bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Mechanisms of Novel CD73-Targeted Antibody and Antibody–Drug Conjugate in Inhibiting Lung Tumor Growth and Promoting Antitumor Immune-Effector Function
Authors: Jin Rui , Liu Liang , Xing Yun , Meng Tao , Ma Lanping , Pei Jinpeng , Cong Ying , Zhang Xuesai , Ren Zhiqiang , Wang Xin , Shen Jingkang , Yu Ker 
Published: September 2020

Abstract
Although tyrosine kinase inhibitor therapy and immunotherapy have significantly improved lung cancer management, many patients do not benefit or become resistant to treatment, highlighting the need for novel treatments. We found elevated CD73 expression to be prevalent in non–small cell lung cancer (NSCLC) including those harboring the RAS- or RTK (EGFR, EML4-ALK) oncogenes. CD73 expression is enriched closely with the transcriptome signature of epithelial–mesenchymal transition and the immune-tolerant tumor microenvironment, which are increasingly relevant for disease progression and therapy resistance. We developed two novel series of CD73 antibody, Ab001/Ab002 and humanized version Hu001/Hu002, which demonstrated high CD73 binding affinity, potent enzyme inhibition, and efficiently protected effector T lymphocyte function from adenosine/cancer-imposed toxicity. Hu001/Hu002 inhibited growth of RAS-mutant NSCLC tumors in mice via enhanced antibody-dependent cell-mediated cytotoxicity and multifaceted remodeling of the tumor immune environment, reflecting diminished levels of tumor-associated macrophages, myeloid-derived suppressor cells, and tumor vasculature. A novel MMAE-conjugated CD73-ADC (Hu001–MMAE) elicited potent cytotoxicity against CD73-high expressing tumor cells (IC50&lt;0.1 nmol/L) and suppressed in vivo growth of multiple NSCLC and glioma tumors, including the RAS-mutant models [minimum effective dose &lt;1 mg/kg]. Treatment with CD73–ADC triggered a robust intratumoral accumulation of proinflammatory macrophages and activated dendritic cells (DC), which were not observed with naked CD73 antibody or standard chemotherapy. Studies with human PBMC-derived systems confirmed CD73-ADC as fully functional in protecting effector T cells and stimulating DCs thus providing dual benefits in killing CD73-high tumors and improving cancer immunity response. These results warrant clinical investigation of CD73-targeted antibody and ADC for treating advanced lung cancer.
p53 Is Not Required for High CIN to Induce Tumor Suppression
Authors: Funk Laura C. , Wan Jun , Ryan Sean D. , Kaur Charanjeet , Sullivan Ruth , Roopra Avtar , Weaver Beth A. 
Published: September 2020

Abstract

Chromosomal instability (CIN) is a hallmark of cancer. While low levels of CIN can be tumor promoting, high levels of CIN cause cell death and tumor suppression. The widely used chemotherapeutic, paclitaxel (Taxol), exerts its anticancer effects by increasing CIN above a maximally tolerated threshold. One significant outstanding question is whether the p53 tumor suppressor is required for the cell death and tumor suppression caused by high CIN. Both p53 loss and reduction of the mitotic kinesin, centromere-associated protein-E, cause low CIN. Combining both genetic insults in the same cell leads to high CIN. Here, we test whether high CIN causes cell death and tumor suppression even in the absence p53. Despite a surprising sex-specific difference in tumor spectrum and latency in p53 heterozygous animals, these studies demonstrate that p53 is not required for high CIN to induce tumor suppression. Pharmacologic induction of high CIN results in equivalent levels of cell death due to loss of essential chromosomes in p53+/+ and p53−/− cells, further demonstrating that high CIN elicits cell death independently of p53 function.

