bluuebunny/crossref_metadata_2025 huggingface dataset:
Teachers’ strategies of everyday diplomacy in peace education: A case study of the “infrapolitics” of peacebuilding in Greek-Cypriot schools
Authors: Zembylas Michalinos , Loukaides Loizos
Published: February 2021

The aim of the article is to describe and analyze the strategies used by teachers in their everyday encounters with those who express concerns towards peace education—parents, colleagues, head teachers, and students. The analysis uses a theoretical framework that builds upon critical peace education and brings into conversation the notions of “everyday peace” and “everyday diplomacy.” The data are drawn from a qualitative case study based on interviews with 25 Greek-Cypriot teachers participating in a peace education intervention. The findings show that everyday diplomatic strategies invented by teachers help create conditions under which this peace education intervention, as a form of everyday peace, can take place, although it is not clear to what extent these strategies challenge the long-term nature of concerns. The implications of the study highlight the need that teachers and policymakers engage with concerns towards peace education in productive, sensitive and strategic ways.
Inclusive education in the diversifying environments of Finland, Iceland and the Netherlands: A multilingual systematic review
Authors: Wolff Charlotte E. , Huilla Heidi , Tzaninis Yannis , Magnúsdóttir Berglind Rós , Lappalainen Sirpa , Paulle Bowen , Seppänen Piia , Kosunen Sonja
Published: February 2021

This review investigates how the scholarly fields, themes and concepts of ‘inclusive education’ are applied in the research and educational contexts of Finland, Iceland and the Netherlands. It identifies and outlines which thematic areas of research and sub-fields of study are referenced in each country by applying a systematic, multilingual approach. We reviewed literature in the local languages of each of these countries over the past decade, from 2007 to 2018, paying particular attention to (a) micro-level, in-depth, classroom interactions; (b) social and political contexts; and (c) social categories. Results of this review emphasise that across all three countries (a) there are similar conceptualisations of inclusive education dominated by categories of disability and special needs, and (b) there is a similar lack of attention to modes of exclusion based on social class, gender, ethnicity and geography as well as to how these can be addressed by more advanced research on inclusive education in these local spheres.
The Practical Alternative to the p Value Is the Correctly Used p Value
Authors: Lakens Daniël
Published: February 2021

Because of the strong overreliance on p values in the scientific literature, some researchers have argued that we need to move beyond p values and embrace practical alternatives. When proposing alternatives to p values statisticians often commit the “statistician’s fallacy,” whereby they declare which statistic researchers really “want to know.” Instead of telling researchers what they want to know, statisticians should teach researchers which questions they can ask. In some situations, the answer to the question they are most interested in will be the p value. As long as null-hypothesis tests have been criticized, researchers have suggested including minimum-effect tests and equivalence tests in our statistical toolbox, and these tests have the potential to greatly improve the questions researchers ask. If anyone believes p values affect the quality of scientific research, preventing the misinterpretation of p values by developing better evidence-based education and user-centered statistical software should be a top priority. Polarized discussions about which statistic scientists should use has distracted us from examining more important questions, such as asking researchers what they want to know when they conduct scientific research. Before we can improve our statistical inferences, we need to improve our statistical questions.
Neurodiversity and the Social Ecology of Mental Functions
Authors: Chapman Robert
Published: February 2021

In psychiatry, mental dysfunction is typically framed in relation to models that seek to be continuous with physiology or evolutionary biology and that compare individual fitness to a broader functional norm. Proponents of the neurodiversity movement, however, challenge the pathologization of minority cognitive styles and argue that we should reframe neurocognitive diversity as a normal and healthy manifestation of biodiversity. Neurodiversity proponents have thus far drawn on social-relational models of disability to challenge the medical model of disability, but they have not developed an alternative functional analysis to replace conceptions of neurological dysfunction or impairment. Here I clarify and defend the neurodiversity perspective by drawing on ecological functional models that take relational contributions to collectives, and group functioning, into account alongside individual functionality. Using the example of autism as well as recent developments in the study of cognitive diversity, I apply these models to human mental functioning and argue that what I call the ecological model has greater utility for research and practice than the leading psychiatric functional analyses of mental functioning.
Identifying and addressing nonrational processes in REB ethical decision-making
Authors: Nuttgens Simon
Published: February 2021

Ethical decision-making is inherent to the research ethics committee (REC) deliberation process. While ethical codes, regulations, and research standards are indispensable in guiding this process, decision-making is nonetheless susceptible to nonrational factors that can undermined the quality, consistency, and perceived fairness REC decisions. In this paper I identify biases and heuristics (i.e., nonrational factors) that are known to influence the reasoning processes among the general population and various professions alike. I suggest that such factors will inevitably arise within the REC review process. To help mitigate this potential, I propose an interventive questioning process that can be used by RECs to identify and minimize the influence of the nonrational factors most likely to impact REC judgment and decision-making.
Intravenous thrombolysis in stroke with admission NIHSS score 0 or 1
Authors: Sykora Marek , Krebs Stefan , Simader Florentina , Gattringer Thomas , Greisenegger Stefan , Ferrari Julia , Bernegger Alexandra , Posekany Alexandra , Lang Wilfried ,   on behalf of the Austrian Stroke Unit Registry Collaborators
Published: February 2021

Background

Up to 30% of stroke patients initially presenting with non-disabling or mild deficits may experience poor functional outcome. Despite, intravenous thrombolysis remains controversial in this subgroup of stroke patients due to its uncertain risk benefit ratio.

