bluuebunny/crossref_metadata_2025 huggingface dataset:
Does identity change matter? Everyday agency, moral authority and generational cascades in the transformation of groupness after conflict
Authors: Todd Jennifer
Published: April 2024

Everyday identity change is common after conflict, as people attempt to move away from oppositional group relations and closed group boundaries. This article asks how it scales up and out to impact these group relations and boundaries, and what stops this? Theoretically, the article focusses on complex oppositional configurations of groupness, where relationality and feedback mechanisms (rather than more easily measured variables) are crucial to change and continuity, and in which moral authority is a key node of reproduction. It uses the normatively weighted concept of transformation to augment existing research on boundary and identity change, while elaborating it to recognise the role of everyday agency in furthering change and moral inertia in impeding it. Substantively, the article compares the processes of everyday transformation of groupness in three cases that are very similar in historical depth, social embeddedness, symbolic opposition and everyday change, but very different in time-scale and with contrasting outcomes: successful transformation of reformation religious groupness; partial transformation of national groupness; and failed transformation of complexly-configured ethnic groupness in Northern Ireland. This allows tracing of the patterns and mechanisms at work. To anticipate, the article argues that everyday identity change can erode the moral authority of groupness. Its impact is generational and dependent on institutional linkages. The article highlights the importance of moral mechanisms as drivers of and obstacles to change; and it suggests ways that the obstacles could be overcome by radical policy interventions.
What does the 7th cooperative principle (concern for community) really mean?
Authors: Osten Flávio Luiz Von Der , Martins Tomas Sparano , Dong Hao , Bailey Adrian R.
Published: April 2024

Cooperatives are an important organizational form that operate under seven principles (Voluntary and Open Membership; Democratic Member Control; Member Economic Participation; Autonomy and Independence; Education, Training, and Information; Cooperation among Cooperatives; Concern for Community). Concern for Community was the last formally stated cooperative principle in 1995, after decades of discussion within the International Cooperative Alliance (ICA). The statement of this “new” principle has provoked questions for cooperatives and the cooperative movement more generally, regarding their definition, scope, and implementation. This article employs a systematic literature review to examine the academic understanding of Concern for Community that has emerged over the past 30 years. The review analyzes 32 academic journal articles from an initial dataset of 438 articles generated by a two-string search (“concern for community” and “cooperative principles”). Five themes are identified: cooperative principles, defining Concern for Community, adoption of Concern for Community, antecedents of Concern for Community, and outcomes. Comparing these themes with the normative instructions proposed by the ICA, the article develops a framework for future research. The review also finds that there is not an established clear difference between Concern for Community and corporate social responsibility in the extant literature, which carries the implication that constructs from the latter can be integrated into the analysis and development of the 7th principle.
AA Amyloidosis: A Contemporary View
Authors: Mirioglu Safak , Uludag Omer , Hurdogan Ozge , Kumru Gizem , Berke Ilay , Doumas Stavros A. , Frangou Eleni , Gul Ahmet
Published: April 2024

Purpose of Review

Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis.

Recent Findings

The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents.

The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed.
What Makes Us Move, What Makes Us Stay: The Role of Language and Culture in Intra-EU Mobility
Authors: Sprenger Ekaterina
Published: April 2024

This article analyses the determinants of international migration flows within the European Union and specifically focuses on the role of cultural and linguistic differences in explaining the size of these flows. For that purpose, a set of indicators of cultural distance is controlled for along with economic, demographic, geographical, political and network variables using data from 28 member states of the EU over the period 1998–2018. Economic factors play an important role in examining migration flows, but economic differentials alone may be insufficient to explain the uneven real-life migration pattern in the EU. The results suggest strong evidence of the importance of linguistic distance in explaining the direction of migration flows across the EU.
Cognitive flexibility and depression: The moderator roles of humor styles
Authors: Altan-Atalay Ayse , Fatih Boluvat Mustafa
Published: April 2024

