bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Brain–Computer Interface and the Impact of Its Design Characteristics on Poststroke Upper-limb Rehabilitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Mansour Salem , Ang Kai Keng , Nair Krishnan P.S. , Phua Kok Soon , Arvaneh Mahnaz
Published: April 2021

Background. A number of recent randomized controlled trials reported the efficacy of brain–computer interface (BCI) for upper-limb stroke rehabilitation compared with other therapies. Despite the encouraging results reported, there is a significant variance in the reported outcomes. This paper aims to investigate the effectiveness of different BCI designs on poststroke upper-limb rehabilitation. Methods. The effect sizes of pooled and individual studies were assessed by computing Hedge’s g values with a 95% confidence interval. Subgroup analyses were also performed to examine the impact of different BCI designs on the treatment effect. Results. The study included 12 clinical trials involving 298 patients. The analysis showed that the BCI yielded significant superior short-term and long-term efficacy in improving the upper-limb motor function compared to the control therapies (Hedge’s g = 0.73 and 0.33, respectively). Based on our subgroup analyses, the BCI studies that used the intention of movement had a higher effect size compared to those used motor imagery (Hedge’s g = 1.21 and 0.55, respectively). The BCI studies using band power features had a significantly higher effect size than those using filter bank common spatial patterns features (Hedge’s g = 1.25 and − 0.23, respectively). Finally, the studies that used functional electrical stimulation as the BCI feedback had the highest effect size compared to other devices (Hedge’s g = 1.2). Conclusion. This meta-analysis confirmed the effectiveness of BCI for upper-limb rehabilitation. Our findings support the use of band power features, the intention of movement, and the functional electrical stimulation in future BCI designs for poststroke upper-limb rehabilitation.
The Industry of Landlords: Exploring the Assetization of the Triple-A Game
Authors: Bernevega Alexander , Gekker Alex
Published: April 2021

The monetization of the modern Triple-A game has undergone severe changes, as free-to-play revenue models and game as a service distribution strategy have become standard for game developers. To date, the established tradition of the industry’s political–economic analysis focused on the value extraction and user exploitation of video game as a cultural commodity, centered on the video game as generating value through the selling of boxed or digital units. In this article, we present a new analytical framework grounded in understanding the modern video game as an asset that continuously generates revenue for its owners. This theoretical lens encapsulates the changes in contemporary game development, distribution, and value generation. To demonstrate, we apply it to the analysis of the monetization strategies of three recent free-to-play Triple-A titles: Fortnite (2017), Apex Legends (2019), and Call of Duty: Warzone (2020).
An autonomous drone-based system for inspection of electrical substations
Authors: Langåker Helge-André , Kjerkreit Håkon , Syversen Christoffer L , Moore Richard JD , Holhjem Øystein H , Jensen Irene , Morrison Aiden , Transeth Aksel A , Kvien Oddgeir , Berg Gunnar , Olsen Thomas A , Hatlestad Alexander , Negård Thomas , Broch Rolf , Johnsen Jørn E
Published: April 2021

In the years to come, large power grid operators will operate and maintain an ever-increasing asset base. New innovative solutions are needed to increase the quality and efficiency of asset management to avoid corresponding growth in resources and cost. To this end, autonomous unmanned aerial vehicles (UAVs) provide a range of possibilities. Here, we present a novel prototype solution for autonomous and remotely operated inspection missions with resident drones on electrical substations, comprising: (1) an autonomous drone with sense and avoid and robustness to harsh weather capability; (2) a drone hangar for remote operations; and (3) drone operations and data acquisition management software. Further, we discuss the possibilities and challenges that such a system offers and give an overview of requirements that are key to realizing the potential of drones for improved asset management. These requirements are based on years of operational experience with electrical substations combined with the lessons learned during the development and testing of our drone system. We also experimentally investigate safety distances between the drone and high-voltage infrastructure. We demonstrate the usefulness of our autonomous inspection solution through extensive field testing at one of Statnett’s fully operational electrical substations.
A fast RFID image matching algorithm for multi-tag identification and distribution optimization
Authors: Zhang Ke , Yu Xiaolei , Li Lin , Liu Zhenlu , Zhou Shanhao , Zhao Zhimin
Published: April 2021

We propose an improved image matching algorithm that combines the minimum feature value algorithm to extract feature points and the direction gradient histogram to calculate the description vector. This algorithm is oriented to RFID multi-tag identification and distribution optimization in the actual scenario, and the traditional SURF algorithm has the problems of low matching accuracy and high complexity in multi-tag matching. This algorithm effectively improves the positioning accuracy of the RFID multi-tag positioning system. The experimental results show that the matching success rate of the improved algorithm in this paper is 87.4%, which is 50% higher than the SURF algorithm. Not only the matching accuracy is greatly improved, but the running speed is also increased by 48%. The algorithm in this paper has high matching accuracy and real-time performance.It provides an effective way for RFID multi-tag real-time fast matching and precise positioning.
The influence of shoulder abduction and external rotation on throwing arm kinetics in professional baseball pitchers
Authors: Manzi Joseph E , Dowling Brittany , Trauger Nicolas , Fu Michael C , Hansen Benjamin R , Dines Joshua S
Published: April 2021

Background

The relationships between shoulder abduction and external rotation with peak kinetic values at the shoulder and elbow in professional baseball pitchers are not well established.