Aim

We aimed to analyze the real-world experience with intravenous thrombolysis in stroke patients presenting with very low NIHSS.

Methods

Data of stroke patients presenting with mild initial stroke severity (NIHSS 0–5) including vascular risk factors, stroke syndrome and etiology, early neurological deterioration, symptomatic intracerebral haemorrhage (sICH), and functional outcome by modified Rankin Scale were extracted from a large nationwide stroke registry and analysed. Patients were categorized and compared according to admission severity NIHSS 0–1 versus NIHSS 2–5 and intravenous thrombolysis use.

Results

Seven hundred and three (2%) of 35,113 patients presenting with NIHSS 0–1 and 6316 (13.9%) of 45,521 of patients presenting with NIHSS 2–5 underwent intravenous thrombolysis. In the NIHSS 0–1 group, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 8.84, CI 6.61–11.83), sICH (adjusted OR 9.32, CI 4.53–19.15) and lower rate of excellent outcome (mRS 0–1) at three months (adjusted OR 0.67, CI 0.5–0.9). In stroke patients with NIHSS 2–5, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 1.7, 1.47–1.98), sICH (adjusted OR 5.75, CI 4.45–7.45), and higher rate of excellent outcome (mRS 0–1) at three months (adjusted OR 1.21, CI 1.08–1.34).

Conclusions

Among patients with NIHSS 0–1, intravenous thrombolysis did not increase the likelihood of excellent outcome. Moreover, potential signals of harm were observed. Further research seems to be warranted.
Home-based, tailored intervention for reducing falls after stroke (FAST): Protocol for a randomized trial
Authors: Dean Catherine , Clemson Lindy , Ada Louise , Scrivener Katherine , Lannin Natasha , Mikolaizak Stefanie , Day Sally , Cusick Anne , Gardner Benjamin , Heller Gillian , Isbel Stephen , Jones Taryn , Mumford Virginia , Preston Elisabeth
Published: February 2021

Rationale

People with stroke experience falls at more than twice the rate of the general older population resulting in high fall-related injuries. However, there are currently no effective interventions that prevent falls after stroke.

Aims

To determine the effect and cost-benefit of an innovative, home-based, tailored intervention to reduce falls after stroke.

Sample size estimate

A total of 370 participants will be recruited in order to be able to detect a clinically important between-group difference of a 30% lower rate of falls with 80% power at a two-tailed significance level of 0.05.

Methods and design

Falls after stroke trial (FAST) is a multistate, Phase III randomized trial with concealed allocation, blinded assessment, and intention-to-treat analysis. Ambulatory stroke survivors within five years of stroke who have been discharged from formal rehabilitation to the community and who have no significant language impairment will be randomly allocated to receive habit-forming exercise, home safety, and community mobility training or usual care.

Study outcomes

The primary outcome is the rate of falls over the previous 12 months. Secondary outcomes are the risk of falling (proportion of fallers), community participation, self-efficacy, balance, mobility, physical activity, depression, and health-related quality of life. Health care utilization will be collected retrospectively at baseline and prospectively to 6 and 12 months.

Discussion

The results of FAST are anticipated to directly influence intervention for stroke survivors in the community. Trial Registration: ANZCTR 12619001114134
The undervalued set piece: Analysis of soccer throw-ins during the English Premier League 2018–2019 season
Authors: Stone Joseph Antony , Smith Adam , Barry Anthony
Published: February 2021

Set pieces in soccer (i.e., free kicks and corners) have been examined in detail and are a common focus for coaches during training and performance preparation. However, limited evidence is available on the impact of throw-ins on soccer performance and if coaches should dedicate time in training towards this specific set piece. Therefore, this research aimed to firstly examine if throw-in performance is linked with soccer performance, and secondly the effect throw-in direction and length has on first contact success rate, possession retention, mean time in possession and shot creation. 16,154 throw-ins from 380 English Premier League matches during the 2018–2019 season were analysed. Higher final league position was correlated to increased throw-in first contact success and possession retention. 83% of throw-in’s resulted in a successful first contact, 54% resulted in possession being retained and 8.8% of throw-ins led to a shot at goal from the possession achieved after a successful first contact. Throw-in’s which went backwards or laterally in direction resulted in increased first contact success, retaining of possession, and shot creation. The least efficient throw-in was forwards and long, which resulted in both reduced first contact success and possession retention. Findings highlight, that throwing the ball laterally or backwards should be a focus for coaches and players during attacking training. In contrast, a team’s defensive strategy should reduce the opportunities to throw backwards or laterally with a higher press and look to force a long forward throw-in, therefore, increasing the likelihood of winning possession and counter attacking.
An exploration of the landscape of fundamental movement skills and strength development in UK professional football academies
Authors: Smothers Neil , Cropley Brendan , Lloyd Rhodri , Oliver Jon
Published: February 2021

