bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies
Authors: Prager Briana C. , Vasudevan Harish N. , Dixit Deobrat , Bernatchez Jean A. , Wu Qiulian , Wallace Lisa C. , Bhargava Shruti , Lee Derrick , King Bradley H. , Morton Andrew R. , Gimple Ryan C. , Pekmezci Melike , Zhu Zhe , Siqueira-Neto Jair L. , Wang Xiuxing , Xie Qi , Chen Clark , Barnett Gene H. , Vogelbaum Michael A. , Mack Stephen C. , Chavez Lukas , Perry Arie , Raleigh David R. , Rich Jeremy N. 
Published: July 2020

AbstractMeningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal, and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally responsive systemic cancers with meningioma subgroups, reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histologic grading. Superenhancer signatures predicted drug dependencies with superior in vitro efficacy to treatment based upon the NF2 genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth in vivo. Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies.Significance:Enhancer landscapes inform prognostic classification of aggressive meningiomas, identifying tumors at high risk of recurrence, and reveal previously unknown therapeutic targets. Druggable dependencies discovered through epigenetic profiling potentially guide treatment of intractable meningiomas.This article is highlighted in the In This Issue feature, p. 1611
The Expected 30-Year Benefits of Early Versus Delayed Primary Prevention of Cardiovascular Disease by Lipid Lowering
Authors: Pencina Michael J. , Pencina Karol M. , Lloyd-Jones Donald , Catapano Alberico L. , Thanassoulis George , Sniderman Allan D. 
Published: July 2020

Background:
Lipid-lowering recommendations for prevention of atherosclerotic cardiovascular disease rely principally on estimated 10-year risk. We sought to determine the optimal time for initiation of lipid lowering in younger adults as a function of expected 30-year benefit.

Methods:
Data from 3148 National Health and Nutrition Examination Survey (2009–2016) participants, age 30 to 59 years, not eligible for lipid-lowering treatment recommendation under the most recent US guidelines, were analyzed. We estimated the absolute and relative impact of lipid lowering as a function of age, age at initiation, and non–high-density lipoprotein cholesterol (HDL-C) level on the expected rates of atherosclerotic cardiovascular disease over the succeeding 30 years. We modeled expected risk reductions based on shorter-term effects observed in statin trials (model A) and longer-term benefits based on Mendelian randomization studies (model B).

Results:
In both models, potential reductions in predicted 30-year atherosclerotic cardiovascular disease risk were greater with older age and higher non–HDL-C level. Immediate initiation of lipid lowering (ie, treatment for 30 years) in 40- to 49-year-old patients with non–HDL-C ≥160 mg/dL would be expected to reduce their average predicted 30-year risk of 17.1% to 11.6% (model A; absolute risk reduction [ARR], 5.5%) or 6.5% (model B; ARR 10.6%). Delaying lipid lowering by 10 years (treatment for 20 years) would result in residual 30-year risk of 12.7% (A; ARR 4.4) or 9.9% (B; ARR 7.2%) and delaying by 20 years (treatment for 10 years) would lead to expected mean residual risk of 14.6% (A; ARR 2.6%) or 13.9% (B; ARR 3.2%). The slope of the achieved ARR as a function of delay in treatment was also higher with older age and higher non–HDL-C level.

Conclusions:
Substantial reduction in expected atherosclerotic cardiovascular disease risk in the next 30 years is achievable by intensive lipid lowering in individuals in their 40s and 50s with non–HDL-C ≥160 mg/dL. For many, the question of when to start lipid lowering might be more relevant than whether to start lipid lowering.
Spillover Impacts on Education from Employment Guarantees
Authors: Adukia Anjali 
Published: July 2020

Abstract
Programs that provide lower-skill employment are a popular anti-poverty strategy in developing countries, with India's employment guarantee program (MGNREGA) employing adults in 23 percent of Indian households. MGNREGA has reduced rural poverty, but some have raised concerns that guaranteeing lower-skill (or uncredentialed) employment opportunities may discourage investment in human capital and long-run income growth. Using large-scale administrative data and household survey data, I estimate precise spillover impacts on education that reject substantive declines in children's education from the government's rollout of MGNREGA. Further, I estimate these small negative impacts are inexpensive to counteract, particularly compared with MGNREGA expenditures on rural employment and poverty alleviation.
Failed Negotiations and the Dark Side of Ripeness: Insights from Egypt
Authors: Matesan Ioana Emy 
Published: July 2020