Methods

Professional pitchers ( n = 322) threw 8–12 fastballs under 3D motion analysis (480 Hz). Pitchers were stratified into quartiles by shoulder abduction and external rotation at distinct timepoints. Regression analyses were performed to quantify associations between shoulder position and kinetics.

Results

Shoulder abduction remained relatively consistent throughout the pitch (foot contact–ball release: 85.5 ± 11.1–90.7 ± 8.4°); shoulder external rotation increased dramatically (foot contact–ball release: 30.8 ± 24.6–165.2 ± 9.7°). For every 10° increase in maximum shoulder rotation, shoulder superior force increased by 2.3% body weight ( p < 0.01), shoulder distraction force increased by 5.9% body weight ( p < 0.01), and ball velocity increased by 0.60 m/s ( p < 0.01). Shoulder abduction was significantly associated with shoulder superior force at all timepoints but not with ball velocity ( p > 0.05). For every 10° increase in shoulder abduction at ball release, shoulder superior force increased by 3.7% body weight ( p < 0.01) and shoulder distraction force increased by 11.7% body weight ( p < 0.01).

Conclusion

Increased shoulder abduction at ball release and increased maximum shoulder external rotation were associated with greater superior and distraction forces in the shoulder. Pitchers can consider decreasing shoulder abduction at later stages of the pitch to around 80° in order to minimize shoulder superior force, with no impact on ball velocity.
Chitosan-based films reinforced with cellulose nanofibrils isolated from Euterpe oleraceae MART
Authors: Braga DG , Bezerra PGF , Lima ABFD , Pinheiro HA , Gomes LG , Fonseca AS , Bufalino L
Published: April 2021

The use of local raw materials for the production of biodegradable films can simultaneously contribute to the development of the Amazon and global sustainability. This work aimed to evaluate the physical and mechanical performance of chitosan-based bionanocomposite films reinforced with different loads of cellulose nanofibrils obtained from açaí ( Euterpe oleraceae Mart.) under two nanofibrillation degrees. Nanofibrils were obtained by 3 and 21 passages in a grinder defibrillator. The films were produced by casting with nanofibril reinforcement at 5 wt.%, 10 wt.%, 15 wt.%, and 20 wt.%. The increase in the nanofibril level and nanofibrillation degree reduced water vapor absorption (75.20% to 51.93%), water solubility (28.33% to 17.91%), and density (0.87 g.cm−3 to 0.61 g.cm−3). The water vapor permeability decreased with higher nanofibril loads for both 3-pass (47.30% to 43.61%) and 21-pass (49.82% to 44.48%) reinforced films, but not with nanofibrillation degree. The increase in 3-pass nanofibril level decreased tensile strength (8.18 MPa to 7.88 MPa), modulus of elasticity (867.62 MPa to 670.02 MPa) and elongation at break (0.02 mm.mm−1 to 0.01 mm.mm−1). However, the opposite effect happened to 21-pass nanofibrils, with increases from 9.16 MPa to 9.73 MPa and from 502.00 MPa to 1119.62 MPa for tensile strength and modulus of elasticity, respectively. Meanwhile, the maximum elongation at rupture did not vary. It was concluded that chitosan-based bionanocomposite films reinforced with 20 wt.% of 21-pass nanofibril were more resistant, except for water vapor permeability. Adding coarser nanofibrils enhanced this property. The 3-pass nanofibrils reinforcement enables water solubility, which benefits other packaging applications.
Astitva: An Unsustainable Social Entrepreneurship Journey
Authors: Singh Shikha , Mittal Shweta , Awasthi Anuraag
Published: April 2021

Astitva was founded as a not-for-profit organization by Anamika Yaduvanshi, in 2013. The objective of the non-governmental organization (NGO) was to make a visible difference in the lives of disadvantaged sections of the society. Within a short period since its inception, the NGO had positively impacted the lives of individuals and families living in the Wazirpur area. The case helps to understand that even after venturing into vast philanthropic activities, Anamika could not create sustainable livelihoods for the disadvantaged sections of Wazirpur. Is it because of lack of focus on surplus management? The case also helps in understanding the challenges faced by NGOs at ground level.

Research questions/Objective:

The aim of this study is to explore the nuances of social entrepreneurship. It explores that there should be a balanced approach between social activities that are mostly provided free and generation of surplus to sustain them. The research questions answered are: Has Astitva created a long-term sustainable impact on the lives of marginalized women and children at Wazirpur? Does the business model of Astitva places even stresses on the social activities to engage the participants and generation of financial surplus to sustain the operation?