Implications:
These results provide support for the efficacy of anticancer therapies that induce high CIN, even in tumors that lack functional p53.
Development of a photovoltaic characteristics generator based on mathematical models for four PV panel technologies
Authors: Jenkal Samia , Kourchi Mustapha , Yousfi Driss , Benlarabi Ahmed , Elhafyani Mohamed Larbi , Ajaamoum Mohamed , Oubella Mhand 
Published: September 2020

A good study of photovoltaic system requests to have very precise
current-voltage characteristic curves of photovoltaic modules for different technologies. The photovoltaic emulator provides an efficient solution to maintain the same current-voltage output of photovoltaic module. It includes three parts: the PV model, the control strategy, and the power converter. This paper provides three classes of modeling and simulation of photovoltaic arrays and presents the synthesis results of the current-voltage characteristic performances obtained by the modeling approaches. The models of the first class are based on electrical circuit model, those of the second class are based on multiple straight lines model, and for the third class, it is based on the look up table. The mathematical model is built using MATLAB/ Simulink, and an experimental bench was carried out to acquire an up-to-date and representative experimental database of four PV panels. This database is used for the validation of these models for the different PV panel technologies under Moroccan meteorological conditions. Following this comparative study, we came to a high agreement between the experimental and simulated current-voltage characteristics for the emulator under study.
Evaluation of lightweight battery management system with field test of electric bus in campus transit system
Authors: Srirattanawichaikul Watcharin , Wirasanti Paramet 
Published: September 2020

A battery management system is a crucial part of a battery-powered electric vehicle, which functions as a monitoring system, state estimation, and protection for the vehicle. Among these functions, the state estimation, i.e., state of charge and remaining battery life estimation, is widely researched in order to find an accuracy estimation methodology. Most of the recent researches are based on the study of the battery cell level and the complex algorithm. In practice, there is a statement that the method should be simple and robust. Therefore, this research work is focused on the study of lightweight methodology for state estimation based on the battery pack. The discrete Coulomb counting method and the data-driven approach, based on the Palmgren-Miner method, are proposed for the estimation of the state of charge and remaining battery life, respectively. The proposed methods are evaluated through a battery-powered electric bus under real scenario-based circumstances in the campus transit system. In addition, the battery life-cycle cost analysis is also investigated. The tested bus has currently been in operation in the transit system for more than
one year.
Inner Rhythms: Vessels as a Sustained Brain-Body Performance Practice
Authors: Leslie Grace 
Published: September 2020

Abstract
Vessels is a brain-body performance practice that combines flute improvisation with live, sonified brain and body data. This article describes the genesis of this performance practice, which coevolved with the author’s brain-music interfacing and physiological data sonification methods. The author presents these novel interface designs and discusses how the affordances and constraints of these systems reflect onto her brain-body performance technique.
The burden of serious health-related suffering among cancer decedents: Global projections study to 2060
Authors: Sleeman Katherine E , Gomes Barbara , de Brito Maja , Shamieh Omar , Harding Richard 
Published: September 2020

Background: Palliative care improves outcomes for people with cancer, but in many countries access remains poor. Understanding future needs is essential for effective health system planning in response to global policy. Aim: To project the burden of serious health-related suffering associated with death from cancer to 2060 by age, gender, cancer type and World Bank income region. Design: Population-based projections study. Global projections of palliative care need were derived by combining World Health Organization cancer mortality projections (2016–2060) with estimates of serious health-related suffering among cancer decedents. Results: By 2060, serious health-related suffering will be experienced by 16.3 million people dying with cancer each year (compared to 7.8 million in 2016). Serious health-related suffering among cancer decedents will increase more quickly in low income countries (407% increase 2016–2060) compared to lower-middle, upper-middle and high income countries (168%, 96% and 39% increase 2016-2060, respectively). By 2060, 67% of people who die with cancer and experience serious health-related suffering will be over 70 years old, compared to 47% in 2016. In high and upper-middle income countries, lung cancer will be the single greatest contributor to the burden of serious health-related suffering among cancer decedents. In low and lower-middle income countries, breast cancer will be the single greatest contributor. Conclusions: Many people with cancer will die with unnecessary suffering unless there is expansion of palliative care integration into cancer programmes. Failure to do this will be damaging for the individuals affected and the health systems within which they are treated.
Effect of Intraoperative Multidimensional Fluoroscopy Versus Conventional Fluoroscopy on Syndesmotic Reduction
Authors: Cunningham Bryce A. , Warner Stephen , Berkes Marschall , Achor Timothy , Choo Andrew , Munz John , “Chip” Routt Milton L. , Gary Joshua L. 
Published: September 2020

