bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer
Authors: Reuss Joshua E , Anagnostou Valsamo , Cottrell Tricia R , Smith Kellie N , Verde Franco , Zahurak Marianna , Lanis Mara , Murray Joseph C , Chan Hok Yee , McCarthy Caroline , Wang Daphne , White James R , Yang Stephen , Battafarano Richard , Broderick Stephen , Bush Errol , Brock Malcolm , Ha Jinny , Jones David , Merghoub Taha , Taube Janis , Velculescu Victor E , Rosner Gary , Illei Peter , Pardoll Drew M , Topalian Suzanne , Naidoo Jarushka , Levy Ben , Hellmann Matthew , Brahmer Julie R , Chaft Jamie E , Forde Patrick M 
Published: September 2020

BackgroundWe conducted the first trial of neoadjuvant PD-1 blockade in resectable non-small cell lung cancer (NSCLC), finding nivolumab monotherapy to be safe and feasible with an encouraging rate of pathologic response. Building on these results, and promising data for nivolumab plus ipilimumab (anti-CTLA-4) in advanced NSCLC, we expanded our study to include an arm investigating neoadjuvant nivolumab plus ipilimumab.MethodsPatients with resectable stage IB (≥4 cm)–IIIA (American Joint Committee on Cancer Tumor Node Metastases seventh edition), histologically confirmed, treatment-naïve NSCLC received nivolumab 3 mg/kg intravenously plus ipilimumab 1 mg/kg intravenously 6 weeks prior to planned resection. Nivolumab 3 mg/kg was given again approximately 4 and 2 weeks preoperatively. Primary endpoints were safety and feasibility with a planned enrollment of 15 patients. Pathologic response was a key secondary endpoint.ResultsWhile the treatment regimen was feasible per protocol, due to toxicity, the study arm was terminated early by investigator consensus after 9 of 15 patients were enrolled. All patients received every scheduled dose of therapy and were fit for planned surgery; however, 6 of 9 (67%) experienced treatment-related adverse events (TRAEs) and 3 (33%) experienced grade ≥3 TRAEs. Three of 9 patients (33%) had biopsy-confirmed tumor progression precluding definitive surgery. Of the 6 patients who underwent resection, 3 are alive and disease-free, 2 experienced recurrence and are actively receiving systemic treatment, and one died postoperatively due to acute respiratory distress syndrome. Two patients who underwent resection had tumor pathologic complete responses (pCRs) and continue to remain disease-free over 24 months since surgery. Pathologic response correlated with pre-treatment tumor PD-L1 expression, but not tumor mutation burden. Tumor KRAS/STK11 co-mutations were identified in 5 of 9 patients (59%), of whom two with disease progression precluding surgery had tumor KRAS/STK11/KEAP1 co-mutations.ConclusionsThough treatment was feasible, due to toxicity the study arm was terminated early by investigator consensus. In light of this, and while the long-term disease-free status of patients who achieved pCR is encouraging, further investigation of neoadjuvant nivolumab plus ipilimumab in patients with resectable NSCLC requires the identification of predictive biomarkers that enrich for response.
De novo mutations of SCN1A are responsible for arthrogryposis broadening the SCN1A-related phenotypes
Authors: Jaber Dana , Gitiaux Cyril , Blesson Sophie , Marguet Florent , Buard David , Varela Salgado Maritzaida , Kaminska Anna , Saada Julien , Fallet-Bianco Catherine , Martinovic Jelena , Laquerriere Annie , Melki Judith 
Published: September 2020

