bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities
Authors: Kelly Marcus R. , Kostyrko Kaja , Han Kyuho , Mooney Nancie A. , Jeng Edwin E. , Spees Kaitlyn , Dinh Phuong T. , Abbott Keene L. , Gwinn Dana M. , Sweet-Cordero E. Alejandro , Bassik Michael C. , Jackson Peter K. 
Published: July 2020

Abstract

Activating mutations in RAS GTPases drive many cancers, but limited understanding of less-studied RAS interactors, and of the specific roles of different RAS interactor paralogs, continues to limit target discovery. We developed a multistage discovery and screening process to systematically identify genes conferring RAS-related susceptibilities in lung adenocarcinoma. Using affinity purification mass spectrometry, we generated a protein–protein interaction map of RAS interactors and pathway components containing hundreds of interactions. From this network, we constructed a CRISPR dual knockout library targeting 119 RAS-related genes that we screened for KRAS-dependent genetic interactions (GI). This approach identified new RAS effectors, including the adhesion controller RADIL and the endocytosis regulator RIN1, and &gt;250 synthetic lethal GIs, including a potent KRAS-dependent interaction between RAP1GDS1 and RHOA. Many GIs link specific paralogs within and between gene families. These findings illustrate the power of multiomic approaches to uncover synthetic lethal combinations specific for hitherto untreatable cancer genotypes.

Significance:
We establish a deep network of protein–protein and genetic interactions in the RAS pathway. Many interactions validated here demonstrate important specificities and redundancies among paralogous RAS regulators and effectors. By comparing synthetic lethal interactions across KRAS-dependent and KRAS-independent cell lines, we identify several new combination therapy targets for RAS-driven cancers.
This article is highlighted in the In This Issue feature, p. 1775
Extracellular Superoxide Dismutase Is Associated With Left Ventricular Geometry and Heart Failure in Patients With Cardiovascular Disease
Authors: Li Xiuwen , Lin Yingying , Wang Shaohua , Zhou Shiyi , Ju Jingmeng , Wang Xiaohui , Chen Yangxin , Xia Min 
Published: July 2020

Background
Extracellular superoxide dismutase (Ec‐SOD) is a major scavenger of reactive oxygen species. However, its relationships with abnormal left ventricular (LV) geometry patterns and heart failure (HF) are still unknown in patients with cardiovascular disease.

Methods and Results

A cross‐sectional study was carried out to evaluate the association of serum Ec‐SOD activity with LV geometry, as well as HF in 1047 patients with cardiovascular disease. All participants underwent standard echocardiography examination and measurement of serum Ec‐SOD activity. Overall, we found a significantly decreased trend of serum Ec‐SOD activity from subjects with normal geometry (147.96±15.94 U/mL), subjects with abnormal LV geometry without HF (140.19±20.12 U/mL), and subjects with abnormal LV geometry and overt HF (129.32±17.92 U/mL) after adjustment for potential confounders (
P
for trend <0.001). The downward trends remained significant in the concentric hypertrophy and eccentric hypertrophy groups after stratification by different LV geometry patterns. Multinomial logistic regression analysis showed that each 10 U/mL increase in serum Ec‐SOD activity was associated with a 16.5% decrease in the odds of concentric remodeling without HF (odds ratio [OR], 0.835; 95% CI, 0.736–0.948), a 40.4% decrease in the odds of concentric hypertrophy with HF (OR, 0.596; 95% CI, 0.486–0.730), a 16.1% decrease in the odds of eccentric hypertrophy without HF (OR, 0.839; 95% CI, 0.729–0.965) and a 34.0% decrease in the odds of eccentric hypertrophy with HF (OR, 0.660; 95% CI, 0.565–0.772).