Abstract
This article revisits ripeness theory and examines whether conflicts with armed Islamist groups can also be ripe for negotiation. The article argues that armed Islamist organizations can be willing to negotiate and demobilize, but talks are particularly vulnerable to spoilers and public backlash. To examine these dynamics, the article investigates the case of al-Gama’a al-Islamiyya in Egypt. Relying on a variety of primary and secondary sources, including organizational documents and testimonies by the leaders, the analysis shows that the absence of ripeness can indeed explain some of the failures of negotiations. However, when the conflict was finally ripe, talks broke down because of elite divisions and public backlash. The case reveals that there is a dark side to ripeness: the conditions that lead to a mutually hurting stalemate can also lead to public outrage, elite divisions, and opposition to negotiations.
The Role of Universities in Shaping the Evolution of Silicon Valley’s Ecosystem of Innovation
Authors: Piqué Josep M. , Berbegal-Mirabent Jasmina , Etzkowitz Henry 
Published: July 2020

Universities play a unique role in ecosystems of innovation. They interact with the other agents of the Triple Helix model, developing their functions in relation to each other and together with industry and government. Grounded in key conceptual frameworks—Triple Helix, Regional Innovation Systems and Entrepreneurial University—we analyze how the leading universities in Silicon Valley (UC Berkeley, Stanford and UC San Francisco) have evolved, adapting to new demands and, in turn, shaping the evolution of Silicon Valley. To do so we use quantitative and qualitative data and examine the changes occurring between 2007 and 2018. A close examination of the data from this period reveals an increased attention to entrepreneurship education and an intensified activity of technology transfer offices. Equally relevant are the increased interactions between universities and investors (business angels, Venture Capital funds and corporate investors), and the improvement of specific infrastructures to incubate and accelerate business ideas.
Puppy love in the time of Corona: Dog ownership protects against loneliness for those living alone during the COVID-19 lockdown
Authors: Oliva Jessica Lee , Johnston Kim Louise 
Published: July 2020

Background: The COVID-19 pandemic has resulted in many countries enforcing a ‘lockdown’, whereby people are instructed to stay at home. Aim: The aim of this study was to capture the experience of such a lockdown in Australians living alone, with and without a dog or a cat. Method: Three hundred and eighty-four participants completed an online survey evaluating their levels of loneliness, mindfulness and mood. For participants who owned a dog or a cat, a measure of dog/cat interactions was also administered as well as two open-ended questions about how being a pet owner affected their experience of COVID-19 and how COVID-19 affected their pet. Results: Contrary to expectations, cat owners were found to be less mindful than non-owners and pet interactions did not account for levels of loneliness or levels of mindfulness. In line with our expectations, however, stress and depression positively predicted loneliness, while mindfulness and being a dog owner were protective against it. Insights from qualitative responses suggest that this might be due to the fact that dogs encourage a routine which involves getting out of the house and walking, which itself offers opportunities to socialise with other people doing the same thing. Conclusion: These findings add to the emerging literature on mental well-being during a lockdown and the unique role that pets play in their owners’ experiences.
Large Program Cost Estimating: Nuanced Implementation Assumptions Make Non-Nuanced Impacts
Authors: Galante Giuliana , Bruzzone Anthony 
Published: July 2020

