bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Prediction of Probable Single Nucleotide Polymorphism-Cancer Relationships
Authors: Bakhtiari Shahab , Sulaimany Sadegh , Talebi Mehrdad , Kalhor Kabmiz
Published: July 2020

Genetic variations such as single nucleotide polymorphisms (SNPs) can cause susceptibility to cancer. Although thousands of genetic variants have been identified to be associated with different cancers, the molecular mechanisms of cancer remain unknown. There is not a particular dataset of relationships between cancer and SNPs, as a bipartite network, for computational analysis and prediction. Link prediction as a computational graph analysis method can help us to gain new insight into the network. In this article, after creating a network between cancer and SNPs using SNPedia and Cancer Research UK databases, we evaluated the computational link prediction methods to foresee new SNP-Cancer relationships. Results show that among the popular scoring methods based on network topology, for relation prediction, the preferential attachment (PA) algorithm is the most robust method according to computational and experimental evidence, and some of its computational predictions are corroborated in recent publications. According to the PA predictions, rs1801394-Non-small cell lung cancer, rs4880-Non-small cell lung cancer, and rs1805794-Colorectal cancer are some of the best probable SNP-Cancer associations that have not yet been mentioned in any published article, and they are the most probable candidates for additional laboratory and validation studies. Also, it is feasible to improve the predicting algorithms to produce new predictions in the future.
Business school space, the hidden curriculum, and the construction of student experience
Authors: Jandrić Jakov , Loretto Wendy
Published: July 2020

Recent trends in business school architecture and design have sparked significant interest in exploring the ways space is used to build organisational identity and reputation. In this article, we add to these conversations by exploring the ways in which spatial designs and practices shape student experiences of business school education. Drawing from Lefebvre’s theorisation of spatiality as simultaneously physical, social and imaginary, we conceptually link spatial designs and practices to the business school’s hidden curriculum. The empirical study we conducted at a UK business school predominately focused on student accounts of their experiences with and within the school. The findings point out three aspects of the relationship between spatiality and the student experience: (1) space is deliberately used to symbolically orientate the school, and to reflect organisational values and ideals; (2) the way in which spatiality shapes student experiences relies on the student contextualisation of spatial designs and practices; (3) student reaction to spatiality is framed by their ideal vision of business school experience. We add to the current conversations on business school spaces and the student experience by showing how spatiality plays an active role not only in student on-course experiences, but also in their conceptualisation of business school education.
Experimental investigation and prediction method of fretting wear in rack-plane spline couplings
Authors: Xue Xiangzhen , Jia Jipeng , Huo Qixin , Jia Junhong
Published: July 2020

To investigate the fretting wear of involute spline couplings in aerospace, rack-plane spline couplings rather than the conventional involute spline couplings in aerospace were used to conduct tribological experiments, and it was assumed that the rack-plane spline couplings exhibit consistent contact stress with the real involute spline couplings in aerospace. The relationships among the static friction coefficient, dynamic friction coefficient, and fretting friction coefficient were established via tribological experiments, as well as the fretting-wear mechanism of the rack-plane spline couplings was examined. A fretting-wear estimation model based on the fretting-wear mechanism was developed. By applying the modified Archard equation and Arbitrary Lagrangian–Eulerian adaptive, mesh smoothing algorithm of Abacus was used. According to our experimental results, the fretting wear of the rack-plane spline couplings consisted primarily of abrasive wear, oxidative wear, and adhesive wear. For both, lubrication and non-lubrication settings, the fretting friction coefficient of 18CrNi4A steel (0.27) fluctuated between 0.12 (dynamic friction coefficient) and 0.35 (static friction coefficient). The fretting-wear results estimated via numerical prediction were consistent with the experimental results. When sm (vibration amplitude) was 20, 35, and 50 µm, the most difference in the fretting wear between the experimental results and numerical estimation was 0.001, 0.0007, and 0.001 mm, respectively. Therefore, the proposed model provides a method for accurate estimation of the fretting-wear. Additionally, the model contributes to the precise design of involute spline couplings in aerospace.
A review on the hydrodynamic characteristics of autonomous underwater vehicles
Authors: Panda Jyoti Prakash , Mitra Arindam , Warrior Hari V
Published: July 2020

Autonomous underwater vehicles play an essential role in geophysical data collection, deep water mining, seafloor mapping, ocean exploration, and in many other related activities starting from military to scientific applications. A detailed understanding of hydrodynamic characteristics will lead to better design, better control, and optimal path planning of autonomous underwater vehicles in the deepest corner of oceans. This article will provide a detailed review of the hydrodynamic characteristics of autonomous underwater vehicles, starting from different experimental techniques used in the analysis of hydrodynamic parameters, methods used for fixing the autonomous underwater vehicles in towing tank, instruments used for measurement of the hydrodynamic parameters. Furthermore, numerical methods employed in performing computational analysis, hydrodynamics-based shape optimization, studies on drag reduction, and finally a detailed list of turbulence models used in the computational fluid dynamics–related numerical simulations. The hydrodynamics-based optimal shape of the autonomous underwater vehicles, the best technique to predict the hydrodynamic parameters, and the best turbulence model for the computational fluid dynamics–based prediction of hydrodynamic parameters will be recommended. At last, the hydrodynamic characteristics of different bio-inspired autonomous underwater vehicles are discussed.
The Public’s Foreign Aid Priorities: Evidence from a Conjoint Experiment
Authors: Doherty David , Bryan Amanda Clare , Hanania Dina , Pajor Matthew
Published: July 2020

