bluuebunny/crossref_metadata_2025 huggingface dataset:
Relugolix: a novel androgen deprivation therapy for management of patients with advanced prostate cancer
Authors: Saad Fred , Shore Neal D.
Published: March 2021

Androgen deprivation therapy (ADT) is the foundation of treatment for patients with locally advanced, recurrent and metastatic prostate cancer, most commonly using luteinizing releasing hormone (LHRH) agonists. More recently, a new approach to ADT has emerged with the development of gonadotropin-releasing hormone (GnRH) antagonists, which aim to overcome some of the potential adverse physiologic effects of LHRH agonists. This article focuses on the newest GnRH antagonist, relugolix – a once-daily treatment and the only oral GnRH antagonist that has now been approved for the treatment of advanced prostate cancer. In phase II and III studies, relugolix achieved rapid and sustained castration without the testosterone surge associated with LHRH agonists, thus avoiding the potential clinical consequences of tumor flare and the necessity for concomitant anti-androgen therapy. Relugolix also achieved rapid testosterone recovery, which may potentially reduce ADT-related adverse events and offer opportunities for combination and intermittent therapy strategies. Cardiovascular safety is a particular concern in men with prostate cancer and ADT further increases cardiovascular risk: indeed, LHRH agonists are required to have a drug label warning about an increased risk of cardiovascular disease. Data from the phase III HERO study demonstrate an improved cardiac safety profile for the GnRH antagonist relugolix compared with the LHRH agonist leuprolide, including a significantly reduced risk for a major adverse cardiovascular event. Taken together, the data indicate that relugolix may mitigate some of the cardiovascular concerns surrounding ADT and has the potential to become a new standard of care for men with prostate cancer. In summary, relugolix represents a novel and recently available prostate cancer management strategy, incorporating the mechanistic advantages of GnRH antagonists and the potential benefits of oral administration.
Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model
Authors: Chen Xin , Ma Yuanchun , Mou Xiongjun , Liu Hao , Ming Hao , Chen Yu , Liu Yanwen , Liu Songlin
Published: March 2021

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.
Patients’ Self-Reported Recovery After an Environmental Intervention Aimed to Support Patient’s Circadian Rhythm in Intensive Care
Authors: Engwall Marie , Jutengren Göran , Bergbom Ingegerd , Lindahl Berit , Fridh Isabell
Published: March 2021

Background:

Patients in intensive care units (ICUs) are among the most vulnerable, and they require support to start their recovery. The design of the patient area in the ICU can play a prominent role in both the quality of care and patients’ recovery. The lighting environment has the opportunity to restore and strengthen the natural human circadian rhythm and health.

Aim:

To evaluate patients’ self-reported recovery after being cared for in an ICU room rebuilt according to evidence-based design principles that promote recovery.

Method:

An intervention was set up in a two-bed patient room including a cycled lighting system. Self-reported recovery was reported at 6 and 12 months after discharge. Data were analyzed using a 2(mechanically ventilated, nonmechanically ventilated) × 2(intervention room, ordinary room) analysis of covariance (ANCOVA) and 2(male, women) × 2(intervention room, ordinary room) ANCOVA.

Results:

Data from the different rooms showed no significant main effects for recovery after 6 months, p = .21; however, after 12 months, it become significant, p. < .05. This indicated that patient recovery was positively influenced for patients cared for in the intervention room ( M = 8.88, SD = 4.07) compared to the ordinary room ( M = 10.90, SD = 4.26). There were no interaction effects for gender or if the patients had been mechanically ventilated either at 6 or 12 months’ postdischarge.

Conclusions:

A cycled lighting system may improve patient self-reported recovery after ICU care; however, more research on the topic is needed.
Four Poems From an Insurrection
Authors: Borchard Kurt
Published: March 2021

I present four poems written in response to the U.S. Capitol insurrection. The poems are constructed through fragments of contemporary phrases, words from national anthems and pledges, and word play through spelling, phonetics, and semantics. They produce discordant, emergent sense-making through free form verse composed during a singular crisis of political legitimacy.
Exploring healthcare professionals’ perceptions of artificial intelligence: Validating a questionnaire using the e-Delphi method
Authors: Shinners Lucy , Aggar Christina , Grace Sandra , Smith Stuart
Published: March 2021

Objective

The aim of this study was to draw upon the collective knowledge of experts in the fields of health and technology to develop a questionnaire that measured healthcare professionals’ perceptions of Artificial Intelligence (AI).

