bluuebunny/crossref_metadata_2025_split huggingface dataset:
DBPA: A Benchmark for Transactional Database Performance Anomalies
Authors: Huang Shiyue , Wang Ziwei , Zhang Xinyi , Tu Yaofeng , Li Zhongliang , Cui Bin 
Published: May 2023

Anomaly diagnosis is vital to the performance of online transaction processing (OLTP) systems. In the meanwhile, machine learning techniques can reason complex relationships beyond human abilities and perform well on such problems. However, they rely on a large number of training samples for anomalies, which are in serious shortage in both industry and academia due to the difficulty of collection. The problem raises the demand of a benchmark for anomaly reproduction and data collection.
In this paper, we propose DBPA, a benchmark for transactional database performance anomalies. Specifically, we identify nine common anomalies rooted in the diverse influence factors. For each anomaly, we carefully design a reproduction procedure, which consists with its root cause in real-world databases. With the reproduction procedures, users can easily generate a dataset in a new environment and extend new anomaly types. For compound anomalies, we provide a generation algorithm that allows users to generate compound anomalies data of any possible combinations with existing collected data. We also provide a large dataset of both normal and anomalous monitoring data collected from various environments, facilitating the training of machine learning models and the evaluation of new algorithms for anomaly diagnosis.
When Tree Meets Hash: Reducing Random Reads for Index Structures on Persistent Memories
Authors: Wang Ke , Yang Guanqun , Li Yiwei , Zhang Huanchen , Gao Mingyu 
Published: May 2023

Indexing structures are widely used in modern data-processing applications to support high-performance queries, and there are a variety of recent designs specifically optimized for the newly available persistent memory (PM). The primary focus of previous PM indexes is on reducing the expensive PM writes for persisting data. However, we find that in tree-based PM indexes, because of the smaller performance gap between writes and random reads on real PM devices, the read-intensive tree traversal phase dominates the overall latency. This observation calls for further optimizations on existing indexing structures for PM.
In this paper, we propose Extendible Radix Tree (ERT), an efficient indexing structure for PM that significantly reduces tree heights to minimize random reads, while still maintaining fast in-node search speed. The key idea is to use extendible hashing for each node in a radix tree. This design allows us to have a relatively large fanout of the radix tree to keep the tree height small, and also to realize constant-time lookups within a node. Using extendible hashing also allows for incremental node modification without excessive writes during inserts and updates. Range queries are efficiently and robustly handled by enforcing partial ordering among the keys in the hash table of each node without introducing more hash collisions. Our experiments on both synthetic and real-world data sets demonstrate that ERT achieves up to 2.65×, 4.41×, and 2.43× speedups for search, insert, and range queries over the respectively state-of-the-art PM index.
The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma
Authors: Shi Linyong , Chen Hanning , Chen Kunxiang , Zhong Chengzong , Song Chong , Huang Yifeng , Wang Tong , Chen Lei , Li Chiyang , Huang Annie , Qi Songtao , Li Hong , Lu Yuntao 
Published: May 2023

Abstract

Purpose:
Temozolomide resistance remains a major obstacle in the treatment of glioblastoma (GBM). The combination of temozolomide with another agent could offer an improved treatment option if it could overcome chemoresistance and prevent side effects. Here, we determined the critical drug that cause ferroptosis in GBM cells and elucidated the possible mechanism by which drug combination overcomes chemoresistance.

Experimental Design:
Haloperidol/temozolomide synergism was assessed in GBM cell lines with different dopamine D2 receptor (DRD2) expression in vitro and in vivo. Inhibitors of ferroptosis, autophagy, endoplasmic reticulum (ER) stress and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) were used to validate the specific mechanisms by which haloperidol and temozolomide induce ferroptosis in GBM cells.

