bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental investigation of the effect of tool material on the performance of AISI 4140 steel in the rotary near dry electrical discharge machining
Authors: Rajabinasab Fereydoon , Abedini Vahid , Hadad Mohammadjafar , Hajighorbani Ramezanali
Published: May 2020

This research conducts in three sections. The first section studies the effect of tool materials and gases on rotary workpiece electrical discharge machining. During the experiments, the effects of three kinds of tool materials (Cu, Cu-Cr, and Cu-Sn) and three types of industrial gases (air, argon, and CO2) on the material removal rate, tool wear rate, and workpiece surface roughness are investigated. The second is a comparison between rotary workpiece, rotary tool, and the fixed workpiece by choosing the appropriate tool material and gas in order to observe the effect of workpieces rotation on the process. Finally, another comparison has been done between wet electrical discharge machining and near dry electrical discharge machining of the fixed workpiece in order to study the effect of the dielectric. The results show the copper tool has the best performance compared with other tools. Scanning electron microscopy output shows the Cu-Sn tool creates shallow micro-cracks on the surface. Air and CO2 gases have the higher material removal rate in low current, but argon has better function than other gases in high current. In addition, a rotational speed causes an increase in material removal rate and tool wear rate and surface roughness decrease in near dry electrical discharge machining. The level of tool wear rate has decreased by 14% in the rotary workpiece compared with the rotary tool.
Microwave absorption performance enhancement using glass fiber-reinforced polymer nanocomposites containing dielectric fillers in X-band
Authors: Santhosi BVSRN , Ramji K , Rao NBR Mohan
Published: May 2020

Microwave absorption properties of radar absorbing structures in X-band frequency have been investigated using carbon-based dielectric filler materials. These structures are composed of E-glass/epoxy laminates filled with various wt% (0–2.5 with an increment of 0.5) of graphene and multiwalled carbon nanotubes individually. Composite fabrication has been done using high-pressure resin transfer molding (HPRTM). The pertinent electromagnetic (EM) parameters of composite structures are measured using the waveguide measurement technique in X-band. From the results, a single-layered polymer composite with 2.5% graphene contains better absorption than others. Among multilayered structures, the 11-layered composite structure has shown the best absorption performance (reflection loss (RL) = −21 dB) which is equal to 99.9% of incident EM radiation absorption in X-band. It is found that the single-layered structure has shown ineffective absorption performance compared to the multilayered structure under low weight concentrations. Moreover, a mathematical model to predict RL of different combinations of multilayered structures based on EM wave theory is proposed for the calculation of optimum layer combination for minimizing time and money. The predictions of the mathematical model are validated for the 11-layered structure using experimentation.
Tweet, Set, Match: Negotiating the Boundaries of Digital Technologies in Elite Tennis
Authors: Subramanian Vidya , Noel Marianne , Paquin Harmony
Published: May 2020

This article attempts to examine the highest tier of elite tennis through a technological lens in order to understand the several imbrications of tennis and technology in Grand Slam events. Using qualitative and quantitative methods, this article studies the version of tennis that exists today—replete with RFID chips, screen interfaces, more powerful racquets than ever before and the ubiquity of social media. As the relationship between players and fans, organisers and visitors, and even gameplay and umpiring have evolved to allow the use of several technologies, Grand Slam tennis has embraced the era of social media and technologically mediated sport. This article views this transformation through the lens of Science Technology and Society in order to better understand the influence that technologies have in shaping the relationships between spectators, players, matches, tournaments and indeed the sport itself.
Impact of Voluntary Disclosure on Valuation of Firms: Evidence from Indian Companies
Authors: Charumathi B. , Ramesh Latha
Published: May 2020

This article investigates the effect of voluntary corporate disclosures on the firm value from the market value perspective. Financial reporting includes disclosures as prescribed by regulators, but few companies go beyond mandatory requirements and provide additional information voluntarily. This study empirically tests the extent of such voluntary disclosures using Corporate Voluntary Disclosure Index containing 81 items of both financial and non-financial information and panel data regression to test the hypotheses. The sample for this study is the non-financial companies in the BSE 100 Index and the period is five financial years from 2010–2011 to 2014–2015. This study finds a positive association between voluntary disclosures and firm value as measured by Tobin’s Q. Especially the market gives a higher valuation for companies disclosing optional information on social and environmental, corporate governance and financial information. This finding has a significant implication for emerging economies like India and it supports various disclosure theories such as agency, stakeholders and positive accounting theories.
‘After all, I have to show that I’m not different’: Muslim women’s psychological coping strategies with dichotomous and dichotomising stereotypes
Authors: Hametner Katharina , Rodax Natalie , Steinicke Katharina , McQuarrie Jessica
Published: May 2020