Links to theory:

The study is based on the business model canvas of Osterwalder and Pigneur (2010). The model explains that social enterprises should maintain a balance between philanthropy and commercial sense to be productive or else their sustainability is at a risk.

Phenomenon studied:

Anamika started Astitva with an aim of social transformation. She wanted to make a concrete difference in the lives of disadvantaged sections of the society as well as contribute in their integration with the mainstream society.

Case context:

The case can be discussed from the angle of business model of a sustainable entrepreneurship and what may go wrong in making a social enterprise successful. Since Anamika had not prepared any blueprint of plan of action, she faced several challenges.

Findings:

An entrepreneur driven by community spirit should not start working without creating a road map of generation of funds to support the social activities. Working model of Astitva is laden with lack of planning and absence of long-term vision that failed to create a sustainable livelihood generation for the marginalized women and children.

Discussions:

The case provokes students to study the need to start a sustainable social enterprise driven by community spirit to uplift the lives of a marginalized section of women and children. Further, the case challenges students to identify the streams of revenue generation and deployment in a business model of a social enterprise to make it sustainable.
What Do We Know About Treating Recalcitrant Auricular Keloids? A Systematic Review and Meta-Analysis
Authors: Zawadiuk Luke R. R. , Van Slyke Aaron C. , Bone Jeffrey , Redfern Baillie , Carr Nicholas J. , Arneja Jugpal S.
Published: April 2021

Background:

Recalcitrant auricular keloids are keloids that have recurred after any previous treatment. They have been shown to have an increased likelihood of recurrence. There is no consensus on how best to treat recalcitrant auricular keloids. Here, we perform the first systematic review and meta-analysis investigating the evidence for treating recalcitrant auricular keloids.

Methods:

We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews using specific keywords. Prespecified inclusion and exclusion criteria were used to assess article eligibility. Data were extracted for number of recalcitrant keloids, treatment modality, recurrence, and minimum follow-up time. Included articles were stratified by treatment and assigned a level of evidence (LOE) based on the Oxford Centre for Evidence-Based Medicine guidelines. A meta-analysis was performed to estimate recurrence rates with 95% confidence intervals for each treatment modality.

Results:

A total of 887 unique articles were identified and 13 included. Eleven were LOE III and 2 were LOE IV. Recurrence rates were found to be 9% (95% CI: 3%-25%) for excision with adjuvant brachytherapy, 14% (95% CI: 12%-17%) for excision with adjuvant compression therapy, 17% (95% CI: 3%-56%) for excision with adjuvant external beam radiation, and 18% (95% CI: 4%-53%) for excision with adjuvant steroid injections. No statistical significant difference was found.

Conclusions:

Data for treatment of auricular keloids are heterogeneous with few high-quality studies. Excision with adjuvant brachytherapy has the lowest recurrence rate in our analysis. Narrow confidence intervals reported here for brachytherapy and compression therapy may help surgeons more confidently recommend either of these treatment modalities to patients.
Addressing Barriers to Health Care Access of Congenital Heart Disease Patients in Guyana
Authors: Ames Sarah , Pillsworth Emma , Sparman-Shelto Arnelle , Isaac Debra Lynne
Published: April 2021

In order to mitigate the late presentation and resulting poor outcomes of children with advanced cardiac disease, the Ministry of Public Health (MOPH) in Guyana has expressed interest in identifying ways to improve access to health care for these children. The goal of this study was to identify barriers faced by CHD patients and their families in accessing pediatric cardiology services in Guyana, and to identify limitations to the diagnosis and referral of CHD patients by health care professionals. Two surveys were used to gain insight into the experiences of practicing health care professionals and the parent(s) or guardian(s) of children with CHD. Patients were identified based on convenience sampling at cardiology clinics and outreach clinics in both urban and rural Guyana. Physicians were identified using convenience sampling at health posts in rural Guyana. Fifty-two (n = 52) families were identified and interviewed throughout the regions visited. The majority of families identified distance, the need to travel, and their inability, financially and practically, to attend clinic as the main barrier to accessing specialized care. Twelve (n = 12) health care providers were interviewed. They identified limited knowledge surrounding the diagnosis and management of CHD, and perceived impracticality of referring patients to specialized services, despite being aware of the referral process. This study identifies the need for improved outreach and support for health care providers and families, especially those living in rural communities. It identifies some of the challenges faced in managing patients with CHD in Guyana, while establishing specific areas for quality improvement.
Health care transitions for persons living with dementia and their caregivers
Authors: Ashbourne Jessica , Boscart Veronique , Meyer Samantha , Tong Catherine E. , Stolee Paul
Published: April 2021

Background

Persons with dementia are likely to require care from various health care providers in multiple care settings, necessitating navigation through an often-fragmented care system. This study aimed to create a better understanding of care transition experiences from the perspectives of persons living with dementia and their caregivers in Ontario, Canada, through the development of a theoretical framework.