The purpose of this study was to investigate the landscape of Fundamental Movement Skills (FMS) and strength development in professional football (soccer) academies in the UK. To achieve this, we interviewed 16 participants, whose primary responsibility was the physical development of youth players from a variety of Elite Player Performance Plan (EPPP) categorised academies. Following abductive analysis, we identified that whilst all participants acknowledged the importance of FMS and strength development for young football players, there was variance across EPPP categories relating to: (a) the time dedicated to developing FMS and strength; (b) the number, level of qualification, and utilisation of staff; and (c) the integration of the evidence informed practice into programme design and delivery. Although the key foci of academy strength and conditioning programmes generally prioritised injury reduction, performance improvement, and building a physical base for future development, the methods used to achieve these outcomes were varied. Finally, participants reported how relationships between support staff and technical coaching staff had a direct impact on the implementation of FMS and strength programmes. We have provided rich insights into a range of factors that may facilitate or hinder FMS and strength development within youth football players and thus helped to advance understanding of the practical implications of focusing on these key skills within athlete development programmes.
Factors associated with coach–athlete conversations about mental health in intercollegiate sport
Authors: Murphy Jessica , Sullivan Philip
Published: February 2021

Increasing conversation about mental health is one way to decrease stigma and prevent/treat maladaptive processes within the context of sport. Due to their proximity and influence over athletes, coaches can increase conversation and change team culture. The objective of this study was to apply the Theory of Planned Behavior (TPB) to explore the factors associated with coach-athlete conversation about mental health. A total of 136 Canadian coaches completed a demographic questionnaire as well as a TPB-based survey measuring Attitudes, Perceived Behavioral Control (PBC), Social Norms and Intention. Intention was measured as Role perception, if a coach believed it was their role to be involved in athlete mental health. Behavior was measured as talking with an athlete(s) about mental health. Approximately 68% of coaches had spoken to athletes about mental health in the last season. The linear regression model predicted a significant amount (42.7%) of the variance in Intention ( p < .05) from the three TPB constructs. Logistic regression found a significant interaction effect of PBC and Intention on Behavior ( p < .01). Measured TPB construct scores were influenced by previous mental health training, personal experience with mental illness, age group and the act of talking ( p < .05). Although a promising amount of coaches spoke to athletes about mental health, improvement is still possible. Mental health training should continue to be promoted to all members of the athletic community. As attitude scores were generally positive, this training should potentially focus more on improving capabilities and social norms.
The orthopaedic experience of COVID-19: A literature review
Authors: Al-kulabi Ali , Mansour Mohamed A , Thahir Azeem
Published: February 2021

This literature review aims to provide an account of the changes to orthopaedics in the era of COVID-19. Herein, the authors explored the use of telemedicine in orthopaedics as well as changes in surgical protocols, screening methods, work priorities and orthopaedic education. There was increased utilisation of telemedicine in orthopaedic training and outpatient cases as a means to provide continuity in education and care. The need to implement social distancing measures, coupled with the reduced availability of staff, has dictated that the practice of orthopaedics shifts to focus on acute care whilst redistributing resources to front-line specialities. This was facilitated by the cancellation of electives and the reduction of outpatient clinics. Thus, it is demonstrated that major changes have been implemented in many aspects of orthopaedic practice in order to address the challenges of the COVID-19 pandemic.
Telemedicine in clinical gastroenterology practice: what do patients prefer?
Authors: Lahat Adi , Shatz Zina
Published: February 2021

Background:

The Coronavirus Disease 2019 pandemic has forced major changes on healthcare systems. Maintaining regular patients’ surveillance became a major challenge. Telemedicine has been promoted as an economic and effective way for long distance patient care. Our aim was to study patients’ acceptance and perspectives on telemedicine.

Methods:

Patients scheduled for clinic appointments were offered telemedicine. Those who agreed were asked to fill in a questionnaire assessing their satisfaction with the medical consultation. Patients’ demographic characteristics and answers were collected and reviewed.

Results:

Out of 358 patients approached 71 agreed to use telemedicine. Of them, 59 completed the questionnaire and were included in the study. All patients’ basic demographic data were collected. Patients’ included in the study mean age was: 43 ± 16.3 years, 35 (59.3%) women. Patients who chose not to use telemedicine were significantly older, mean age: 61 ± 15.2 years ( p = 0.036), 134 (46.7%) women. Most patients included (38; 64.4%) had inflammatory bowel disease (IBD). Most patients who chose not to use telemedicine were non-IBD patients (206, 72%). Fifty-one patients (86.4%) assessed their experience as ‘good’ or ‘excellent’. Satisfied patients had significantly less time under medical follow-up (3.7 versus 6.1 years, p = 0.028) and tended to be younger ( p = non-significant). Women were statistically significantly more satisfied than men (33 versus 18, p = 0.05). Advantages reported were ‘time saving’ (31.3%), accessibility (26.1%), availability (25%). The main disadvantage was absence of physical examination (70%).