BackgroundArthrogryposis multiplex congenita (AMC) is the direct consequence of reduced fetal movements. AMC includes a large spectrum of diseases which result from variants in genes encoding components required for the formation or the function of the neuromuscular system. AMC may also result from central nervous involvement. SCN1A encodes Nav1.1, a critical component of voltage-dependent sodium channels which underlie action potential generation and propagation. Variants of SCN1A are known to be responsible for Dravet syndrome, a severe early-onset epileptic encephalopathy. We report pathogenic heterozygous missense de novo variants in SCN1A in three unrelated individuals with AMC.MethodsWhole-exome sequencing was performed from DNA of the index case of AMC families. Heterozygous missense variants in SCN1A (p.Leu893Phe, p.Ala989Thr, p.Ile236Thr) were identified in three patients. Sanger sequencing confirmed the variants and showed that they occurred de novo.ResultsAMC was diagnosed from the second trimester of pregnancy in the three patients. One of them developed drug-resistant epileptic seizures from birth. We showed that SCN1A is expressed in both brain and spinal cord but not in skeletal muscle during human development. The lack of motor denervation as established by electromyographic studies or pathological examination of the spinal cord or skeletal muscle in the affected individuals suggests that AMC is caused by brain involvement.ConclusionWe show for the first time that SCN1A variants are responsible for early-onset motor defect leading to AMC indicating a critical role of SCN1A in prenatal motor development and broadening the phenotypic spectrum of variants in SCN1A.
Primordial universe with the running cosmological constant
Authors: Ruiz Jhonny A. Agudelo , de Paula Netto Tibério , Fabris Júlio C. , Shapiro Ilya L. 
Published: September 2020

AbstractTheoretically, the running of the cosmological constant in the IR region is not ruled out. On the other hand, from the QFT viewpoint, the energy released due to the variation of the cosmological constant in the late Universe cannot go to the matter sector. For this reason, the phenomenological bounds on such a running are not sufficiently restrictive. The situation can be different in the early Universe when the gravitational field was sufficiently strong to provide an efficient creation of particles from the vacuum. We develop a framework for systematically exploring this possibility. It is supposed that the running occurs in the epoch when the Dark Matter already decoupled and is expanding adiabatically, while the usual matter should be regarded approximately massless and can be abundantly created from vacuum due to the decay of vacuum energy. By using the handy model of Reduced Relativistic Gas for describing the warm Dark Matter, we consider the dynamics of both cosmic background and linear perturbations and evaluate the impact of the vacuum decay on the matter power spectrum and to the first CMB peak. Additionally, using the combined SNIa+BAO data, we find the best-fit values for the free parameters of the model.
Integrated Cretaceous–Cenozoic plate tectonics and structural geology in southern Mexico
Authors: Graham Rod , Pindell James , Villagómez Diego , Molina-Garza Roberto , Granath James , Sierra-Rojas Maria 
Published: September 2020

Abstract
The structural evolution of southern Mexico is described in the context of its plate tectonic evolution and illustrated by two restored crustal scale cross-sections through Cuicateco and the Veracruz Basin and a third across Chiapas. We interpret the Late Jurassic–Early Cretaceous opening of an oblique hyper-stretched intra-arc basin between the Cuicateco Belt and Oaxaca Block of southern Mexico where Lower Cretaceous deep-water sediments accumulated. These rocks, together with the hyper-stretched basement beneath them and the Oaxaca Block originally west of them, were thrust onto the Cretaceous platform of the Cuicateco region during a Late Cretaceous–Eocene orogenic event. The mylonitic complex of the Sierra de Juárez represents this hyper-stretched basement, perhaps itself an extensional allochthon. The Chiapas fold-and-thrust belt is mainly Neogene in age. Shallowing of the subduction angle of the Cocos Plate in the wake of the Chortis Block, suggested by seismicity and migrating arc volcanism, is thought to play an important role in the development of the Chiapas fold-and-thrust belt itself, helping to explain the structural dilemma of a vertical transcurrent plate boundary fault (the Tonalá Fault) at the back of an essentially dip-slip fold-and-thrust belt.
Is Endovascular Treatment Still Good for Ischemic Stroke in Real World?
Authors: Zhao Zixu , Zhang Jiarui , Jiang Xin , Wang Li , Yin Zixiao , Hall Michael , Wang Yang , Lai Lingfeng 
Published: September 2020

Background and Purpose:
Although endovascular treatment (EVT) for acute ischemic stroke is classified as I evidence, outcomes after EVT in real-world practice appear to be less superior than those in randomized clinical trials (RCTs). Additionally, the effect of EVT is unclear compared with medical treatment (MT) for patients with mild symptoms defined by National Institutes of Health Stroke Scale score <6 or with severe symptoms defined by Alberta Stroke Program Early CT Score <6.