Methods

Constructivist grounded theory guided the study. Seventeen individual caregiver interviews, and 12 dyad interviews including persons with dementia and their caregivers, were recorded and transcribed verbatim. The data were coded using NVivo 10 software; analysis occurred iteratively until saturation was reached.

Results

A theoretical framework outlining the context, processes, and influencing factors of care transitions was developed and refined. Gaining an in-depth understanding of the complex care transitions of individuals with dementia and their caregivers is an important step in improving the quality of care and life for this population.

Conclusion

The framework developed in this study provides a focal point for efforts to improve the health care transitions of persons living with dementia.
High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia
Authors: Li Jun , Ge Zheng
Published: April 2021

Background

Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role ofHSPA8in AML is still undetermined.

Methods

In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression ofHSPA8and clinical phenotypes of CN-AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role ofHSPA8in CN-AML.

Results

HSPA8was highly expressed in the AML patients compared to the healthy controls. The highHSPA8expression had lower overall survival (OS) rate than those with lowHSPA8expression. High expression ofHSPA8was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated withHSPA8high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway.HSPA8high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, andIDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA).

Conclusions

Our research revealedHSPA8 asa novel potential prognostic factor to predict the survival of CN-AML patients. Our data also revealed the possible carcinogenic mechanism and the complicated microRNA-mRNA network associated with theHSPA8high expression in AML.
Challenges and opportunities from the COVID-19 pandemic in medical education: a qualitative study
Authors: Hayat Ali Asghar , Keshavarzi Mohmmad Hasan , Zare Soolmaz , Bazrafcan Leila , Rezaee Rita , Faghihi Seyed Aliakbar , Amini Mitra , Kojuri Javad
Published: April 2021

Introduction

Since the onset of the COVID-19 pandemic, many higher education and health centers have faced challenges. Educational leaders have tried to manage the new situation, but the human infrastructure was not ready for such an event. This study aims to explain the challenges and opportunities of the COVID-19 pandemic for medical education.

Method

This qualitative study used conventional content analysis to collect data from face-to-face and semi-structured interviews. The interviews continued until data saturation was reached. The participants were 12 students and 14 faculty members at Shiraz University of Medical Sciences. To ensure data rigor, we used member checks, peer checks and an external observer.

Results

Three main categories and 15 subcategories were extracted. The findings showed that four subcategories, e.g. perception on feasibility of e-learning, standardizing of e-learning, dedicated teaching, and networking and interdisciplinary collaborations, affected the development of medical e-learning. The main opportunities from the COVID-19 pandemic for medical education were classified into five subcategories: attitudes to e-learning and adaptability, preventing students’ separation from the educational environment, documentation and monitoring education, take control of own learning, and increasing perceived usefulness. The main challenges were divided into four subcategories, e.g. noncompliance with virtual classroom etiquette, inadequate interactions, time limitations, and infrastructure defects and problems. Finally, participants believed that methods of evaluation in e-learning were more suitable for diagnosis and formative evaluations. Generally, two subcategories were extracted, e.g. formative and summative.

Conclusion

Medical schools have necessarily moved towards e-learning to compensate for the interruption in classroom education, such that traditional classes have been replaced with e-learning. These rapid, extensive changes in teaching and learning approaches have consequences for medical schools.
A qualitative systematic review and thematic synthesis exploring the impacts of clinical academic activity by healthcare professionals outside medicine
Authors: Newington Lisa , Wells Mary , Adonis Adine , Bolton Lee , Bolton Saghdaoui Layla , Coffey Margaret , Crow Jennifer , Fadeeva Costa Olga , Hughes Catherine , Savage Matthew , Shahabi Lillie , Alexander Caroline M.
Published: April 2021

Background

There are increasing opportunities for healthcare professionals outside medicine to be involved in and lead clinical research. However, there are few roles within these professions that include time for research. In order to develop such roles, and evaluate effective use of this time, the range of impacts of this clinical academic activity need to be valued and understood by healthcare leaders and managers. To date, these impacts have not been comprehensively explored, but are suggested to extend beyond traditional quantitative impact metrics, such as publications, citations and funding awards.

Methods

Ten databases, four grey literature repositories and a naïve web search engine were systematically searched for articles reporting impacts of clinical academic activity by healthcare professionals outside medicine. Specifically, this did not include the direct impacts of the research findings, rather the impacts of the research activity. All stages of the review were performed by a minimum of two reviewers and reported impacts were categorised qualitatively according to a modified VICTOR (making Visible the ImpaCT Of Research) framework.

Results

Of the initial 2704 identified articles, 20 were eligible for inclusion. Identified impacts were mapped to seven themes: impacts for patients; impacts for the service provision and workforce; impacts to research profile, culture and capacity; economic impacts; impacts on staff recruitment and retention; impacts to knowledge exchange; and impacts to the clinical academic.