Conclusions:

Telemedicine gained a high satisfaction rate among patients under regular medical surveillance. Most patients stated this that method is convenient, time saving and increases their compliance. Patients who agreed to telecare were younger, and tended to be of female gender and experiencing IBD. Further studies are needed to characterize specific barriers to telecare usage.
The value of anti-CarP and anti-PAD4 as markers of rheumatoid arthritis in ACPA/RF negative rheumatoid arthritis patients
Authors: Kolarz Bogdan , Ciesla Marek , Rosenthal Ann K. , Dryglewska Magdalena , Majdan Maria
Published: February 2021

Background:

Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs).

Methods:

A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies.

Results:

Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs ( rs = 0.39), RF and ACPAs, ( rs = 0.3) and RF and anti-CarP, ( rs = 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF.

Conclusion:

Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.
Capsaicin Acts Through Reducing P38 MAPK-Dependent Thymidylate Synthase Expression to Enhance 5-Fluorouracil-Induced Cytotoxicity in Human Lung Cancer Cells
Authors: Tung Chun-Liang , Chen Jyh-Cheng , Ko Jen-Chung , Liu Li-Ling , Chien Chin-Cheng , Huang I-Hsiang , Tsao Yong-Cing , Cheng Hsiang-Hung , Chen Tzu-Ying , Yen Ting-Chuan , Lin Yun-Wei
Published: February 2021

Capsaicin, an ingredient of green and red bell peppers, shows anticancer activity in several malignant cell lines. Thymidylate synthase (TS) is a well-validated anticancer drug target in non-small cell lung cancer (NSCLC) cells. However, whether capsaicin and 5-fluorouracil (5-FU) induce synergistic cytotoxicity in NSCLC cells by regulating TS expression is unclear. This study investigated the cytotoxicity of capsaicin and 5-FU co-treatment on two hoursuman lung adenocarcinoma cell lines, H520 and H1703, and the underlying mechanisms. Capsaicin decreased TS expression in a p38 mitogen-activated protein kinase (MAPK) inactivation–dependent manner in H520 and H1703 cells. Enhancement of p38 MAPK activity by transfection with constitutive active mitogen-activated protein kinase kinase six vectors increased TS expression and cell survival. In addition, capsaicin and 5-FU co-treatment enhanced synergistic cytotoxicity and inhibited cell growth associated with TS downregulation and p38 MAPK inactivation in H520 and H1703 cells. Capsaicin and 5-FU co-treatment did not affect the cellular content of capsaicin. These results show that capsaicin may be combined with 5-FU to treat NSCLC.
Vertical and Horizontal Hop Performance: Contributions of the Hip, Knee, and Ankle
Authors: Kotsifaki Argyro , Korakakis Vasileios , Graham-Smith Philip , Sideris Vasileios , Whiteley Rod
Published: February 2021

Background:

Single-leg vertical and horizontal hop tests are commonly used to assess performance of healthy athletes and as a measure of progress during rehabilitation from knee injury. It is unclear if they measure similar aspects of leg function, as the relative joint contributions of the hip, knee, and ankle joints during propulsion and landing are unknown.

Hypothesis:

The proportion of work done by the hip, knee, and ankle will not be the same for these 2 jump types and will vary for propulsive and landing phases.

Study Design:

Cross-sectional cohort study.

Level of Evidence:

Level 3.

Methods:

Twenty physically active participants completed instrumented single-leg hop analysis in both vertical and horizontal directions. Joint peak power, work generated or absorbed, and percentage contribution of each joint during propulsive and landing phases were compared between tasks using paired t tests.

Results:

Vertical hop was performed with roughly similar contributions of the hip, knee, and ankle for both propulsion (31%, 34%, 35%, respectively) and landing (29%, 34%, 37%, respectively). Horizontal hop distance was mostly (87%) determined by the hip and ankle (44% and 43%), but landing was mostly (65%) performed by the knee with lesser contribution from the hip and ankle (24% and 11%). Propulsive phase showed a proximal-to-distal temporal sequence for both hop types, but landing was more complex.

Conclusion:

Performance during vertical and horizontal hops (jump height and jump distance, respectively) measures different aspects of hip, knee, and ankle function during the propulsive and landing phases.