Humor style, which involves both adaptive and maladaptive forms, refers to the ways people use humor in daily life. Maladaptive humor styles (self-defeating and aggressive) can be risk factors for various mental disorders, including depression and anxiety. In contrast, adaptive humor styles (affiliative and self-enhancing) are perceived as resilience factors and buffer the negative impact of other risk factors. Cognitive flexibility reflects a capacity to come up with alternative interpretations and resolutions to demanding situations while perceiving them as controllable. Although the connection of high cognitive flexibility with low depression levels has been consistently documented, its interaction with trait-like factors received limited attention. The current study aims to explore the moderator role of humor styles in the association of cognitive flexibility with depression. Data were gathered from 436 (320 women) participants aged 18 and 70 (M = 35.4, SD = 9.18) through scales assessing humor styles, cognitive flexibility, and depression. The results revealed that the interaction of affiliative humor style with cognitive flexibility was significantly linked to the individual differences in depression levels, highlighting that affiliative humor is functional if individuals have difficulty approaching problematic situations from different angles. However, a similar pattern was not observed for other humor styles.
BRD4 inhibitors broadly promote erastin-induced ferroptosis in different cell lines by targeting ROS and FSP1
Authors: Fan Chenyang , Guo Xiaohong , Zhang Jie , Zheng Wen , Shi Chonglin , Qin Yongwei , Shen Haoliang , Lu Yang , Fan Yihui , Li Yanli , Chen Liuting , Mao Renfang
Published: April 2024

Ferroptosis, an iron-dependent form of programmed cell death, is a promising strategy for cancer treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and a promising target for cancer therapeutics. However, the role of BRD4 in ferroptosis is controversial and the value of the interaction between BRD4 inhibitors and ferroptosis inducers remains to be explored. Here, we found that BRD4 inhibition greatly enhanced erastin-induced ferroptosis in different types of cells, including HEK293T, HeLa, HepG2, RKO, and PC3 cell lines. Knocking down BRD4 in HEK293T and HeLa cells also promoted erastin-induced cell death. BRD4 inhibition by JQ-1 and I-BET-762 or BRD4 knockdown resulted in substantial accumulation of reactive oxygen species (ROS) in both HEK293T and HeLa cells. The effect of BRD4 inhibition on ferroptosis-associated genes varied in different cells. After using BRD4 inhibitors, the expression of FTH1, Nrf2, and GPX4 increased in HEK293T cells, while the levels of VDAC2, VDAC3, and FSP1 decreased. In HeLa cells, the expression of FTH1, VDAC2, VDAC3, Nrf2, GPX4, and FSP1 was reduced upon treatment with JQ-1 and I-BET-762. Consistently, the level of FSP1 was greatly reduced in HEK293T and HeLa cells with stable BRD4 knockdown compared to control cells. Furthermore, ChIP-sequencing data showed that BRD4 bound to the promoter of FSP1, but the BRD4 binding was greatly reduced upon JQ-1 treatment. Our results suggest that ROS accumulation and FSP1 downregulation are common mechanisms underlying increased ferroptosis with BRD4 inhibitors. Thus, BRD4 inhibitors might be more effective in combination with ferroptosis inducers, especially in FSP1-dependent cancer cells.
Development of chitosan-folate modified PLGA nanoparticles for targeted delivery of diosgenin as an anticancer agent
Authors: Teymouri Fatemeh , Karimi Ehsan
Published: April 2024

Diosgenin as a potential phytoconstituent and steroidal saponin manifested significant anticancer agents against various cancers. To enhance its solubility and bioavailability in cancer treatment, we loaded diosgenin (PubChem CID: 99474) in poly(lactic-co-glycolide) (PLGA) nanoparticle coated with folic acid-chitosan (Da-PFC-NPs). The diosgenin nano-formulation was characterized and its antioxidant and anticancer properties were surveyed respectively. The obtained results illustrated that the Da-PFC-NPs were spherical and stable with a size of 218 nm and a polydispersity index of 0.41. The Da-PFC-NPs indicated potential free radical scavenging using ABTS and DPPH assay. Meanwhile, it demonstrated selective toxicity against the TUBO breast cancer cell with IC50 values of 104.45 μg/ml and did not show toxicity on normal cells (I929 cell line). The invivo funding exhibited that Da-PFC-NPs notably  altered the liver enzymes (AST, ALT, ALP) and immunoglobulins (IgA, IgG, IgM). Besides that, different doses of Da-PFC-NPs (50 and 100 mg/kg) remarkedly enhance the expression of caspase 3 and decrease HER2 genes. In light of this experiment, we can conclude that Da-PFC-NPs have promise as novel carrier for improving the delivery of diosgenin in cancer therapy.
MAP3K4 kinase action and dual role in cancer
Authors: Huang Yuxin , Wang Guanwen , Zhang Ningning , Zeng Xiaohua
Published: April 2024

