bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4538: A safe and potent agonist ADG106 targeting a unique epitope of CD137 with novel mechanism of actions
Authors: Liu Guizhong , Du Felix , She Xiaohong , Zhu Yi , Tolcher Anthony W. , Luo Peter 
Published: September 2020

Abstract
Antagonist antibodies targeting immune checkpoint co-inhibitory receptor such as PD-1/PD-L1 have achieved great clinical success in cancer immunotherapy. However, agonistic antibodies targeting the co-stimulatory T cell receptors in the TNFR superfamily, and CD137 in particular, has suffered significant setback due to either dose-dependent severe liver toxicity by Urelumab, or modest clinical anti-tumor activity by Utomilumab. ADG106, a safe and potent antibody targeting a unique epitope of CD137, is shown to hold the great promise to achieve much better efficacy and safety profile for immunotherapy in preclinical and phase 1 studies. ADG106, a fully human agonistic anti-CD137 IgG4 mAb, binds to a unique and conserved epitope with multiple cross-species reactivity, and overlaps with CD137 ligand binding site. This unique antibody acts in a novel mechanism with the following attributes: 1) it agonizes CD137 in a natural ligand-like fashion; 2) it blocks ligand to disable its reverse signaling; 3) it exhibits strong but specific Fc receptor mediated crosslinking in comparison with Utomilumab. ADG106 shows robust dose-dependent single agent anti-tumor activity in multiple syngeneic mouse tumor models and induces durable antigen-specific memory immunity that protects animals from the same re-challenged tumor cells. Consistent with the preclinical observations, ongoing phase I trial shows that the same antibody, ADG106, is well-tolerated in cancer patients in dose escalation from 0.03 to 3 mg/kg; and it also shows single agent activity on circulating T cell activation and clonal expansion in anti-tumor activity. Furthermore, ADG106 has also induced complete remission of the liver metastatic lesion in a lymphoma patient at 1mg/kg dose. Preclinical studies demonstrate that ADG106 enhances activation and inflammatory cytokine release of primed T cells alone or together with other immunomodulatory agents in vitro, as well as exhibits synergistic in vivo anti-tumor activity in combination with variety of other cancer therapies, including checkpoint inhibitors, chemotherapies and targeted agents. Mechanistic analyses suggest that ADG106 stimulates tumor infiltration and expansion of CD4+ and CD8+ T cells, thereby promoting the antitumor responses. These findings support that ADG106-boosted immune response could offer an effective but alternative solution for cancer immunotherapy in single and combination therapies, especially for non-responders to current PD-1/PD-L1 based immunotherapies.
Citation Format: Guizhong Liu, Felix Du, Xiaohong She, Yi Zhu, Anthony W. Tolcher, Peter Luo. A safe and potent agonist ADG106 targeting a unique epitope of CD137 with novel mechanism of actions [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4538.
Abstract 4806: SIRT5 inhibition causes increased oxidative stress and impairs tumor progression and metastasis
Authors: Fernandez Irma , Abril Yashira N. , Hong Jun Y. , Yang Min , Sadhukhan Sushabhan , Lin Hening , Weiss Robert 
Published: September 2020

Abstract
Cancer cells undergo metabolic reprogramming, producing energy through aerobic glycolysis followed by lactic acid fermentation. Consequently, targeting key metabolic enzymes has emerged as a potential avenue to selectively inhibit tumor growth. The sirtuin family of deacylases has roles in both metabolism and cancer. The mitochondrial sirtuin SIRT5 regulates protein post-translational modifications on metabolic enzymes by catalyzing the removal of succinyl, malonyl, and glutaryl moieties. SIRT5 is over-expressed in many cancers, including breast cancer. Therefore, we hypothesized that SIRT5 promotes breast cancer progression by facilitating metabolic reprogramming. SIRT5 knockdown in human cancer cells inhibited anchorage independent growth but had little effect on non-transformed cells. To examine how SIRT5 loss impacts tumorigenesis in vivo, we utilized MMTV-PyMT transgenic mice, which are prone to mammary adenocarcinoma and lung metastasis. SIRT5 knockout (KO) MMTV-PyMT mice had increased survival, decreased tumor size, and reduced lung metastases, as compared to SIRT5 wild-type (WT) MMTV-PyMT controls. SIRT5 KO cancer cells had higher levels of reactive oxygen species and displayed lower levels of important antioxidants such as NADPH and GSH. These results suggest that SIRT5 KO cells are more susceptible to oxidative stress, hinting that SIRT5 may be promoting breast cancer by mitigating ROS through one or more of its key metabolic substrates. To determine the therapeutic potential of SIRT5 inhibition, we created potent and specific small molecule SIRT5 inhibitors. Pharmacological inhibition of SIRT5 impaired mammary tumor growth in both transgenic and human breast cancer xenograft mouse models, with no apparent toxicity. Considering that Sirt5 knockout mice are generally normal, with only mild phenotypes observed, these data establish SIRT5 as a promising target for treating breast cancer.
Citation Format: Irma Fernandez, Yashira N. Abril, Jun Y. Hong, Min Yang, Sushabhan Sadhukhan, Hening Lin, Robert Weiss. SIRT5 inhibition causes increased oxidative stress and impairs tumor progression and metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4806.
Abstract 586: Anti-leukemia activities of selenium nanoparticles embedded in nanotube consisted of triple-helix β-D-glucan
Authors: Jin Yanxia , Cai Liqin , Yang Qian , Luo Ziyi , Zhang Lina , Zhou Fuling 
Published: September 2020