Transformative transportation programs often comprise discrete complex projects to deliver an overall vision. Even with substantial benefits, the cost, complexity, and risk of the entire program often creates a “sticker-shock” reaction that dominates public discussion. When escalation is factored into the program, costs can appear unreasonable or not financeable. In this scenario, benefits and costs are never discussed in a parallel (and equal) basis. If this leads to more delay, escalation creates an ever-more expensive output, leading to ever less support for the transformative program. Aviation and highway industries often deliver their programs as discrete projects of independent utility (for example, an additional lane of highway, or a new airport terminal). Rail and bus transit infrastructure projects, in contrast, are usually presented as the entire program (new vehicles, infrastructure, stations, facilities) even if some aspects of the program could be presented as a discrete project. By focusing on the program, rather than projects, transit proposals present stretch delivery dates and feature mountains of escalated costs. This paper uses the recent Boston North-South Rail Link (NSRL) Reassessment (Massachusetts, U.S.) as a case study. An examination is made of the potential benefits of packaging the program to advance independent but complementary projects. The expectation is that this approach reduces escalation, resulting in overall program cost savings in real dollars. While further research to validate this premise is suggested, the concepts of the paper can be used to reassess traditional megaproject schedule and delivery assumptions, reducing the identified cost escalation over the years.
Portable Chest Radiography Through Glass During COVID-19 Pandemic—Initial Experience in a Tertiary Care Center
Authors: Rai Archana , Ditkofsky Noah , Hunt Bryce , Dubrawski Margaret , Deva Djeven , Mathur Shobhit 
Published: July 2020

Background: Portable chest radiograph for COVID-19 positive patients and persons under investigation can be acquired through glass doors or walls of isolation rooms to limit exposure to the pathogen and conserve resources. Purpose: To report our initial experience with acquiring portable chest radiographs through glass doors of isolation rooms. Methods: Only 1 of 2 radiology technologist team members donned personal protective equipment and stayed inside the isolation room, while the second technologist and the radiography unit remained outside during the procedure. First hundred radiographs acquired through glass at the emergency department of our institute formed the “through glass radiograph” group. Hundred consecutive portable chest radiographs performed in a conventional manner formed the “conventional radiograph” group for comparison. Imaging database and feedback from operations leader were used to identify occurrences of a failed procedure. Suggestion of repeating the study and comments related to quality of the study were recorded from the reports of the staff radiologist. Results: There was no instance of failed acquisition, nondiagnostic examination, or suggestion of repetition in both groups. No significant difference in the number of reports with quality related remarks ( P > .05) was found between the 2 groups. Radiography through glass doors was associated with increased suboptimal positioning related remarks in radiology reports ( P < .05). No significant association was identified among other comments about image quality. Conclusion: Our initial clinical experience suggests that the acquisition of portable chest radiographs through the glass doors of isolation rooms is technically feasible and results in diagnostic quality studies.
Perceived susceptibility to developing cancer and screening for colorectal and prostate cancer: A longitudinal analysis of Alberta’s Tomorrow Project
Authors: Gilfoyle Meghan , Chaurasia Ashok , Garcia John , Oremus Mark 
Published: July 2020

Introduction To assess the association between perceived susceptibility of developing cancer and being screened via sigmoidoscopy/colonoscopy and prostate-specific antigen, respectively. Methods Participants aged 35–69, who resided in Alberta, Canada, were enrolled into the study between 2000 and 2008. We used general linear mixed models, adjusted for age, marital status, work status, education, family history and place of residence, to explore the association. Results Perceived susceptibility of developing cancer was associated with both screening tests at baseline and a maximum of 14-year follow-up: (i) colorectal cancer screening – adjusted odds ratios were 1.97 (95% CI = 1.52–2.55) per one-unit increase in participants' personal belief in susceptibility to cancer, and 1.03 (95% CI = 1.00–1.04) per one-percent increase in participants’ estimate of their own chance of developing cancer; (ii) prostate cancer screening – adjusted odds ratios were 1.36 times greater (95% CI = 1.07–1.72), and 1.02 times higher (95% CI = 1.01–1.03), for each respective perceived susceptibility measure. Conclusion Health promotion can focus on targeting and heightening personal perceived susceptibility of developing cancer in jurisdictions with low screening rates for colorectal or prostate cancer.
Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma
Authors: Halford Zachery , Anderson Mary Kate , Bennett Lunawati L. 
Published: July 2020