It is commonly known that the MAPK pathway is involved in translating environmental inputs, regulating downstream reactions, and maintaining the intrinsic dynamic balance. Numerous essential elements and regulatory processes are included in this pathway, which are essential to its functionality. Among these, MAP3K4, a member of the serine/threonine kinases family, plays vital roles throughout the organism's life cycle, including the regulation of apoptosis and autophagy. Moreover, MAP3K4 can interact with key partners like GADD45, which affects organism's growth and development. Notably, MAP3K4 functions as both a tumor promotor and suppressor, being activated by a variety of factors and triggering diverse downstream pathways that differently influence cancer progression. The aim of this study is to provide a brief overview of physiological functions of MAP3K4 and shed light on its contradictory roles in tumorigenesis.
Tracking long-term modal behaviour of a footbridge and identifying potential SHM approaches
Authors: Ao Wai Kei , Hester David , O’Higgins Connor , Brownjohn James
Published: April 2024

Numerous studies have investigated the long-term monitoring of natural frequencies, primarily focusing on medium–large highway bridges, using expensive monitoring systems with a large array of sensors. However, this paper addresses the less explored issue of monitoring a footbridge, examining four critical aspects: (i) sensing system, (ii) frequency extraction method, (iii) data modelling techniques, and (iv) damage detection. The paper proposes a low-cost all-in-one sensor/logger unit instead of a conventional sensing system to address the first issue. For the second issue, many studies use natural frequency data extracted from measured acceleration for data modelling, the paper highlights the impact of the input parameters used in the automated frequency extraction process, which affects the number and quality of frequency data points extracted and subsequently influences the data models that can be created. After that, the paper proposes a modified PCA model optimised for computational efficiency, designed explicitly for sparse data from a low-cost monitoring system, and suitable for future on-board computation. It also explores the capabilities and limitations of a data model developed using a limited data set. The paper demonstrates these aspects using data collected from a 108 m cable-stayed footbridge over several months. Finally, the detection of damage is achieved by employing the one-class SVM machine learning technique, which utilises the outcomes obtained from data modelling. In summary, this paper addresses the challenges associated with the long-term monitoring of a footbridge, including selecting a suitable sensing system, automated frequency extraction, data modelling techniques, and damage detection. The proposed solutions offer a cost-effective and efficient approach to monitoring footbridges while considering the challenges of sparse data sets.
Sensitivity analysis of near solidus forming (NSF) process with digital twin using Taguchi approach
Authors: Sajjad Muhammad , Trinidad Javier , Plata Gorka , Lozares Jokin , Mendiguren Joseba
Published: April 2024

Forging at near solidus material state takes advantage of the high ductility of the material at the semi solid or soft-solid state while keeping most of the mechanical properties of a forged part. The technology is at maturity level ready for its industrial implementation. However, to implement the process for complex cases the development of an appropriate digital twin (DT) is necessary. While developing a material model, a strong experimental and DT is necessary to be able to evaluate the accuracy of the model. Aimed at having a reliable DT under control, for future material model validations, the main objective of this work is to develop a sensitivity analysis of three NSF industrial cases such as Hook, R spindle and H spindle to develop an adequate DT calibration procedure. Firstly, the benchmark experimentation process parameter noise and experimentation boundary conditions (BCs) parameter uncertainty are identified. Secondly, the three industrial benchmark DTs are constructed, and a Taguchi design of experiments (DoEs) methodology is put in place to develop the sensitivity analysis. Finally, after simulations the results are critically evaluated and the sensitivity of each benchmark to the different inputs (process parameter noise and BC parameter uncertainty) is studied. Lastly, the optimum DT calibration procedure is developed. Overall, the results stated the minimum impact of the material model in terms of dies filling. Nevertheless, even if the material model is the highest impacting factor for the forging forces other inputs, such as heat transfer and friction must be under control first.
Effect of temperature on tribofilm growth and the lubrication of the piston ring-cylinder liner system in two-stroke marine engines
Authors: Lyu Xiuyi , Hu Jiang , Wang Yunchuan , Sheng Jinlu , Ma Xuan , Li Tongyang , Ge Chang , Lu Xiqun
Published: April 2024

This study is an optimized extension based on the authors’ previous research on the tribo-chemical reaction under constant temperature field of two-stroke internal combustion engines (ICEs). It establishes a coupled analysis model that considers the tribo-chemical reactions, dynamic contact, and interface lubrication of the piston ring-cylinder liner (PRCL) system under transient temperature conditions. In this study, for the first time, the prediction of the tribofilm thickness and its influence on the surface micro-topography (the comprehensive roughness) are coupled in the working temperature field of the PRCL system, forming an effective model framework and providing a model basis and analytical basis for subsequent research. This study findings reveal that by incorporating temperature and tribofilm into the simulation model, the average friction deviation throughout the stroke decreases from 8.92% to 0.93% when compared to experimental results. Moreover, the deviation during the combustion regime reduces from 39.56% to 7.34%. The proposed coupled model provides a valuable tool for the evaluation of lubrication performance of the PRCL system and supports the analysis software forward design in two-stroke ICEs.
A novel method for imitating true-triaxial stress path with conventional triaxial apparatus
Authors: Li Xuefeng , Ma Zhigang
Published: April 2024