Foreign aid is one of the few areas where Americans say the government should spend less. We leverage a unique conjoint experiment to assess how characteristics of an aid package, as well as characteristics of the targeted country, affect public support. We find that people are far more inclined to support economic aid than military aid and are disinclined to provide aid to undemocratic countries. We also find that people are more averse to providing aid—particularly economic aid—to countries in the “greater Middle East” than those countries’ other characteristics would suggest. These effects are comparable to those associated with substantial increases in the cost of the aid package, suggesting that public wariness of foreign aid is not rooted in a fundamental aversion to spending in this domain. Our findings offer new insights into the contours of public opinion regarding foreign aid.
Apps of Empire: Global Capitalism and the App Economy
Authors: Nieborg David B.
Published: July 2020

This article interrogates Dyer-Witheford and De Peuter’s Games of Empire. Since its publication in 2009, the game industry evolved significantly, adding billions of players, dollars, and devices. One of the driving forces of this transformation has been the global diffusion of mobile media. This raises the question: Do mobile platforms and the app stores operated by Apple and Google allow for a radical departure from global hypercapitalism? This question will be explored by taking on three themes: shifts in labor, the political economy of platformization, and the capital-intensive mode of app production and circulation. Doing so addresses two gaps in Games of Empire’ s approach: a dearth of empirical economic analysis and the acknowledgment of work in critical platform studies and mainstream economics. It is concluded that rather than providing a staging ground for dissent or collective action, apps of empire signal the foreclosure of an exodus from global hypercapitalism.
Navigating Student Gender Identity Issues
Authors: Baule Steven M. , Leeper T.
Published: July 2020

This case study provides a summary of a district leader’s dilemma on how to approach a number of gender identity issues that are raised within the first few months of his new superintendency. It identifies the various facets of policy and practice that need to be addressed in light of gender no longer being considered as a simple binary choice. Then discussed is how school administrators work with a variety of constituent groups to navigate implementing the necessary changes to policy and practices. Teaching notes and suggested class activities are included.
Improved ensemble local mean decomposition based on cubic trigonometric cardinal spline interpolation and its application for rotating machinery fault diagnosis
Authors: Chen Pei , Chen Huanguo , Chen Wenhua , Pan Jun , Li Jianmin , Liang Xihui
Published: July 2020

Ensemble local mean decomposition has been gradually introduced into mechanical vibration signal processing due to its excellent performance in electroencephalogram signal analysis. However, an unsatisfactory problem is that ensemble local mean decomposition cannot effectively process vibration signals of complex mechanical system due to the constraints of moving average. The process of moving average is time-consuming and inaccurate in complex signal analysis. Therefore, an improved ensemble local mean decomposition method called C-ELMD with modified envelope algorithm based on cubic trigonometric cardinal spline interpolation is proposed in this article. First, the shortcomings in sifting process of ensemble local mean decomposition is discussed and, furthermore, advantages and disadvantages of the common interpolation methods adopted to improve ensemble local mean decomposition are compared. Then, cubic trigonometric cardinal spline interpolation is employed to construct the local mean and envelope curves in a more precise way. In addition, the influence of shape-controlling parameter on envelope estimation accuracy in cubic trigonometric cardinal spline interpolation is also discussed in detail to select an optimal shape-controlling parameter. The effectiveness of cubic trigonometric cardinal spline interpolation for improving the accuracy of ensemble local mean decomposition is demonstrated using a synthetic signal. Finally, the proposed cubic trigonometric cardinal spline interpolation is tested to be effective in gear and bearing fault detection and diagnosis.
Highly efficient clinical trial designs for reliable screening of under-performing treatments: Application to the COVID-19 Pandemic
Authors: Piantadosi Steven
Published: July 2020

Background:

The COVID-19 pandemic presents challenges for clinical trials including urgency, disrupted infrastructure, numerous therapeutic candidates, and the need for highly efficient trial and development designs. This paper presents design components and rationale for constructing highly efficient trials to screen potential COVID-19 treatments.

Methods:

Key trial design elements useful in this circumstance include futility hypotheses, treatment pooling, reciprocal controls, ranking and selection, and platform administration. Assuming most of the many candidates for COVID-19 treatment are likely to be ineffective, these components can be combined to facilitate very efficient comparisons of treatments.