More than ever, ‘the headscarf’ is a dominant trope in contemporary ‘Western’ discourses on migration. Within controversies on Muslim ‘others’, ethnicity and gender frequently interweave. In discussions about the Muslim woman, a problematic dichotomy frequently emerges: namely the representation of a Muslim woman who wears the headscarf and is seen as ‘oppressed’ or ‘traditional’. This is opposed to the position of a Muslim woman who does not wear the headscarf and is simultaneously considered a ‘self-determined’ or ‘modern’ Muslim woman. Against this backdrop, this contribution adopts a critical perspective on dichotomising discourses on Muslim women’s practices in relation to wearing the headscarf. In this article the authors examine narrative interviews with four Muslim women, focusing on their subjective experiences and psychological coping strategies with dichotomous and dichotomising stereotypes. An in-depth qualitative analysis shows that these women display a need to constantly justify and negotiate their own positions in relation to wearing the headscarf, regardless of whether the interviewed women actually wear a headscarf or not. Based on this, the authors identify different psychological coping strategies and discuss them critically in a wider framework that draws attention to existing social hierarchies.
Democracy and the global spread of progressive taxes
Authors: Seelkopf Laura , Lierse Hanna
Published: May 2020

The adoption of modern tax policies is crucial for social development. Taxes raise revenue, which allows governments to invest in public goods and social protection. At the same time, they can be highly redistributive and thus are complementary to social policies. Hence, the adoption of modern taxes is a critical step towards social development as it allows for the very financial foundation for investing in and increasing the well-being of individuals. But how can we explain the global spread of taxes around the world? While most countries nowadays have adopted similar tax instruments, the timing of legislation has varied widely. A common explanation is that democracies are more likely to adopt new and redistributive forms of taxes as they are more accountable to the poor. In this article, we shed light on the link between regime type and tax legislation based on a new historical and global dataset for up to 131 countries since the 19th century. Our findings show that whereas regime type has no influence on the introduction of regressive taxes, democratic countries are more likely to adopt progressive taxes.
Corruption Perceptions and Contentious Politics in Africa: How Different Types of Corruption Have Shaped Africa’s Third Wave of Protest
Authors: Lewis Jacob S
Published: May 2020

Does corruption increase general and anti-government protest? Scholarship has produced seemingly incompatible results, with some research demonstrating a strong connection between corruption and the onset of contentious politics and other research finding that heightened perceptions of corruption decrease activism. This article addresses this puzzle by examining how different types of corruption condition diverging contentious outcomes. Focusing on two highly salient forms of corruption in the African context—elite corruption and police corruption—this article argues that the different consequences, salience, and costs associated with these two forms help to condition whether citizens rise up or stay home. This argument is tested via two methods. First, it draws from a survey experiment conducted in five Nigerian states in 2017. The survey experiment tests whether exposure to different types of corruption affects willingness to join in protests. Second, it draws from statistical analysis of geo-located perceptions of corruption and protest across Africa, incorporating checks for both collinearity and endogeneity into the model. The statistical analysis examines whether heightened perceptions of corruption correlate with increased counts of general and anti-government protest. The results from both methods demonstrate that elite corruption is positively correlated with protest, whereas police corruption is not.
The Sociogenesis of Vincent van Gogh’s Fundamental Artistic Disposition
Authors: Atkinson Will
Published: May 2020

Vincent van Gogh is one of the most well-known and influential artists in the western tradition. A sociological analysis of his creative practice, therefore, not only illuminates particularly consequential interventions in the history of art, with its knock-on effects for cultural consumption, but affords an opportunity for deepening our understanding of cultural production per se. At stake, I argue, is a fundamental artistic disposition – in this case, an aesthetic orientation toward nature and sentiment – persisting through, if not underpinning, changes of style. This article reconstructs the myriad forces involved in the genesis of this disposition in van Gogh’s early years. It draws upon the conceptual tools of Pierre Bourdieu to do so, but goes beyond them by stressing the importance of familial heritage and ‘second order’ field effects in shaping the young van Gogh’s aesthetic sympathies, long before he briefly entered the French artistic field in his final year of life.
The contribution of epigenetics to the pathogenesis and gender dimorphism of systemic sclerosis: a comprehensive overview
Authors: Saveria Fioretto Bianca , Rosa Irene , Romano Eloisa , Wang Yukai , Guiducci Serena , Zhang Guohong , Manetti Mirko , Matucci-Cerinic Marco
Published: May 2020

Systemic sclerosis (SSc) is a life-threatening connective tissue disorder of unknown etiology characterized by widespread vascular injury and dysfunction, impaired angiogenesis, immune dysregulation and progressive fibrosis of the skin and internal organs. Over the past few years, a new trend of investigations is increasingly reporting aberrant epigenetic modifications in genes related to the pathogenesis of SSc, suggesting that, besides genetics, epigenetics may play a pivotal role in disease development and clinical manifestations. Like many other autoimmune diseases, SSc presents a striking female predominance, and even if the reason for this gender imbalance has yet to be completely understood, it appears that the X chromosome, which contains many gender and immune-related genes, could play a role in such gender-biased prevalence. Besides a short summary of the genetic background of SSc, in this review we provide a comprehensive overview of the most recent insights into the epigenetic modifications which underlie the pathophysiology of SSc. A particular focus is given to genetic variations in genes located on the X chromosome as well as to the main X-linked epigenetic modifications that can influence SSc susceptibility and clinical phenotype. On the basis of the most recent advances, there is realistic hope that integrating epigenetic data with genomic, transcriptomic, proteomic and metabolomic analyses may provide in the future a better picture of their functional implications in SSc, paving the right way for a better understanding of disease pathogenesis and the development of innovative therapeutic approaches.
Bispecific T-cell engaging antibodies in B-cell precursor acute lymphoblastic leukemias: focus on blinatumomab
Authors: Ribera Jose-Maria , Genescà Eulalia , Ribera Jordi
Published: May 2020