The stress paths of the cylindrical specimen in the p–q stress space by controlling the ratio of the axial and the radial loading is guaranteed to be consistent with the cuboid specimen, a novel method for imitating true-triaxial stress path by conventional triaxial apparatus was presented. Under the condition that p and q were variables and b was constant, the true-triaxial stress paths were realized by conventional triaxial apparatus strictly and easily. Under the condition that b and p were invariants, the b was used to control the ratio of axial and radial loading to ensure p constant, the method can be used to measure the strength on the π plane. If the tests were conducted at the different p with the same b, the critical state line of different b could be obtained. Under the condition that p and q were constant, the proposed method of nonlinear loading with b as a parameter could be used to design the various stress paths of true-triaxial under the condition of deviatoric stress consolidation, and which could be used to determine the deformation and the plastic flow of soil in 3D space. The proposed method could be used to achieve the equivalent stress path in the p–q stress space to obtain the 3D mechanical properties, and the stress path controlled by stress, strain, and a hybrid of stress and strain. Once the software of conventional triaxial apparatus was developed by the novel method, the measuring range of stress paths could be expanded greatly.
Die Verbreitung antisemitischer Einstellungen in Deutschland: Befunde aktueller repräsentativer Befragungen zu Trends seit 2021 und den Einflüssen von Migrationshintergrund, Religionszugehörigkeit und Religiosität
Authors: Fischer Jannik M. K. , Wetzels Peter
Published: April 2024

Seit den Anschlägen vom 7. Oktober 2023 und im Gefolge des anschließenden Gaza-Krieges erfährt Antisemitismus in Deutschland wieder erheblich gesteigerte Aufmerksamkeit. Ein besonders sensibles Thema ist dabei Antisemitismus unter in Deutschland lebenden Muslim:innen. Auf Basis der Daten aus drei repräsentativen, bundesweiten Befragungen untersucht der vorliegende Beitrag Trends der Verbreitung antisemitischer Einstellungen seit 2021. Analysen erfolgen sowohl in Bezug auf die erwachsene Bevölkerung insgesamt als auch kontrastierend für verschiedene gesellschaftliche Subgruppen. Im Ergebnis finden sich für die erwachsene Gesamtbevölkerung keine signifikanten Anstiege von Formen tradierter antisemitischer Einstellungen zwischen 2021 und 2023. Es sind jedoch deutliche Binnendifferenzen zu erkennen. Insbesondere sind bei Muslim:innen nicht nur erheblich erhöhte Raten antisemitischer Einstellungen zu registrieren, sondern auch statistisch signifikante Zuwächse zwischen 2021 und 2023, die sich bei anderen Gruppen so nicht finden. Auch nach multivariaten Kontrollen soziodemografischer Merkmale und weiterer aus der Forschung bekannter sozialer Einflussgrößen sind bei ihnen weiterhin signifikant erhöhte Ausprägungen antisemitischer Einstellungen nachweisbar. Ferner erweisen sich Neigungen zur Akzeptanz von Verschwörungsnarrativen für alle Gruppen als ein stabiler, signifikanter Prädiktor. Bei Christ:innen wie Muslim:innen finden sich daneben keine Zusammenhänge der persönlichen Gläubigkeit oder der Zentralität der Religion mit Antisemitismus. Es zeigen sich aber Zusammenhänge der Ausprägung eines fundamentalistischen Religionsverständnisses mit erhöhten antisemitischen Ressentiments bei beiden Gruppen. Nur bei Muslim:innen ist darüber hinaus die Intensität der kollektiven Religionspraxis, gemessen über die Häufigkeit des Besuchs von Moscheen, nach multivariaten Kontrollen der Intensität der individuellen Gläubigkeit sowie sozialer Kontrollvariablen, mit einer Erhöhung antisemitischer Vorurteile verbunden. Politische Implikationen dieser Ergebnisse für die Prävention von Antisemitismus in der modernen deutschen Migrationsgesellschaft werden daran anknüpfend diskutiert.
Analyzing the influence of web search behavior on electricity market price: a case study of Japan electric power exchange
Authors: Gotoh Ryosuke
Published: April 2024