Abstract
Background: Acute myeloid leukemia (AML) is a hematological malignant tumor. The common chemotherapy results in various side-effect and drug-resistance for AML, so it is urgent to find a non-toxic natural drug for AML therapy. Herein, for the first time, the Se nanoparticles embedded in nanotube consisted of triple helix β-D-glucan (BFP) exhibit the high anti-leukemia effects.
Methods: A triple helix β-(1, 3)-D-glucan (BFP) extracted from the black fungus was self-assembled into nanotube in water, and Se nanoparticles (SeNPs) were wrapped to form stable inclusion complex BFP-Se. The CCK8 assays, lactose dehydrogenase release assays, optofluidics chips and flow cytometry were used to test the anti-leukemia effects of BFP-Se in vitro and in vivo.
Results: The SeNPs embedded in the BFP nanotubes exhibited high stability in water, avoiding aggregation and dispersion to out. In vitro, the BFP-Se significantly inhibited the proliferation of AML cell lines and patient cells and markedly increased the cytotoxicity on AML cells. BFP-Se slowed the Molm-13 GFP+ cells growth. On single-cell levels, the U937 cells were gradually swelled and lysed with BFP-Se treatment. In addition, BFP-Se had little toxic to hematopoietic stem cells (HSC) and T cells compared to Ara-c. Flow cytometry indicated that BFP-Se promoted the cell apoptosis and blocked cell cycle of AML cells. Further, after injection of BFP-Se, the survival was longer on AML PDX model constructed with B-NSG mice. The blood and bone marrow analysis indicated the anti-leukemia effects of BFP-Se in vivo. Moreover, BFP-Se extremely increased the total antioxidant capacity (T-AOC) of AML cells, and decreased the expression of c-Jun activation domain-binding protein-1 (Jab1) and thioredoxin 1 (Trx1).
Conclusion: This biocompatible polysaccharide nanotube containing Se nanoparticles - against AML would provide a novel strategy for AML therapy.
Citation Format: Yanxia Jin, Liqin Cai, Qian Yang, Ziyi Luo, Lina Zhang, Fuling Zhou. Anti-leukemia activities of selenium nanoparticles embedded in nanotube consisted of triple-helix β-D-glucan [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 586.
Examining factors that effect on the acceptance of mobile commerce in Malaysia based on revised UTAUT
Authors: Sabri Alrawi Mohammed A. , Narayana Samy Ganthan , Mohd Yusoff Rasimah Che , Shanmugam Bharanidharan , Lakshmiganthan Rajasekaran , Maarop Nurazean , Kamaruddin Norshaliza 
Published: September 2020