Bispecific T-cell engaging antibodies are constructs engineered to bind to two different antigens, one to a tumor-specific target and the other to CD3-positive T cells or natural killer (NK) cells. Blinatumomab engages CD19 and CD3, performing effective serial lysis. The clinical development program in acute lymphoblastic leukemia (ALL) includes clinical trials in relapsed or refractory (R/R) patients and in B-cell precursor (BCP) ALL patients with measurable residual disease. Several trials are currently being conducted in de novo BCP-ALL, either in induction, consolidation, or before or after hematopoietic stem cell transplant. Combination with other targeted therapies or with other immunotherapeutic approaches are also underway. Several strategies are aimed to optimize the use of blinatumomab either by overcoming the mechanisms of resistance (e.g. inhibition of PD-1/PD-L1) or by improvements in the route of application, among others.
Prevalence and determinants of the precursor stages of heart failure: results from the population-based STAAB cohort study
Authors: Morbach Caroline , Gelbrich Götz , Tiffe Theresa , Eichner Felizitas A , Christa Martin , Mattern Renate , Breunig Margret , Cejka Vladimir , Wagner Martin , Heuschmann Peter U , Störk Stefan ,   the STAAB consortium, Frantz S , Maack C , Ertl G , Fassnacht M , Wanner C , Leyh R , Volkmann J , Deckert J , Faller H , Jahns R
Published: May 2020

Aims

Prevention of heart failure relies on the early identification and control of risk factors. We aimed to identify the frequency and characteristics of individuals at risk of heart failure in the general population.

Methods and Results

We report cross-sectional data from the prospective Characteristics and Course of Heart Failure Stages A–B and Determinants of Progression (STAAB) cohort study investigating a representative sample of residents of Würzburg, Germany. Sampling was stratified 1:1 for sex and 10:27:27:27:10 for age groups of 30–39/40–49/50–59/60–69/70–79 years. Heart failure precursor stages were defined according to American College of Cardiology/American Heart Association: stage A (risk factors for heart failure), stage B (asymptomatic cardiac dysfunction). The main results were internally validated in the second half of the participants. The derivation sample comprised 2473 participants (51% women) with a distribution of 10%/28%/25%/27%/10% in respective age groups. Stages A and B were prevalent in 42% and 17% of subjects, respectively. Of stage B subjects, 31% had no risk factor qualifying for stage A (group ‘B-not-A’). Compared to individuals in stage B with A criteria, B-not-A were younger, more often women, and had left ventricular dilation as the predominant B qualifying criterion (all P < 0.001). These results were confirmed in the validation sample (n = 2492).

Conclusion

We identified a hitherto undescribed group of asymptomatic individuals with cardiac dysfunction predisposing to heart failure, who lacked established heart failure risk factors and therefore would have been missed by conventional primary prevention. Further studies need to replicate this finding in independent cohorts and characterise their genetic and -omic profile and the inception of clinically overt heart failure in subjects of group B-not-A.
Analysis of drug-induced interstitial lung disease using the Japanese Adverse Drug Event Report database
Authors: Matsumoto Kiyoka , Nakao Satoshi , Hasegawa Shiori , Matsui Toshinobu , Shimada Kazuyo , Mukai Ririka , Tanaka Mizuki , Uranishi Hiroaki , Nakamura Mitsuhiro
Published: May 2020

Objectives:

Drug-induced interstitial lung disease occurs when exposure to a drug causes inflammation and, eventually, fibrosis of the lung interstitium. Drug-induced interstitial lung disease is associated with substantial morbidity and mortality. The aim of this retrospective study was to obtain new information on the time-to-onset profiles of drug-induced interstitial lung disease by consideration of other associated clinical factors using the Japanese Adverse Drug Event Report database.

Methods:

We identified and analyzed reports of drug-induced interstitial lung disease between 2004 and 2018 from the Japanese Adverse Drug Event Report database. The reporting odds ratio and 95% confidence interval was used to detect the signal for each drug-induced interstitial lung disease incidence. We evaluated the time-to-onset profile of drug-induced interstitial lung disease and used the applied association rule mining technique to uncover undetected relationships, such as possible risk factors.

Results:

The reporting odds ratios (95% confidence intervals) of drug-induced interstitial lung disease due to temsirolimus, gefitinib, sho-saiko-to, sai-rei-to, osimertinib, amiodarone, alectinib, erlotinib, everolimus, and bicalutamide were 18.3 (15.6–21.3), 17.8 (16.5–19.2), 16.3 (11.8–22.4), 14.5 (11.7–18.2), 12.5 (10.7–14.7), 10.9 (9.9–11.9), 10.6 (8.1–13.9), 9.6 (8.8–10.4), 9.4 (8.7–10.0), and 9.2 (7.9–10.6), respectively. The median durations (day (interquartile range)) for drug-induced interstitial lung disease were as follows: amiodarone (123.0 (27.0–400.5)), methotrexate (145.5 (67.8–475.8)), fluorouracil (86.0 (35.5–181.3)), gemcitabine (53.0 (20.0–83.0)), paclitaxel (52.0 (28.5–77.5)), docetaxel (47.0 (18.8–78.3)), bleomycin (92.0 (38.0–130.5)), oxaliplatin (45.0 (11.0–180.0)), nivolumab (56.0 (21.0–135.0)), gefitinib (24.0 (11.0–55.0)), erlotinib (21.0 (9.0–49.0)), temsirolimus (38.0 (14.0–68.5)), everolimus (56.0 (35.0–90.0)), osimertinib (51.5 (21.0–84.8)), alectinib (78.5 (44.3–145.8)), bicalutamide (50.0 (28.0–147.0)), pegylated interferon-2α (140.0 (75.8–233.0)), sai-rei-to (35.0 (20.0–54.5)), and sho-saiko-to (33.0 (13.5–74.0)) days. Association rule mining suggested that the risk of drug-induced interstitial lung disease was increased by a combination of amiodarone or sho-saiko-to and aging.

Conclusion:

Our results showed that patients who receive gefitinib or erlotinib should be closely monitored for the development of drug-induced interstitial lung disease within a short duration (4 weeks). In addition, elderly people who receive amiodarone or sho-saiko-to should be carefully monitored for the development of drug-induced interstitial lung disease.
Ocrelizumab-induced alopecia areata—A series of five patients from Ontario, Canada: A case report
Authors: Chin Laura D , AbuHilal Mohn’d
Published: May 2020

Background:

Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen found on B-cells. It is indicated in the treatment of both relapsing–remitting multiple sclerosis and primary progressive multiple sclerosis.

Objective:

The aim of this study is to report and describe the characteristics of alopecia areata following treatment with ocrelizumab for multiple sclerosis.

Results:

Five patients were reported, two female and three male. Four of the five patients had alopecia areata of the scalp, one of the five having alopecia to the beard area. All patients responded well to conventional treatment with topical and intralesional corticosteroids and topical minoxidil foam. Ocrelizumab can be associated with the development of alopecia areata. Initiation of proper treatment may lead to quick improvement or resolution of this potentially reversible adverse effect.
Anti-Epcam Aptamer (Syl3c)-Functionalized Liposome for Targeted Delivery Of Doxorubicin: In Vitro And In Vivo Antitumor Studies in Mice Bearing C26 Colon Carcinoma
Authors: Mashreghi Mohammad , Zamani Parvin , Moosavian Seyedeh Alia , Jaafari Mahmoud Reza
Published: May 2020

In this study, we have surface-functionalized PEGylated-nanoliposomal doxorubicin (DOX) with anti-EpCAM (epithelial cell adhesion molecule) aptamer via post-insertion of anti-EpCAM aptamer-conjugated DSPE-mPEG2000 into Caelyx® (ED-lip). The size, charge, release profile, and cytotoxicity and cellular uptake of formulation were determined. The characterization of the ED-lip demonstrated the slightly increase in size and PDI along with the decrease in zeta potential which indicated that post-insertion efficiently done. The results of flow cytometry and fluorescent microscopy have shown that ED-lip enhanced the rate of cell uptake on C26 cell line compared to Caelyx®. The ED-lip also had more cytotoxic effects than Caelyx® which indicated the efficacy of anti-EpCAM aptamer as targeting ligand. The pharmacokinetic and tissue biodistribution of formulations in mice bearing C26 tumors demonstrated that ED-lip did not affect the distribution profile of DOX compared to Caelyx® in animal model. In addition, ED-lip effectively improved the tumor accumulation of DOX and promoted survival of animals compared to Caelyx®. These results suggest that the functionalization of Caelyx® with anti-EpCAM aptamer is promising in cancer treatment and merits further investigation.
Correction to: Improving inbound logistic planning for large-scale real-world routing problems: a novel ant-colony simulation-based optimization
Authors: Calabrò Giovanni , Torrisi Vincenza , Inturri Giuseppe , Ignaccolo Matteo
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Generation and evaluation of synthetic patient data
Authors: Goncalves Andre , Ray Priyadip , Soper Braden , Stevens Jennifer , Coyle Linda , Sales Ana Paula
Published: May 2020

Background

Machine learning (ML) has made a significant impact in medicine and cancer research; however, its impact in these areas has been undeniably slower and more limited than in other application domains. A major reason for this has been the lack of availability of patient data to the broader ML research community, in large part due to patient privacy protection concerns. High-quality, realistic, synthetic datasets can be leveraged to accelerate methodological developments in medicine. By and large, medical data is high dimensional and often categorical. These characteristics pose multiple modeling challenges.

Methods

In this paper, we evaluate three classes of synthetic data generation approaches; probabilistic models, classification-based imputation models, and generative adversarial neural networks. Metrics for evaluating the quality of the generated synthetic datasets are presented and discussed.

Results

While the results and discussions are broadly applicable to medical data, for demonstration purposes we generate synthetic datasets for cancer based on the publicly available cancer registry data from the Surveillance Epidemiology and End Results (SEER) program. Specifically, our cohort consists of breast, respiratory, and non-solid cancer cases diagnosed between 2010 and 2015, which includes over 360,000 individual cases.