The Japan Electric Power Exchange (JEPX) has introduced a feed-in premium to promote the trading of renewable energy electricity in the market; thus, the exchange has become increasingly important for RE companies to maintain profitability in market trading. However, electricity prices are not only affected by directly measurable factors such as electricity demand, fuel prices, and weather but also by corporate bidding strategies, social conditions, and other human behaviors, making it difficult to predict electricity prices. Given that electricity demand is related to human behavior, this study focuses on web search behavior and clarifies the relationship between keyword search volumes and electricity market prices in Japan. Correlation and vector autoregression analyses results show a moderately strong positive correlation between the logarithmic difference of the keyword search volume and that of the electricity price. In addition, we find that the logarithmic difference of the electricity price tends to increase when that of the keyword search volume on the previous day increases. These results suggest that search volumes of specific keywords can be effective explanatory variables for area price prediction models and can help identify signs of price spikes.
From video to vital signs: using personal device cameras to measure pulse rate and predict blood pressure using explainable AI
Authors: van Putten Lieke Dorine , Bamford Kate Emily , Veleslavov Ivan , Wegerif Simon
Published: April 2024

In this study, we address the need for low-cost, rapid, and reliable methods for blood pressure measurement to facilitate timely diagnosis and treatment of hypertension. We aim to enhance understanding and trust in the novel remote photoplethysmography technology, specifically as deployed by Lifelight$$^\circledR$$

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, for vital sign monitoring. Lifelight$$^\circledR$$

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 utilizes remote photoplethysmography to extract physiologically meaningful features from video recordings on personal devices. This study describes the accurate calculation of pulse rates and the extraction of morphological and time series features from the remote photoplethysmography signal for blood pressure prediction. Unlike common approaches, distinct model types are employed for predicting systolic and diastolic blood pressure. Evaluation on an independent clinical laboratory’s dataset demonstrates the efficacy of the proposed method. The pulse rate accuracy, measured as root mean square error, is 1.9 beats per minute. The model for systolic blood pressure prediction shows a mean error of 1.2 mmHg and a standard deviation of 15.9 mmHg. The model for diastolic prediction shows a mean error of $$-$$
-
3.2 mmHg and a standard deviation of 13.1 mmHg. This research establishes the validity of remote photoplethysmography technology by showcasing accurate pulse rate calculations and effective feature extraction for blood pressure prediction. The results indicate the potential for widespread adoption of remote photoplethysmography in measuring blood pressure and other vital signs.
Design and simulation of soft decision decoding based on chaotic M-ary spread spectrum system
Authors: Liu Ruopeng , Wang Pengyi , Wang Xiduo
Published: April 2024

In this paper, chaos sequence is used to replace the traditional spread spectrum sequence. From the perspective of the communication partner, a new method of generating the initial value of chaotic sequence is proposed, which is more suitable for the multi-base spread spectrum system and easy to extract. In order to further improve the error performance of the system and ensure the integrity of the system, an improved suboptimal soft information extraction method based on log-likelihood ratio (LLR) is proposed in the channel coding module, which can further improve the error performance of the system. On this basis, we choose the synchronization mode of multiple transmission of one reference signal to solve the problem that chaotic sequence is difficult to obtain synchronization because of its aperiodic characteristics. Finally, the system is simulated in the channel with low SNR. The simulation results show that chaotic sequence as spread spectrum code can make the signal transmit accurately in the worse channel environment. The performance gain of applying soft information decoding decision in the multibase spread spectrum system with chaotic sequence as spread spectrum code can reach 5.2 dB compared with the traditional direct spread spectrum system.
Ethical decision-making in human-automation collaboration: a case study of the nurse rostering problem
Authors: Bebien Vincent , Bellenguez Odile , Coppin Gilles , Ma-Wyatt Anna , Stephens Rachel
Published: April 2024

As artificial intelligence (AI) is increasingly present in different aspects of society and its harmful impacts are more visible, concrete methods to help design ethical AI systems and limit currently encountered risks must be developed. Taking the example of a well-known Operations Research problem, the Nurse Rostering Problem (NRP), this paper presents a way to help close the gap between abstract principles and on-the-ground applications with two different steps. We first propose a normative step that uses dedicated scientific knowledge to provide new rules for an NRP model, with the aim of improving nurses’ well-being. However, this step alone may be insufficient to comprehensively deal with all key ethical issues, particularly autonomy and explicability. Therefore, as a complementary second step, we introduce an interactive process that integrates a human decision-maker in the loop and allows practical ethics to be applied. Using input from stakeholders to enrich a mathematical model may help compensate for flaws in automated tools.
Bringing clarity and transparency to the consultative process underpinning the implementation of an ethics framework for AI-based healthcare applications: a qualitative study
Authors: Goirand Magali , Austin Elizabeth , Clay-Williams Robyn
Published: April 2024