Methods

The panel for this study were carefully selected participants who demonstrated an interest and/or involvement in AI from the fields of health or information technology. Recruitment was accomplished via email which invited the panel member to participate and included study and consent information. Data were collected from three rounds in the form of an online survey, an online group meeting and email communication. A 75% median threshold was used to define consensus.

Results

Between January and March 2019, five healthcare professionals and three IT experts participated in three rounds of study to reach consensus on the structure and content of the questionnaire. In Round 1 panel members identified issues about general understanding of AI and achieved consensus on nine draft questionnaire items. In Round 2 the panel achieved consensus on demographic questions and comprehensive group discussion resulted in the development of two further questionnaire items for inclusion. In a final e-Delphi round, a draft of the final questionnaire was distributed via email to the panel members for comment. No further amendments were put forward and 100% consensus was achieved.

Conclusion

A modified e-Delphi method was used to validate and develop a questionnaire to explore healthcare professionals’ perceptions of AI. The e-Delphi method was successful in achieving consensus from an interdisciplinary panel of experts from health and IT. Further research is recommended to test the reliability of this questionnaire.
Concussion assessment potentially aided by use of an objective multimodal concussion index
Authors: Jacquin Arnaud E , Bazarian Jeffrey J , Casa Douglas J , Elbin Robert J , Hotz Gillian , Schnyer David M , Yeargin Susan , Prichep Leslie S , Covassin Tracey
Published: March 2021

Objective

Prompt, accurate, objective assessment of concussion is crucial as delays can lead to increased short and long-term consequences. The purpose of this study was to derive an objective multimodal concussion index (CI) using EEG at its core, to identify concussion, and to assess change over time throughout recovery.

Methods

Male and female concussed ( N = 232) and control ( N = 206) subjects 13–25 years were enrolled at 12 US colleges and high schools. Evaluations occurred within 72 h of injury, 5 days post-injury, at return-to-play (RTP), 45 days after RTP (RTP + 45); and included EEG, neurocognitive performance, and standard concussion assessments. Concussed subjects had a witnessed head impact, were removed from play for ≥ 5 days using site guidelines, and were divided into those with RTP < 14 or ≥14 days. Part 1 describes the derivation and efficacy of the machine learning derived classifier as a marker of concussion. Part 2 describes significance of differences in CI between groups at each time point and within each group across time points.

Results

Sensitivity = 84.9%, specificity = 76.0%, and AUC = 0.89 were obtained on a test Hold-Out group representing 20% of the total dataset. EEG features reflecting connectivity between brain regions contributed most to the CI. CI was stable over time in controls. Significant differences in CI between controls and concussed subjects were found at time of injury, with no significant differences at RTP and RTP + 45. Within the concussed, differences in rate of recovery were seen.

Conclusions

The CI was shown to have high accuracy as a marker of likelihood of concussion. Stability of CI in controls supports reliable interpretation of CI change in concussed subjects. Objective identification of the presence of concussion and assessment of readiness to return to normal activity can be aided by use of the CI, a rapidly obtained, point of care assessment tool.
A Simple Physical Therapy Algorithm Is Successful in Decreasing Skilled Nursing Facility Length of Stay and Increasing Cost Savings After Hip Fracture With No Increase in Adverse Events
Authors: Adrados Murillo , Wang Kaicheng , Deng Yanhong , Bozzo Janis , Messina Tara , Stevens Amie , Moore Anne , Morris Jensa , O’Connor Mary I.
Published: March 2021

Introduction:

Shorter length of stays (LOS) at a Skilled Nursing Facility (SNF) after hip fracture surgery would be expected to lead to costs savings for the healthcare system. Evidence also suggests that shorter SNF stays also leads to improved 30-day outcomes, thus compounding this value proposition. Our Integrated Fragility Hip Fracture Program created a simple algorithm at discharge to provide each post-operative hip fracture patient with an expected SNF LOS. We studied whether this intervention produced a shorter SNF LOS and other observable short-term outcomes.