Clinical Relevance:

Assessment of knee joint function during rehabilitation should not be done using a horizontal hop. The knee contributes about a third to vertical hop height, but only about an eighth to horizontal hop distance. Practitioners carrying out performance testing using either vertical or horizontal hops should be mindful of the relative contributions for meaningful training inferences to be derived.
Return to Play After Symptomatic Lumbar Disc Herniation in Elite Athletes: A Systematic Review and Meta-analysis of Operative Versus Nonoperative Treatment
Authors: Sedrak Phelopater , Shahbaz Mustafa , Gohal Chetan , Madden Kim , Aleem Ilyas , Khan Moin
Published: February 2021

Context:

The prevalence of symptomatic lumbar disc herniation (LDH) in athletes can be as high as 75%. For elite athletes diagnosed with LDH, return to play (RTP) is a major concern, and thus comparing surgical with nonoperative care is essential to guide practitioners and athletes, not just in terms of recovery rates but also speed of recovery.

Objective:

The purpose of this systematic review is to provide an update on RTP outcomes for elite athletes after lumbar discectomy versus nonoperative treatment of LDHs.

Data Sources:

A search of the literature was conducted using 3 online databases (MEDLINE, EMBASE, and PubMed) to identify pertinent studies.

Study Selection:

Yielded studies were screened according to the inclusion criteria.

Study Design:

Systematic review with meta-analysis.

Level of Evidence:

Level 4.

Data Extraction:

Relevant data were extracted. A meta-analysis was performed comparing RTP rate for all comparative studies.

Results:

Twenty studies met the inclusion criteria and were included in this review. Overall, 663 out of 799 patients (83.0%) returned to play in the surgical group and 251 out of 308 patients (81.5%) returned to play in the nonoperative group. No statistically significant difference for RTP rate was found (odds ratio, 1.39; 95% CI, 0.58-3.34; P = 0.46; I2, 71%). The mean time to RTP for patients undergoing lumbar discectomy was 5.19 months (range 1.00-8.70 months), and 4.11 months (range 3.60-5.70 months) for those treated conservatively.

Conclusion:

There was no significant difference in RTP rate between athletes treated with operative or nonoperative management of LDHs, nor did operative management have a faster time to RTP. Athletes should consider the lack of difference in RTP rate in addition to the potential risks associated with spinal surgery when choosing a treatment option. Future randomized controlled trials are needed on this topic to allow for high-powered conclusions.
Association of Air Pollutant Exposure and Sinonasal Histopathology Findings in Chronic Rhinosinusitis
Authors: Patel Tirth R. , Tajudeen Bobby A. , Brown Hannah , Gattuso Paolo , LoSavio Phillip , Papagiannopoulos Peter , Batra Pete S. , Mahdavinia Mahboobeh
Published: February 2021

Background

Ambient air pollution is well known to cause inflammatory change in respiratory epithelium and is associated with exacerbations of inflammatory conditions such as asthma and chronic obstructive pulmonary disease. However, limited work has been done on the impact of air pollution on pathogenesis of chronic rhinosinusitis and there are no reports in the literature of how pollutant exposure may impact sinonasal histopathology in patients with chronic rhinosinusitis.

Objective

This study aims to identify associations between certain histopathologic characteristics seen in sinus tissue of patients with chronic rhinosinusitis (CRS) and levels of particulate air pollution (PM2.5) and ground-level ozone in their place of residence.

Methods

A structured histopathology report was created to characterize the tissues of CRS patients undergoing sinus surgery. An estimate for each patient’s exposure to air pollutants including small particulate matter (PM2.5) and ground-level ozone was obtained using the Environmental Protection Agency’s (EPA) Environmental Justice Screening and Mapping Tool (EJSCREEN). Mean pollutant exposures for patients whose tissues exhibited varying histopathologic features were compared using logistic regression models.

Results

Data from 291 CRS patients were analyzed. Higher degree of inflammation was significantly associated with increased ozone exposure (p = 0.031). Amongst the patients with CRSwNP (n=131), presence of eosinophilic aggregates (p = 0.018) and Charcot-Leyden crystals (p = 0.036) was associated with increased ozone exposure.

Conclusion

Exposure to ambient air pollutants may contribute to pathogenesis of CRS. Increasing ozone exposure was linked to both higher tissue inflammation and presence of eosinophilic aggregates and Charcot-Leyden crystals in CRSwNP patients.
Sirt5 Deficiency Causes Posttranslational Protein Malonylation and Dysregulated Cellular Metabolism in Chondrocytes Under Obesity Conditions
Authors: Zhu Shouan , Batushansky Albert , Jopkiewicz Anita , Makosa Dawid , Humphries Kenneth M. , Van Remmen Holly , Griffin Timothy M.
Published: February 2021

Objective

Obesity accelerates the development of osteoarthritis (OA) during aging and is associated with altered chondrocyte cellular metabolism. Protein lysine malonylation (MaK) is a posttranslational modification (PTM) that has been shown to play an important role during aging and obesity. The objective of this study was to investigate the role of sirtuin 5 (Sirt5) in regulating MaK and cellular metabolism in chondrocytes under obesity-related conditions.

Methods

MaK and SIRT5 were immunostained in knee articular cartilage of obese db/db mice and different aged C57BL6 mice with or without destabilization of the medial meniscus surgery to induce OA. Primary chondrocytes were isolated from 7-day-old WT and Sirt5−/− mice and treated with varying concentrations of glucose and insulin to mimic obesity. Sirt5-dependent effects on MaK and metabolism were evaluated by western blot, Seahorse Respirometry, and gas/chromatography-mass/spectrometry (GC-MS) metabolic profiling.