Artificial intelligence (AI) has been applied in healthcare to address various aspects of the COVID-19 crisis including early detection, diagnosis and treatment, and population monitoring. Despite the urgency to develop AI solutions for COVID-19 problems, considering the ethical implications of those solutions remains critical. Implementing ethics frameworks in AI-based healthcare applications is a wicked issue that calls for an inclusive, and transparent participatory process. In this qualitative study, we set up a participatory process to explore assumptions and expectations about ethical issues associated with development of a COVID-19 monitoring AI-based app from a diverse group of stakeholders including patients, physicians, and technology developers. We also sought to understand the influence the consultative process had on the participants’ understanding of the issues. Eighteen participants were presented with a fictitious AI-based app whose features included individual self-monitoring of potential infection, physicians’ remote monitoring of symptoms for patients diagnosed with COVID-19 and tracking of infection clusters by health agencies. We found that implementing an ethics framework is systemic by nature, and that ethics principles and stakeholders need to be considered in relation to one another. We also found that the AI app introduced a novel channel for knowledge between the stakeholders. Mapping the flow of knowledge has the potential to illuminate ethical issues in a holistic way.
Combining multi-mode thermal therapy with IL-6 and IL-17A neutralization amplifies antitumor immunity to facilitate long-term survival in LLC1-bearing mice
Authors: Zheng Jiamin , Zou Jincheng , Lou Yue , Wang Shicheng , Zhang Zelu , Wang Junjun , Du Peishan , Zhu Yongxin , You Jiaqi , Yao Yichen , Hao Yuankai , Zhang Aili , Liu Ping
Published: April 2024

Non-small cell lung cancer (NSCLC) is known for rapid development and chronic inflammation-induced immunosuppression. IL-6 and IL-17A are the essential cytokines that facilitate NSCLC progression and myeloid-derived suppressive cell (MDSC)-mediated evasion. IL-6 or IL-17A targeting, especially IL-6, shown outstanding efficacy in patient NSCLC controlling, but failed to completely eradicate tumor. The local tumor multi-mode thermal therapy developed in our prior research was demonstrated to stimulate systemic and durable tumor-specific immune response thereby promoting long-term tumor-free survival of mice and prolong the progression-free survival of patients, although the therapeutic efficacy was still affected by high-level preoperative MDSCs. To further improve the efficacy, in this study, IL-6 and IL-17A neutralization were combined with multi-mode thermal therapy in mouse LLC1 NSCLC model. Study revealed that combined with single cytokine neutralization only prolonged the survival time while triple combination therapy efficiently improved the survival rate. Additionally, triple combination therapy reduced the accumulation of MDSCs but promoted their maturation with strengthened activation and function of myeloid cells, thereby triggering a Th1-dominant-CD4+ T cell-response and enhancing the malignant cell-killing capacity of immune cells. Our study highlights the extraordinary efficacy of combining multi-mode thermal therapy with IL-6 and IL-17A neutralization, revealing a new strategy for refractory NSCLC patients.

Graphical Abstract
Aggrieved Labor Strikes Back
Authors: Metinsoy Saliha
Published: April 2024

Why do we see large-scale labor protests and strikes under some IMF programs such as in Greece in 2010 and not in others such as in Ireland in the same year? This Element argues that extensive labor market reform conditions in an immobile labor market generate strong opposition to programs. Labor market reform conditions that decentralize and open up an immobile labor market cause workers either to lose in terms of rights and benefits, while being stuck in the same job or to fall into a less protected sector with fewer benefits. Conversely, in more mobile labor markets, wage and benefit differentials are low, and movement across sectors is easier. In such markets, labor groups do not mobilize to the same extent to block programs. The author tests this theory in a global sample and explores the causal mechanism in four case studies on Greece, Ireland, Latvia, and Portugal.
104 Perceived Barriers to the Recruitment and Retention of Underrepresented Racial and Ethnic Groups (URGs) in Clinical Research
Authors: McNamara Victoria , Smith Elise , Tumilty Emma
Published: April 2024

OBJECTIVES/GOALS: The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research. METHODS/STUDY POPULATION: An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams' perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: There was a total of 63 responses. A majority of respondents have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts. Approximately half of the respondents believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues, distrust in doctors and/or researchers, fear of unknown side effects, and unavailability of medical interpreters. Respondents report that they are not discouraged from enrolling URGs and would utilize resources related to encouraging the inclusion of URGs DISCUSSION/SIGNIFICANCE: Language appears more influential than ethnicity or race when it comes to enrolling and retaining URGs. Additionally, it appears that enrolling is a bigger challenge than retaining. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation.
111 Evaluating Patient Influences on Comfortability for LGBTQIA2+ Patients in Clinical Spaces (EPIC)
Authors: Lee Gabriel , Shihabuddin Bashar , Shihabuddin Courtney
Published: April 2024