Results:

Simulations indicate such designs can reliably discard underperforming treatments using sample size to treatment ratios under 30.

Conclusions:

Methods to create very efficient clinical trial comparisons of treatments for COVID-19 are available. Such designs might be helpful in the pandemic and should be considered for similar needs in the future.
Protocol adherence rates in superiority and noninferiority randomized clinical trials published in high impact medical journals
Authors: Bamat Nicolas A , Ekhaguere Osayame A , Zhang Lingqiao , Flannery Dustin D , Handley Sara C , Herrick Heidi M , Ellenberg Susan S
Published: July 2020

Background/aims:

Noninferiority clinical trials are susceptible to false confirmation of noninferiority when the intention-to-treat principle is applied in the setting of incomplete trial protocol adherence. The risk increases as protocol adherence rates decrease. The objective of this study was to compare protocol adherence and hypothesis confirmation between superiority and noninferiority randomized clinical trials published in three high impact medical journals. We hypothesized that noninferiority trials have lower protocol adherence and greater hypothesis confirmation.

Methods:

We conducted an observational study using published clinical trial data. We searched PubMed for active control, two-arm parallel group randomized clinical trials published in JAMA: The Journal of the American Medical Association, The New England Journal of Medicine, and The Lancet between 2007 and 2017. The primary exposure was trial type, superiority versus noninferiority, as determined by the hypothesis testing framework of the primary trial outcome. The primary outcome was trial protocol adherence rate, defined as the number of randomized subjects receiving the allocated intervention as described by the trial protocol and followed to primary outcome ascertainment (numerator), over the total number of subjects randomized (denominator). Hypothesis confirmation was defined as affirmation of noninferiority or the alternative hypothesis for noninferiority and superiority trials, respectively.

Results:

Among 120 superiority and 120 noninferiority trials, median and interquartile protocol adherence rates were 91.5 [81.4–96.7] and 89.8 [83.6–95.2], respectively; P = 0.47. Hypothesis confirmation was observed in 107/120 (89.2%) of noninferiority and 64/120 (53.3%) of superiority trials, risk difference (95% confidence interval): 35.8 (25.3–46.3), P < 0.001.

Conclusion:

Protocol adherence rates are similar between superiority and noninferiority trials published in three high impact medical journals. Despite this, we observed greater hypothesis confirmation among noninferiority trials. We speculate that publication bias, lenient noninferiority margins and other sources of bias may contribute to this finding. Further study is needed to identify the reasons for this observed difference.
The use of ultrasound in the emergency department for the detection of thoracic outlet syndrome: A single case study
Authors: Tung-Chen Yale , Marín-Baselga Raquel , Tejada-Sorados Renzo , Enfedaque-Castilla Israel
Published: July 2020

Introduction

Thoracic outlet syndrome (TOS) refers to a spectrum of syndromes related to the compression of the brachial plexus (neurogenic TOS), subclavian vein or artery in the general region of the thoracic outlet, which is the area just above the first rib and behind the clavicle.

Case report

We report a 27-year-old healthy man who presented to the emergency department with right upper limb pain, tingling and weakness. Point-of-care ultrasonography was performed following a dynamic protocol in the supraclavicular fossa in the right upper limb. A congenital cervical rib, as well as narrowing of the costoclavicular gap, causing vein, artery and spinal roots compression was evidenced. This maneuver reproduced the symptoms, confirming the suspicion of neurogenic TOS.

Discussion

Early diagnosis is important, because the neurogenic compression associated with neurogenic TOS, if prolonged, can lead to muscle weakness and atrophy, being irreversible. Selected patients with neurogenic TOS who have progressive weakness, disabling pain, or who have failed to improve with conservative measures are considered for first rib resection.

Conclusion

Using the dynamic approach during point-of-care ultrasonography examination, in combination with physical examination and cervical radiography, could help identify neurogenic TOS.
Democratizing politics and politicizing education: Critical pedagogy for active citizenship in the Taiwanese Sunflower Movement
Authors: Themelis Spyros , Hsu Tao-Chen
Published: July 2020

This article is the first to employ a Freirean framework to discuss the Taiwanese Sunflower Student Movement and its political, pedagogical and social significance. We analyse lecturers’ and students’ perspectives and experiences of civic responsibility in order to explore the relationship between critical pedagogy and student participation in the movement. The latter is an important development in politics and student activism, as it touched the lives of an entire generation of young Taiwanese and highlighted the value of active citizenship in the fight to improve democracy as praxis for social justice. This article makes a threefold contribution: first, it adds to our understanding of the processes through which movement participants cultivate their critical consciousness; second, it offers a new angle on a politically significant moment in Taiwanese history; and third, it uses this movement to illuminate forms of oppression that exist in society and education and ways to transform it.
Early COPD: current evidence for diagnosis and management
Authors: Fazleen Aishath , Wilkinson Tom
Published: July 2020