Results

MaK was significantly increased in cartilage of db/db mice and in chondrocytes treated with high concentrations of glucose and insulin (GluhiInshi). Sirt5 was increased in an age-dependent manner following joint injury, and Sirt5 deficient primary chondrocytes had increased MaK, decreased glycolysis rate, and reduced basal mitochondrial respiration. GC-MS identified 41 metabolites. Sirt5 deficiency altered 13 distinct metabolites under basal conditions and 18 metabolites under GluhiInshi treatment. Pathway analysis identified a wide range of Sirt5-dependent altered metabolic pathways that include amino acid metabolism, TCA cycle, and glycolysis.

Conclusion

This study provides the first evidence that Sirt5 broadly regulates chondrocyte metabolism. We observed changes in SIRT5 and MaK levels in cartilage with obesity and joint injury, suggesting that the Sirt5-MaK pathway may contribute to altered chondrocyte metabolism that occurs during OA development.
T2 mapping of the peritumoral infiltration zone of glioblastoma and anaplastic astrocytoma
Authors: Auer Timo Alexander , Kern Maike , Fehrenbach Uli , Tanyldizi Yasemin , Misch Martin , Wiener Edzard
Published: February 2021

Purpose

To characterise peritumoral zones in glioblastoma and anaplastic astrocytoma evaluating T2 values using T2 mapping sequences.

Materials and methods

In this study, 41 patients with histopathologically confirmed World Health Organization high grade gliomas and preoperative magnetic resonance imaging examinations were retrospectively identified and enrolled. High grade gliomas were differentiated: (a) by grade, glioblastoma versus anaplastic astrocytoma; and (b) by isocitrate dehydrogenase mutational state, mutated versus wildtype. T2 map relaxation times were assessed from the tumour centre to peritumoral zones by means of a region of interest and calculated pixelwise by using a fit model.

Results

Significant differences between T2 values evaluated from the tumour centre to the peritumoral zone were found between glioblastoma and anaplastic astrocytoma, showing a higher decrease in signal intensity (T2 value) from tumour centre to periphery for glioblastoma ( P = 0.0049 – fit-model: glioblastoma –25.02± 19.89 (–54–10); anaplastic astrocytoma –5.57±22.94 (–51–47)). Similar results were found when the cohort was subdivided by their isocitrate dehydrogenase profile, showing an increased drawdown from tumour centre to periphery for wildtype in comparison to mutated isocitrate dehydrogenase ( P = 0.0430 – fit model: isocitrate dehydrogenase wildtype –10.35±16.20 (–51) – 0; isocitrate dehydrogenase mutated 12.14±21.24 (–15–47)). A strong statistical proof for both subgroup analyses ( P = 0.9987 – glioblastoma R2 0.93±0.08; anaplastic astrocytoma R2 0.94±0.15) was found.

Conclusion

Peritumoral T2 mapping relaxation time tissue behaviour of glioblastoma differs from anaplastic astrocytoma. Significant differences in T2 values, using T2 mapping relaxation time, were found between glioblastoma and anaplastic astrocytoma, capturing the tumour centre to the peritumoral zone. A similar curve progression from tumour centre to peritumoral zone was found for isocitrate dehydrogenase wildtype high grade gliomas in comparison to isocitrate dehydrogenase mutated high grade gliomas. This finding is in accordance with the biologically more aggressive behaviour of isocitrate dehydrogenase wildtype in comparison to isocitrate dehydrogenase mutated high grade gliomas. These results emphasize the potential of mapping techniques to reflect the tissue composition of high grade gliomas.
Venetoclax-containing regimens in acute myeloid leukemia
Authors: Aldoss Ibrahim , Pullarkat Vinod , Stein Anthony S.
Published: February 2021

Venetoclax in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) has demonstrated exceptional activity in elderly and unfit patients with newly diagnosed acute myeloid leukemia (AML). Notably, the safety profile of venetoclax-based induction regimens was favorable, with a low rate of early treatment-related mortality, even in frail study participants. Thus, the introduction of venetoclax has transformed the landscape of AML therapy in elderly patients. Given these promising results, venetoclax in combination with other agents is now being studied as a frontline therapy in younger patients with AML, as well as in relapsed/refractory AML patients. Here, we review clinical data for venetoclax-based therapy in AML, both from prospective as well as retrospective studies, and highlight ongoing novel studies of venetoclax-containing regimens and discuss future research directions.
Chinese traditional medicine (GuiZhi-ShaoYao-ZhiMu decoction) as an add-on medication to methotrexate for rheumatoid arthritis: a meta-analysis of randomized clinical trials
Authors: Feng Chenxi , Chen Rongrong , Wang Keer , Wen Chengping , Xu Zhenghao
Published: February 2021

Background:

GuiZhi-ShaoYao-ZhiMu decoction (GSZD), a traditional Chinese herbal medication, has been frequently used as an add-on medication to methotrexate (MTX) for rheumatoid arthritis (RA) treatment in China. This meta-analysis evaluated the efficacy and safety of adding GSZD to MTX for RA treatment.