Conclusions
Serum Ec‐SOD activity was independently associated with abnormal LV geometry patterns with and without overt HF. Our results indicate that Ec‐SOD might be a potential link between LV structure remodeling and the development of subsequent HF in patients with cardiovascular disease.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier NCT03351907.
The Ugly Psyche: Arendt and the Right to Opacity
Authors: O’Byrne Anne 
Published: July 2020

Abstract
Arendt was famously dismissive of the work of psychologists, claiming that they did nothing more than reveal the pervasive ugliness and monotony of the psyche. If we want to know who people are, she argued, we should observe what they do and say rather than delving into the turmoil of their inner lives; if we want to understand humanity, we would be better off reading Oedipus Rex than hearing about someone’s Oedipus complex. The rejection has a certain coherence in the context of her understanding of public life as the realm of appearance and opinion, but examining it through the specific question of ugliness complicates that understanding. While beauty invites us to contemplate the world and admire it, ugliness repels our attention and sows the seed of a worry that the world might not want to be known. Working with Eichmann in Jerusalem, The Life of the Mind: Thinking, the Kant lectures and a striking Denktagebuch entry in which she reacts with revulsion to Matisse’s Heads of Jeannette, I argue that Arendt’s response to the ugly psyche requires a re-examination of the sensus communis. If the psyche does not want to be known, and if not all points of view are open to imaginative occupation, the ideal and practice of enlarged mentality must reckon with a right to opacity.
Towards an Arendtian Conception of Justice
Authors: Sari Yasemin 
Published: July 2020

Abstract
This article argues that Arendt’s rich account of the political necessarily involves an implicit, but never fully worked out, phenomenological articulation of justice in her work. Arendt’s unique articulation of the role of judgment in political action provides us with the outline of an Arendtian principle of justice that relieves the tension between idealist and realist theories of justice. Building on this role of judgment, I aim to emphasize the phenomenological premise of identifying the conditions for the possibility of the political in empirico-historical events rooted in her ideas of plurality and freedom. By showing that, for Arendt, justice is a phenomenon like power and equality, we can make progress on an implicit account of justice in her work. Taking seriously Arendt’s articulation of freedom-manifesting and principled political action, I will show that a principle of justice guides political action based on political judgment that is affectively oriented to the world.
A Failed Politician, a Disputed Jesuit: Cardinal Johann Eberhard Nithard (1607–81)
Authors: Salmerón Miguel Córdoba 
Published: July 2020

One of the most controversial Jesuit cardinals was Johann Eberhard Nithard, not only because of the intriguing circumstances of his promotion, but also because he was a favorite of Queen Mariana of Austria, regent of Spain and mother of King Charles ii. The aim of this essay is to examine a series of events in Nithard’s life, focusing in particular on the details surrounding his consecration as bishop and creation as cardinal. This task is performed through an analysis of various sources, many of which—including the Jesuit ones—have been responsible for forging Nithard’s black legend, which resulted in his eventual expulsion from Spain and in distorted narratives of historians of Nithard’s role in the church and state politics in the seventeenth century.
Generalized convulsive status epilepticus after retrograde type A aortic dissection surgery
Authors: Li Yuan , Wu Qingchen , Shi Haoming , Chen Dan , Zhang Cheng 
Published: July 2020

Introduction: Generalized convulsive status epilepticus is defined as a generalized and convulsive seizure with 5 minutes or more of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery between seizures. For the first time, we present a case with retrograde type A aortic dissection after endovascular repairment and received thoracotomy intensely. Case report: The patient experienced frequent generalized seizures in the immediate postoperative period, and status epilepticus was considered for his medical history, clinic symptoms and related examinations. Discussion and Conclusion: Generalized convulsive status epilepticus should be alert for avoiding delay in the rehabilitation particularly after aortic dissection surgery. Under the good condition of ventilation, combining morphine with midazolam or diazepam can more effectively relieve the symptoms.
Myocardial perfusion imaging and appropriateness of the test for preoperative cardiac risk evaluation in an Iranian population: clinical role of Duke Activity Status Index
Authors: Salehi Yalda , Farzanehfar Saeed , Naseri Maryam , Sherafati Alborz , Ranjbar Shaghayegh , Abbasi Mehrshad 
Published: July 2020