Chronic obstructive pulmonary disease (COPD) affects one-tenth of the world’s population and has been identified as a major global unmet health need by the World Health Organisation, which predicts that within 10 years, COPD will become the third leading cause of death. Despite active research, there have been no recent major strides in terms of disease modifying treatment for COPD; smoking cessation remains the only intervention known to alter disease progression and improve mortality. As established COPD is a key driver of disease burden, earlier diagnosis coupled with disease-modifying intervention carries promise as a route to address this global health priority. The concept of early COPD is emerging as an area of focus for research and consideration of new treatment modalities, as it has been hypothesised that intervention at this stage may potentially halt or reverse the disease process. However, at present, a globally accepted criteria for defining early COPD does not exist. Several studies propose small airways disease as the earliest stage in the development of COPD, and this has been demonstrated to be a precursor to development of emphysema and to correlate with subsequent development of airflow obstruction. However, treatment strategies for early disease, which pre-date the development of airflow obstruction, remain uncertain. This review addresses the rationale and current evidence base for the diagnosis and treatment of early COPD and highlights the challenges of implementing trials and clinical pathways to address COPD earlier in the life course, particularly in the absence of a universally accepted definition of COPD.

The reviews of this paper are available via the supplemental material section.
Adverse outcome of acute splenic sequestration crisis in pregnancy
Authors: Malinowski Ann Kinga , Parrish Jacqueline , D’Souza Rohan , Kuo Kevin HM , Ward Richard , Shehata Nadine
Published: July 2020

Background

Acute splenic sequestration crisis, characterized by abrupt fall in hemoglobin, splenomegaly, hypovolemia, and often thrombocytopenia, occurs infrequently in adults with sickle cell disease and extremely rarely during pregnancy.

Case

A 25-year-old woman with HbSC presented at 33 weeks’ gestation with vaso-occlusive pain. Sudden worsening of abdominal pain and non-reassuring fetal surveillance on day 3 of admission led to emergent delivery. Acute splenic sequestration crisis was the diagnosis of exclusion based on clinical presentation and intra-operative hemoglobin of 37 g/L. Five- and 10-minute Apgar scores were 4. Neonatal brain magnetic resonance imaging revealed significant diffuse white matter abnormalities.

Conclusion

Acute splenic sequestration crisis in pregnancy must be considered in the differential diagnosis for this patient population as it can evolve rapidly and lead to maternal and fetal compromise.
Study on the networked integration model and its efficiency of private company taking part in state-owned company mixed ownership reform
Authors: Zhou Zhiqiang , Xu Xinyu , Qu Xilong , Li Shun
Published: July 2020

Based on the concept of sharing in the new era, following the goal orientation of ‘common progress of the people, sharing and win–win’, this article builds a networked integration model of private company taking part in state-owned company mixed ownership reform with industrial clusters as the core and integrating equity sharing, power sharing and benefit sharing from the three levels of capital structure, governance structure and distribution structure. Furthermore, 602 state-owned mixed company from 2007 to 2017 are taken as research samples to conduct an empirical study on the efficiency of networked integration model. The results show that the networked integration model can significantly improve the business performance of company. Equity sharing, power sharing and benefit sharing have obvious and positive effect on business performance. Compared with non-industrial clusters, the networked integration model under the condition of industrial clusters has more effect on promoting business performance. State-owned capital is the most critical factor affecting business performance in the overall sample and the non-industrial cluster sample, while private capital is the most critical factor affecting business performance in the industrial cluster sample.
Do Stairs Inhibit Seniors Who Live on Upper Floors From Going Out?
Authors: Yu Yifan , Chen Zheng , Bu Jiatian , Zhang Qinglai
Published: July 2020

Background:

Walk-up buildings are common in China today since they were almost the only type of residential buildings constructed from the 1950s to the 1990s.

Objectives:

This study examined how a vertical mobility obstacle, that is, mandatory stair climbing in walk-up residential buildings, may impact whether seniors go outdoors.

Methods:

We collected and examined 1,608 valid data records from 64 Chinese senior participants in Shanghai wearing Fitbit HR wristbands that tracked their mobility and physical activity for 31 consecutive days. Multilevel mixed-effects logistic regressions were performed on the binary leaving-home-or-not probability by the level of vertical obstacles controlled for physical–demographic factors, socioeconomic factors, outdoor activity habits, and weather.

Results:

Our observations revealed that each floor above ground level reduced the likelihood of outdoor trips by approximately one third per floor. After controlling for the physical, demographic, and socioeconomic factors of the participants as well as weather and holidays, we found that significantly fewer going-out incidents were also associated with more frequent outdoor activities within the community, especially in paved areas, but no associations were observed with self-reported visit frequencies to green spaces, senior centers within the community, or other places outside the community.