Results:
In the present work, we demonstrate that the DRD2 level is increased by temozolomide in a time-dependent manner and is inversely correlated with temozolomide sensitivity in GBM. The DRD2 antagonist haloperidol, a butylbenzene antipsychotic, markedly induces ferroptosis and effectively enhances temozolomide efficacy in vivo and in vitro. Mechanistically, haloperidol suppressed the effect of temozolomide on cAMP by antagonizing DRD2 receptor activity, and the increases in cAMP/PKA triggered ER stress, which led to autophagy and ferroptosis. Furthermore, elevated autophagy mediates downregulation of FTH1 expression at the posttranslational level in an autophagy-dependent manner and ultimately leads to ferroptosis.

Conclusions:
Our results provide experimental evidence for repurposing haloperidol as an effective adjunct therapy to inhibit adaptive temozolomide resistance to enhance the efficacy of chemoradiotherapy in GBM, a strategy that may have broad prospects for clinical application.
Abstract ND06: AMG 305, a dual targeting BiTE®molecule with selective activity for solid tumors that co-express CDH3 and MSLN
Authors: Pham Elizabeth , Lutterbuese Petra , Deegen Petra , Mariano Natalie , Matthes Katja , Wahl Joachim , Bogner Pamela , Lane Joan , Wilson Kristin Lewis , Yabut Rodolfo , Naegele Virginie , Ullrich Ines , Everts Stephanie , Muenz Markus , Boehm Thomas , Stienen Sabine , Coxon Angela , Kufer Peter , Raum Tobias , Bailis Julie M. 
Published: May 2023

Abstract
T cell engager (TCE) molecules are a targeted immune therapy that redirect a patient’s T cells to kill tumor cells. While several TCE molecules have now advanced to approval, clinical development has been challenging, especially in the solid tumor setting. There are few solid tumor surface antigens that are tumor-specific, and antigens with even low levels of expression in normal tissue can be recognized by a TCE and result in on-target off-tumor toxicity. To overcome this challenge, we have developed AMG 305, a first-in-class, dual targeting BiTE® (bispecific T cell engager) molecule that requires binding to both P-cadherin (CDH3) and mesothelin (MSLN) for potent cytotoxic activity. Immunohistochemistry analysis shows that CDH3 and MSLN are co-expressed in multiple solid tumor types. In normal tissues, immunostaining shows fewer tissues have overlapping co-expression than expression of just one or the other target. AMG 305 relies on an avidity-based approach to engage T cells to preferentially kill CDH3+MSLN+ tumor cells, with limited activity against normal cells that express only one of the target antigens. In vitro, AMG 305 induces potent cytotoxicity against tumor cells co-expressing CDH3 and MSLN, with greatly attenuated activity against cells expressing only CDH3 or MSLN. In vivo, AMG 305 demonstrates dose-dependent antitumor activity in a CDH3+MSLN+ xenograft tumor model. AMG 305 was clinically well-tolerated in a nonclinical safety study in cynomolgus monkey. Data from IND-enabling preclinical studies support initiation of the first-in-human study of AMG 305 in CDH3+MSLN+ solid tumors in 2023.
Citation Format: Elizabeth Pham, Petra Lutterbuese, Petra Deegen, Natalie Mariano, Katja Matthes, Joachim Wahl, Pamela Bogner, Joan Lane, Kristin Lewis Wilson, Rodolfo Yabut, Virginie Naegele, Ines Ullrich, Stephanie Everts, Markus Muenz, Thomas Boehm, Sabine Stienen, Angela Coxon, Peter Kufer, Tobias Raum, Julie M. Bailis. AMG 305, a dual targeting BiTE®molecule with selective activity for solid tumors that co-express CDH3 and MSLN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr ND06.
Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function
Authors: Renauer Paul , Park Jonathan J. , Bai Meizhu , Acosta Arianny , Lee Won-Ho , Lin Guang Han , Zhang Yueqi , Dai Xiaoyun , Wang Guangchuan , Errami Youssef , Wu Terence , Clark Paul , Ye Lupeng , Yang Quanjun , Chen Sidi 
Published: May 2023