Background: Despite multiple techniques to improve syndesmotic reduction accuracy, syndesmotic malreduction in unstable ankle fractures remains prevalent. We performed a prospective, observational study to assess the ability of intraoperative multidimensional fluoroscopy to lead a surgeon to change the syndesmotic reduction obtained by conventional fluoroscopic techniques with the goal of achieving an accurate reduction. Methods: Thirty patients with unilateral malleolar ankle fractures and syndesmotic instability were enrolled. Following fixation of the malleollar fractures, the syndesmosis was provisionally reduced. Once the surgeon believed acceptable reduction was obtained by comparison with the contralateral, uninjured ankle mortise and lateral fluoroscopic images, provisional fixation was used to maintain reduction. Intraoperative, multidimensional fluoroscopy was used to generate cross-sectional images to assess the reduction. The surgeon then decided if a change in the reduction was needed, and fixation proceeded per surgeon preference. Postoperative bilateral computed tomography (CT) scans of the ankles were used to assess the reduction. Results: The main outcome recorded was syndesmotic reduction change by the attending surgeon following 3-dimensional (3D) fluoroscopic imaging. The secondary outcome was syndesmotic reduction accuracy on postoperative CT scan. Fourteen of 30 patients had intraoperative reduction change following 3D fluoroscopic imaging. Three of 30 patients had residual malreduction compared with the contralateral ankle on bilateral postoperative CT scan. Conclusion: Intraoperative 3D fluoroscopy frequently led the surgeon to change the syndesmotic reduction obtained by conventional techniques and provided additional information not available with 2-dimensional fluoroscopy. A 10% syndesmotic malreduction rate was obtained with this technique. Level of Evidence: Diagnostic level II, prospective comparative study.
An Intersection of Mathematics Educational Values and Cultural Values: Pāsifika Students’ Understanding and Explanation of Their Mathematics Educational Values
Authors: Hunter Jodie 
Published: September 2020

Purpose: This article investigates the mathematics educational values of Pāsifika students in New Zealand. It draws on student voice to examine Pāsifika students’ understanding of mathematics educational values and their reasons for rating values at different levels of importance. Design/Approach/Methods: The study involved Years 7 and 8 Pāsifika students from two low-socioeconomic middle schools. Students selected their most and least important mathematics educational value statements on a survey. Semi-structured individual interviews were used to investigate their reasons for selecting the values. Findings: The mathematics educational values ranked highly by the greatest percentage of students were practice, family, respect, and persistence. In contrast, the values of accuracy and utility were rated as least important. Student interview data revealed commonalities in accounting for the importance of different values. The findings indicate an intersection between the mathematics educational values and cultural values of Pāsifika people. Originality/Value: There have been few studies that have explored the mathematics educational values of Pāsifika students. The current study provides insight into why specific values are important to Pāsifika students and how these may influence classroom interactions. The use of student interview data widens the existing literature focused on values in mathematics education.
Cysteine sulfenylation by CD36 signaling promotes arterial thrombosis in dyslipidemia
Authors: Yang Moua , Li Wei , Harberg Calvin , Chen Wenjing , Yue Hong , Ferreira Renan B. , Wynia-Smith Sarah L. , Carroll Kate S. , Zielonka Jacek , Flaumenhaft Robert , Silverstein Roy L. , Smith Brian C. 
Published: September 2020

Abstract
Arterial thrombosis in the setting of dyslipidemia promotes clinically significant events, including myocardial infarction and stroke. Oxidized lipids in low-density lipoproteins (oxLDL) are a risk factor for athero-thrombosis and are recognized by platelet scavenger receptor CD36. oxLDL binding to CD36 promotes platelet activation and thrombosis by promoting generation of reactive oxygen species. The downstream signaling events initiated by reactive oxygen species in this setting are poorly understood. In this study, we report that CD36 signaling promotes hydrogen peroxide flux in platelets. Using carbon nucleophiles that selectively and covalently modify cysteine sulfenic acids, we found that hydrogen peroxide generated through CD36 signaling promotes cysteine sulfenylation of platelet proteins. Specifically, cysteines were sulfenylated on Src family kinases, which are signaling transducers that are recruited to CD36 upon recognition of its ligands. Cysteine sulfenylation promoted activation of Src family kinases and was prevented by using a blocking antibody to CD36 or by enzymatic degradation of hydrogen peroxide. CD36-mediated platelet aggregation and procoagulant phosphatidylserine externalization were inhibited in a concentration-dependent manner by a panel of sulfenic acid–selective carbon nucleophiles. At the same concentrations, these probes did not inhibit platelet aggregation induced by the purinergic receptor agonist adenosine diphosphate or the collagen receptor glycoprotein VI agonist collagen-related peptide. Selective modification of cysteine sulfenylation in vivo with a benzothiazine-based nucleophile rescued the enhanced arterial thrombosis seen in dyslipidemic mice back to control levels. These findings suggest that CD36 signaling generates hydrogen peroxide to oxidize cysteines within platelet proteins, including Src family kinases, and lowers the threshold for platelet activation in dyslipidemia.
Platelets function as an acute viral reservoir during HIV-1 infection by harboring virus and T-cell complex formation
Authors: Simpson Sydney R. , Singh Meera V. , Dewhurst Stephen , Schifitto Giovanni , Maggirwar Sanjay B. 
Published: September 2020