Conclusions

We discuss the trade-offs of the different methods and metrics, providing guidance on considerations for the generation and usage of medical synthetic data.
Kidney disease progression and all-cause mortality across estimated glomerular filtration rate and albuminuria categories among patients with vs. without type 2 diabetes
Authors: Nichols Gregory A. , Déruaz-Luyet Anouk , Brodovicz Kimberly G. , Kimes Teresa M. , Rosales A. Gabriela , Hauske Sibylle J.
Published: May 2020

Background

Studies of progression of kidney dysfunction typically focus on renal replacement therapy or percentage decline in estimated glomerular filtration rate (eGFR) as outcomes. Our aim was to compare real-world patients with and without T2D to estimate progression from and to clinically defined categories of kidney disease and all-cause mortality.

Methods

This was an observational cohort study of 31,931 patients with and 33,201 age/sex matched patients without type 2 diabetes (T2D) who had a serum creatinine and urine albumin-to-creatinine ratio (UACR) or dipstick proteinuria (DP) values. We used the first available serum creatinine value between 2006 and 2012 to calculate baseline eGFR and categorized them and the corresponding UACR/DP values using the Kidney Disease Improving Global Outcomes (KDIGO) categories. To assess our primary outcomes, we extracted probabilities of eGFR progression or mortality from life-table analyses and conducted multivariable Cox regression analyses of relative risk adjusted for age, sex, race/ethnicity, smoking, ischemic heart disease, heart failure, and use of renal-angiotensin-aldosterone system inhibitors.

Results

Patterns of eGFR decline were comparable among patients with vs. without T2D with larger percentage declines at higher albuminuria levels across all eGFR categories. eGFR decline was generally larger among T2D patients, particularly in those with severely increased albuminuria. Across all CKD categories, risk of progression to the next higher category of eGFR was substantially increased with increasing albuminuria. For example, the risk was 23.5, 36.2, and 65.1% among T2D patients with eGFR 30–59 ml/min/1.73m2 and UACR < 30, 30–299, and > 300 mg/dL, respectively (p < 0.001). Other comparisons were similarly significant. Among patients with low eGFR and normal to mildly increased albuminuria, the relative risk was up to 8-fold greater for all-cause mortality compared with the non-CKD subgroup (eGFR> 60 ml/min/1.73m2 with normal to mildly increased albuminuria).

Conclusions

Presence of albuminuria was associated with accelerated eGFR decline independent of T2D. Risk for adverse outcomes was remarkably high among patients with CKD and normal to mildly increased albuminuria levels. Independent of T2D or albuminuria, a substantial risk for adverse outcomes exists for CKD patients in a routine care setting.
Longitudinal changes in health-related quality of life according to clinical course among patients with non-tuberculous mycobacterial pulmonary disease: a prospective cohort study
Authors: Kwak Nakwon , Kim Sung A , Choi Sun Mi , Lee Jinwoo , Lee Chang-Hoon , Yim Jae-Joon
Published: May 2020

Background

Improvement in health-related quality of life (HRQL) has been suggested as an alternative treatment goal of non-tuberculous mycobacterial pulmonary disease (NTM-PD). This study was performed to elucidate the longitudinal changes in HRQL using St. George’s Respiratory Questionnaire (SGRQ) among patients with NTM-PD according to their clinical course.

Methods

Patients with NTM-PD who participated in Seoul National University Hospital’s prospective NTM cohort were screened. Participants for whom the SGRQ score was estimated with the one-year interval for ≥ three times were included. The longitudinal trends of the SGRQ score were assessed. The impact of the clinical course on the change in the SGRQ score was elucidated using multilevel mixed-effects linear regression with a repeated-measures model.

Results

In total, 114 patients were analyzed. During the median 5-year observation period, 53 patients started anti-mycobacterial treatment and 61 patients were observed without treatment. Among the treated patients, 24 (45.2%) achieved microbiological cure. Patients who required treatment eventually had worsening SGRQ scores with time compared with patients who could be observed without treatment (P < 0.001). In cured patients, the SGRQ score decreased from 33.9 at baseline to 20.8 at 1 year post-treatment (P < 0.001), 21.3 at 2 years (P < 0.001), and 17.6 at 3 years (P < 0.001). The SGRQ scores also decreased for 2 years of treatment in patients with NTM-PD that could not be cured, although this decrease did not last for 3 years of treatment.

Conclusion

Worsening HRQL scores were associated with the initiation of treatment and, in turn, treatment improved HRQL scores of patients with NTM-PD.

Trial registration

This study was registered to the ClinicalTrials.gov (Identifier: NCT01616745 / registration date: June 12, 2012). The protocol was retrospectively registered.
Synovial sarcoma presenting as an intra-articular mass in a pediatric patient: a case report
Authors: Al-Mohrej Omar A. , Al-Jarallah Saeed A. , Al-Dakhil Allah Hamad H. , Pant Rajeev , Al-Zayed Zayed S.
Published: May 2020

Background

Synovial sarcoma (SS) is one of the reported sarcomas in the pediatric and adult populations. Delay in diagnosis and treatment is common in SS cases. SS may be excised before the correct diagnosis is made.