Methods:

We retrospectively reviewed all original Medicare hip fracture patients treated with operative fixation who were admitted to our hospital in 2015, 2017 and 2018. We selected patients who were discharged to a single SNF following hospitalization, and excluded patients with incomplete records. The algorithm for the expected LOS recommendation was based on the degree of assistance the patient needed for ambulation: 7 days (“0-person assist”), 14 days (“1-person assist”), or 21 days (“2-person assist”). We compare the SNF LOS of our hip fracture patient population between those discharged to a program participant, those SNF that agreed to this algorithm, and those discharged to a non-program participant SNF.

Results:

We identified 246 patients meeting our selection criteria. 69 were discharged to a program participant SNF. Patients discharged to a participant SNF had similar baseline demographics and ASA distributions to those discharged to a non-participant provider. There was a statistically significant difference in length of stay between the groups, with program participant patients spending an average of 23 days at the SNF while the control group spent an average of 31 days. (p < 0.001). Program participant discharges were also associated with additional cost savings. There was no significant difference in ED visits within 90 days of discharge.

Discussion:

SNF LOS for geriatric hip fractures can be decreased with implementation of a simple physical therapy driven algorithm based on the patient’s ambulatory independence at hospital discharge. Conclusion: This is a simple, yet completely unique program that seems to have increased the value of healthcare provided.
Trade in Intermediates and Agro-Food Value Chain Integration: The Case of the Arab Region
Authors: Boughanmi Houcine , Al-Saadi Fatma , Zaibet Lokman , Al Abri Ibtisam , Akintola Abdallah
Published: March 2021

Arab intra-regional trade in agro-food accounts for more than half of the total Arab agro-food trade, displaying strong “trade-intensity” over the past decade. This indicates the potential of developing agro-food regional production networks aligning with the region’s comparative advantage in agro-food products. However, intermediates trade, as an indicator of value chain integration, has been low and sluggish due to various structural and policy factors. This article aims to analyze the determinants of trade in agro-food intermediates in the Arab region, focusing on the role and significance of regional trade arrangements and trade facilitation. The Broad Economic Category (BEC) classification is used to categorize goods into intermediate and final goods. Our analysis, using the gravity model, shows that regional trade arrangements in their current form do not significantly affect regional trade (except in the Gulf Cooperation Council [GCC]). We also reveal that timeliness in export delivery is an important determinant of trade in agro-food intermediates. Thus, Arab countries should simplify their customs clearance procedures and engage in a deeper form of regional integration to help build trade corridors and enhance regional value-added chains (RVCs).
One and Done: The Long Eclipse of Women’s Televised Sports, 1989–2019
Authors: Cooky Cheryl , Council LaToya D. , Mears Maria A. , Messner Michael A.
Published: March 2021

For 3 decades we have tracked and analyzed the quantity and quality of coverage of women’s and men’s sports in televised news and highlights shows. In this paper, we report on our most recent iteration of the longitudinal study, which now includes an examination of online sports newsletters and social media. The study reveals little change in the quantitative apportionment of coverage of women’s and men’s sports over the past 30 years. Men’s sports—especially the “Big Three” of basketball, football and baseball—still receive the lion’s share of the coverage, whether in-season or out of season. When a women’s sports story does appear, it is usually a case of “one and done,” a single women’s sports story obscured by a cluster of men’s stories that precede it, follow it, and are longer in length. Social media posts and online sports newsletters’ coverage, though a bit more diverse in some ways, mostly reflected these same patterned gender asymmetries. Gender-bland sexism continued as the dominant pattern in 2019 TV news and highlights’ stories on women’s sports. Three themes of this “gender-bland” coverage include: 1) nationalism, 2) asymmetrical gender marking coupled with local parochialism, and 3) community service/ charitable contributions.
Metrics of OsteoChondral Allografts (MOCA) Group Consensus Statements on the Use of Viable Osteochondral Allograft
Authors: Görtz Simon , Tabbaa Suzanne M. , Jones Deryk G. , Polousky John D. , Crawford Dennis C. ,   the MOCA Committee, Bugbee William D. , Cole Brian J. , Farr Jack , Fleischli James E. , Getgood Alan , Gomoll Andreas H. , Gross Allan E. , Krych Aaron J. , Lattermann Christian , Mandelbaum Bert R. , Mandt Peter R. , Mirzayan Raffy , Mologne Timothy S. , Provencher Matthew T. , Rodeo Scott A. , Safir Oleg , Strauss Eric D. , Wahl Christopher J. , Williams Riley J. , Yanke Adam B.
Published: March 2021

