidemic isolates in vitro.
Physiological and comparative proteomic analysis provides new insights into the effects of shade stress in maize (Zea mays L.)
Authors: Gao Jia , Liu Zheng , Zhao Bin , Liu Peng , Zhang Ji-Wang
Published: February 2020

Background

Shade stress, a universal abiotic stress, suppresses plant growth and production seriously. However, little is known regarding the protein regulatory networks under shade stress. To better characterize the proteomic changes of maize leaves under shade stress, 60% shade (S) and supplementary lighting (L) on cloudy daylight from tasseling stage to physiological maturity stage were designed, the ambient sunlight treatment was used as control (CK). Isobaric tag for relative and absolute quantification (iTRAQ) technology was used to determine the proteome profiles in leaves.

Results

Shading significantly decreased the SPAD value, net photosynthetic rate, and grain yield. During two experimental years, grain yields of S were reduced by 48 and 47%, and L increased by 6 and 11%, compared to CK. In total, 3958 proteins were identified by iTRAQ, and 2745 proteins were quantified including 349 proteins showed at least 1.2-fold changes in expression levels between treatments and CK. The differentially expressed proteins were classified into photosynthesis, stress defense, energy production, signal transduction, and protein and amino acid metabolism using the Web Gene Ontology Annotation Plot online tool. In addition, these proteins showed significant enrichment of the chloroplasts (58%) and cytosol (21%) for subcellular localization.

Conclusions

60% shade induced the expression of proteins involved in photosynthetic electron transport chain (especially light-harvesting complex) and stress/defense/detoxification. However, the proteins related to calvin cycle, starch and sucrose metabolisms, glycolysis, TCA cycle, and ribosome and protein synthesis were dramatically depressed. Together, our results might help to provide a valuable resource for protein function analysis and also clarify the proteomic and physiological mechanism of maize underlying shade stress.
The University of Limerick Education and Research Network for General Practice (ULEARN-GP): practice characteristics and general practitioner perspectives
Authors: O’Regan Andrew , Hayes Peter , O’Connor Ray , Casey Monica , O’Dwyer Pat , Culhane Aidan , O’Donnell Patrick , Stack Gary , Cuddihy John , O’Connell Billy , O’Flynn Jerry , Cullen Walter , O’Doherty Jane , O’Connell Maurice , Glynn Liam
Published: February 2020

Background

A well-functioning general practice sector that has a strong research component is recognised as a key foundation of any modern health system. General practitioners (GPs) are more likely to collaborate in research if they are part of an established research network. The primary aims of this study are to describe Ireland’s newest general practice-based research network and to analyse the perspectives of the network’s members on research engagement.

Method

A survey was sent to all GPs participating in the network in order to document practice characteristics so that this research network’s profile could be compared to other national profiles of Irish general practice. In depth interviews were then conducted and analysed thematically to explore the experiences and views of a selection of these GPs on research engagement.

Results

All 134 GPs responded to the survey. Practices have similar characteristics to the national profile in terms of location, size, computerisation, type of premises and out of hours arrangements. Twenty-two GPs were interviewed and the resulting data was categorised into subthemes and four related overarching themes: GPs described catalysts for research in their practices, the need for coherence in how research is understood in this context, systems failures, whereby the current health system design is prohibitive of GP participation and aspirations for a better future.

Conclusion

This study has demonstrated that the research network under examination is representative of current trends in Irish general practice. It has elucidated a better understanding of factors that need to be addressed in order to encourage more GPs to engage in the research process.