<p>This <span>study presents an amended unified theory of acceptance and use of technology (UTAUT) which explores key factors affecting Malaysian consumers ' willingness to accept mobile-commerce. A questionnaire survey has been used to collect information from 400 Malaysian smartphone users using a random stratified sample and analyzed using structural equation modelling (SEM); with the use of Smart PLS 3.0. Results show that acceptance and use of mobile-commerce services can also be predicted by the behavioural intentions of users, whose performance expectancy, efforts expectations, social effects, mobility, personal innovations and perceived trust are significantly affected. From these variables, perceived trust is the most significant determinant that directly affects behavioural intention to use mobile-commerce services in Malaysia. It is then followed by mobility, personal innovation, social influence, performance expectancy then effect expectancy. Facilitating Conditions and moderating variables such as gender, age, education, income, marital status, experience and payment have no significant effect on Behavioral Intention to use mobile-commerce services in Malaysia. In conclusion, this study shows that behavioural intention and the use of mobile commerce services in Malaysia have a direct effect. The study will help dealers to avoid spending thousands of dollars on investments that have little impact on whether the customer is embracing and using mobile-commerce. The study also provides quantified indicators and offers a framework for the understanding of the Malaysia mobile-commerce system. The report concludes with a study of the effects of the research findings and provides recommendations for future research.</span></p>
Association Between 90-Minute Door-to-Balloon Time, Selective Exclusion of Myocardial Infarction Cases, and Access Site Choice
Authors: Nathan Ashwin S. , Raman Swathi , Yang Nancy , Painter Ian , Khatana Sameed Ahmed M. , Dayoub Elias J. , Herrmann Howard C. , Yeh Robert W. , Groeneveld Peter W. , Doll Jacob A. , McCabe James M. , Hira Ravi S. , Giri Jay , Fanaroff Alexander C. 
Published: September 2020

Background:
For patients presenting with ST-segment–elevation myocardial infarction, national quality initiatives monitor hospitals’ proportion of cases with door-to-balloon (D2B) time under 90 minutes. Hospitals are allowed to exclude patients from reporting and may modify behavior to improve performance. We sought to identify whether there is a discontinuity in the number of cases included in the D2B time metric at 90 minutes and whether operators were increasingly likely to pursue femoral access in patients with less time to meet the 90-minute quality metric.

Methods:
Adult patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention from 2011 to 2018 were identified from the Cardiac Care Outcomes Assessment Program, a quality improvement registry in Washington state. We used the regression discontinuity framework to test for discontinuity at 90 minutes among the included cases. We defined a novel variable, remaining D2B as 90 minutes minus the time between hospital arrival and catheterization laboratory arrival. We estimated multivariable logistic regression models to assess the relationship between remaining D2B time and access site.

Results:

A total of 19 348 patients underwent primary percutaneous coronary intervention and were included in the analysis. Overall, 7436 (38.4%) were excluded from the metric. There appeared to be a visual discontinuity in included cases around 90 minutes; however, local quadratic regression around the 90-minute cutoff did not reveal evidence of a significant discontinuity (
P
=0.66). Multivariable analysis showed no significant relationship between remaining D2B time and the odds of undergoing femoral access (
P
=0.73).

Conclusions:
Among patients undergoing percutaneous coronary intervention for ST-segment–elevation myocardial infarction, we did not find evidence of a statistically significant discontinuity in the frequency of included cases around 90 minutes or an increased preference for femoral access correlated with decreasing time to meet the 90-minute D2B time quality metric. Together, these findings indicate no evidence of widespread inappropriate methods to improve performance on D2B time metrics.
Predicting Risk of Atherosclerotic Cardiovascular Disease Using Pooled Cohort Equations in Older Adults With Frailty, Multimorbidity, and Competing Risks
Authors: Nguyen Quoc Dinh , Odden Michelle C. , Peralta Carmen A. , Kim Dae Hyun 
Published: September 2020

Background
Assessment of atherosclerotic cardiovascular disease (ASCVD) risk is crucial for prevention and management, but the performance of the pooled cohort equations in older adults with frailty and multimorbidity is unknown. We evaluated the pooled cohort equations in these subgroups and the impact of competing risks.

Methods and Results
In 4249 community‐dwelling adults, aged ≥65 years, from the CHS (Cardiovascular Health Study), we calculated 10‐year risk of hard ASCVD. Frailty was determined using the Fried phenotype. Latent class analysis was used to identify individuals with multimorbidity patterns using chronic conditions. We assessed discrimination using the C‐statistic and calibration by comparing predicted ASCVD risks with estimated risk using cause‐specific and cumulative incidence models, by multimorbidity patterns and frailty status. A total of 917 (21.6%) participants had an ASCVD event, and 706 (16.6%) had a competing event of death. C‐statistic was 0.68 in men and 0.69 in women; calibration was good when compared with cause‐specific and cumulative incidence estimated risks (males, −0.1% and 3.3%; females, 0.6% and 1.4%). Latent class analysis identified 4 patterns: minimal disease, cardiometabolic, low cognition, musculoskeletal‐lung depression. In the cardiometabolic pattern, ASCVD risk was overpredicted compared with cumulative incidence risk in men (7.4%) and women (6.8%). Risk was underpredicted in men (−10.7%) and women (−8.2%) with frailty compared with cause‐specific risk. Miscalibration occurred mostly at high predicted risk ranges.

