bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four-lepton production in gluon fusion at NLO matched to parton showers
Authors: Alioli Simone , Ravasio Silvia Ferrario , Lindert Jonas M. , Röntsch Raoul 
Published: August 2021

AbstractWe present a calculation of the next-to-leading order (NLO) QCD corrections to gluon-induced electroweak gauge boson pair production, $$gg \rightarrow ZZ$$

g
g
→
Z
Z

and $$gg \rightarrow W^+W^-$$

g
g
→

W
+

W
-

, matched to the parton shower in the approach. The calculation consistently incorporates the continuum background, the Higgs-mediated $$gg\rightarrow H^* \rightarrow VV$$

g
g
→

H
∗

→
V
V

process, and their interference. We consider leptonic decay modes of the vector bosons and retain offshell and non-resonant contributions. The processes considered are loop-induced at leading order and thus contain two-loop virtual contributions as well as loop-squared real contributions. Parton-shower effects are found to be marginal in inclusive observables and quite sizeable in observables that are exclusive in additional jet radiation. The Monte Carlo generator presented here allows for realistic experimental effects to be incorporated in state-of-the-art precision analyses of diboson production and of the Higgs boson in the offshell regime.
Rlf–Mycl Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer
Authors: Ciampricotti Metamia , Karakousi Triantafyllia , Richards Allison L. , Quintanal-Villalonga Àlvaro , Karatza Angeliki , Caeser Rebecca , Costa Emily A. , Allaj Viola , Manoj Parvathy , Spainhower Kyle B. , Kombak Faruk E. , Sanchez-Rivera Francisco J. , Jaspers Janneke E. , Zavitsanou Anastasia-Maria , Maddalo Danilo , Ventura Andrea , Rideout William M. , Akama-Garren Elliot H. , Jacks Tyler , Donoghue Mark T.A. , Sen Triparna , Oliver Trudy G. , Poirier John T. , Papagiannakopoulos Thales , Rudin Charles M. 
Published: August 2021

Abstract

Small cell lung cancer (SCLC) has limited therapeutic options and an exceptionally poor prognosis. Understanding the oncogenic drivers of SCLC may help define novel therapeutic targets. Recurrent genomic rearrangements have been identified in SCLC, most notably an in-frame gene fusion between RLF and MYCL found in up to 7% of the predominant ASCL1-expressing subtype. To explore the role of this fusion in oncogenesis and tumor progression, we used CRISPR/Cas9 somatic editing to generate a Rlf–Mycl-driven mouse model of SCLC. RLF–MYCL fusion accelerated transformation and proliferation of murine SCLC and increased metastatic dissemination and the diversity of metastatic sites. Tumors from the RLF–MYCL genetically engineered mouse model displayed gene expression similarities with human RLF–MYCL SCLC. Together, our studies support RLF–MYCL as the first demonstrated fusion oncogenic driver in SCLC and provide a new preclinical mouse model for the study of this subtype of SCLC.

Significance:
The biological and therapeutic implications of gene fusions in SCLC, an aggressive metastatic lung cancer, are unknown. Our study investigates the functional significance of the in-frame RLF–MYCL gene fusion by developing a Rlf–Mycl-driven genetically engineered mouse model and defining the impact on tumor growth and metastasis.
This article is highlighted in the In This Issue feature, p. 2945
Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy
Authors: Abou-el-Enein Mohamed , Elsallab Magdi , Feldman Steven A. , Fesnak Andrew D. , Heslop Helen E. , Marks Peter , Till Brian G. , Bauer Gerhard , Savoldo Barbara 
Published: August 2021

Abstract

As of April 2021, there are five commercially available chimeric antigen receptor (CAR) T cell therapies for hematologic malignancies. With the current transition of CAR T cell manufacturing from academia to industry, there is a shift toward Good Manufacturing Practice (GMP)–compliant closed and automated systems to ensure reproducibility and to meet the increased demand for patients with cancer. In this review, we describe current CAR T cell clinical manufacturing models and discuss emerging technologic advances that embrace scaling and production optimization. We summarize measures being used to shorten CAR T cell manufacturing times and highlight regulatory challenges to scaling production for clinical use.