Objective: For preoperative radionuclide myocardial perfusion imaging, metabolic equivalent is one of the key factors to evaluate the appropriateness. Duke Activity Status Index is a practical method to calculate metabolic equivalents. We intended to validate Duke Activity Status Index in our population for the assessment of preoperative myocardial perfusion imaging appropriateness. Methods: A total of 542 patients referred for myocardial perfusion imaging were recruited. A questionary compiled from Duke Activity Status Index was filled out based on which metabolic equivalents were calculated. Demographic data and history of cardiac risk factors were also collected. Myocardial perfusion imaging was performed using a 2-day stress-rest protocol either by exercise tolerance test or by pharmacologic stress through injection of Tc-MIBI and imaging by a dual-head gamma camera. Results: Out of 542 patients, 369 (68.1%) were evaluated for preoperative risk assessment. Metabolic equivalents (oxygen consumption/min/kg) were calculated at 9.3 ± 5.1, 10.8 ± 4.8, and 8.7 ± 5.1 in total, preoperative patients and patients evaluated for ischemia due to nonsurgical purposes, respectively (p = 0.001). The myocardial perfusion imaging was rarely appropriate in 291 (79.5%), maybe appropriate in 67 (18.3%), and appropriate in 8 (2.2%) patients. The prevalence of abnormal myocardial perfusion imaging was 22.5%, 28.4%, and 12.5% in “rarely appropriate,” “maybe appropriate,” and “appropriate” scenarios, respectively. Metabolic equivalents were similar between patients with normal and abnormal myocardial perfusion imaging (8.7 ± 5.0 vs. 8.5 ± 5.4). Conclusion: Either Duke Activity Status Index is not a proper tool for calculation of metabolic equivalents or the appropriate use criteria is not operational in the population of Iranian preoperative patients in which cultural factors may contribute.
Identification of potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma via integrated bioinformatics analysis
Authors: Meng Ziqi , Wu Jiarui , Liu Xinkui , Zhou Wei , Ni Mengwei , Liu Shuyu , Guo Siyu , Jia Shanshan , Zhang Jingyuan 
Published: July 2020

Objective The objective was to identify potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Methods Gene expression profile datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HCC and normal samples were identified via an integrated analysis. A protein–protein interaction network was constructed and analyzed using the STRING database and Cytoscape software, and enrichment analyses were carried out through DAVID. Gene Expression Profiling Interactive Analysis and Kaplan–Meier plotter were used to determine expression and prognostic values of hub genes. Results We identified 11 hub genes ( CDK1, CCNB2, CDC20, CCNB1, TOP2A, CCNA2, MELK, PBK, TPX2, KIF20A, and AURKA) that might be closely related to the pathogenesis and prognosis of HCC. Enrichment analyses indicated that the DEGs were significantly enriched in metabolism-associated pathways, and hub genes and module 1 were highly associated with cell cycle pathway. Conclusions In this study, we identified key genes of HCC, which indicated directions for further research into diagnostic and prognostic biomarkers that could facilitate targeted molecular therapy for HCC.
Pain freedom after 2 hours should be the primary outcome in controlled trials treating migraine attacks
Authors: Tfelt-Hansen Peer , Diener Hans-Christoph 
Published: July 2020

Background Pain freedom after 2 hours is the recommended primary endpoint by the International Headache Society in randomized trials investigating drug treatment of acute migraine attacks. In order to demonstrate an early effect of a drug, some drug companies, however, have promoted headache relief (improvement from severe or moderate pain to mild or no pain) at earlier time points than 2 hours as outcome parameter. Methods and results We analyzed the relationship between pain freedom and headache relief in acute migraine trials and observed that persistent mild headache constituted 90% of headache relief after 0.5 hour and 40% of headache relief after 2 hours. Conclusion Headache relief at 2 hours should in our view only be used as an outcome measure for comparison with historic data. Prior to 2 hours, headache relief varies with time from intake and the therapeutic gain is very small. Therefore, pain freedom should be used at these early time points.
Proposed modified diagnostic criteria for recurrent painful ophthalmoplegic neuropathy: Five case reports and literature review
Authors: Liu Yinglu , Wang Miao , Bian Xiangbing , Qiu Enchao , Han Xun , Dong Zhao , Yu Shengyuan 
Published: July 2020