Methods:
Literatures were searched in big databases and major meetings from December 6, 2009, to December 6, 2019, including RCTs and observational studies comparing EVT against MT for patients with acute ischemic stroke. Observational studies were precategorized into 3 groups based on imaging data on admission: mild stroke group with National Institutes of Health Stroke Scale score <6, severe stroke group with Alberta Stroke Program Early CT Score <6 or ischemic core ≥50 mL, and normal stroke group for all others. Outcome was measured as modified Rankin Scale score of 0 to 2, mortality at 90 days, and symptomatic intracranial hemorrhage (sICH) at 24 hours.

Results:
Fifteen RCTs (n=3694) and 37 observational studies (n=9090) were included. EVT was associated with higher modified Rankin Scale 0 to 2 rate and lower mortality in RCTs and normal stroke group, whereas EVT was associated with higher sICH rate in normal stroke group, and no difference of sICH rate appeared between EVT and MT in RCTs. In severe stroke group, EVT was associated with higher modified Rankin Scale 0 to 2 rate and lower mortality, whereas no difference of sICH rate was found. In mild stroke group, there was no difference in modified Rankin Scale 0 to 2 rate between EVT and MT, whereas EVT was associated with higher mortality and sICH rate.

Conclusions:
Evidence from RCTs and observational studies supports the use of EVT as the first-line choice for eligible patients corresponding to the latest guideline. For patients with Alberta Stroke Program Early CT Score <6, EVT showed superiority over MT, also in line with the guidelines. On the contrary to the guideline, our data do not support EVT for patients with National Institutes of Health Stroke Scale score <6.
Do Obese Patients Present With More Advanced Breast Cancer?
Authors: Wang Melinda , Huang Julian , Chagpar Anees B. 
Published: September 2020

Background Obesity is a known risk factor for breast cancer development; however, it is unclear whether obesity is associated with more aggressive disease. We sought to determine the relationship between obesity and tumor characteristics in breast cancer patients. Methods Medical records of invasive breast cancer patients undergoing mastectomy at our institution between January 2010 and April 2018 were reviewed. Patients who had received neoadjuvant therapy were excluded. Patients were separated into obese (body mass index [BMI] ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) categories and compared using nonparametric statistical analyses. Results Of the 415 patients in this cohort, 124 (29.9%) were obese. Obese patients were more likely to present with larger tumors (tumor size ≥ 2 cm: 53.2% vs 41.0%, P = .024) and more node-positive disease (46.8% vs 28.9%, P = .001). Controlling for confounders, obesity was independently associated with node-positive disease (odds ratio [OR] = 2.00; 95% CI 1.24-3.21, P = .004), but not with tumor size ≥ 2 cm (OR = 1.38; 95% CI 0.87-2.21, P = .174). Conclusion Obesity is associated with node-positive disease at presentation independent of other factors.
Post-acquisition Performance Analysis of Indian Target Firms: The Role of Deal Characteristics
Authors: Kapil Sheeba , Barick Gaurav 
Published: September 2020

The aim of this article is to identify and determine various dimensions of deal characteristics affecting the post-acquisition performance of Indian target firms. Available researches have focussed on the stock market reaction as the indicator of target firm performance. Nonetheless, various determinants are found to affect the post-acquisition performance of target firms. Bearing that in mind, this article focusses on the significance of deal characteristics while assessing the performance of the Indian target firms post-acquisition. The article attempts to analyse the post-acquisition performance of target firms independent of the acquirer firm to get a more appropriate perception of their position. The change model, generalised method of moments (GMM) model and the regression model has been employed to assess the changes in operating performance, analyse the importance of financial variables in post-acquisition performance and study the impact of deal characteristics in the post-acquisition performance of the Indian target firms. The outcomes reveal that there has been a significant difference in the improvement of targets depending on whether it has been taken over by a domestic acquirer or inbound acquirer.
Constitutional Scholars as Constitutional Actors
Authors: Lazarus Liora 
Published: September 2020