Conclusion:

This study offered the in situ observation that seniors’ probability of leaving their homes is correlated with the degree of vertical circulation as a mobility barrier (i.e., the number of stairs between their living space and access to the outdoors), which may impact policy making for regulations concerning elevators in residential codes and renovations.
Differentiation of Clinical Patterns Associated With Rhinologic Disease
Authors: Parsel Sean M. , Riley Charles A. , Todd Cameron A. , Thomas Andrew J. , McCoul Edward D.
Published: July 2020

Background

Common rhinologic diagnoses have similar presentations with a varying degree of overlap. Patterns may exist within clinical data that can be useful for early diagnosis and predicting outcomes.

Objective

To explore the feasibility of artificial intelligence to differentiate patterns in patient data in order to develop clinically-meaningful diagnostic groups.

Methods

A cross-sectional study of prospectively-acquired patient data at a tertiary rhinology clinic was performed. Data extracted included objective findings on nasal endoscopy, patient reported quality of life (PRQOL) instrument ratings, peripheral eosinophil fraction, and past medical history. Unsupervised non-hierarchical cluster analysis was performed to discover patterns in the data using 22 input variables.

Results

A total of 545 patients were analyzed after application of inclusion and exclusion criteria yielding 7 unique patient clusters, highly dependent on PRQOL scores and demographics. The clusters were clinically-relevant with distinct characteristics. Chronic rhinosinusitis without nasal polyposis (CRSsNP) was associated with two clusters having low frequencies of asthma and low eosinophil fractions. Chronic rhinosinusitis with nasal polyposis (CRSwNP) was associated with high frequency of asthma, mean (standard deviation [SD]) NOSE scores of 66 (19) and SNOT-22 scores of 41 (15), and high eosinophil fractions. AR was present in multiple clusters. RARS was associated with the youngest population with mean (SD) NOSE score of 54 (23) and SNOT-22 score of 41 (19).

Conclusion

Broader consideration of initially available clinical data may improve diagnostic efficiency for rhinologic conditions without ancillary studies, using computer-driven algorithms. PRQOL scores and demographic information appeared to be useful adjuncts, with associations to diagnoses in this pilot study.
Neurovascular and perfusion imaging findings in coronavirus disease 2019: Case report and literature review
Authors: Soldatelli Matheus Dorigatti , Amaral Lázaro Faria do , Veiga Viviane Cordeiro , Rojas Salomón Soriano Ordinola , Omar Samir , Marussi Victor Hugo Rocha
Published: July 2020

Central nervous system involvement in severe acute respiratory syndrome caused by coronavirus disease 2019 (COVID-19) has increasingly been recognised in the literature, and possible mechanisms of neuroinvasion, neurotropism and neurovirulence have been described. Neurological signs have been described in 84% of COVID-19 intensive care unit patients, and haemostatic abnormalities in such patients may play an important role, with a broad spectrum of neuroimaging findings. This report describes the magnetic resonance imaging neurovascular findings in an acutely ill patient with COVID-19, including perfusion abnormalities depicted in the arterial spin labelling technique.
An approach to a perceived risk of venous thromboembolism in non-ICU COVID-19 patients in Singapore
Authors: Pothiawala Sohil
Published: July 2020

Coronavirus disease 2019 (COVID-19) can lead to coagulation activation and venous thromoembolism (VTE), with an incidence of around 25–27%. Patients admitted to the intensive care unit (ICU) are at highest risk. There are not many studies reporting its incidence in non-ICU patients. A large number of COVID-19 patients in Singapore, with symptoms ranging from mild to moderate, have been admitted to either Community Care Facilities (CCF) or in general wards of Public Healthcare Institutions (PHI). In case there is a surge of COVID-19 patients, there is a possibility that general wards in PHIs may need to admit an increasing numbers of acutely ill patients, with only the critical ones being admitted to ICU. The incidence of VTE in non-ICU patients is not exactly known and its detection in these patients is challenging. Thus, the healthcare staff managing these patients at the CCFs and general wards at the PHIs should be vigilant and monitor these patients for development of signs and symptoms of deep vein thrombosis, as well as trend D-dimer level. An algorithm for a potential approach to manage VTE in non-ICU COVID-19 patients is described. A prospective study is needed to establish the incidence of VTE in non-ICU patients in Singapore and the predictive value of D-dimer levels to detect this risk, as well as a therapeutic protocol to initiate appropriate pharmacological thromboprophylaxis in these patients.
Cost-effectiveness of dapagliflozin in chronic heart failure: an analysis from the Australian healthcare perspective
Authors: Savira Feby , Wang Bing H , Kompa Andrew R , Ademi Zanfina , Owen Alice J , Zoungas Sophia , Tonkin Andrew , Liew Danny , Zomer Ella
Published: July 2020

Aim

To assess the cost-effectiveness of dapagliflozin in addition to standard care versus standard care alone in patients with chronic heart failure and reduced ejection fraction.

Methods

A Markov model was constructed based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial to assess the clinical outcomes and costs of 1000 hypothetical subjects with established heart failure and reduced ejection fraction. The model consisted of three health states: ‘alive and event-free’, ‘alive after non-fatal hospitalisation for heart failure’ and ‘dead’. Costs and utilities were estimated from published sources. The main outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. An Australian public healthcare perspective was employed. All outcomes and costs were discounted at a rate of 5% annually.