Background Recurrent painful ophthalmoplegic neuropathy (RPON) is an uncommon disorder characterized by recurrent unilateral headache attacks associated with ipsilateral ophthalmoplegia. We intend to study the clinical picture in our case series along with the published literature to discuss the pathogenesis and propose modified diagnostic criteria for recurrent painful ophthalmoplegic neuropathy. Methods We reported five cases diagnosed as ophthalmoplegic migraine/RPON in our medical centers and reviewed the published literature related to RPON from the Pubmed database between 2000 and 2020. In one of these cases, a multiplanar reformation was performed to look at the aberrant cranial nerve. Results The mean onset age for RPON was 22.1 years, and the oculomotor nerve was the most commonly involved cranial nerve (53.9%) in 165 reviewed patients. In most patients, ophthalmoplegia started within 1 week of the headache attack (95.7%, 67/70). Additionally, 27.6% (40/145) of patients presented enhancement of the involved nerve(s) from MRI tests. Finally, 78 patients received corticosteroids, out of which 96.2% benefited from them. Conclusion This is the first time multiplanar reformation has been performed to reveal the distortion of the oculomotor nerve. Modified diagnostic criteria are proposed. We hope to expand the current knowledge and increase the detection of recurrent painful ophthalmoplegic neuropathy in the future.
Speckle tracking echocardiography for the evaluation of left ventricular function in children with systemic lupus erythematosus
Authors: Emara Mai , Hafez Maher Abdel , El-Bendary Aml , Razaky Osama El 
Published: July 2020

Background Many studies in adult patients with systemic lupus erythematosus (SLE) have demonstrated that myocardial dysfunction was significantly associated with enhanced disease activity. However, similar studies in paediatric patients with SLE are limited. The aim of this study was to evaluate the role of speckle tracking echocardiography (STE) to detect left ventricular dysfunction in children with active and inactive SLE. Methods This prospective case–control study was carried out on 50 children with SLE. Thirty healthy age- and sex-matched children comprised the control group. The patients were further subdivided into two subgroups: active SLE and inactive SLE. Laboratory investigations undertaken included complete blood count, renal function, C3, C4, ANA, anti-dsDNA and serum N-terminal pro-B type natriuretic peptide. Echocardiographic examinations were performed on all children and included conventional echocardiography, tissue Doppler imaging (TDI) and two- and three-dimensional STE. Results There was no statistically significant difference in N-terminal pro B natriuretic peptide between the studied groups. The myocardial performance index by TDI was statistically significantly higher in SLE patients compared to controls. STE parameters were statistically significantly lower in SLE patients compared to controls. There was no correlation between STE parameters and disease activity. Conclusions STE could be a promising technique in the early detection of subclinical left ventricular dysfunction in children with SLE.
Conserved regression patterns of retinopathy of prematurity after intravitreal ranibizumab: A class effect
Authors: Ji Marco H , Moshfeghi Darius M , Shields Ryan A , Bodnar Zachary , Ludwig Cassie A , Callaway Natalia F , Orazi Lorenzo , Amorelli Giulia M , Lepore Domenico 
Published: July 2020