Abstract
Immune evasion is a critical step of cancer progression that remains a major obstacle for current T cell–based immunotherapies. Hence, we investigated whether it is possible to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism whereby cancer cells suppress T-cell function by generating a metabolically unfavorable tumor microenvironment (TME). In an in silico screen, we identified ADA and PDK1 as metabolic regulators. We then showed that overexpression (OE) of these genes enhanced the cytolysis of CD19-specific chimeric antigen receptor (CAR) T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampened this effect. ADA-OE in CAR T cells improved cancer cytolysis under high concentrations of adenosine, the ADA substrate, and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics analysis of these CAR T cells revealed alterations of global gene expression and metabolic signatures in both ADA- and PDK1-engineered CAR T cells. Functional and immunologic analyses demonstrated that ADA-OE increased proliferation and decreased exhaustion in CD19-specific and HER2-specific CAR T cells. ADA-OE improved tumor infiltration and clearance by HER2-specific CAR T cells in an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR T cells and reveal potential targets for improving CAR T-cell therapy.
Evolved Open-Endedness in Cultural Evolution: A New Dimension in Open-Ended Evolution Research
Authors: Borg James M. , Buskell Andrew , Kapitany Rohan , Powers Simon T. , Reindl Eva , Tennie Claudio 
Published: May 2023

Abstract
The goal of Artificial Life research, as articulated by Chris Langton, is “to contribute to theoretical biology by locating life-as-we-know-it within the larger picture of life-as-it-could-be.” The study and pursuit of open-ended evolution in artificial evolutionary systems exemplify this goal. However, open-ended evolution research is hampered by two fundamental issues: the struggle to replicate open-endedness in an artificial evolutionary system and our assumption that we only have one system (genetic evolution) from which to draw inspiration. We argue not only that cultural evolution should be seen as another real-world example of an open-ended evolutionary system but that the unique qualities seen in cultural evolution provide us with a new perspective from which we can assess the fundamental properties of, and ask new questions about, open-ended evolutionary systems, especially with regard to evolved open-endedness and transitions from bounded to unbounded evolution. Here we provide an overview of culture as an evolutionary system, highlight the interesting case of human cultural evolution as an open-ended evolutionary system, and contextualize cultural evolution by developing a new framework of (evolved) open-ended evolution. We go on to provide a set of new questions that can be asked once we consider cultural evolution within the framework of open-ended evolution and introduce new insights that we may be able to gain about evolved open-endedness as a result of asking these questions.
Evaluating the compressive strength of stepped scarf repaired single stiffener composite panels
Authors: Psarras Spyridon , Loutas Theodoros , Sotiriadis George , Kostopoulos Vassilis 
Published: May 2023

In this study, tests were carried out on repaired 300 × 250 mm composite stiffened panels. The initial damage was assumed to be extended in a depth of the first six plies and a repair with scarf ratio of 1:50 was employed. A circular repair took place, utilizing laser-assisted ablation and the wet patches approach. The panels were tested in compression and Digital Image Correlation (DIC) and Acoustic Emission (AE) were used in order to monitor the damage initiation and propagation of the panels. In addition, Phased Array (PA) was used in order to monitor the patch failure. Detailed Finite Elements (FE) models were validated against the test findings and their performance as a prediction tool for the performance of repairs on composite aeronautical structures was assessed.
Dysphagia in Older Adults is Associated With Food Insecurity and Being Homebound
Authors: Jones Harrison N. , Leiman David A. , Porter Starr Kathryn N. , North Rebecca , Pieper Carl F. , Robison Raele D. , Cohen Seth M. 
Published: May 2023