Objective To evaluate the literature for axicabtagene ciloleucel (axi-cel), a first-in-class chimeric antigen receptor (CAR) T-cell therapy, in the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Data Sources We conducted a PubMed (inception to June 22, 2020) and ClinicalTrials.gov search using the following terms: CD19, chimeric antigen receptor, and lymphoma. Study Selection and Data Extraction All retrospective and prospective studies evaluating the use of axi-cel in LBCL were reviewed. Data Synthesis In the pivotal ZUMA-1 trial, axi-cel exhibited unprecedented overall and complete response rates of 83% and 58%, respectively. With a median follow-up of 27.1 months, 39% of patients had ongoing responses. Furthermore, postmarketing retrospective analyses found similar response rates in a more clinically diverse LBCL patient population. Novel CAR T-cell therapy elicits unique and potentially life-threatening toxicities that include cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Studies reported grade ≥3 CRS in 7% to 14% of patients and grade ≥3 ICANS in 31% to 55% of patients. Relevance to Patient Care and Clinical Practice Axi-cel was the first US Food and Drug Administration–approved genetically engineered autologous CAR T-cell agent in r/r LBCL, representing an important milestone and paradigm shift in cancer treatment. Adoptive T-cell immunotherapy is a breakthrough treatment modality requiring careful patient selection, multidisciplinary collaboration, comprehensive patient counseling, and expert training to ensure optimal treatment. Conclusions The initial and ongoing results with axi-cel are encouraging, but long-term safety and efficacy data are lacking. Additional studies are required to identify axi-cel’s ideal place in LBCL therapy.
Effectiveness of Quetiapine as a Sedative Adjunct in Mechanically Ventilated Adults Without Delirium
Authors: Ohman Kelsey L. , Schultheis Jennifer M. , Kram Shawn J. , Cox Christopher E. , Gilstrap Daniel L. , Yang Zidanyue , Kram Bridgette L. 
Published: July 2020

Background: Quetiapine is an atypical antipsychotic that is commonly used in the Intensive Care Unit (ICU). The utility of quetiapine as a sedative adjunct has not yet been evaluated, but has been described previously in studies evaluating quetiapine for delirium or delirium prophylaxis. Objective: To determine if adjunctive use of quetiapine reduces sedative dosage requirements among mechanically ventilated adults without delirium. Methods: This retrospective intrapatient comparator study included all mechanically ventilated adults admitted to a medical ICU who received quetiapine between July 1, 2013, and July 1, 2018. The primary outcome was the change in sedative dosage requirements over 24 hours following quetiapine initiation. Secondary outcomes included change in sedative dosage requirements 48 hours postquetiapine initiation, opioid dosage requirements 24 hours postquetiapine initiation, percent time at goal for both pain and sedation scores, depth of sedation, and QTc. Results: A total of 57 patients were included in the study cohort. There was no significant difference in 24-hour cumulative doses of propofol ( P = 0.10), dexmedetomidine ( P = 0.14), or benzodiazepines ( P = 0.14). During the 48-hour treatment period, there was a significant increase in dexmedetomidine requirements ( P = 0.03). There were no differences in 24-hour opioid dosage requirements, percent time at goal pain or sedation scores, depth of sedation, or QTc following quetiapine initiation. Conclusion and Relevance: Adjunctive use of quetiapine was not associated with a significant reduction in sedative dosage requirements 24 or 48 hours following initiation among mechanically ventilated adults without delirium.
Comparison of corneal biomechanical changes after LASIK and F-SMILE with CorVis ST
Authors: Abd El-Fattah Eman A , El Dorghamy Alaa A , Ghoneim Ahmed M , Saad Hisham A 
Published: July 2020