Purpose: To determine if fluorescein angiographic (FA) findings after intravitreal ranibizumab (IVR) for retinopathy of prematurity (ROP) conform to a class effect previously described with bevacizumab. Methods: Single-center retrospective case series of all infants treated with 0.2 mg (0.02 mL) IVR for Type 1 ROP from July 2016 to November 2018. FA were obtained at 40, 52, 62, and 72 weeks of postmenstrual age (PMA) using wide-angle photography. FA images were analyzed and the peripheral avascular areas measured with ImageJ using a reference disc diameter (DD). Based on the extent of the avascular area and tortuosity of the retinal vessels all eyes were classified into four categories: complete vascular maturity (vascularization within 2 DD of the ora serrata), VAA (avascular area >2 DD of the ora serrata), VAT (avascular area >2 DD of the ora serrata and posterior tortuosity), and reactivation (recurrence of stage disease). Results: About 13 infants were enrolled and 24 eyes were available in this study. None of the eyes reached complete vascular maturity at an average PMA of 60 weeks, 7 (29%) eyes presented with VAA, 8 (33%) with VAT, and 9 (37.5%) reactivated. The reactivated eyes presented with the largest area of peripheral ischemia, followed by the VAT and then the VAA groups ( p = 0.02). Conclusion: IVR conforms to the previously described regression patterns following intravitreal bevacizumab for ROP indicative of a class effect. Follow-up using FA might help to optimize the management of these infants after injection of the drug.
Efficacy of omega-3 fatty acids and punctal plugs in the prevention of isotretinoin-associated ocular surface disease
Authors: Elhamaky Tarek Roshdy 
Published: July 2020

Purpose: To investigate the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in patients receiving systemic isotretinoin therapy. Methods: This is a prospective randomized study that included 180 eyes of 90 patients who had systemic isotretinoin therapy (120–150 mg/kg for at least 4–6 months). Exclusion criteria: DED according to the diagnostic criteria of TFOS DEWS II. Patients were assigned into three groups; (1) O3FAs/PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral O3FAs two capsules twice daily total daily dose of 1040 mg/day for 6 months. (2) PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral placebo. (3) Isotretinoin group: No intervention was done. At baseline, 1 week, 1, 3, and 6 months of study, Ocular surface evaluation tests were done in following order: OSDI, tear osmolarity, Schirmer’s I test, TBUT, ocular surface staining score, and meibomian gland expression. Primary outcome measures: The changes in measurement of ocular surface evaluation tests including ocular surface disease index (OSDI), tear film breakup time (TFBUT), corneal staining, tear osmolarity, and meibomian gland expression at 6 months. Results: There are significant changes between all groups at 6 months follow-up. The ocular surface parameters were better for the PPs and O3FAs/PPs groups than the isotretinoin group. The isotretinoin group showed worsening of ocular surface parameters including a significant decrease of FTBUT and an increase of OSDI score, corneal staining score, tear osmolarity, and meibomian expression score. There was no significant difference in ST1 throughout the whole study in all groups. At 6 months follow-up, there were no statistically significant differences between PPs and O3FAs/PPs groups except meibomian expression score which showed a significant increase in PPs group. Conclusion: Our cohort highlights the beneficial effects of the combination of O3FAs supplementation with PPs in the prevention of isotretinoin-associated OSD in this sample study.
The demographics and traumatic causes of spinal cord injury in Nepal: An observational study
Authors: Willott Arran , Dhakal Raju , Groves Christine , Mytton Julie , Ellis Matthew 
Published: July 2020

Introduction There has been little systematic study of the epidemiology of traumatic spinal cord injury (TSCI) in Nepal, South-East Asia, and low- and middle-income countries (LMICs) in general. One third of the global morbidity and mortality due to injuries is concentrated in South-East Asia. We need to better understand the circumstances leading to TSCI if we are to make progress with prevention. Method The Spinal Injury Rehabilitation Centre (SIRC) in Nepal systemically collected prospective data describing people with TSCI admitted between September 2015 and August 2016. Descriptive analyses of variables yielded demographic, aetiological and clinical descriptors of this cohort. Cross-tabulations were used to explore the associations between variables. Results Of 184 admissions over one year, males were admitted to SIRC almost 2.3 times more often than females. Young adults (21–30 years) were the largest age group (34%). The majority of TSCI resulted in paraplegia (67%) and was complete in nearly half (49%). Falls caused the majority of TSCI (69%), and falls from trees were the most common. Road traffic injuries (RTIs) were the second leading cause (29%); the majority involved two- or three-wheeled motorised vehicles and patients were most commonly driving. Conclusion Falls were the leading cause of TSCI across both genders and all age groups, followed by RTIs, which occurred most often in young adults and men. Injury surveillance and further research would provide a greater understanding of the pattern of TSCI and enable progress in TSCI prevention and rehabilitation.