AbstractThis article explores the idea that constitutional scholars may be thought of as constitutional actors analogous to integrity institutions and examines the normative implications of conceiving of constitutional scholars in this way. One implication of such an analogy is to strengthen academic freedom and protect the integrity and independence of constitutional scholarship. Moreover, viewing constitutional scholars as constitutional actors also sharpens our understanding of the ethical obligations of constitutional scholarship: of ‘academic self-awareness’ and of ‘decisional’ and ‘institutional’ independence. This duty of independence may be equally important to the public standing, expert status and integrity of the constitutional law discipline in this highly politicised populist moment.
Review of Current Vaccine Development Strategies to Prevent Coronavirus Disease 2019 (COVID-19)
Authors: Bennet Bindu M. , Wolf Jayanthi , Laureano Rodrigo , Sellers Rani S. 
Published: September 2020

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak that started in Wuhan, China, in 2019 resulted in a pandemic not seen for a century, and there is an urgent need to develop safe and efficacious vaccines. The scientific community has made tremendous efforts to understand the disease, and unparalleled efforts are ongoing to develop vaccines and treatments. Toxicologists and pathologists are involved in these efforts to test the efficacy and safety of vaccine candidates. Presently, there are several SARS-CoV-2 vaccines in clinical trials, and the pace of vaccine development has been highly accelerated to meet the urgent need. By 2021, efficacy and safety data from clinical trials are expected, and potentially a vaccine will be available for those most at risk. This review focuses on the ongoing SARS-CoV-2 vaccine development efforts with emphasis on the nonclinical safety assessment and discusses emerging preliminary data from nonclinical and clinical studies. It also provides a brief overview on vaccines for other coronaviruses, since experience gained from these can be useful in the development of SARS-CoV-2 vaccines. This review will also explain why, despite this unprecedented pace of vaccine development, rigorous standards are in place to ensure nonclinical and clinical safety and efficacy. [Box: see text]
Awareness of the risk of developing medication-related osteonecrosis of the jaw among bisphosphonate users
Authors: El-Ma’aita Ahmad , Da’as Noor , Al-Hattab Mais , Hassona Yazan , Al-Rabab’ah Mohammad , Al-Kayed Mohammad-Awni 
Published: September 2020

Objective In this retrospective observational study, we evaluated awareness among patients using bisphosphonates (BPs) regarding the risk of developing medication-related osteonecrosis of the jaw (MRONJ) and whether they received appropriate dental screening and treatment prior to commencing medication. Methods Patients using BPs who attended the endodontics clinic at Jordan University Hospital in 2019 were interviewed using a pre-designed questionnaire. Data were analysed using descriptive statistics and chi-squared tests. Results In total, 110 patients were interviewed (84 women, 26 men; age 40–78 years). A total of 94 patients were using oral BP and 16 received intravenous (IV) BP. We found that only 12.4% of participants were aware about the risk of MRONJ following BP use, and only one third of them has received information from their prescribing physicians. In total, 5% of participants were referred to a dentist for screening prior to initiating BP treatment. Patients receiving IV BP and those with a university-level education had better awareness about the risk of MRONJ than oral BP users and those with a high school education level. Conclusion Patients’ awareness about MRONJ risk was low in our population. Better patient education and collaboration among physicians and dentists are needed prior to starting BP treatment.
Quality of Life Among Breast and Colon Cancer Patients Before and After First-Cycle Chemotherapy
Authors: Zamel Osama N. , Inocian Ergie P. , Alshehry Abdualrahman S. , Tumala Regie B. , Patalagsa Joel G. , Alsaleh Khalid A. 
Published: September 2020