Methods:

We performed a systematic search of PubMed, Web of Science, EMBASE, and the Cochrane Library (all databases) for English-language studies and WanFang, VIP, and CNKI for Chinese-language studies up to 28 July 2020. Data from selected studies, mainly the response rates and rate of adverse events (AEs), were extracted independently by two authors, and a random-effects model (Mantel–Haenszel method) was used for the meta-analysis.

Results:

A total of 14 randomized controlled trials and 1224 patients were included (623 patients in the GSZD + MTX group and 601 patients in the MTX group). For efficacy, the meta-analysis found that combining GSZD with MTX increased the effective rate [relative risk (RR) = 1.24, 95% confidence interval (CI): 1.18–1.30, based on 1069 patients], defined as >30% efficacy, American College of Rheumatology 20, or a decrease of disease activity score 28 >0.6. Adding GSZD reduced the swollen and tender joint counts, the duration of morning stiffness, the levels of C-reactive protein and rheumatoid factor, and erythrocyte sedimentation rate. The adjuvant therapeutic effect of GSZD was independent of the dose of MTX or the combined utilization of other drugs in both groups. For safety, adding GSZD was associated with a lower rate of total AEs (RR = 0.46, 95% CI: 0.26–0.83, based on 615 patients) and gastrointestinal tract AEs (RR = 0.46, 95% CI: 0.24–0.88, based on 537 patients).

Conclusion:

Combining GSZD with MTX may be a more efficacious and safer strategy for treating RA compared with MTX alone. Further large studies are warranted to investigate the long-term efficacy and safety of adding GSZD to MTX for RA treatment.
Primary aldosteronism subtyping in the setting of partially successful adrenal vein sampling
Authors: Lee Seung-Eun , Park Sung Woon , Choi Min Sun , Kim Gyuri , Yoo Jee Hee , Ahn Jiyeon , Jun Ji Eun , Park Hong Suk , Hyun Dongho , Cho Sung Ki , Ko Seong Eun , Kim Beom-Jun , Kim Jong Woo , Yoon Hyun-Ki , Koh Jung-Min , Lee Seung Hun , Kim Jae Hyeon
Published: February 2021

Background and aims:

Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side.

Methods:

Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden’s index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side.

Results:

Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. Scatterplot cutoffs of RIR <0.5 or >7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity.

Conclusion:

In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.
Systematic review of immunosuppressant guidelines in the COVID-19 pandemic
Authors: Barlow-Pay Fenella , Htut Thura Win , Khezrian Mina , Myint Phyo Kyaw
Published: February 2021

Aims:

Individuals taking immunosuppressants are at increased susceptibility to viral infections in general. However, due to the novel nature of the COVID-19, there is a lack of evidence about the specific risks of the disease in this patient group. This systematic review aims to summarize the current international clinical guidelines to highlight areas where research is needed through critical appraisal of the evidence base of these guidelines.

Methods:

We conducted a systematic review of clinical practice guidelines about the usage of immunosuppressants during the COVID-19 pandemic. Electronic databases including MEDLINE and the websites of relevant professional bodies were searched for English language guidelines that were published or updated between March 2020 and May 2020 in this area. We assessed the quality and consistency of guidelines. The evidence base underpinning these guidelines was critically appraised using GRADE criteria.

Results:

Twenty-three guidelines were included. Most guidelines ( n = 15, 65.2%) informed and updated evidence based on expert opinion. The methodological quality of the guidelines varied, ranging from ‘very low’ to ‘moderate’. Guidelines consistently recommended that high-risk patients, including those who are taking high doses of steroids for more than a month, or a combination of two or more immunosuppressants, should be shielding during the outbreak. Most guidelines stated that steroids usage should not be stopped abruptly and advised on individualized risk–benefit analysis considering the risk of the effect of COVID-19 infection and the relapse of the autoimmune condition in patients.

Discussion:

Clinical practice guidelines on taking immunosuppressants during the COVID-19 outbreak vary in quality. The level of evidence informing the available guidelines was generally low. Given the novel nature of COVID-19, the guidelines draw on existing knowledge and data, refer to the use of immunosuppressants and risks of serious infections of other aetiologies and have extrapolated these to form their evidence base.
Practice patterns of pulmonary hypertension secondary to left heart disease among pediatric pulmonary hypertension providers
Authors: Nawaytou Hythem , Fineman Jeffrey R. , Moledina Shahin , Ivy Dunbar , Abman Steven H. , Del Cerro Maria J.
Published: February 2021