Background:

Osteochondral allograft (OCA) transplantation has evolved into a first-line treatment for large chondral and osteochondral defects, aided by advancements in storage protocols and a growing body of clinical evidence supporting successful clinical outcomes and long-term survivorship. Despite the body of literature supporting OCAs, there still remains controversy and debate in the surgical application of OCA, especially where high-level evidence is lacking.

Purpose:

To develop consensus among an expert group with extensive clinical and scientific experience in OCA, addressing controversies in the treatment of chondral and osteochondral defects with OCA transplantation.

Study Design:

Consensus statement.

Methods:

A focus group of clinical experts on OCA cartilage restoration participated in a 3-round modified Delphi process to generate a list of statements and establish consensus. Questions and statements were initially developed on specific topics that lack scientific evidence and lead to debate and controversy in the clinical community. In-person discussion occurred where statements were not agreed on after 2 rounds of voting. After final voting, the percentage of agreement and level of consensus were characterized. A systematic literature review was performed, and the level of evidence and grade were established for each statement.

Results:

Seventeen statements spanning surgical technique, graft matching, indications, and rehabilitation reached consensus after the final round of voting. Of the 17 statements that reached consensus, 11 received unanimous (100%) agreement, and 6 received strong (80%-99%) agreement.

Conclusion:

The outcomes of this study led to the establishment of consensus statements that provide guidance on surgical and perioperative management of OCAs. The findings also provided insights on topics requiring more research or high-quality studies to further establish consensus and provide stronger evidence.
Risk Factors for Failure After Anterior Cruciate Ligament Reconstruction in a Pediatric Population: A Prediction Algorithm
Authors: Lemme Nicholas J. , Yang Daniel S. , Barrow Brooke , O’Donnell Ryan , Daniels Alan H. , Cruz Aristides I.
Published: March 2021

Background:

Anterior cruciate ligament reconstruction (ACLR) in pediatric patients is becoming increasingly common. There is growing yet limited literature on the risk factors for revision in this demographic.

Purpose:

To (1) determine the rate of pediatric revision ACLR in a nationally representative sample, (2) ascertain the associated patient- and injury-specific risk factors for revision ACLR, and (3) examine the differences in the rate and risks of revision ACLR between pediatric and adult patients.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

The PearlDiver patient record database was used to identify adult patients (age ≥20 years) and pediatric patients (age <20 years) who underwent primary ACLR between 2010 and 2015. At 5 years postoperatively, the risk of revision ACLR was compared between the adult and pediatric groups. ACLR to the contralateral side was also compared. Multivariate logistic regression was used to determine the significant risk factors for revision ACLR and the overall reoperation rates in pediatric and adult patients; from these risk factors, an algorithm was developed to predict the risk of revision ACLR in pediatric patients.

Results:

Included were 2055 pediatric patients, 1778 adult patients aged 20 to 29 years, and 1646 adult patients aged 30 to 39 years who underwent ACLR. At 5 years postoperatively, pediatric patients faced a higher risk of revision surgery when compared with adults (18.0 % vs 9.2% [adults 20-29 years] and 7.1% [adults 30-39 years]; P < .0001), with significantly decreased survivorship of the index ACLR ( P < .0001; log-rank test). Pediatric patients were also at higher risk of undergoing contralateral ACLR as compared with adults (5.8% vs 1.6% [adults 20-29 years] and 1.9% [adults 30-39 years]; P < .0001). Among the pediatric cohort, boys (odds ratio [OR], 0.78; 95% CI, 0.63-0.96; P = .0204) and patients >14 years old (OR, 0.62; 95% CI, 0.45-0.86; P = .0035) had a decreased risk of overall reoperation; patients undergoing concurrent meniscal repair (OR, 1.84; 95% CI, 1.43-2.38; P < .0001) or meniscectomy (OR, 2.20; 95% CI, 1.72-2.82; P < .0001) had an increased risk of revision surgery. According to the risk algorithm, the highest probability for revision ACLR was in girls <15 years old with concomitant meniscal and medial collateral ligament injury (36% risk of revision).