Case presentation

we present a case involving a 4-year-old boy who visited our service with complaints of left knee pain and limited knee flexion. Initially, the child was diagnosed with osteochondromatosis. Surgical excision was opted, and initial histopathological examination revealed a fibrous histiocytoma. The slide and blocks were then brought to the King Faisal Specialist Hospital Research Center (KFSH&RC) and histopathologic analysis has shown a well-circumscribed nodule in the synovium with a sub-synovial monomorphic spindle cell sarcoma, confirmed by fluorescence in situ hybridization (FISH).

Conclusions

Therefore, we strongly recommend considering all differential diagnoses for soft-tissue masses when planning surgical management.
Treating patients in a safe environment: a cross-sectional study of patient safety attitudes among doctors in the Gaza Strip, Palestine
Authors: Alfaqawi Maha , Böttcher Bettina , Abuowda Yousef , Alaloul Enas , Elnajjar Ibrahem , Elhout Somaya , Abu-El-Noor Mysoon , Abu-El-Noor Nasser
Published: May 2020

Background

Patient safety is important, as in increasingly complex medical systems, the potential for unintended harm to patients also increases. This study assessed the attitudes of doctors in the Gaza Strip towards patient safety and medical error. It also explored variables that impacted their attitudes.

Methods

Doctors, working for at least 6 months in one of the four major government hospitals of the Gaza Strip, were invited to complete a 28-item, self-administered Arabic version of the Attitudes to Patient Safety Questionnaire III (APSQ-III); which assessed patient safety attitudes over nine domains, independent of the workplace.

Results

A total of 150 doctors from four government hospitals participated in this study, representing 43.5% of all 345 doctors working in the four study hospitals at the time of the study. The mean age was 36.6 (±9.7) years. The majority (72.7%) were males, 28.7% worked in surgical, 26.7% in pediatric, 23.3% in medical, 16.7% in obstetrics and gynecology, and 4.7% in other departments. Most participants (62.0%) had never received patient safety training. The overall APSQ score was 3.58 ± 0.3 (of a maximum of 5). The highest score was received by the domain “Working hours as a cause of errors” (4.16) and the lowest score by “Importance of Patient Safety in the Curriculum” (3.25). Older doctors with more professional experience had significantly higher scores than younger doctors (p = 0.003), demonstrating more positive attitudes toward patient safety. Furthermore, patient safety attitudes became more positive with increasing years of experience in some domains. However, no significant impact on overall APSQ scores was found by workplace, specialty or whether the participants had received previous training about patient safety.

Conclusion

Doctors in Gaza demonstrated relatively positive patient safety attitudes in areas of “team functioning” and “working hours as a cause for error”, but neutral attitudes in understanding medical error or patient safety training within the curriculum. Patient safety concepts appear to be acquired by doctors via informal learning over time in the job. Inclusion of such concepts into formal postgraduate curricula might improve patient safety attitudes among younger and less experienced doctors, support behaviour change and improve patient outcomes.
Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis
Authors: Rønnow Sarah Rank , Dabbagh Rand Qais , Genovese Federica , Nanthakumar Carmel B. , Barrett Vikki J. , Good Robert B. , Brockbank Sarah , Cruwys Simon , Jessen Henrik , Sorensen Grith Lykke , Karsdal Morten Asser , Leeming Diana Julie , Sand Jannie Marie Bülow
Published: May 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a rapidly progressing disease with challenging management. To find novel effective therapies, better preclinical models are needed for the screening of anti-fibrotic compounds. Activated fibroblasts drive fibrogenesis and are the main cells responsible for the accumulation of extracellular matrix (ECM). Here, a prolonged Scar-in-a-Jar assay was combined with clinically validated biochemical markers of ECM synthesis to evaluate ECM synthesis over time. To validate the model as a drug screening tool for novel anti-fibrotic compounds, two approved compounds for IPF, nintedanib and pirfenidone, and a compound in development, omipalisib, were tested.

Methods

Primary human lung fibroblasts from healthy donors were cultured for 12 days in the presence of ficoll and were stimulated with TGF-β1 with or without treatment with an ALK5/TGF-β1 receptor kinase inhibitor (ALK5i), nintedanib, pirfenidone or the mTOR/PI3K inhibitor omipalisib (GSK2126458). Biomarkers of ECM synthesis were evaluated over time in cell supernatants using ELISAs to assess type I, III, IV, V and VI collagen formation (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6), fibronectin (FBN-C) deposition and α-smooth muscle actin (α-SMA) expression.

Results

TGF-β1 induced synthesis of PRO-C1, PRO-C6 and FBN-C as compared with unstimulated fibroblasts at all timepoints, while PRO-C3 and α-SMA levels were not elevated until day 8. Elevated biomarkers were reduced by suppressing TGF-β1 signalling with ALK5i. Nintedanib and omipalisib were able to reduce all biomarkers induced by TGF-β1 in a concentration dependent manner, while pirfenidone had no effect on α-SMA.