Objective: Our aim was to evaluate relationships between swallowing difficulty (dysphagia) and social determinants of health (SDOH) in older adults ≥65 years. Method: Cross-sectional analyses were performed in community-dwelling Medicare beneficiaries from the National Health & Aging Trends Study (NHATS). The primary exposure was self-reported difficulty chewing/swallowing in the prior month. Dependent measures included a variety of SDOH outcomes (e.g., food insecurity [FI]). Weighted logistic regression models were estimated to determine associations between dysphagia and SDOH outcomes. Results: Of 4041 participants, 428 (10.6%) self-reported dysphagia. In the adjusted model, dysphagia was associated with significantly increased odds for FI (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.06, 2.07, p = .023) and being homebound (OR = 1.32, 95% CI = 1.13, 1.55, p= < .001). Discussion: Older adults with dysphagia had increased odds of FI and being homebound. These associations have implications for health-promoting interventions at the individual and policy levels in older adults.
Use of Fixed-dose Combination Therapy with Remogliflozin and Vildagliptin as an Add-on Drug in Improving the Glycemic Control of Type 2 Diabetes Mellitus: An Observational Study
Authors: Petchiappan Velammal , Mathew Elsa , Jose Josna , Fardan Mohamed , Chidambaram Yoganathan , Thangavelu Saravanan 
Published: May 2023

Objective To evaluate whether a fixed dose combination (FDC) with remogliflozin and vildagliptin as an add-on therapy can improve the glycemic control in the management of type 2 diabetes mellitus and also the non-glycemic effects on physical profile, blood pressure, lipids, and insulin resistance. Materials and Methods An observational study that included 50 poorly controlled diabetics from April 2021 to September 2021. Patients were divided into two groups – those who were prescribed this FDC by their treating physician as an add-on drug were formed as group 1 ( n = 28). Comparison group was age-matched patients who received other standard anti-diabetic medications, categorized as group 2 ( n = 22). Fasting and postprandial sugars were done at baseline, the third and sixth month; glycated hemoglobin, body mass index, blood pressure, and lipids were done at baseline and the sixth month. Changes in blood sugar levels and glycated hemoglobin (HbA1C) at the third and sixth month from the baseline were compared using the Mann-Whitney U test. P-value less than 5% was considered statistically significant. Results A statistically significant reduction in mean HbA1c was noted in group 1 [–1.80 (−3.20, −0.15)] when compared to group 2 [0.50 (0.05, 0.80)] at the end of the third month. At the end of the sixth month, a significant reduction in the HbA1c level was noted in group 1 [(7.83 ± 0.87 %) when compared to baseline (10.3 ± 1.75%)]. Change in PPBS value at the third month from baseline was also statistically significant between groups 1 and 2 (−62.0 mg%, 19.0, P = 0.003). With respect to the body mass index and blood pressure, we did not find any significant difference. Conclusion The fixed drug combination improves glycemic control by significantly reducing mean HbA1c at the third and sixth month from baseline and there was no significant effect on body mass index, blood pressure, and lipids.
The Impact of Midodrine Tapering Versus Nontapering Regimens on the Clinical Outcomes of Critically Ill Patients: A Retrospective Cohort Study
Authors: Gramish Jawaher , Hattan Ahmed , Aljuhani Ohoud , Parameaswari P. J. , Alshehri Shaden , Korayem Ghazwa B. , Alkofide Hadeel , Alalawi Mai , Vishwakarma Ramesh , Alsowaida Yazed Saleh , Alqahtani Rahaf , Binorayir Luluh , Abutaleb Mohammed , Alotaibi Alanoud , Aljohani Majidah , Aljohani Sarah , Samreen Sana , Jawhari Suad , Alanazi Raghad , Al Sulaiman Khalid A. 
Published: May 2023

Background: Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. Objectives: To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. Methods: A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. Results: The incidence of inotropes or vasopressors’ re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. Conclusion and Relevance: These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.
The effect of autistic traits on prosocial behavior: The chain mediating role of received social support and perceived social support
Authors: Zhang Shuhua , Li Hong , Li Hai , Zhao Shuo 
Published: May 2023