OBJECTIVES/GOALS: The objective of this project was to evaluate the factors that contribute to LGBTQIA2+ patient comfortability. This information was then used to understand how best to create a comfortable space for LGBTQIA2+ patients. METHODS/STUDY POPULATION: This survey was focused on underinsured and uninsured patients seen at the Rainbow Clinic - a free student-run LGBTQIA2+ clinic. Surveys were distributed by undergraduate volunteers on tablets as a qualtrics survey. Surveys collected demographic information in addition to 5 questions that assessed patient comfortability. These questions included evaluating the patient’s comfort with sharing information with the provider and the patient’s comfort of coming into clinical spaces. These surveys were distributed before and after clinic appointments to capture any changes in comfortability that could have occurred as a result of the appointment. RESULTS/ANTICIPATED RESULTS: Up to May of 2023, 49 patients were seen in Rainbow Clinic. 33 patients filled out the intake survey and 31 patients filled out the check-out survey resulting in a 67% and 63% response rate respectively. Questions were asked on a likert scale (1-5) from Strongly Disagree to Strongly Agree. Questions evaluating patient comfort in sharing information with their provider yielded an average score that was statistically significant, suggesting patients felt comfortable at the Rainbow Clinic. Additionally, patients indicated that the LGBTQIA2+ specific labeling of the Rainbow Clinic made them significantly more comfortable coming into the clinic. DISCUSSION/SIGNIFICANCE: This project suggests that patient comfortability can be improved by training and intentional LGBTQIA2+ labeling. Considering the hesitancy of this community towards healthcare, improving comfortability not only benefits clinical care and outcomes but can also bolster the body of research on this community.
114 Reimagining Entryways: Innovative Apprenticeship Models for New Clinical Research Professionals
Authors: Jenkerson Michelle , Freel Stephanie , Keyes Anthony , Cranfill Jessica , Cody Rachel
Published: April 2024

OBJECTIVES/GOALS: 1. Standardize pathways, training and evaluations 2. Expose apprentices to a variety of research experiences 3. Remove barriers to hiring early talent 4. Expand opportunities for underrepresented minority applicants to obtain clinical research professional positions METHODS/STUDY POPULATION: Collaborators connected by the Clinical Research Professional Taskforce ACTS SIG conducted a landscape analysis survey to identify aspects of CRP Apprentice models and formed a Subgroup. Members will share plans for multiple apprenticeship programs, including specific training modalities and skill sets used to prepare apprentices for a successful clinical research professional career. Methods across institutions include: • Increasing awareness of the profession • Facilitating talent identification for managers • Making the business case for funding and staffing • Implementing work-based learning for fundamental competency development Survey results from CRP institutions demonstrated apprenticeships are value added to teaching how to conduct research. RESULTS/ANTICIPATED RESULTS: The landscape survey of Apprentice programs revealed multiple models in use. The newly formed Apprentice subgroup is engaging in analysis and actively working to build a standardized repository of competency-aligned, research courses and experiences for apprentices. Results will help make the business case for starting or growing programs. Subgroup members have focused on a shared goal of expanding opportunities for underrepresented minority applicants, with current outreach efforts that are extending awareness of the CRP profession. We anticipate a continuous strengthening of connections between institutions to share a variety of models to implement, develop shared tools (e.g., proficiency tests), and share existing tools to standardize pathways and training for CRP apprenticeships. #_msoanchor_1 DISCUSSION/SIGNIFICANCE: Academic Medical Centers (AMCs) need novel strategies to support clinical research portfolios.Innovative Apprenticeship Models improve efficiency and sustainability of the clinical research professional (CRP) workforce to train the next generation of CRPs in an effective and timely way.
115 Strategies for Training and Advancing under-represented Researchers (STARs)
Authors: James Laura P. , Sparks Crystal , Duguid Paul , Snowden Jessica , Schootman Mario , Gittens Brian , Boateng Beatrice , Allen Antiño R.
Published: April 2024