Conclusions
ASCVD prediction was good in this cohort of adults aged ≥65 years. Although calibration varied by multimorbidity patterns, frailty, and competing risks, miscalibration was mostly present at high predicted risk ranges and thus less likely to alter decision making for primary prevention therapy.
Associations of B‐Type Natriuretic Peptide and Its Coding Gene Promoter Methylation With Functional Outcome of Acute Ischemic Stroke: A Mediation Analysis
Authors: Wang Aili , Zhang Mingzhi , Ding Yi , Mo Xingbo , Zhong Chongke , Zhu Zhengbao , Guo Daoxia , Zheng Xiaowei , Xu Tan , Liu Yan , Zhang Yonghong , Peng Hao 
Published: September 2020

BackgroundThe prognostic role of B‐type natriuretic peptide (BNP) in stroke has been suggested, but limited studies have shown mixed results and unknown underlying mechanisms. DNA methylation, a molecular modification that alters gene expression, may represent a candidate mechanism for this purpose. We aimed to examine the associations of BNP and methylation of its coding gene (natriuretic peptide B [NPPB]) with the functional outcome in a large sample of patients with acute ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke).Methods and ResultsLeveraging participants from CATIS with available specimens, serum proBNP (equimolarly produced with BNP) was measured in 3216 patients (mean age, 62 years; 64% men), and peripheral blood DNA methylation of theNPPBpromoter was quantified by targeted bisulfite sequencing in 806 patients (mean age, 62 years; 54% men). The functional outcome was defined as an ordered modified Rankin Scale score assessed at 14 days or hospital discharge after stroke onset. Mediation analysis was conducted to test the potential mediating effect of proBNP on the relationship betweenNPPBmethylation and functional outcome. The results showed that a higher level of proBNP was significantly associated with a higher risk of having a poorer functional outcome (odds ratio [OR], 1.14;P=0.006). Every 5% of hypermethylation at 2 (Chr1:11919160 [OR, 0.93;P=0.022] and Chr1:11918989 [OR, 0.92;P=0.032]) of 11 CpG loci assayed was associated with 7% and 8% lower risk, respectively, of having a poor functional outcome. In addition, proBNP was negatively correlated to hypermethylation at 1 CpG (Chr1:11918989 [β=−0.029;P=0.009]) and mediated approximately 7.69% (95% CI, 2.50%–13.82%) of the association between this CpG methylation and the functional outcome.ConclusionsHypermethylation at theNPPBpromoter is associated with the functional outcome after ischemic stroke, at least partially by suppressing BNP expression or excretion.
Revising NCEI’s Climate Extremes Index and the CDC’s Social Vulnerability Index to Analyze Climate Extremes Vulnerability across the United States
Authors: Pauline Emily L. , Knox John A. , Seymour Lynne , Grundstein Andrew J. 
Published: September 2020

AbstractThe occurrence of extreme weather and climate events has increased in recent decades. This increasing frequency has adversely impacted economic and health outcomes, leading to an increasingly urgent need to study climate extremes. The National Centers for Environmental Information (NCEI) created the Climate Extremes Index (CEI) in 1996 to quantify climate extremes. In this article, we explore the potential for enhancing the CEI via the use of the Z-score statistic to calculate the CEI on a numerical scale, to increase usability at smaller spatial scales, and to allow the creation of a new climate Extremes Vulnerability Index (EVI). The EVI combines the results from the revised CEI with values from the Social Vulnerability Index from the Centers for Disease Control and Prevention (CDC). The EVI can be used by policy-makers, planners, and the public to understand a subregion’s vulnerability to climate extremes. This information from the EVI could then be used to implement policies and changes in infrastructure that mitigate risk in vulnerable climate divisions. In a trial application, it is found that the southeastern and portions of the central United States had the highest levels of vulnerability for the abnormal month of December 2015.
Refining the Short Version of the Leadership Scale for Sports: Factorial Validation and Measurement Invariance
Authors: Teques Pedro , Silva Carlos , Rosado António , Calmeiro Luís , Serpa Sidónio 
Published: September 2020