Significance:
As the demand for CAR T cell cancer therapy increases, several closed and automated production platforms are being deployed, and others are in development. This review provides a critical appraisal of these technologies, which can be leveraged to scale and optimize the production of next-generation CAR T cells.
See related video: https://aacrjournals.org/content/webinar-car-t-cell-manufacturing
Assessment of Satellite-based Precipitation Products Performance over the Hyper-arid Climate of Kuwait
Authors: AlMutairi Bandar S. 
Published: August 2021

AbstractPrecipitation is a complex natural parameter that is essential for water and environmental systems. Due to its variability on the spatial and temporal scales, satellite-based precipitation products (SPPs) have arisen interest in hydrology and meteorology applications. This study measures the performance of six high resolutions SPPs (GPM IMERG products (IMERG-E, IMERG-L, and IMERG-F), TMPA products (3B42 V7, 3B42RT V7), and PERSIANN product) in producing the observed precipitation over a hyper-arid climate, water scarce region for the period 2013-2018. It also evaluates their performance dependency on the aggregation time-step and topographic elevations. According to a number of continuous and categorical evaluation metrics: (a) SPPs overestimate the observed daily annual and seasonal precipitation, particularly with near real-time products, (b) all SPPs estimates depict correlation ranging from 0.68 to 0.84 with the annual and seasonal precipitation and weak correlations in dry season, and (c) their ability to detect rain/no-rain events is measured by Peirce Skill Score (PSS), ranging from 0.73 to 0.92 across annual and seasonal scales, whereas 3B42RT V7 reproduces lower PSSs. Furthermore, the study finds that aggregation to a monthly time-step improves only SPPs correlations. The performance of near real-time products shows significant dependency on elevations, especially with 3B42RT V7 that shows low skills at coastlands. The TMPA products ability to detect rain/no-rain events dramatically drops from highlands to coastlands, with low skills to generate observed no/tiny and light precipitation classes. The study addresses an adequate ability of IMERG-F and PERSIANN to be utilized in water and environmental studies over hyper-arid climate regions, with highlighting for the superiority of IMERG-F.
The Racial Divide at Micro Places: A Pre/Post Analysis of the Effects of the Newark Consent Decree on Field Inquiries (2015–2017)
Authors: Chillar Vijay F. 
Published: August 2021

Objectives: An initial investigation by the Department of Justice (DOJ) found that the Newark Police Department (NPD) had engaged in a “pattern or practice” of constitutional violations with regard to stop and arrest practices, prompting the city to enter a consent decree. Methods: This study draws on official event-level data on FIs recorded by NPD officers (N = 50,322) and uses random effects panel regression models to examine how socioeconomic characteristics interact with the implementation of the consent decree at micro places in the short term. Results: Spatial analyses indicate a concentration of FI encounters. The implementation of the consent decree coincided with improvements in the quality of data collected by officers conducting FIs of citizens. It was also associated with decreased rates of reported FIs for the city’s Black and Latino citizens relative to their share of the local population, and patterns of FI encounters. Conclusions: Newark’s consent decree improved the quality of data collection. However, the spatial concentration of reported FIs and subsequent arrest of Black and Latino individuals have not experienced the same effect as they presumably require a culture change that is likely to necessitate a longer time frame to manifest.
Value of pre-intervention computed tomography perfusion imaging in the assessment of tissue outcome and long-term clinical prognosis in patients with anterior circulation acute ischemic stroke receiving reperfusion therapy: a systematic review
Authors: Katyal Anubhav , Bhaskar Sonu Menachem Maimonides 
Published: August 2021