Conclusions

Several overlapping sub-themes were identified across the main themes. These included the challenges and benefits of balancing clinical and academic roles, the creation and implementation of new evidence, and the development of collaborations and networks. These may be key areas for organisations to explore when looking to support and increase academic activity among healthcare professionals outside medicine. The modified VICTOR tool is a useful starting point for individuals and organisations to record the impact of their research activity. Further work is needed to explore standardised methods of capturing research impact that address the full range of impacts identified in this systematic review and are specific to the context of clinical academics outside medicine.
HRP2 and HRP3 cross-reactivity and implications for HRP2-based RDT use in regions with Plasmodium falciparum hrp2 gene deletions
Authors: Kong Amy , Wilson Scott A. , Ah Yong , Nace Douglas , Rogier Eric , Aidoo Michael
Published: April 2021

Background

The Plasmodium falciparum antigen histidine rich protein 2 (HRP2) is a preferred target for malaria rapid diagnostic tests (RDTs) because of its abundant production by the parasite and thermal stability. As a result, a majority of RDTs procured globally target this antigen. However, previous reports from South America and recent reports from sub-Saharan Africa and Asia indicate that certain P. falciparum parasites have deletions of the gene coding for HRP2. The HRP2 antigen is paralogous to another P. falciparum antigen HRP3 and some antibodies to HRP2 cross-react with HRP3. Multiple parasites have been described with deletions of one or both hrp2 and hrp3 genes. It is unclear how the various combinations of hrp2 and hrp3 deletion genotypes affect clinical sensitivity of HRP2-based RDTs.

Methods

Cross-reactivity between HRP2 and HRP3 was tested on malaria RDTs using culture-adapted P. falciparum parasites with both hrp2 and hrp3 intact or with one or both genes deleted. Ten-fold serial dilutions of four culture-adapted P. falciparum parasites [3D7 (hrp2+/hrp3+), Dd2 (hrp2−/hrp3+), HB3 (hrp2+/hrp3−) and 3BD5 (hrp2−/hrp3−)] ranging from 100,000 to 0.01 parasites/µL were prepared. HRP2, Plasmodium lactate dehydrogenase (pLDH) and aldolase concentrations were determined for the diluted samples using a multiplex bead assay. The samples were subsequently tested on three RDT products designed to detect P. falciparum by HRP2 alone or in combination with pLDH.

Results

At parasite densities of approximately 1000 parasites/µL, parasites that expressed either hrp2 or hrp3 were detected by all three RDTs. Multiplex based antigen measurement using HRP2- conjugated beads demonstrated higher antigen concentration when both hrp2 and hrp3 genes were intact (3D7 parasites, 47.9 ng/ml) compared to HB3 (3.02 ng/mL) and Dd2 (0.20 ng/mL) strains that had one gene deleted. 3D7 at 10 parasites/µL (0.45 ng/mL) was reactive on all three RDT products whereas none of the other parasites were reactive at that density.

Conclusions

Above a certain antigen threshold, HRP3 cross-reactivity on HRP2-based RDTs is sufficient to mask the effects of deletions of hrp2 only. Studies of hrp2 deletion and its effects on HRP2-based RDTs must be studied alongside hrp3 deletions and include clinical sample reactivity on HRP2-based tests.
Shaping applied epidemiology workforce training to strengthen emergency response: a global survey of applied epidemiologists, 2019–2020
Authors: Parry Amy Elizabeth , Kirk Martyn D. , Durrheim David N. , Olowokure Babatunde , Colquhoun Samantha M. , Housen Tambri
Published: April 2021

Background

Rapid and effective emergency response to address health security relies on a competent and suitably trained local and international workforce. The COVID-19 pandemic has highlighted that the health security workforce needs to be well equipped to tackle current and future challenges. In this study, we explored whether training in applied epidemiology was meeting the current needs of the applied epidemiology workforce.

Method

We conducted a cross-sectional online survey that was available in English and French. We used purposive and snowballing sampling techniques to identify potential survey respondents. An online social media advertisement campaign was used to disseminate a REDCap survey link between October 2019 and February 2020 through field epidemiology networks. Survey questions included demographic details of participants, along with their technical background, level of formal education, topics studied during epidemiology training, and years of experience as an epidemiologist. We used Pearson Chi-squared (Chi2) to test the difference between categorical variables, and content analysis to evaluate responses to open-ended questions.

Results

In total, 282 people responded to the survey. Participants had a range of formal public health and epidemiology training backgrounds. Respondents applied epidemiology experience spanned almost 30 years, across 64 countries. Overall, 74% (n = 210) were alumni of Field Epidemiology Training Programs (FETP). Basic outbreak and surveillance training was well reported by respondents, however training in specialised techniques related to emergency response, communication, and leadership was less common. FETP graduates reported higher levels of formal training in all survey topics.