Purpose: To evaluate changes in corneal biomechanics after LASIK and F-SMILE. Setting: Elite Eye Center, Tanta, Egypt. Design: Prospective, randomized, unmasked, interventional comparative case series. Patients and methods: A total of 60 eyes were equally divided into two groups; group A: received LASIK and group B: received F-SMILE. Pentacam and CorVis ST parameters were compared before and 6 months after procedures. P ⩽ 0.05 was used for significance of results. Results: bIOP decreased by 0.762 ± 1.211 mmHg in group A ( p = 0.092), and by 2.52 ± 1.389 mmHg in group B ( p < 0.001) and the difference between groups became significant ( p = 0.001). A1 increased significantly in group A only ( p = 0.036); while A2 decreased insignificantly in both groups. DAR increased significantly in both groups ( p < 0.001, p = 0.022), but the difference between groups remained insignificant ( p = 0.461). IR increased significantly in group A only ( p < 0.001) and the difference between groups became significant ( p = 0.026). ARTH decreased in both groups ( p = 0.245, p = 0.695) and the difference remained insignificant ( p = 0.928). SP-A1 decreased in group A by 8.89 ± 1.38 mmHg/mm ( p = 0.637), and by 32.6 ± 4.39 mmHg/mm in group B ( p < 0.001) and the postoperative difference between groups was significant ( p = 0.013). CBI increased significantly in group A ( p < 0.001), but insignificantly in group B ( p = 0.098) and postoperative difference between groups was highly significant ( p < 0.001). A significant correlation was found between change in CCT and corresponding changes in DAR, IR, and ARTH after surgery in both groups. Conclusion: The significant differences between groups postoperatively as regards bIOP ( p = 0.001), IR ( p = 0.026), SP-A1 ( p = 0.013), and CBI ( p < 0.001) indicate stiffer corneas after F-SMILE and suggest less influence on corneal biomechanics than LASIK.
Assessing Imageability of Port Cities Through the Visibility of Public Spaces: The Cases of Famagusta and Limassol
Authors: Özgece Nezire , Edgü Erincik , Ayıran Nezih 
Published: July 2020

Characteristics of port cities are significantly different than inland cities since they have a spatial relation with water. Waterfronts, main urban squares, and major streets are specified as the predominant components affecting socio-spatial configurations. The research assumes that the imageability of port cities, which refers to “port city identity” in this research, is associated with the visibility of these key public spaces. The port cities of Famagusta and Limassol—the current major port cities of divided Cyprus—were selected to be evaluated on the specified public spaces to reveal this association. The specified spaces are scrutinized through both the space syntax methodology and land-use and movement patterns in relation to visibility parameters. The results show that Limassol is more successful than Famagusta in terms of imageability, as it presents higher spatial and social visibility of public spaces, which also strengthens its port city identity.
Novel serum peptide model revealed by MALDI-TOF-MS and its diagnostic value in early bladder cancer
Authors: Ding Dapeng , Chen Mingying , Xiao Xiaoguang , Cao Penglong , Li Shijun 
Published: July 2020

Background: Bladder cancer is the ninth most common cancer worldwide and has high morbidity and mortality. We aimed to search for potential serum peptide biomarkers and establish a diagnostic model for early bladder cancer. Methods: A total of 67 bladder cancer patients and 64 healthy volunteers were randomly divided into a training set and testing set 1. There were 30 hematuria patients used as testing set 2. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry based on weak cation exchange magnetic beads was used to obtain and analyze the serum peptide profiles between bladder cancer patients and healthy volunteers in the training set. Serum peptide diagnostic model through a k-nearest neighbor algorithm, was established and validated, and significantly differentially expressed protein biomarkers were ultimately identified. Results: We constructed a diagnostic model containing five peptides (m/z 1954.9, m/z 2081.0, m/z 3938.3, m/z 3946.5, and m/z 4268.8). In the training set, the area under the curve (AUC) value of the five-peptide model was 0.923, and the sensitivity and specificity was 93.75% and 96.77%, respectively. In testing set 1, the sensitivity and specificity was 91.43% and 90.91%, respectively, and the specificity of testing set 2 was 73.33%. For early-stage bladder cancer, the sensitivity and specificity was 92.31% and 93.75%, respectively; the sensitivity of early low-grade bladder cancer was 90.00%; and the AUC value was 0.944. Conclusion: The five-peptide diagnostic model established in this study had high sensitivity and specificity, especially in the diagnosis of early bladder cancer, and could differentiate between healthy volunteers and hematuria patients.