Conclusions

TGF-β1 stimulated synthesis of type I, III and VI collagen, fibronectin and α-SMA but not type IV or V collagen. Synthesis was increased over time, although temporal profiles differed, and was modulated pharmacologically by ALK5i, nintedanib, pirfenidone and omipalisib. This prolonged 12-day Scar-in-a-Jar assay utilising biochemical markers of ECM synthesis provides a useful screening tool for novel anti-fibrotic compounds.
Lost in the shadows: reflections on the dark side of co-production
Authors: Williams Oli , Sarre Sophie , Papoulias Stan Constantina , Knowles Sarah , Robert Glenn , Beresford Peter , Rose Diana , Carr Sarah , Kaur Meerat , Palmer Victoria J.
Published: May 2020

This article is a response to Oliver et al.’s Commentary ‘The dark side of coproduction: do the costs outweigh the benefits for health research?’ recently published inHealth Research Policy and Systems(2019, 17:33). The original commentary raises some important questions about how and when to co-produce health research, including highlighting various professional costs to those involved. However, we identify four related limitations in their inquiry, as follows: (1) the adoption of a problematically expansive definition of co-production that fails to acknowledge key features that distinguish co-production from broader collaboration; (2) a strong focus on technocratic rationales for co-producing research and a relative neglect of democratic rationales; (3) the transposition of legitimate concerns relating to collaboration between researchers and practitioners onto work with patients, service users and marginalised citizens; and (4) the presentation of badpracticeas an inherent flaw, or indeed ‘dark side’, of co-production without attending to the corrupting influence ofcontextualfactors within academic research that facilitate and even promote such malpractice. The Commentary’s limitations can be seen to reflect the contemporary use of the term ‘co-production’ more broadly. We describe this phenomenon as ‘cobiquity’ – an apparent appetite for participatory research practice and increased emphasis on partnership working, in combination with the related emergence of a plethora of ‘co’ words, promoting a conflation of meanings and practices from different collaborative traditions. This phenomenon commonly leads to a misappropriation of the term ‘co-production’. Our main motivation is to address this imprecision and the detrimental impact it has on efforts to enable co-production with marginalised and disadvantaged groups. We conclude that Oliver et al. stray too close to ‘the problem’ of ‘co-production’ seeing only the dark side rather than what is casting the shadows. We warn against such a restricted view and argue for greater scrutiny of the structural factors that largely explain academia’s failure to accommodate and promote the egalitarian and utilitarian potential of co-produced research.
The prevalence of depression among patients with tuberculosis: a systematic review and meta-analysis
Authors: Duko Bereket , Bedaso Asres , Ayano Getinet
Published: May 2020

Background

Evidence has shown that the prevalence of depression is much higher among patients with tuberculosis (TB) and this, in turn, may adversely impact compliance with anti-TB medications. Therefore, this systematic review and meta-analysis aimed to quantitatively summarize epidemiologic evidence on the prevalence of depression among patients with TB and formulate a recommendation for future clinical practice as well as research.

Methods

We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to conduct this review. We searched PubMed, EMBASE, SCOPUS and Psych INFO to identify relevant studies that investigated the prevalence of depression among TB patients. We also supplemented our electronic search with manual searching to include all pertinent studies in the analysis. We used a Comprehensive Meta-Analysis software version 3.0 (CMA 3.0) to conduct a meta-analysis. We conducted a subgroup and sensitivity analysis and Cochran’s Q- and the I2-statistics were used to assess heterogeneity. The evidence for the presence of publication bias was checked by using Egger’s test and visual inspection of the symmetry in funnel plots.

Results

We identified a total of 25 studies that included 4903 participants across seven countries. In our analysis, the pooled estimated prevalence of depression among TB patients was found to be 45.19% (95% CI 38.04–52.55). The prevalence was higher in MDR-TB 52.34% (95% CI 38.09–66.22) than non-MDR-TB 43.47% (95% CI 35.88–51.37) patients. We also found that the pooled prevalence of depression was higher among females 51.54% (95% CI 40.34–62.60) when compared to males 45.25% (95% CI 35.19–55.71). The pooled prevalence of depression was 45.45% as measured by HRDS, and it was 55.62%, 45.52%, and 38.36% as measured by BDI, HADS and PHQ-9, respectively.

Conclusion

Our finding suggested that the pooled estimated prevalence of depression among tuberculosis patients was relatively high. Screening and management of depression among TB patients were warranted to alleviate suffering. Moreover, the integration of tuberculosis program with regular psychiatry services may substantially reduce the burden.
Anti-inflammatory properties of uvaol on DSS-induced colitis and LPS-stimulated macrophages
Authors: Du Shi-yun , Huang Hai-feng , Li Xian-qian , Zhai Li-xiang , Zhu Qin-chang , Zheng Kai , Song Xun , Xu Chen-shu , Li Chen-yang , Li Ying , He Zhen-dan , Xiao Hai-tao
Published: May 2020

Background

Apocynum venetum leaves are used as a kind of phytomedicine and the main ingredient in some traditional Chinese medicine products for the relief of colitis. To understand the bioactive constituents of A. venetum L., we did a phytochemistry study and investigated anti-Inflammatory effects of compounds and explored the underlying mechanisms.

Methods

We isolated compounds from ethanol extract of A. venetum L. leaf and detected the most effective compound by NO inhibition assay. We investigated anti-Inflammatory effects on dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological damage was analyzed by H&E staining; macrophages change in the colon were analyzed by immunohistochemistry (IHC); myeloperoxidase activity was measured by myeloperoxidase assay kits; levels of proinflammatory cytokines were determined by qPCR and ELISA; protein production such as COX-2, iNOS, STAT3 and ERK1/2 were determined by western blotting.