Conclusion:

As compared with adults, pediatric patients had an increased likelihood of revision ACLR, contralateral ACLR, and meniscal reoperation within 5 years of an index ACLR. Families of pediatric patients—especially female patients, younger patients, and those with concomitant medial collateral ligament and meniscal injuries—should be counseled on such risks.
Resilient Aging: Psychological Well-Being and Social Well-Being as Targets for the Promotion of Healthy Aging
Authors: Kim Eric S. , Tkatch Rifky , Martin David , MacLeod Stephanie , Sandy Lewis , Yeh Charlotte
Published: March 2021

Population aging is one of the most important social trends of the 21st century and in the United States, the number of people aged ≥65 is projected to increase by nearly 50% in the next 15 years. Most biomedical and public health efforts have focused on reducing harmful risk factors when targeting chronic disease—an approach that has contributed greatly to prevention and treatment programs. However, evidence suggests that the number of years lost to disability is increasing and historic gains we have made in life expectancy are eroding, and even reversing in some groups. As our society ages and grapples with these issues, expanding the focus to include resilience, as well as psychosocial assets in our prevention and treatment programs might help inform the multidisciplinary response effort we need. Here we synthesize research evaluating associations between different dimensions of psychological well-being (e.g., purpose in life, optimism, life satisfaction) and social well-being (e.g., structural, functional, quality) with chronic conditions. We also evaluate evidence around three biopsychosocial pathways hypothesized to underlie these associations. These factors are meaningful, measurable, and potentially modifiable; thus, further pursuing this line of inquiry might unveil innovative paths to enhancing the health of our rapidly aging society.
Correlation of Students’ Academic Achievements at a Professional Course of Ethics and Pediatrics Clinical Practice at Mizan-Tepi University, South Nations, Nationalities and People’s Region, Ethiopia
Authors: Gamtessa Lalisa Chewaka
Published: March 2021

Nursing is a respect for dignity and treating every person equally. Qualifying competent and ethical nurses requires the incorporation of a professional code of ethics with clinical nursing practice. However, no study was conducted on the relationship between professional ethics and clinical nursing practice. Therefore this study aimed to determine correlation between professional ethics and pediatrics clinical practice from an achievement perspective. Accordingly, cross-sectional study design was conducted at Mizan-Tepi University using nursing students’ academic achievements at professional ethics and pediatric practice. Collected data were entered into Epi info 7. SPSS version 21.0 was used to calculate spearman’s rho correlation ( rs) and coefficient of determination ( R2) at P  < .05. A total of 316 study participants comprising of 209 (66.14%) male and 107 (33.86%) female nursing students included in the current study. Nursing students’ academic achievements at professional ethics was significantly and positively associated with achievements at pediatrics clinical practice ( rs  = 0.4-0.6), P < .001. Linear regression results revealed 25% to 26.7% coefficient determination for regular students and 18% to 22.9% for summer nursing students. To sum up, there was a significant positive association between achievements of students at professional ethics and pediatrics clinical practice. Therefore increasing students’ academic achievement in professional ethics can further improve their achievements at pediatrics clinical practice. However, academic achievement in professional ethics explained 22.35% of the variability in achievements at pediatric clinical practice. 77.65% of the variability in pediatrics clinical practice was due to other factors that deserve another study.
Public Reactions in Online Newspapers to Workplace Violence Against Nurses
Authors: Tung Le Thanh , Anh Truong Tuan , Chinh Nguyen Thi Minh , Long Nguyen Hoang
Published: March 2021

Background

Nurses frequently suffer from workplace violence, but the public is often not fully aware of the situation because many events are not widely reported.

Methods

This study is an attempt to describe public perceptions of and reactions to reports of incidents of violence against nurses in online newspapers. Articles about such violence in Vietnamese online newspapers published from January to December 2019 as well as readers’ comments on those articles were collected for thematic analysis.