There is growing evidence that the defining characteristics of autism spectrum disorder are distributed across the general population; therefore, understanding the correlates of prosocial behavior in individuals with high levels of autistic traits could shed light on autism spectrum disorder and prosocial behavior. In this study, the mechanism underlying the influence of individuals’ autistic traits on their prosocial behavior was explored by conducting a questionnaire survey of 414 Chinese college students. The results showed that autistic traits can influence individuals’ prosocial behavior not only through the separate effects of received social support and perceived social support but also through the chain mediating effects of received social support and perceived social support; however, the direct effect of autistic traits on individuals’ prosocial behavior is not significant. This study is conducive to understanding the internal mechanism underlying the relationship between autistic traits and prosocial behavior. Future work is required to further investigate the clinical autism spectrum disorder samples and cross-cultural applicability of the model found in this study. Lay abstract Autistic traits are known to be associated with a set of core symptoms of autism spectrum disorder. The impact of autistic traits on prosocial behavior, including a consideration of the role of social support, has never been explored. We investigated whether and how social support mediates the autistic trait–prosocial behavior relationship. We found that autistic traits can influence prosocial behavior not only through received social support and perceived social support but also indirectly through the chain mediating effects of received social support and perceived social support. This study contributes to the understanding of how and to what extent prosocial behavior is influenced by autistic traits. Future work is required to further investigate the clinical autism spectrum disorder samples and cross-cultural applicability of the model found in this study.
Distinguishing Servant Leadership from Transactional and Transformational Leadership
Authors: Martinez Seth-Aaron , Leija Nahari 
Published: May 2023

ProblemThe scholarship of leadership abounds with the affordances, limitations, antecedents, and outcomes associated with the different theories in Human Resource Development (HRD) literature. However, a clear delineation between the host of individual leadership theories does not exist. Absent is a nuanced view of the similarities, differences, and any overlap between the various leadership theories. Without a clear understanding of the relationships between leadership theories, knowing when to apply which theories and when becomes difficult.SolutionA systematic review of the literature surrounding servant leadership (SL) through 2022 was conducted to position SL among the more extensively researched transactional and transformational leadership theories. This article outlines the histories of the three theories, focusing on the characteristics, pervasiveness, antecedents, outcomes, and measurement of SL to distinguishing it from transactional and transformational leadership.; Stakeholders: Human resource development, human resource management, and organizational behavior scholars, practitioners, educators, and students. In addition, organizational leaders responsible for setting the organization’s vision and practitioners responsible for designing leadership development programs will benefit from this article.
A History of Heart Attack and Experiencing Frequent Mental Distress Among US Veterans and Adult Civilians: A 2019 National Level Cross-Sectional Study
Authors: Passini Jessica N. , Oancea S. Cristina 
Published: May 2023

Introduction Frequent mental distress (FMD) is poor mental health for ≥14 days in the past month. Prevalence and risk for depression and suicide are higher among US veterans (USV) than US civilians (USC). Limited research has been done among USV regarding FMD. Anyone can experience mental distress without being clinically depressed—examining FMD more broadly captures health burden of poor mental state. This study’s purpose was to examine the association between having a history of heart attack (HHHA) and FMD among USV vs USC. Methods This cross-sectional study used the 2019 Behavioral Risk Factor Surveillance System (n = 274 352) data. Weighted and adjusted logistic regression models were conducted overall and by USV/USC status. Results HHHA increases weighted adjusted odds (WAO) of FMD. Among insured not obese USV with HHHA, the WAO of FMD were 1.4x significantly greater ( P < .05) than among insured not obese USV without HHHA. Among uninsured obese USC with HHHA, the WAO of FMD were 3.2x significantly greater ( P < .0001) than among uninsured obese USC without HHHA, and significantly lower among USV. Conclusions Study findings suggest a distinction in FMD among USV/USC with HHHA. Understanding this association can inform policy for FMD screening post-heart attack as another potential intervention to prevent/reduce suicide among USV/USC.