Abstract
Platelets were recently found to harbor infectious HIV virions in infected individuals who are on antiretroviral treatment with poor CD4+ T-cell recovery. In this study, we screened platelets from recently infected individuals, before and after antiretroviral therapy, for the presence of virus and examined platelet activation, as well as CD4+ T-cell recovery. This was followed by in vitro studies assessing platelet–CD4+ T-cell complex formation as a contributing factor to viral transmission. HIV+ platelets were detected in 10 of 10 acutely infected individuals with no prior history of antiretroviral therapy. The percentage of HIV+ platelets dropped significantly after 3 months of antiretroviral therapy in all of the study participants. These individuals also demonstrated significant recovery of CD4+ T cells. Interestingly, the percentage of HIV+ platelets correlated positively with viral load but not with CD4+ T-cell count. Furthermore, we found that platelet activation with soluble CD40L or thrombin receptor activator peptide 6 (TRAP6) increased platelet-virus interactions in vitro. TRAP6-mediated interactions were reduced by platelet antagonists, aspirin, and R406. We demonstrated that platelets transmit the virus to CD4+ T cells, and this transinfection was abolished by inhibiting platelet–T-cell complex formation via exposure to an anti-CD62P antibody. Additionally, treatment with TRAP6 significantly increased the transinfection, which was also inhibited by aspirin and R206. These results reveal that platelets have the potential to promote HIV viral spread during the acute stage of infection, by harboring infectious virus transmitting infection to susceptible CD4+ T cells through complex formation.
Incidental Richter transformation in chronic lymphocytic leukemia patients during temporary interruption of ibrutinib
Authors: Hampel Paul J. , Cherng Hua-Jay J. , Call Timothy G. , Ding Wei , Khanlari Mahsa , McPhail Ellen D. , Miranda Roberto N. , Lin Pei , Tawbi Hussein A. , Ferrajoli Alessandra , Wierda William G. , Jain Nitin , Parikh Sameer A. 
Published: September 2020

Key Points
An incidental histologic diagnosis of DLBCL was identified during temporary interruption of ibrutinib treatment in patients with CLL. In contrast to an aggressive clinical course typical of Richter transformation, these patients responded to reinitiation of ibrutinib alone.
Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases
Authors: Kubo Ayano , Hidaka Teruo , Nakayama Maiko , Sasaki Yu , Takagi Miyuki , Suzuki Hitoshi , Suzuki Yusuke 
Published: September 2020