The purpose of this investigation was to examine the factorial validity and measurement invariance of the short version of the Leadership Scale for Sports (LSS; Chelladurai & Saleh, 1980 ): coaches’ perceptions of their own behavior, athletes’ preferences and athletes’ perceptions of their coaches’ behavior. This validation will allow researchers to minimize time demands on participants. Three independent samples of athletes ( n1 = 373; n2 = 817; n3 = 246) and two samples of coaches ( n1 = 115; n2 = 351) were studied to examine the factorial validity and measurement invariance of the 25-item version of the LSS (LSS-25; Chiu et al., 2016 ). Findings indicated that a 15-item version (LSS-15) fits the data better than the LSS-25. The LSS-15 showed factorial validity and proved to have adequate reliability, convergent validity and discriminant validity. Multiple-group confirmatory factor analysis showed that its factor structure was invariant across two independent samples and across gender for athletes’ perceived and preferred versions. Significant relationships between the LSS-15 subscales and athlete satisfaction also demonstrate criterion validity. These findings support a valid and reliable alternative to the original LSS long-form, especially in applied settings when time constraints require a brief measure of leadership or when study designs include multiple variables.
Angiotensin converting enzyme inhibitors do not increase the risk of poor outcomes in COVID-19 disease. A multi-centre observational study
Authors: Khan Khurram Shahzad , Reed-Embleton Hamish , Lewis Jen , Bain Pamela , Mahmud Sajid 
Published: September 2020

Background and aims Hypertension is associated with an increased risk of severe outcomes with COVID-19 disease. Angiotensin Converting Enzyme (ACE) inhibitors are widely used as a first line medication for the treatment of hypertension in the UK, although their use was suggested in early reports to increase the risk associated with SARS-CoV-2 infection. Methods A prospective cohort study of hospitalised patients with laboratory confirmed COVID-19 was conducted across three hospital sites with patients identified on the 9th April 2020. Demographic and other baseline data were extracted from electronic case records, and patients grouped depending on ACE inhibitor usage or not. The 60-day all-cause mortality and need for intubation compared. Results Of the 173 patients identified, 88 (50.8%) had hypertension. Of these 27 (30.7%) used ACE inhibitors. We did not find significant differences in 60-day all-cause mortality, the requirement for invasive ventilation or length of stay between our patient cohorts after adjusting for covariates. Conclusion This study contributes to the growing evidence supporting the continued use of ACE inhibitors in COVID-19 disease, although adequately powered randomised controlled trials will be needed to confirm effects.
Desk-Top Publishing: Current Approaches and Future Trends
Authors: Black George 
Published: September 2020

In order to assess future trends in desk-top publishing (DTP), it is necessary to understand the problems encountered in today's solutions. The environment addressed by this paper is the single-user interactive workstation for a business, technical or publishing professional. A local or shared low-cost printer is assumed. High-quality and high-volume printing is treated as a remote or an external function to which a document can be transferred in machine-readable form.
Polyvictimization and Recurrent Falling in Older Ecuadorian Adults: The Mediation Role of Depressive Symptoms
Authors: Reyes-Ortiz Carlos A. , Perez-Zepeda Mario U. , Ocampo-Chaparro José M. , Campo-Arias Adalberto , Borda Miguel G. , Holmes Holly M. , Luque John S. 
Published: September 2020

Objective: To assess depressive symptoms as a mediator in the association between polyvictimization and recurrent falling. Methods: Using data from the Salud, Bienestar y Envejecimiento (Health, Well-being, and Aging) Ecuador Study, we analyzed community-dwelling adults 60 years and older ( n = 5227). Recurrent falling was determined as ≥2 falls during the prior 12 months. Polyvictimization was determined as a history of ≥2 types of abuse. The mediator was depressive symptoms. Mediation analyses were based on the VanderWeele method. Results: Polyvictimization was significantly associated with higher odds of recurrent falling, and odds ratio (OR) = 1.45 (95% confidence intervals [CI] 1.20–1.76). Higher depressive symptoms increase the odds for recurrent falling (OR = 1.09 and 95% CI 1.07–1.11). Moreover, depressive symptoms were a significant mediator between polyvictimization and recurrent falling. The mediating effect was 28.4%. Discussion: Polyvictimization was associated with higher odds of recurrent falling, and this association was mediated by depressive symptoms.