Results

Nine assaults were reported in 152 articles, and 367 comments were left in the threads. The analysis found four themes: 1) proposing punishment, 2) showing sympathy, 3) being skeptical, and 4) taking gender into account. In particular, the audience called for stricter punishment of the assaulters and showed sympathy for the nurses. However, commenters’ prior experiences with poor nursing services sometimes made them skeptical about the motivations of the attackers. Additionally, commenters saw the violence as a conflict between a man (assaulter) and a woman (assaultee) rather than between a client and a professional nurse.

Conclusions

In general, the public showed support to nurses. Nurses should take advantage of this support to advocate improved policies and measures to protect themselves from violence at work.
Cancer therapy-induced hyponatremia: A case-illustrated review
Authors: Pelletier Karyne , Škrtić Marko , Kitchlu Abhijat
Published: March 2021

Hyponatremia is the most common electrolyte disorder in patients with cancer and is associated with significant morbidity and mortality. Innovation in cancer therapies has led to substantial improvement in cancer outcomes, but also to new therapy-related toxicities, including electrolyte disturbance. Improvement in clinicians understanding of hyponatremia may mitigate adverse outcomes and improve quality of life in cancer patients. In this case-illustrated review, we discuss the mechanisms underlying drug-induced hyponatremia both in “classical” antineoplastic drugs and novel cancer therapies. Via these clinical cases, we describe hyponatremia caused by conventional chemotherapies (e.g. platinum compounds, vinca alkaloid, and alkylating agents) as well as hyponatremia related to tyrosine kinase inhibitors and other targeted therapies. We also focus on checkpoint inhibitors-induced hyponatremia, as these agents are increasingly used for a wide variety of malignancies. Lastly, we summarize therapy-related hyponatremia among recipients of newer treatments for multiple myeloma.
Understanding Mixed-Effects Models Through Data Simulation
Authors: DeBruine Lisa M. , Barr Dale J.
Published: March 2021

Experimental designs that sample both subjects and stimuli from a larger population need to account for random effects of both subjects and stimuli using mixed-effects models. However, much of this research is analyzed using analysis of variance on aggregated responses because researchers are not confident specifying and interpreting mixed-effects models. This Tutorial explains how to simulate data with random-effects structure and analyze the data using linear mixed-effects regression (with the lme4 R package), with a focus on interpreting the output in light of the simulated parameters. Data simulation not only can enhance understanding of how these models work, but also enables researchers to perform power calculations for complex designs. All materials associated with this article can be accessed at https://osf.io/3cz2e/ .
Simulation Studies as a Tool to Understand Bayes Factors
Authors: van Ravenzwaaij Don , Etz Alexander
Published: March 2021

When social scientists wish to learn about an empirical phenomenon, they perform an experiment. When they wish to learn about a complex numerical phenomenon, they can perform a simulation study. The goal of this Tutorial is twofold. First, it introduces how to set up a simulation study using the relatively simple example of simulating from the prior. Second, it demonstrates how simulation can be used to learn about the Jeffreys-Zellner-Siow (JZS) Bayes factor, a currently popular implementation of the Bayes factor employed in the BayesFactor R package and freeware program JASP. Many technical expositions on Bayes factors exist, but these may be somewhat inaccessible to researchers who are not specialized in statistics. In a step-by-step approach, this Tutorial shows how a simple simulation script can be used to approximate the calculation of the Bayes factor. We explain how a researcher can write such a sampler to approximate Bayes factors in a few lines of code, what the logic is behind the Savage-Dickey method used to visualize Bayes factors, and what the practical differences are for different choices of the prior distribution used to calculate Bayes factors.
Novel therapeutics in nystagmus: what has the genetics taught us so far?
Authors: Self Jay E , Lee Helena
Published: March 2021

Nystagmus is a disorder characterised by uncontrolled, repetitive, to-and-fro movement of the eyes. It can occur as a seemingly isolated disorder but is most commonly the first, or most obvious, feature in a host of ophthalmic and systemic disorders. The number of underlying causes is vast, and recent improvements in the provision of genetic testing have shown that many conditions can include nystagmus as a feature, but that phenotypes overlap significantly. Therefore, an increase in the understanding of the genetic causes of nystagmus has shown that successful novel therapeutics for ‘nystagmus’ can target either specific underlying disorders and mechanisms (aiming to treat the underlying condition as a whole), or a final common pathway (aiming to treat the nystagmus directly).