AbstractBackgroundDipeptidyl peptidase-4 (DPP-4) is a serine protease that inhibits the degradation of glucagon-like peptide 1. DPP-4 inhibitors are used worldwide to treat type 2 diabetes mellitus and were recently shown to have pleiotropic effects such as anti-oxidant, anti-inflammatory, and anti-fibrotic actions. DPP-4 inhibitors improve albuminuria and renal injury including glomerular damage independent of its hypoglycemic effect. Although DPP-4 is mainly expressed in the kidney, the physiological function of DPP-4 remains unclear.MethodsThe localization of renal DPP-4 activity was determined in human renal biopsy specimens with glycyl-1-prolyl-4-methoxy-2-naphthylamide and the effects of a DPP-4 inhibitor were examined in human cultured podocyte.ResultsDPP-4 activity under normal conditions was observed in some Bowman’s capsular epithelial cells and proximal tubules, but not in the glomerulus. DPP-4 activity was observed in crescent formation in anti-neutrophil myeloperoxidase cytoplasmic antigen antibody nephritis, nodular lesions in diabetic nephropathy, and some podocytes in focal segmental glomerulosclerosis. Notably, the DPP-4 inhibitor saxagliptin suppressed DPP-4 activity in podocytes and the proximal tubules. To assess the effect of DPP-4 inhibitor on podocytes, human cultured podocytes were injured by Adriamycin, which increased DPP-4 activity; this activity was dose-dependently suppressed by saxagliptin. Treatment with saxagliptin maintained the structure of synaptopodin and RhoA. Saxagliptin also improved the detachment of podocytes.ConclusionsDPP-4 activity induces degradation of synaptopodin and reduction of RhoA, resulting in destruction of the podocyte cytoskeleton. Saxagliptin may have pleiotropic effects to prevent podocyte injury.
miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer
Authors: Pudova Elena A. , Krasnov George S. , Nyushko Kirill M. , Kobelyatskaya Anastasiya A. , Savvateeva Maria V. , Poloznikov Andrey A. , Dolotkazin Daniyar R. , Klimina Kseniya M. , Guvatova Zulfiya G. , Simanovsky Sergey A. , Gladysh Nataliya S. , Tokarev Artemy T. , Melnikova Nataliya V. , Dmitriev Alexey A. , Alekseev Boris Y. , Kaprin Andrey D. , Kiseleva Marina V. , Snezhkina Anastasiya V. , Kudryavtseva Anna V. 
Published: September 2020

AbstractBackgroundProstate cancer is one of the most common and socially significant cancers among men. The aim of our study was to reveal changes in miRNA expression profiles associated with lymphatic dissemination in prostate cancer and to identify the most prominent miRNAs as potential prognostic markers for future studies.MethodsHigh-throughput miRNA sequencing was performed for 44 prostate cancer specimens taken from Russian patients, with and without lymphatic dissemination (N1 – 20 samples; N0 – 24 samples).ResultsWe found at least 18 microRNAs with differential expression between N0 and N1 sample groups:miR-182-5p, miR-183-5p, miR-96-5p, miR-25-3p, miR-93-5p, miR-7-5p, miR-615-3p, miR-10b, miR-1248(N1-miRs; elevated expression in N1 cohort;p < 0.05);miR-1271-5p, miR-184, miR-222-3p, miR-221-5p, miR-221-3p, miR-455-3p, miR-143-5p, miR-181c-3pandmiR-455-5p(N0-miRs; elevated expression in N0;p < 0.05).The expression levels of N1-miRs were highly correlated between each other (the same is applied for N0-miRs) and the expression levels of N0-miRs and N1-miRs were anti-correlated. The tumor samples can be divided into two groups depending on the expression ratio between N0-miRs and N1-miRs.ConclusionsWe found the miRNA expression signature associated with lymphatic dissemination, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.
Multiple paragangliomas: a case report
Authors: Pavlov Vladislav S. , Kalinin Dmitry V. , Lukyanova Elena N. , Golovyuk Alexander L. , Fedorova Maria S. , Pudova Elena A. , Savvateeva Maria V. , Lipatova Anastasiya V. , Guvatova Zulfiya G. , Kaprin Andrey D. , Kiseleva Marina V. , Demidova Tatiana B. , Simanovsky Sergey A. , Melnikova Nataliya V. , Dmitriev Alexey A. , Krasnov George S. , Snezhkina Anastasiya V. , Kudryavtseva Anna V. 
Published: September 2020

Abstract
Background
Carotid and vagal paragangliomas (CPGLs and VPGLs) are rare neoplasms that arise from the paraganglia located at the bifurcation of carotid arteries and vagal trunk, respectively. Both tumors can occur jointly as multiple paragangliomas accounting for approximately 10 to 20% of all head and neck paragangliomas. However, molecular and genetic mechanisms underlying the pathogenesis of multiple paragangliomas remain elusive.

Case presentation
We report a case of multiple paragangliomas in a patient, manifesting as bilateral CPGL and unilateral VPGL. Tumors were revealed via computed tomography and ultrasound study and were resected in two subsequent surgeries. Both CPGLs and VPGL were subjected to immunostaining for succinate dehydrogenase (SDH) subunits and exome analysis. A likely pathogenic germline variant in the SDHD gene was indicated, while likely pathogenic somatic variants differed among the tumors.

Conclusions
The identified germline variant in the SDHD gene seems to be a driver in the development of multiple paragangliomas. However, different spectra of somatic variants identified in each tumor indicate individual molecular mechanisms underlying their pathogenesis.