Background Computed tomography perfusion (CTP) imaging has emerged as an important adjunct to the current armamentarium of acute ischemic stroke (AIS) workflow. However, its adoption in routine clinical practice is far from optimal. Purpose To investigate the putative association of CTP imaging biomarkers in the assessment of prognosis in acute ischemic stroke. Material and Methods We performed a systematic review of the literature using MEDLINE, EMBASE, and Cochrane Central Register of Clinical Trials focusing on CTP biomarkers, tissue-based and clinical-based patient outcomes. We included randomized controlled trials, prospective cohort studies, and case-controlled studies published from January 2005 to 28 August 2020. Two independent reviewers conducted the study appraisal, data extraction, and quality assessment of the studies. Results A total of 60 full-text studies were included in the final systematic review analysis. Increasing infarct core volume is associated with reduced odds of achieving functional independence (modified Rankin score 0–2) at 90 days and is correlated with the final infarct volume when reperfusion is achieved. Conclusion CTP has value in assessing tissue perfusion status in the hyperacute stroke setting and the long-term clinical prognosis of patients with AIS receiving reperfusion therapy. However, the prognostic use of CTP requires optimization and further validation.
Fingolimod attenuates renal ischemia/reperfusion-induced acute lung injury by inhibiting inflammation and apoptosis and modulating S1P metabolism
Authors: Shi Zu-an , Li Ting-ting , Kang Dao-ling , Su Hang , Tu Fa-ping 
Published: August 2021

Objective This study examined whether the immunomodulator fingolimod (FTY720) could alleviate renal ischemia/reperfusion (I/R)-induced lung injury and explored the potential mechanisms. Methods Renal I/R was established in a rat model, and FTY720 (0.5, 1, or 2 mg/kg) was injected intraperitoneally after 15 minutes of ischemia. Pro-inflammatory cytokine levels, oxidative stress, apoptosis, and the mRNA expression of the sphingosine-1-phosphate (S1P)-related signaling pathway genes sphingosine kinase-1 (SphK1) and sphingosine kinase-2 were analyzed in lung tissue. Results Increased pro-inflammatory cytokine levels; decreased total superoxide dismutase, catalase, and glutathione peroxidase levels; increased apoptosis; and increased S1P lyase and SphK1 expression were observed following renal I/R. FTY720 reversed renal I/R-induced changes and effectively attenuated lung injury. Conclusion FTY720 protected against acute lung injury in rats subjected to renal I/R by decreasing pulmonary inflammation and apoptosis, increasing oxidative stress, and modulating S1P metabolism.
Awareness of Colorectal Cancer and Associated Factors Among Adult Patients in Jimma, South-West Ethiopia: An Institution-Based Cross-Sectional Study
Authors: Hamza Abdulmenan , Argaw Zeleke , Gela Debela 
Published: August 2021

Background Colorectal cancer (CRC) is the first commonest diagnosed cancer in men and the fourth commonest in women in Ethiopia. Awareness of CRC and associated factors is crucial in the prevention of CRC. However, there have not been studies about the awareness of CRC and associated factors among adult patients in Ethiopia. Therefore, the study aimed to assess the awareness of CRC and associated factors among adult patients in Jimma, South-West Ethiopia, 2020. Methods This institution-based cross-sectional study design was conducted among 422 adult patients. The study respondents were recruited by a systematic random sampling method. The Cancer Awareness Measure questions were used to measure awareness of CRC of adult patients. Descriptive and logistic regression analyses were conducted. Results More than half (57.6%) of respondents had low-level awareness of CRC. Respondents who were females (adjusted odds ratio [AOR] = 1.86; 95% CI: 1.26, 2.75), who are residing in urban areas (AOR = .45; 95% CI: .30, .67), who had a monthly income of 3000 Ethiopian Birr and above (AOR = 4.72; 95% CI: 3.11, 7.15), who heard about CRC (AOR = 4.48; 95% CI: 2.90, 6.93), who get information through social media about CRC (AOR = 2.51; 95% CI: 1.18, 5.37), and who had a family history of CRC (AOR = 3.27; 95% CI: 1.45, 7.36) had a high level of awareness of CRC, while those who cannot read and write (AOR = 2.83; 95% CI: 1.49, 5.37) and learn elementary school (AOR = 2.12; 95% CI: 1.15, 3.93) had a low level of awareness of CRC. Conclusion This study indicated that awareness of CRC of adult patients was inadequate. Adult patients’ gender, residency, level of education, monthly income, heard about CRC, sources of information about CRC, and a family history of CRC were found to be independent predictors of the awareness of CRC. Therefore, there is a need for health education and awareness campaigns for promoting awareness of CRC of adult patients, and the government should develop policy on CRC prevention and screening program.
A Parsimonious Prognostic Model and Heat Map for Predicting Survival Following Adjuvant Radiotherapy in Parotid Gland Carcinoma With Lymph Node Metastasis
Authors: Jiang Wen-Mei , Wu Lei-Lei , Wei Huan-Ye , Ma Qi-Long , Zhang Quan 
Published: August 2021