Conclusion

It is critical for the health security workforce to be well-trained and equipped with skills needed to ensure a rapid and effective response to acute public health events. Leadership, communication, interpersonal skills, and specialist training in emergency response are lacking in current training models. Our study has demonstrated that applied epidemiology workforce training must evolve to remain relevant to current and future public health challenges.
Expression and regulatory roles of lncRNAs in G-CIMP-low vs G-CIMP-high Glioma: an in-silico analysis
Authors: Datta Indrani , Noushmehr Houtan , Brodie Chaya , Poisson Laila M.
Published: April 2021

Background

Clinically relevant glioma subtypes, such as the glioma-CpG island methylator phenotype (G-CIMP), have been defined by epigenetics. In this study, the role of long non-coding RNAs in association with the poor-prognosis G-CMIP-low phenotype and the good-prognosis G-CMIP-high phenotype was investigated. Functional associations of lncRNAs with mRNAs and miRNAs were examined to hypothesize influencing factors of the aggressive phenotype.

Methods

RNA-seq data on 250 samples from TCGA’s Pan-Glioma study, quantified for lncRNA and mRNAs (GENCODE v28), were analyzed for differential expression between G-CIMP-low and G-CIMP-high phenotypes. Functional interpretation of the differential lncRNAs was performed by Ingenuity Pathway Analysis. Spearman rank order correlation estimates between lncRNA, miRNA, and mRNA nominated differential lncRNA with a likely miRNA sponge function.

Results

We identified 4371 differentially expressed features (mRNA = 3705; lncRNA = 666; FDR ≤ 5%). From these, the protein-coding gene TP53 was identified as an upstream regulator of differential lncRNAs PANDAR and PVT1 (p = 0.0237) and enrichment was detected in the “development of carcinoma” (p = 0.0176). Two lncRNAs (HCG11, PART1) were positively correlated with 342 mRNAs, and their correlation estimates diminish after adjusting for either of the target miRNAs: hsa-miR-490-3p, hsa-miR-129-5p. This suggests a likely sponge function for HCG11 and PART1.

Conclusions

These findings identify differential lncRNAs with oncogenic features that are associated with G-CIMP phenotypes. Further investigation with controlled experiments is needed to confirm the molecular relationships.
Avian corticosteroid-binding globulin: biological function and regulatory mechanisms in physiological stress responses
Authors: Lin Hai-Yan , Song Gang , Lei Fumin , Li Dongming , Qu Yanhua
Published: April 2021

Corticosteroid-binding globulin (CBG) is a high-affinity plasma protein that binds glucocorticoids (GCs) and regulates their biological activities. The structural and functional properties of CBG are crucial to understanding the biological actions of GCs in mediating stress responses and the underlying mechanisms. In response to stress, avian CBGs modulate the free and bound fractions of plasma corticosterone (CORT, the main GC), enabling them to mediate the physiological and behavioral responses that are fundamental for balancing the trade-off of energetic investment in reproduction, immunity, growth, metabolism and survival, including adaptations to extreme high-elevation or high-latitude environments. Unlike other vertebrates, avian CBGs substitute for sex hormone-binding globulin (SHBG) in transporting androgens and regulating their bioavailability, since birds lack anShbggene. The three-dimensional structures of avian and mammalian CBGs are highly conserved, but the steroid-binding site topographies and their modes of binding steroids differ. Given that CBG serves as the primary transporter of both GCs and reproductive hormones in birds, we aim to review the biological properties of avian CBGs in the context of steroid hormone transportation, stress responses and adaptation to harsh environments, and to provide insight into evolutionary adaptations in CBG functions occurred to accommodate physiological and endocrine changes in birds compared with mammals.
Hyperoxemia during resuscitation of trauma patients and increased intensive care unit length of stay: inverse probability of treatment weighting analysis
Authors:   on behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) Study Group, Yamamoto Ryo , Fujishima Seitaro , Sasaki Junichi , Gando Satoshi , Saitoh Daizoh , Shiraishi Atsushi , Kushimoto Shigeki , Ogura Hiroshi , Abe Toshikazu , Mayumi Toshihiko , Kotani Joji , Nakada Taka-aki , Shiino Yasukazu , Tarui Takehiko , Okamoto Kohji , Sakamoto Yuichiro , Shiraishi Shin-Ichiro , Takuma Kiyotsugu , Tsuruta Ryosuke , Masuno Tomohiko , Takeyama Naoshi , Yamashita Norio , Ikeda Hiroto , Ueyama Masashi , Hifumi Toru , Yamakawa Kazuma , Hagiwara Akiyoshi , Otomo Yasuhiro
Published: April 2021

Background

Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes.

Methods

A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016–2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models.

Results

Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10–21) vs 23 (16–26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12–22) vs 23 (19–26), p = 0.004], but not among those intubated at the ED [18 (9–20) vs 15 (8–23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay.

Conclusions

Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED.