Results

Over a lifetime horizon, the addition of dapagliflozin to standard care in patients with heart failure and reduced ejection fraction prevented 88 acute heart failure hospitalisations (including readmissions) and yielded an additional 416 years of life and 288 quality-adjusted life-years (discounted) at an additional cost of A$3,692,440 (discounted). This equated to an incremental cost-effectiveness ratio of A$12,482 per quality-adjusted life-year gained, well below the Australian willingness-to-pay threshold of A$50,000 per quality-adjusted life-year gained. Subanalyses in subjects with and without diabetes resulted in similar incremental cost-effectiveness ratios of A$13,234 and A$12,386 per quality-adjusted life-year gained, respectively.

Conclusion

Dapagliflozin is likely to be cost-effective when used as an adjunct therapy to standard care compared with standard care alone for the treatment of chronic heart failure and reduced ejection fraction.
Sudden rhabdomyolysis in an elderly patient after single atorvastatin dose: The need for early and frequent creatine kinase monitoring in high-risk patients
Authors: Xiao Min , Zhang Lu , Zhong Yan , Xiao Guirong
Published: July 2020

An 80-year-old patient with diabetes mellitus, chronic bronchitis, and chronic heart failure presented with pain in the right calf after one dose of atorvastatin. Significant increases in creatine kinase, myoglobin, and potassium levels were also observed. Based on the symptoms and laboratory results, the patient was diagnosed with rhabdomyolysis. Older patients with co-morbidities may have a higher risk of statin-associated myopathy. However, there is currently no recommendation for creatine kinase monitoring in this population. This case emphasizes the need to identify high-risk populations and provide early and more frequent creatine kinase measurements to help avoid statin-associated myopathy.
The management of septic shock and Ludwig’s angina: A case report of a life-threatening condition
Authors: Sjamsudin Endang , Manurung Basaria , Arumsari Asri , Maulina Tantry
Published: July 2020

Ludwig’s angina is a high severity infection because of the risk of airway obstruction due to the rapid spread of the abscess into the deeper spaces. Therefore, performing the correct treatment is one of the keys to a successful result. A 44-year-old male patient came to the Emergency Unit of Hasan Sadikin Hospital, complaining of shortness of breath, severe pain, and progressive swelling. Extraoral examination showed a localized-fluctuated swelling located at the right lower jaw that extended to the chin, left lower jaw, and the frontal region of the neck region while a sequential organ failure assessment revealed a score of 2. A diagnosis of Ludwig’s angina and septic shock was confirmed. Intravenous infusion of norepinephrine was administered and a tracheostomy was performed. The next treatment phase consisted of a drainage procedure, tooth extraction, and placement of the Penrose drain. The patient was discharged 10 days later with a satisfactory outcome.
Delayed brain infarction caused by mechanical compression of the anterior choroidal artery after coil embolization for a large internal carotid-posterior communicating artery aneurysm: A case report
Authors: Wakuta Naoki , Yamamoto Satoshi
Published: July 2020

A 65-year-old male received coil embolization for a large internal carotid-posterior communicating artery aneurysm. Pre- and postoperative angiography at surgery demonstrated that the ipsilateral anterior choroidal artery branched from the internal carotid artery near the distal side of the aneurysm, and elevated and expanded on the aneurysmal dome, but was clearly visualized. Three days following endovascular treatment, the patient presented hemiparesis on the left side, with brain infarction in the territory of the right anterior choroidal artery despite antithrombotic therapy. The delayed brain infarction was likely caused by a reduction in anterior choroidal artery perfusion caused by mechanical compression following a postoperative increase in internal carotid-posterior communicating artery aneurysmal volume during intra-aneurysmal thrombosis. Transient volume expansion after coil embolization for intracranial aneurysms is rarely reported as a cause of brain infarction. It is important to recognize these arteries as potential postoperative complication risks, and consider the use of open surgery to avoid this risk.
Comparing concussion rates as reported by hockey Canada with head contact events as observed across minor ice-hockey age categories
Authors: Robidoux Michael A , Kendall Marshall , Laflamme Yannick , Post Andrew , Karton Clara , Hoshizaki T Blaine
Published: July 2020

Head injuries in elite and youth sport have garnered growing public attention in part because of high-profile cases of professional athletes suffering career-ending/threatening concussions and because of the increase in medical studies identifying how repeated concussive events can lead to long-term health problems, most notably degenerative brain disease. Public concerns around youth ice hockey are intensifying in light of recent evidence which suggests that effects of head injury are worse for youth than they are for athletes in later stages of life. To better understand concussion injury rate trends across all levels of youth hockey, this paper provides a retrospective analysis of concussion related hockey injury as recorded in Hockey Canada’s Injury Reporting System from the period covering 2009 to 2016, combined with two years of observational research documenting head contact events in minor hockey in the Ottawa and Gatineau regions of Ontario and Quebec. By comparing two different data sets through different methodological designs, it provides important insight into the levels of head contact in youth hockey, how head contact is occurring, and offers commentary about the levels of risk players are exposed to in minor hockey in Canada.
The Mediating Effect of Psychache on the Relationship Between Psychological Strains and Suicidal Behaviors Among Chinese Hui and Han Medical Students
Authors: Ha Lina , Chang Qingning , Wang ZhiZhong
Published: July 2020