Purpose: This study aimed to compare the functioning, symptoms, and quality of life (QoL) of patients with breast or colon cancer before and after their first-cycle (FC) chemotherapy. Design: One-group pretest/posttest design. Method: The study utilized the standardized Arabic-translated Quality of Life Questionnaire Version 3 from the European Organization for Research and Treatment of Cancer in measuring the functioning, symptoms, and QoL of 120 Saudi patients diagnosed with breast or colon cancer. Dependent t test was used in analyzing the presence of significant differences in mean scores before and after chemotherapy with periods ranging from 14 days to 21 days following the treatment protocol. Results: The findings revealed significant differences in the functioning, symptoms, and QoL among patients with breast or colon cancer before and after FC chemotherapy ( p < .001). Baseline scores showed higher physical, role, emotional, cognitive, and social functioning; lesser symptoms; lower financial difficulties; and better overall global health status compared to post-FC chemotherapy. Conclusion: Assessing the QoL of patients with breast or colon cancer undergoing FC chemotherapy is essential to establish a holistic care plan in supporting and alleviating the unfavorable effects of chemotherapy and implement patient-centered interventions that aid in the enhancement of their overall QoL.
Cell-free DNA profiling in patients with lupus nephritis
Authors: Truszewska Anna , Wirkowska Agnieszka , Gala Kamila , Truszewski Piotr , Krzemień-Ojak Łucja , Perkowska-Ptasińska Agnieszka , Mucha Krzysztof , Pączek Leszek , Foroncewicz Bartosz 
Published: September 2020

Background Increased level of cell-free DNA (cf-DNA) is associated with systemic lupus erythematosus (SLE) and might be related to disease activity. The aim of this study was to evaluate whether cfDNA integrity, size distribution and concentration of different cfDNA fractions is associated with lupus activity and kidney involvement. Methods Blood samples were collected from 43 SLE patients and 50 healthy controls. Nuclear and mitochondrial fractions of cfDNA and intracellular DNA were quantified by real-time qPCR. Sizing and quantification of total cfDNA level was performed on Bioanalyzer. Results We determined four parameters that characterized cfDNA profile: fragmentation index, ratio of intra- to extracellular mtDNA copy number, cfDNA concentration, and presence of 54–149 bp and 209–297 bp fragments. Patients with healthy-like cfDNA profile had higher eGFR ( P = 0.009) and more often no indications for kidney biopsy or less advanced lupus nephritis (LN) ( P = 0.037). In contrary, SLE patients with distinct cfDNA profile (characterized by increased cfDNA concentration and fragmentation, higher discrepancy between intra- to extracellular mtDNA copy number, and the presence of 54–149 bp and 209–297 bp fragments) had lower eGFR ( P = 0.005) and more often advanced LN or history of renal transplantation ( P = 0.001). Conclusions We showed that cfDNA profiling may help to distinguish SLE patients with renal involvement and severe disease course from patients with more favorable outcomes. We suggest cfDNA profile a promising SLE biomarker.
The Longitudinal Relationship Between Screen Time, Sleep and a Diagnosis of Attention-Deficit/Hyperactivity Disorder in Childhood
Authors: Levelink Birgit , van der Vlegel Marjolein , Mommers Monique , Gubbels Jessica , Dompeling Edward , Feron Frans J.M. , van Zeben-van der Aa Dorothea M.C.B. , Hurks Petra , Thijs Carel 
Published: September 2020

Objective: To evaluate longitudinal associations between recreational screen time and sleep in early childhood, and attention-deficit/hyperactivity disorder (ADHD) at age 8 to 10 years. Method: Questionnaires from 2,768 mother-child pairs from the Dutch KOALA Birth Cohort Study were used. General estimating equation logistic regression analyses examined associations between screen time and sleep at age 2, 4, and 6, and ADHD at age 8 to 10. Linear regression analysis examined associations between television time, sleep and CBCL/2-3 scores at age 2. Results: Longitudinally, neither screen time nor sleep were associated with ADHD. Cross-sectionally, CBCL/2-3 externalizing symptom scores increased by 0.03 with every hour television time (95% CI 0.002–0.05) and increased by 0.02 per hour of less sleep (95% CI −0.03–−0.01). Conclusion: Despite an association with externalizing symptoms at age 2, screen time and sleep in early childhood were not associated with ADHD. Carefulness is warranted when extrapolating cross-sectional associations at early age to an ADHD diagnosis.