Trial registration

UMIN-CTR, UMIN000019588. Registered on November 15, 2015.
Emergency surgery for splenic flexure cancer: results of the SFC Study Group database
Authors:   on behalf of the SFC Study Group, de’Angelis Nicola , Espin Eloy , Ris Frederic , Landi Filippo , Le Roy Bertrand , Coccolini Federico , Celentano Valerio , Gurrado Angela , Pezet Denis , Bianchi Giorgio , Memeo Riccardo , Vitali Giulio C. , Solis Alejandro , Denet Christine , Di Saverio Salomone , de’Angelis Gian Luigi , Kraft Miquel , Gonzálvez-Guardiola Paula , Stakelum Aine , Catena Fausto , Fuks David , Winter Des C. , Testini Mario , Martínez-Pérez Aleix
Published: April 2021

Background

The effectiveness of surgical treatment for splenic flexure carcinomas (SFCs) in emergency settings remains unexplored. This study aims to compare the perioperative and long-term outcomes of different alternatives for emergency SFC resection.

Method

This multicenter retrospective study was based on the SFC Study Group database. For the present analysis, SFC patients were selected if they had received emergency surgical resection with curative intent between 2000 and 2018. Extended right colectomy (ERC), left colectomy (LC), and segmental left colectomy (SLC) were evaluated and compared.

Results

The study sample was composed of 90 SFC patients who underwent emergency ERC (n = 55, 61.1%), LC (n = 18, 20%), or SLC (n = 17, 18.9%). Bowel obstruction was the most frequent indication for surgery (n = 75, 83.3%), and an open approach was chosen in 81.1% of the patients. A higher incidence of postoperative complications was observed in the ERC group (70.9%) than in the LC (44.4%) and SLC groups (47.1%), with a significant procedure-related difference for severe postoperative complications (Dindo-Clavien ≥ III; adjusted odds ratio for ERC vs. LC:7.23; 95% CI 1.51-34.66; p = 0.013). Anastomotic leakage occurred in 8 (11.2%) patients, with no differences between the groups (p = 0.902). R0 resection was achieved in 98.9% of the procedures, and ≥ 12 lymph nodes were retrieved in 92.2% of patients. Overall and disease-free survival rates at 5 years were similar between the groups and were significantly associated with stage pT4 and the presence of synchronous metastases.

Conclusion

In the emergency setting, ERC and open surgery are the most frequently performed procedures. ERC is associated with increased odds of severe postoperative complications when compared to more conservative SFC resections. Nonetheless, all the alternatives seem to provide similar pathologic and long-term outcomes, supporting the oncological safety of more conservative resections for emergency SFCs.
Long non-coding RNA AFAP1-AS1 facilitates ovarian cancer progression by regulating the miR-107/PDK4 axis
Authors: Liu Bao , Yan Li , Chi Yugang , Sun Yuhan , Yang Xiaoyu
Published: April 2021

Background

Abnormally expressed in various tumors, long non-coding RNAs (lncRNAs) feature prominently in tumor development, yet little is still known regarding the functional roles of lncRNA AFAP1 antisense RNA 1 (AFAP1-AS1) in ovarian cancer (OC).

Methods

The relative expression levels of lncRNA AFAP1-AS1, microRNA (miR)-107 and pyruvate dehydrogenase kinase isozyme 4 (PDK4) mRNA were assessed by quantitative real-time PCR. PDK4, PCNA and cyclin D1 expression levels were determined using Western blot analysis. Bioinformatics analysis and dual-luciferase gene reporter assay were conducted for identifying and validating the binding sequences between AFAP1-AS1 and miR-107, as well as between miR-107 and PDK4. Cell counting kit-8 assay was employed for detecting cell proliferation. Cell migration and invasion abilities were examined using Transwell assays.

Results

The present study revealed that AFAP1-AS1 expression was elevated in OC cells and tissues. AFAP1-AS1 expression and FIGO stage were positively correlated. AFAP1-AS1 knockdown repressed OC cell proliferation, migration and invasion. AFAP1-AS1 functioned as a sponge of miR-107, and miR-107 reversed the effects of AFAP1-AS1 on OC cells. It was validated that miR-107 was able to bind to PDK4, and AFAP1-AS1 regulated PDK4 expression by competitively binding with miR-107. Additionally, miR-107 modulated OC cell proliferation, migration and invasion via targeting PDK4.

Conclusions

LncRNA AFAP1-AS1 serves as a tumor driver in the pathogenesis of OC via the miR-107/PDK4 axis.
CD36 polymorphisms and the age of disease onset in patients with pathogenic variants within the mutation cluster region of APC
Authors: Connor T , McPhillips M , Hipwell M , Ziolkowski A , Oldmeadow C , Clapham M , Pockney PG , Lis E , Banasiewicz T , Pławski A , Scott RJ
Published: April 2021

Background

Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes patients to colorectal cancer. FAP is the result of a loss of APC function due to germline pathogenic variants disrupting gene expression. Genotype-phenotype correlations are described for FAP. For example attenuated forms of the disease are associated with pathogenic variants at the 5’ and 3’ ends of APC whilst severe forms of the disease appear to be linked to variants occurring in the mutation cluster region (MCR) of the gene. Variants occurring in the MCR are phenotypically associated with hundreds to thousands of adenomas carpeting the colon and rectum and patients harbouring changes in this region have a high propensity to develop colorectal cancer. Not all patients who carry pathogenic variants in this region have severe disease which may be a result of environmental factors. Alternatively, phenotypic variation observed in these patients could be due to modifier genes that either promote or inhibit disease expression. Mouse models of FAP have provided several plausible candidate modifier genes, but very few of these have survived scrutiny. One such genetic modifier that appears to be associated with disease expression is CD36. We previously reported a weak association between a polymorphism in CD36 and a later age of disease onset on a relatively small FAP patient cohort.