Objectives: To construct a simplified prognostic risk model to predict overall survival after adjuvant radiotherapy for parotid gland carcinoma patients with stage T1-4aN1-3M0. Materials and Methods: We evaluated 879 patients who were pathological diagnosed as stage T1-4aN1-3M0 parotid gland cancer. Those eligible patients treated with parotidectomy and neck lymph node dissection between 2004 and 2015 in the Surveillance Epidemiology and End Results database. All cases received adjuvant radiotherapy. Independent prognostic factors included in the original model were identified by Cox regression analysis. The primary endpoint was overall survival. The model’s prediction power was evaluated by the concordance index. The entire cohort was categorized into new low- and high-risk groups using X-tile software according to the results of prognostic model. Kaplan-Meier method was used to depict the survival curves. And the statistical significance was determined by log-rank test. Besides, a heat map was visually described the association between the survival time and 2 most significant prognostic factors. Results: In the univariable and multivariate analyses, 4 independent factors for overall survival were age, tumor size, pTNM stage, and the number of positive lymph nodes, which were all selected in the parsimonious prognostic model. The concordance indices of the prognostic model and pTNM stage were 0.652 and 0.565, respectively. Patients in the low-risk group had better overall survival over patients in the high-risk group [unadjusted hazard ratio =  2.578, 95% confidence interval 2.095-3.172, P  < 0.001]. The results of the heat map revealed that patients with smaller tumor size and fewer positive lymph nodes had much longer survival time. Conclusions: This parsimonious prognostic model could estimate the long-term survival after adjuvant radiotherapy for parotid gland carcinoma with stage T1-4aN1-3N0M0. The tools may be valuable to guide multidisciplinary team in making treatment decisions.
Diallyl Disulfide Attenuates Ionizing Radiation-Induced Migration and Invasion by Suppressing Nrf2 Signaling in Non–small-Cell Lung Cancer
Authors: Xu Shuai , Huang Hefa , Tang Deping , Xing Mengjie , Zhao Qiuyue , Li Jianping , Si Jing , Gan Lu , Mao Aihong , Zhang Hong 
Published: August 2021

Non–small-cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths. Radiotherapy remains the primary treatment method for NSCLC. Despite great advances in radiotherapy techniques and modalities, recurrence and resistance still limit therapeutic success, even low-dose ionizing radiation (IR) can induce the migration and invasion. Diallyl disulfide (DADS), a bioactive component extracted from garlic, exhibits a wide spectrum of biological activities including antitumor effects. However, the effect of DADS on IR-induced migration and invasion remains unclear. The present study reported that IR significantly promoted the migration and invasion of A549 cells. Pretreatment with 40 μM DADS enhanced the radiosensitivity of A549 cells and attenuated IR-induced migration and invasion. In addition, 40 μM DADS inhibited migration-related protein matrix metalloproteinase-2 and 9 (MMP-2/9) expression and suppressed IR-aggravated EMT by the upregulation of the epithelial marker, E-cadherin, and downregulation of the mesenchymal marker, N-cadherin, in A549 cells. Furthermore, DADS was found to inhibit the activation of Nrf2 signaling. Based on our previous results that knockdown of Nrf2 by siRNA suppressed IR-induced migration and invasion in A549 cells, we speculated that DADS attenuated IR-induced migration and invasion by suppressing the activation of Nrf2 signaling in A549 cells.
Comparison of 4 Different Fixation Strategies for Midfoot Arthrodesis: A Retrospective Comparative Study
Authors: Lee Wonyong , Prat Dan , Wapner Keith L. , Farber Daniel C. , Chao Wen 
Published: August 2021