Psychological strain is associated with suicidal behavior; however, the way that psychological strain leads to suicidal behavior remains unclear. The current study examines the mediation effect of psychache on the relationship between psychological strain and suicidal behavior among Chinese Hui and Han medical students. A total of 1,696 enrolled medical students (974 Han and 722 Hui) were administered the Psychological Strain Scale (PSS), the Suicide Behavior Questionnaire-Revised (SBQ-R) scale, and the Psychache Scale. There were significant differences in the PSS between different ethnic groups. Correlation analysis showed that both psychological strain and psychache were positively correlated with suicidal behaviors, and the two predictive variables were also positively correlated. The mediation effect test procedure showed that the direct and indirect effects (mediator effect) of psychological strain on suicidal behaviors were significant. The findings indicate that psychological strain partially induced psychache in both two ethnicity groups, leading to suicidal behavior in Chinese medical college students.
Perspective Shifting: Engaging Leaders-of-Leaders in Patient and Caregiver Experience
Authors: Barden Agnes , Giammarinaro Nicole , Petrosino Leah
Published: July 2020

Leadership drives quality, experience, and engagement. It is the responsibility of the organization to equip its leaders with ongoing education and professional development. This case article explores the development, implementation, and impact of an immersive patient experience leadership education course across a large, integrated health system. Placing senior leaders on the “other side of the hospital bed,” they were able to emotionally connect and personalize to the human side of health care. Post-course surveys validated that experiential role play was a positive and insightful method to teach and bring heightened awareness to patient and family member experience.
Does finasteride treatment for benign prostatic hyperplasia influence sperm DNA integrity in dogs?
Authors: Angrimani Daniel S. R. , Bicudo Luana C. , Llamas Luceño Nuria , Rui Bruno R. , Silva Matheus F. , Losano João D. A. , Leemans Bart , Van Soom Ann , Vannucchi Camila I.
Published: July 2020

Background

Benign prostatic hyperplasia (BPH) is one of the most common reproductive disorders in both male dogs and men. Finasteride, a synthetic inhibitor of the enzyme 5α-reductase, is widely used as medical treatment. Although sperm can be affected by both BPH and finasteride treatment, the direct influence on DNA integrity remains unclear. Thus, the aim of this study was to verify the direct effect of BPH and/or finasteride treatment on DNA integrity of dog spermatozoa. A 2 × 2 factorial experiment was designed with 20 male dogs assigned to 4 experimental groups: BPH Group (n = 5), BPH-Finasteride Group (n = 5), Non-BPH Finasteride-Treated Group (n = 5) and Non-BPH Untreated Group (n = 5). Sperm evaluation was performed monthly for 60 days after the start of finasteride therapy or BPH diagnosis (D0, D30 and D60). Sperm DNA integrity was analyzed through fragmentation susceptibility (toluidine blue staining and Sperm Chromatic Structure Assay - SCSA), direct evaluation of DNA fragmentation (Sperm Chromatin Dispersion Assay - SCDA) and sperm protamination (chromomycin A3).

Results

Sperm DNA integrity was not affected by finasteride treatment. However, BPH dogs had higher susceptibility to sperm DNA acid denaturation (SCSA) compared to dogs not presenting BPH, as well as lower percentage of sperm with DNA integrity (toluidine blue staining).

Conclusion

In conclusion, benign prostatic hyperplasia causes post-testicular sperm DNA damage, albeit finasteride treatment itself does not directly influence sperm DNA integrity.
Knockdown of DEPDC1B inhibits the development of glioblastoma
Authors: Chen Xu , Guo Zheng-Qian , Cao Dan , Chen Yong , Chen Jian
Published: July 2020

Background

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis. DEPDC1B (DEP domain-containing protein 1B) has been shown to be associated with some types of malignancies. However, the role and underlying regulatory mechanisms of DEPDC1B in GBM remain elusive.

Methods

In this research, the expression level of DEPDC1B in GBM tissues was detected by IHC. The DEPDC1B knockdown cell line was constructed, identified by qRT-PCR and western blot and used to construct the xenotransplantation mice model and intracranial xenograft model. MTT assay, colony formation assay, flow cytometry, and Transwell assay were used to detected cell proliferation, apoptosis and migration.