Methods

In the current study, we enlarged the FAP cohort. 395 patients all carrying pathogenic variants in APC were tested against three CD36 Single Nucleotide Polymorphisms (SNP)s (rs1049673, rs1761667 rs1984112), to determine if any of them were associated with differences in the age of disease expression.

Results

Overall, there appeared to be a statistically significant difference in the age of disease onset between carriers of the variant rs1984112 and wildtype. Furthermore, test equality of survivor functions for each SNP and mutation group suggested an interaction in the Log Rank, Wilcoxon, and Tarone-Ware methods for rs1049673, rs1761667, and rs1984112, thereby supporting the notion that CD36 modifies disease expression.

Conclusions

This study supports and strengthens our previous findings concerning CD36 and an association with disease onset in FAP, AFAP and FAP-MCR affected individuals. Knowledge about the role CD36 in adenoma development may provide greater insight into the development of colorectal cancer.
Hesperidin alleviates insulin resistance by improving HG-induced oxidative stress and mitochondrial dysfunction by restoring miR-149
Authors: Tian Miao , Han Yu-Bo , Zhao Cheng-Cheng , Liu Li , Zhang Fu-Li
Published: April 2021

Background

Hesperidin, a natural flavanone, has been proven to have multiple protective effects in diabetic rats, such as antioxidant, anti-inflammatory and anti-apoptotic effects. However, the molecular mechanisms underlying the effects of hesperidin are not well elucidated.

Methods

LO2 cells were stimulated with high glucose (HG, 33 mM) for 24 h to establish a model of oxidative stress. Then, cell viability was determined using the MTT assay. The antioxidant activities, including the reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, mitochondrial membrane potential (MMP) and adenosine-triphosphate (ATP) production, were measured with the corresponding kits. The levels of gene expression, protein expression and methylation were detected using qRT-PCR, western blotting and methylation-specific PCR (MSP) assays, respectively.

Results

Compared to the NG treatment, hesperidin treatment increased the viability and improved the oxidative stress, mitochondrial dysfunction and insulin resistance of HG-treated LO2 cells, and these effects were correlated with heightened SOD and GPx activities, increased MMP level and ATP generation, reduced MDA, ROS and glucose levels, and activated GSK3β/AKT and inactivated IRS1 signals. Mechanistically, hesperidin treatment enhanced the miR-149 expression level by reducing its promoter methylation by inhibiting DNMT1. Importantly, knockdown of miR-149 obviously abolished the biological roles of hesperidin.

Conclusions

Our findings demonstrated that hesperidin treatment ameliorated HG-induced insulin resistance by reducing oxidative stress and mitochondrial dysfunction partly by suppressing DNMT1-mediated miR-149 silencing.
Estimands in epigenome-wide association studies
Authors: Kruppa Jochen , Sieg Miriam , Richter Gesa , Pohrt Anne
Published: April 2021

Background

In DNA methylation analyses like epigenome-wide association studies, effects in differentially methylated CpG sites are assessed. Two kinds of outcomes can be used for statistical analysis: Beta-values and M-values. M-values follow a normal distribution and help to detect differentially methylated CpG sites. As biological effect measures, differences of M-values are more or less meaningless. Beta-values are of more interest since they can be interpreted directly as differences in percentage of DNA methylation at a given CpG site, but they have poor statistical properties. Different frameworks are proposed for reporting estimands in DNA methylation analysis, relying on Beta-values, M-values, or both.

Results

We present and discuss four possible approaches of achieving estimands in DNA methylation analysis. In addition, we present the usage of M-values or Beta-values in the context of bioinformatical pipelines, which often demand a predefined outcome. We show the dependencies between the differences in M-values to differences in Beta-values in two data simulations: a analysis with and without confounder effect. Without present confounder effects, M-values can be used for the statistical analysis and Beta-values statistics for the reporting. If confounder effects exist, we demonstrate the deviations and correct the effects by the intercept method. Finally, we demonstrate the theoretical problem on two large human genome-wide DNA methylation datasets to verify the results.

Conclusions

The usage of M-values in the analysis of DNA methylation data will produce effect estimates, which cannot be biologically interpreted. The parallel usage of Beta-value statistics ignores possible confounder effects and can therefore not be recommended. Hence, if the differences in Beta-values are the focus of the study, the intercept method is recommendable. Hyper- or hypomethylated CpG sites must then be carefully evaluated. If an exploratory analysis of possible CpG sites is the aim of the study, M-values can be used for inference.