Background Midfoot arthrodesis is a common procedure performed both for arthritis and correction of deformity. The optimal fixation for midfoot arthrodesis has not been established, though numerous studies have been investigating the fixation techniques of midfoot arthrodesis. The purpose of this study was to compare the union rate of midfoot arthrodesis using 4 different fixation strategies and investigate risk factors of nonunion following midfoot arthrodesis. Methods A retrospective chart review was performed for patients who underwent midfoot joint arthrodesis between January 2014 and May 2019. The rates of nonunion and postoperative complication were compared among 4 different fixation constructs: staple fixation, compression plate fixation, compression plate with lag screw fixation, and compression screw fixation. Predictors of nonunion following midfoot arthrodesis were investigated through a multivariable logistic regression analysis. A total of 95 patients (99 feet), including 240 midfoot joints were included in this study. The mean follow-up period was 78.4 weeks. Results Overall, bony union was achieved in 86 out of 99 (86.9%) patients, which included 218 out of 240 (90.8%) midfoot joints. A significant difference in the nonunion rate according to the type of fixation construct was found ( P = .011); the compression screw alone fixation construct was noted to have a significantly higher nonunion rate than other fixation constructs. Diabetes mellitus (odds ratio [OR] = 0.179 [95% CI: 0.059, 0.542]), the type of fixation construct (compression screw alone; OR =1.789 [95% CI: 1.071, 2.978]), lack of adjuvant bone graft (OR = 2.803 [95% CI: 1.081, 7.268], and postoperative nonanatomical alignment (OR = 3.937 [95% CI: 1.278, 12.126]) were identified as independent predictors of nonunion following midfoot arthrodesis. Conclusion The rate of nonunion following midfoot arthrodesis among 4 different commonly used fixation constructs was compared in this study. Risk factors of nonunion were investigated revealing that diabetes mellitus, compression screw fixation alone, lack of adjuvant bone graft, and postoperative nonanatomical alignment are independent predictors of nonunion following midfoot arthrodesis. Levels of Evidence: Level III: Comparative cohort study
V3-Loop genotypes do not predict maraviroc susceptibility of CCR5-tropic virus or clinical response through week 48 in HIV-1–infected, treatment-experienced persons receiving optimized background regimens
Authors: Lewis ME , Simpson P , Mori J , Jubb B , Sullivan J , McFadyen L , van der Ryst E , Craig C , Robertson DL , Westby M 
Published: August 2021

Viruses from 15 of 35 maraviroc-treated participants with virologic failure and CCR5-tropic (R5) virus in the MOTIVATE studies at Week 24 had reduced maraviroc susceptibility. On-treatment amino acid changes were observed in the viral envelope glycoprotein 120 third variable (V3)–loop stems and tips and differed between viruses. No amino acid change reliably predicted reduced susceptibility, indicating that resistance was genetic context–dependent. Through Week 24, poor adherence was associated with maraviroc-susceptible virologic failure, whereas reduced maraviroc susceptibility was associated with suboptimal background regimen activity, highlighting the importance of overall regimen activity and good adherence. Predictive values of pretreatment V3-loop sequences containing these Week 24 mutations or other variants present at >3% in pretreatment viruses of participants with virologic failure at Week 48 were retrospectively assessed. Week 48 clinical outcomes were evaluated for correlates with pretreatment V3-loop CCR5-tropic sequences from 704 participants (366 responders; 338 virologic failures [83 with R5 virus with maraviroc susceptibility assessment]). Seventy-five amino acid variants with >3% prevalence were identified among 23 V3-loop residues. Previously identified variants associated with resistance in individual isolates were represented, but none were associated reliably with virologic failure alone or in combination. Univariate analysis showed virologic-failure associations with variants 4L, 11R, and 19S ( P < 0.05). However, 11R is a marker for CXCR4 tropism, whereas neither 4L nor 19S was reliably associated with reduced maraviroc susceptibility in R5 failure. These findings from a large study of V3-loop sequences confirm lack of correlation between V3-loop genotype and clinical outcome in participants treated with maraviroc. Clinical trial registration numbers (ClinicalTrials.gov): NCT00098306 and NCT00098722
Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)
Authors: Charles Elcha , Dumont Benjamin L. , Bonneau Steven , Neagoe Paul-Eduard , Villeneuve Louis , Räkel Agnès , White Michel , Sirois Martin G. 
Published: August 2021

Abstract
Background
Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM.

Results
Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF without (w/o) T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF w/o T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin.

Conclusions
Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.