Results

The results proved that DEPDC1B was significantly upregulated in tumor tissues, and silencing DEPDC1B could inhibit proliferation, migration and promote apoptosis of GBM cell. In addition, human apoptosis antibody array detection showed that after DEPDC1B knockdown, the expression of apoptosis-related proteins was downregulated, such as IGFBP-2, Survivin, N-cadherin, Vimentin and Snail. Finally, we indicated that knockdown of DEPDC1B significantly inhibited tumor growth in vivo.

Conclusions

In summary, DEPDC1B was involved in the development and progression of GBM, which may be a potential therapeutic target and bring a breakthrough in the treatment.
Screening and verification of long noncoding RNA promoter methylation sites in hepatocellular carcinoma
Authors: Lin Zhuo , Ni Xiaofeng , Dai Shengjie , Chen Hao , Chen Jianhui , Wu Boda , Ao Jianyang , Shi Keqing , Sun Hongwei
Published: July 2020

Background

Long noncoding ribonucleic acid (lncRNA) promoter methylation is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Thus, we aim to screen and verify the lncRNA promoter methylation sites associated with overall survival (OS), vascular invasion, pathological grade, and clinical stage in HCC.

Methods

Methylation-related data including clinical characteristic, transcriptome, methylation, and messenger RNA (mRNA) expression were taken from the Cancer Genome Atlas (TCGA) database. The OS, vascular invasion, pathological grade, and clinical stage-related lncRNA promoter methylation models were developed by the least absolute shrinkage and selection operator (LASSO) algorithm based on the lncRNA promoter methylation sites screened via R software. The Kaplan–Meier analysis, the area under the receiver operating characteristic (ROC) curve (AUC), the calibration curve (C-index) were performed to evaluate the performance of these models. Finally, the methylation-specific polymerase chain reaction (MS-PCR) was performed to verify the accuracy of these models based on 146 HCC tissues from our hospital.

Results

A total of 10 methylation sites were included in the OS-related lncRNA promoter methylation model that could effectively divide HCC patients into high-risk and low-risk groups (P < 0.0001) via survival analysis. COX univariable and multivariable regression analysis found that the OS-related model (P < 0.001, 95% CI 1.378–2.942) and T stage (P < 0.001, 95% CI 1.490–3.418) were independent risk factors affecting OS in HCC patients. The vascular invasion-related model contained 8 methylation sites with its AUC value of 0.657; the pathological grade-related model contained 22 methylation sites with its AUC value of 0.797; the clinical stage-related model contained 13 methylation sites with its AUC of 0.724. Target genes corresponded to vascular invasion-related lncRNA promoter methylation sites were involved in many kinds of biological processes in HCC such as PI3K-Akt signaling pathway. The accuracy of the vascular invasion-related model was consistent with our bioinformatics conclusion after being verified via MS-PCR.

Conclusion

The lncRNA promoter methylation sites are closely correlated with the process of HCC and can be utilized to improve the therapy and prognosis of HCC.
A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3
Authors: He Xiaoyu , Chai Peiwei , Li Fang , Zhang Leilei , Zhou Chuandi , Yuan Xiaoling , Li Yongyun , Yang Jie , Luo Yingxiu , Ge Shengfang , Zhang He , Jia Renbing , Fan Xianqun
Published: July 2020

Background

Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis.

Methods

RBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs.

Results

Here, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo.Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells.

Conclusions

RBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.
Single-cell lineage analysis reveals genetic and epigenetic interplay in glioblastoma drug resistance
Authors: Eyler Christine E. , Matsunaga Hironori , Hovestadt Volker , Vantine Samantha J. , van Galen Peter , Bernstein Bradley E.
Published: July 2020

Background

Tumors can evolve and adapt to therapeutic pressure by acquiring genetic and epigenetic alterations that may be transient or stable. A precise understanding of how such events contribute to intratumoral heterogeneity, dynamic subpopulations, and overall tumor fitness will require experimental approaches to prospectively label, track, and characterize resistant or otherwise adaptive populations at the single-cell level. In glioblastoma, poor efficacy of receptor tyrosine kinase (RTK) therapies has been alternatively ascribed to genetic heterogeneity or to epigenetic transitions that circumvent signaling blockade.

Results

We combine cell lineage barcoding and single-cell transcriptomics to trace the emergence of drug resistance in stem-like glioblastoma cells treated with RTK inhibitors. Whereas a broad variety of barcoded lineages adopt a Notch-dependent persister phenotype that sustains them through early drug exposure, rare subclones acquire genetic changes that enable their rapid outgrowth over time. Single-cell analyses reveal that these genetic subclones gain copy number amplifications of the insulin receptor substrate-1 and substrate-2 (IRS1 or IRS2) loci, which activate insulin and AKT signaling programs. Persister-like cells and genomic amplifications of IRS2 and other loci are evident in primary glioblastomas and may underlie the inefficacy of targeted therapies in this disease.

Conclusions

A method for combined lineage tracing and scRNA-seq reveals the interplay between complementary genetic and epigenetic mechanisms of resistance in a heterogeneous glioblastoma tumor model.