Results

We isolated uvaol from ethanol extract of A. venetum L. leaf and found uvaol has excellent potential of inhibiting NO production. We further found uvaol could attenuate disease activity index (DAI), colon shortening, colon injury, and colonic myeloperoxidase activity in DSS-induced colitis mice. Moreover, uvaol significantly reduces mRNA expression and production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1) and infiltration of macrophages in colonic tissues of colitis mice. Studies on LPS challenged murine macrophage RAW246.7 cells also revealed that uvaol reduces mRNA expression and production of pro-inflammatory cytokines and mediators. Mechanically, uvaol inhibits the pro-inflammatory ERK/STAT3 axis in both inflamed colonic tissues and macrophages.

Conclusions

A. venetum leaf contains uvaol and uvaol has potent anti-inflammatory effects on DSS-induced experimental colitis and LPS-stimulated RAW264.7 macrophage cells. These results suggest uvaol is a prospective anti-inflammatory agent for colonic inflammation.
Sur-X, a novel peptide, kills colorectal cancer cells by targeting survivin-XIAP complex
Authors: Fang Wanxia , Che Xiaofang , Li Guohui , Wang Anhui , Wang Yizhe , Shi Xiaonan , Hou Kezuo , Zhang Xiaojie , Qu Xiujuan , Liu Yunpeng
Published: May 2020

Background

Survivin and XIAP are two important members of the inhibitor of apoptosis protein family and have been considered as potential targets for cancer treatment due to their overexpression in large variety of cancers including colorectal cancer. It has been reported that survivin and XIAP can synergistically inhibit apoptosis by forming survivin-XIAP complex. In this study, we aimed to design a peptide that targets the survivin-XIAP complex and elucidate its anticancer mechanisms in colorectal cancer cells.

Methods

We designed and synthetized Sur-X, the peptide targeting survivin-XIAP complex. The anticancer effects of Sur-X were evaluated both in vitro and in vivo. The underlying molecular mechanisms were also investigated.

Results

Sur-X exhibited potent inhibitory effects on four colorectal cancer cell lines HCT116, HCT15, RKO and HT29, but not on human peritoneal mesothelial cell line HMrSV5. Mechanistically, Sur-X induced Caspase 9-dependent intrinsic apoptosis in colorectal cancer cells by disrupting the survivin-XIAP complex and subsequently destabilizing survivin and XIAP. Interestingly, we found that Sur-X can also promote necroptosis. It was demonstrated that Sur-X destroyed the interaction between XIAP and TAB1 in the XIAP-TAB1-TAK1 complex, leading to the instability of TAK1, an endogenous necroptosis inhibitor. Subsequently, the accelerated degradation of TAK1 attenuated its inhibition on necroptosis in colorectal cancer cells. Moreover, knockdown of TAK1 restored the sensitivity of TAB1-overexpressing colorectal cancer cells to Sur-X-induced necroptosis. The in vivo pro-apoptotic effect of Sur-X was confirmed by the enhanced TUNEL staining and the decreased expression of survivin and XIAP in tumor tissues from xenograft mouse models. In addition, extensive necrosis and weaker MLKL expression in xenografts provided evidence for the in vivo pro-necroptotic effect of Sur-X.

Conclusions

Peptide Sur-X exhibits strong pro-apoptotic and pro-necroptotic effects in colorectal cancer cells and has a high clinical translation potential in the treatment of colorectal cancer.
Educational strategy for the development of skills in exchange transfusion: a randomized clinical trial protocol
Authors: Maldonado María José , Agudelo Sergio Iván , Suarez Juan David , Gamboa Oscar
Published: May 2020

Background

Exchange transfusion is a highly complex procedure that requires high levels of expertise. Trainee paediatricians do not have adequate training in exchange transfusion because opportunities to perform this procedure in practice are scarce. This protocol seeks to compare two educational interventions for exchange transfusion that allow students to develop competencies to perform the technique in an appropriate and safe way.

Methods/design

This is a randomized parallel single-blind clinical trial with allocation by simple randomization to the educational intervention (simulation or a digital didactic environment). Students from the paediatric specialization who volunteer to participate will be included. A practical evaluation of the procedure will be performed through a simulated scenario using a standardized clinical case. The main outcome is defined as the result of evaluation using the Objective Structured Clinical Examination; superior performance will be defined when the percentage is greater than or equal to 85%, and non-superior performance will be defined when the result is less than 84%. The chi-square independence test or the Fisher exact test will be used to evaluate the effect of the interventions. Multivariate analysis will be performed using a non-conditional logistic regression model. Stata 15® software will be used.

Discussion

Exchange transfusion is a procedure that requires expertise to achieve adequate outcomes. The inclusion of new educational strategies, such as simulation and digital didactic environments, is seen as a training option that can improve performance in clinical skills, reduce adverse events and increase the level of trust.

Trial registration

ClinicalTrials.gov: NCT04070066. Registered on 28 August 2019. https://clinicaltrials.gov.