Plain language summary

Novel treatments for a disorder of eye movement (nystagmus): what has the genetics taught us so far? Nystagmus is a disorder of eye movement characterised by uncontrolled, to-and-fro movements. It can occur as an isolated disorder, in conditions affecting other parts of the eye, in conditions affecting multiple other parts of the body or secondary to neurological diseases (brain diseases). In recent years, advances in genetic testing methods and increase in genetic testing in healthcare systems have provided a greater understanding of the underlying causes of nystagmus. They have highlighted the bewildering number of genetic causes that can result in what looks like a very similar eye movement disorder. In recent years, new classes of drugs have been developed for some of the causes of nystagmus, and some new drugs have been developed for other conditions which have the potential to work in certain types of nystagmus. For these reasons, genetics has taught us that identifying new possible treatments for nystagmus can either be dependent on identifying the underlying genetic cause and aiming to treat that, or aiming to treat the nystagmus per se by targeting a final common pathway. A toolkit based on specific treatments for specific conditions is more to have meaningful impact on ‘nystagmus’ than pursuing a panacea based on a ‘one size fits all’ approach.
Disaster management of the psychological impact of the COVID-19 pandemic
Authors: Sheek-Hussein Mohamud , Abu-Zidan Fikri M. , Stip Emmanuel
Published: March 2021

Background

The COVID-19 pandemic has exposed a suboptimal response to this threatening global disaster, including the response to the psychological impact. Both the economic hardship and the continuous media coverage of alarming news have exacerbated this effect which also includes increased domestic violence.

Aim

To address this important aspect of disaster management and provide recommendations on how to mitigate these effects.

Methods

This is a narrative review written by three experts in community medicine, disaster medicine and psychiatry reflecting the interdisciplinary approach in managing disasters. Selected important papers, personal published papers, PUBMED articles and media news related to the disaster management of the psychological effects of COVID-19 pandemic were collected over the last year, critically appraised and used in writing this manuscript.

Results

The COVID-19 pandemic causes majoremotional distress. Lack of effective treatments and availability of the current vaccines for this virus increases the fear of being infected and infecting others. Negative emotions are common and are related to adjustment but may progress in the long term to anxiety, depression, and post-traumatic stress syndrome. The COVID-19 pandemic has a major impact onmental health. The most common distress reactions include anxiety, insomnia, perception of insecurity, anger, fear of illness, and risky behaviors. Patients having mental disorders are vulnerable during the pandemic because of (1) somatic vulnerability, (2) cognitive and behavioral vulnerability, (3) psychosocial vulnerability, and (4) disruption to psychiatric care. Psychiatric wards, which are commonly separate from main hospitals, should be included in the disaster management plans. Acute care physicians carry the psychological and ethical impact of difficult triage decisions when ending the support of some patients to save others. A combination of fear and guilt may overcome normal human tolerance levels in vulnerable health workers. The moral injuries can be carried for a long time.

Conclusions

Addressing the psychological effects is an essential component of disaster management of infectious pandemics. This should be implemented through the whole spectrum of disaster management including preparedness, mitigation, response, and recovery.
Efficacy and safety of Levamisole treatment in clinical presentations of non-hospitalized patients with COVID-19: a double-blind, randomized, controlled trial
Authors: Roostaei Firozabad Amirreza , Meybodi Zohreh Akhoundi , Mousavinasab Seyed Ruhollah , Sahebnasagh Adeleh , Jelodar Mohsen Gholinataj , Karimzadeh Iman , Habtemariam Solomon , Saghafi Fatemeh
Published: March 2021

Background

Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease.

Methods

This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care.

Results

With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05).

Conclusion

The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance.

Trial registration

The trial was registered as IRCT20190810044500N7 (19/09/2020).
Winter is coming: the future of cryopreservation
Authors: Bojic Sanja , Murray Alex , Bentley Barry L. , Spindler Ralf , Pawlik Piotr , Cordeiro José L. , Bauer Roman , de Magalhães João Pedro
Published: March 2021