Development of pulmonary hypertension (PH) in patients with left side heart disease (LHD) is a predictor of poor prognosis. The use of pulmonary vasodilators in PH associated with LHD (PH‐LHD) is controversial. In this study, we describe the practice patterns regarding the use of pulmonary vasodilators in PH‐LHD among a group of international pediatric PH specialists. A survey was distributed to the members of three pediatric PH networks: PPHNet, PVRI, and REHIPED. The survey queried participants on the rationale, indications, and contraindications of the use of pulmonary vasodilators in children with PH‐LHD. Forty‐seven PH specialists from 39 PH centers completed the survey. Participants included PH specialists from North America (57%), South America (15%), and Europe (19%). The majority of participants (74%) recommended the use of pulmonary vasodilators only in patients with combined pre‐capillary and post‐capillary pulmonary hypertension. Participants required the presence of clinical symptoms or signs of heart failure (68%) or right ventricular dysfunction by echocardiography (51%) in order to recommend pulmonary vasodilator therapy. There was no agreement regarding hemodynamic criteria used to recommend pulmonary vasodilators or the etiologies of LHD considered contraindications for using pulmonary vasodilators to manage PH‐LHD. Of the available PH‐targeted drugs, most participants preferred the use of phosphodiesterase‐5‐inhibitors for this indication. In conclusion, the practice of recommending pulmonary vasodilators in PH‐LHD is highly variable among international pediatric PH specialists. Most specialists of those surveyed (57% in North America) would consider the use of pulmonary vasodilators in PH‐LHD only if pre‐capillary pulmonary hypertension and right ventricular dysfunction are present.
The concept of rationality in introductory economics textbooks
Authors: Jones Martin K
Published: February 2021

The paper reviews major Economics textbooks used in the UK from the point of view of their use of rationality as a teaching tool. The textbooks vary widely in their explicit analysis of rationality from finding it important to totally ignoring it. When textbooks do use the concept as part of their analysis, the definitions vary considerably. In fact, there are some implicit uses of rationality in all textbooks although these are not always acknowledged. This complexity is reflected in the history of economic thought and modern economic analysis. The future use of rationality as a teaching tool is discussed in the context of current research in economics.

JEL Classification: A22
Family technoference: Exploring parent mobile device distraction from children’s perspectives
Authors: Meeus Anneleen , Coenen Lennert , Eggermont Steven , Beullens Kathleen
Published: February 2021

The goal of the present study is to understand how preadolescents’ perceptions of their parents’ mobile device distraction (“technoference”) are related to their global assessment of family satisfaction. Building on existing research, a model is established that investigates this association through three mediators: parent–child conflict; companionship; and perceived emotional support. Data from a cross-sectional survey ( n = 742, 9–13 years, 50.9% girls, mean age =10.85, standard deviation = 0.73) supported most of the associations specified in our model. First, our findings demonstrate that preadolescents who perceived higher amounts of parent technoference also rated the relationship with their parents significantly higher in conflict, and lower in terms of perceived companionship. Moreover, maternal mobile device distraction was significantly associated with less emotional support. All but one of the indirect associations were found to be statistically significant, thus revealing a number of pathways through which technoference is related to preadolescents’ assessments of family satisfaction.
A challenging case of COVID-19 infection presented with isolated acute abdominal pain: A case report and literature review
Authors: Altermanini Mohammad , Habib Mhd Baraa , Elzouki Abdel-Naser
Published: February 2021

COVID-19 is an infectious disease, which often presents with fever and respiratory symptoms. However, gastrointestinal symptoms have also been reported to occur in patients with COVID-19. Although abdominal pain was described in some reports of COVID-19, it was uncommon and often associated with other symptoms. We describe a challenging case of a COVID-19 patient who presented with severe isolated abdominal pain initially, then developed pneumonia symptoms which led to the diagnosis of COVID-19 thereafter.
Digital failure: Unbecoming the “good” data subject through entropic, fugitive, and queer data
Authors: Bridges Lauren E
Published: February 2021

This paper explores the political potential of digital failure as a refusal to work in service of today’s dataveillance society. Moving beyond criticisms of flawed digital systems, this paper traces the moments of digital failure that seek to break, rather than fix, existing systems. Instead, digital failure is characterized by pesky data that sneaks through the cracks of digital capitalism and dissipates into the unproductive; it supports run-away data prone to misidentifications by digital marketers, coders, and content moderators; and it celebrates data predisposed to “back-talk” with playful irreverence toward those that seek to bring order through normative categorization and moderation. I call these data entropic, fugitive, and queer and explore their mischievous practices through three case studies: the unaccountable data in identity resolution, public shaming of the ImageNet training data, and reading practices of sex worker and influencer, @Charlieshe. Together these case studies articulate the political potential of digital failure as a process of unbecoming the good data subject by pushing past the margins of legibility, knowability, and thinkability, to reveal what is made illegible, unknowable, and unthinkable to data’s seeing eye. As predictive analytics, automated decision-systems, and artificial intelligence take on increasingly central roles in public governance, digital failure reveals how data itself is a flawed concept prone to political abuse and social engineering to protect the interests of the powerful, while keeping those marginalized over-surveilled and underrepresented.