The preservative effects of low temperature on biological materials have been long recognised, and cryopreservation is now widely used in biomedicine, including in organ transplantation, regenerative medicine and drug discovery. The lack of organs for transplantation constitutes a major medical challenge, stemming largely from the inability to preserve donated organs until a suitable recipient is found. Here, we review the latest cryopreservation methods and applications. We describe the main challenges—scaling up to large volumes and complex tissues, preventing ice formation and mitigating cryoprotectant toxicity—discuss advantages and disadvantages of current methods and outline prospects for the future of the field.
Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling
Authors: Naia Luana , Pinho Catarina M. , Dentoni Giacomo , Liu Jianping , Leal Nuno Santos , Ferreira Duarte M. S. , Schreiner Bernadette , Filadi Riccardo , Fão Lígia , Connolly Niamh M. C. , Forsell Pontus , Nordvall Gunnar , Shimozawa Makoto , Greotti Elisa , Basso Emy , Theurey Pierre , Gioran Anna , Joselin Alvin , Arsenian-Henriksson Marie , Nilsson Per , Rego A. Cristina , Ruas Jorge L. , Park David , Bano Daniele , Pizzo Paola , Prehn Jochen H. M. , Ankarcrona Maria
Published: March 2021

Background

Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential.

Results

Using differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. Further validation in neuronal models indicated that luteolin increased mitochondrial respiration in primary neurons, despite not affecting mitochondrial mass, structure, or mitochondria-derived reactive oxygen species. However, we found that luteolin increased contacts between mitochondria and endoplasmic reticulum (ER), contributing to increased mitochondrial calcium (Ca2+) and Ca2+-dependent pyruvate dehydrogenase activity. This signaling pathway likely contributed to the observed effect of luteolin on enhanced mitochondrial complexes I and II activities. Importantly, we observed that increased mitochondrial functions were dependent on the activity of ER Ca2+-releasing channels inositol 1,4,5-trisphosphate receptors (IP3Rs) both in neurons and in isolated synaptosomes. Additionally, luteolin treatment improved mitochondrial and locomotory activities in primary neurons and Caenorhabditis elegans expressing an expanded polyglutamine tract of the huntingtin protein.

Conclusion

We provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases.
Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension
Authors: Naguib Yahya M. , Samaka Rehab M. , Rizk Mohamed S. , Ameen Omnia , Motawea Shaimaa M.
Published: March 2021

Background

The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model.

Methods

Thirty male Wistar rats weighing 150–200 g were equally divided into: 1—Control group (fed normal laboratory diet for 24 weeks), 2—Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3—Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies.

Results

High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions.

Conclusion

Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.
Delivery of cancer therapies by synthetic and bio-inspired nanovectors
Authors: Briolay Tina , Petithomme Tacien , Fouet Morgane , Nguyen-Pham Nelly , Blanquart Christophe , Boisgerault Nicolas
Published: March 2021

Background

As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety.

Main

Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of ‘smart’ drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and micro-organism-derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy.

Conclusion

This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting “type” for efficient and specific delivery of diverse anticancer therapies.
Microglia activated by microbial neuraminidase contributes to ependymal cell death
Authors: Fernández-Arjona María del Mar , León-Rodríguez Ana , López-Ávalos María Dolores , Grondona Jesús M.
Published: March 2021

The administration of microbial neuraminidase into the brain ventricular cavities of rodents represents a model of acute aseptic neuroinflammation. Ependymal cell death and hydrocephalus are unique features of this model. Here we demonstrate that activated microglia participates in ependymal cell death. Co-cultures of pure microglia with ependymal cells (both obtained from rats) were performed, and neuraminidase or lipopolysaccharide were used to activate microglia. Ependymal cell viability was unaltered in the absence of microglia or inflammatory stimulus (neuraminidase or lipopolysaccharide). The constitutive expression by ependymal cells of receptors for cytokines released by activated microglia, such as IL-1β, was demonstrated by qPCR. Besides, neuraminidase induced the overexpression of both receptors in ventricular wall explants. Finally, ependymal viability was evaluated in the presence of functional blocking antibodies against IL-1β and TNFα. In the co-culture setting, an IL-1β blocking antibody prevented ependymal cell death, while TNFα antibody did not. These results suggest that activated microglia are involved in the ependymal damage that occurs after the administration of neuraminidase in the ventricular cavities, and points to IL-1β as possible mediator of such effect. The relevance of these results lies in the fact that brain infections caused by neuraminidase-bearing pathogens are frequently associated to ependymal death and hydrocephalus.