OBJECTIVES/GOALS: Minority faculty have inequitable access to information, professional development, and research resources. A structured research-mentoring program could help strengthen the research acumen of underrepresented (UR) faculty, provide a community, and support to ensure their success in becoming independent investigators. METHODS/STUDY POPULATION: The Translational Research Institute (TRI) STARs program aims to build a peer support community of UR in biomedical, clinical, behavioral and social sciences to support career development and research success. The program provides a structured peer support group with a 3-month grant training and development program and addresses issues of isolation often felt by UR faculty in academic settings. It encourages the development of innovative research ideas in a safe environment. This peer support group can also help improve confidence and self-efficacy in clinical and translational research development and execution by UR faculty. At the didactic program’s conclusion and seed grant application submission, STARs provides $10,000 as a TRI DEI Equity, Diversity, and Grantsmanship Expertise project. RESULTS/ANTICIPATED RESULTS: Since its launch in 2021, 11 scholars have enrolled in the program;three have fully completed the program, and all three have received subsequent grant funding. Four scholars have completed the didactic program and are in the process of using seed funding to collect initial data and working on initial publications. The remaining scholars are currently in the didactic program. Initial scholar satisfaction with the program is high: 100% reported satisfaction with their participation (Very Satisfied/Satisfied), and 100% agree the program provides adequate support to their research project (Strongly Agree/Agree). Overall, scholars reported an average increase in confidence of 7.9% in grantsmanship skills (Scale 0-10). The return on investment is 3106%, with over $1.9 million in subsequent funding. DISCUSSION/SIGNIFICANCE: Research shows diverse teams working together, capitalizing on innovative ideas, and distinct perspectives outperform homogenous teams. Our preliminary experience demonstrates success for the model. Additional, long-term support will be furthered developed to address additional challenges experienced by UR faculty across their careers.
119 Academic Innovation through the interdisciplinary (elective) course Introduction to Clinical and Translational Research (CTR) to increase the number of undergraduate students in Puerto Rico with the knowledge, skills, abilities, and opportunities in CTR
Authors: Rosado-Santiago Edgardo L. , Soto-Santiago Juan C. , Rosado-Santiago Edgardo L. , De Jesús-Ojeda Lizbelle
Published: April 2024

OBJECTIVES/GOALS: The Title V project team is offering an elective course to teach the historical development of CTR, make a compelling scientific presentation, and use bibliographic databases. In addition, students learn: to write the research question, design a career development plan, protect human subjects in research, and the mentor-mentee relationship. METHODS/STUDY POPULATION: The course includes a variety of educational strategies and activities that allow the student to increase their knowledge and initiate their interest in the field of CTR. Both academic semesters (August to December and January to May) are offered remotely in two-hour synchronous sessions on Fridays from 3:00 p.m. to 5:00 p.m. through videoconferences, in addition to asynchronous activities. Invited expert lecturers and faculty reinforce the course content in each topic they address. In addition, course coordinators assign guided tasks where the students perform the work. Then, they present or send their work to the course coordinators for evaluation. RESULTS/ANTICIPATED RESULTS: The course began in January 2020 and has had six offerings, including one in the current academic semester (August to December 2023). Its first offering was in the semester from January to May, and due to the interest generated in students in August 2022, it is now available in both semesters. From its beginning to the present, the course has included students from the University of Puerto Rico (UPR) Bayamon, Cayey, Humacao, Mayagüez, and Rio Piedras campuses, impacting all geographic areas of Puerto Rico. The course has also represented an opportunity for graduate faculty to teach CTR to undergraduate students. Until 2023, 56 students have enrolled. DISCUSSION/SIGNIFICANCE: Upon completing six-course offerings, the evaluation carried out by the students demonstrates satisfaction with the learning obtained. The knowledge and skills achieved have led them to participate in CTR with the mentoring of collaborating course professors and starting a new professional development opportunity for undergraduate students.
124 An educational curriculum, mentors’ preparedness and certification, a mentored research experience and a support network: strategies to increase diversity and inclusion in the Clinical and Translational Research (CTR) workforce among underrepresented researchers.
Authors: Irizarry-Ramirez Margarita , Noboa-Ramos Carlamarie , Pabon-Cruz Karen
Published: April 2024

OBJECTIVES/GOALS: The Professional Development Core (PDC) of the Hispanic Alliance for Clinical and Translational Research (The Alliance) has implemented a multifaceted program to support Early-Stage Investigators (ESI) and mid-career investigators to increase productivity and achieve success in their research endeavors. METHODS/STUDY POPULATION: Since 2021, PDC launched an educational program tailored for ESI or mid-career investigators, addressing specific gaps in research competencies. A needs assessment survey gathered information from these investigators, and its results served as the foundation for the program’s design. In addition, recognizing the need for excellence in mentoring, PDC spearheaded a program to provide a certification curriculum for new or experienced mentors. Experienced researchers were encouraged to participate in the certification process with ample opportunities to discuss their mentoring experiences and the incorporation of new approaches that emphasize diversity and inclusion. A structured mentored research experience with support for protected time for the investigator and the mentors was also implemented. RESULTS/ANTICIPATED RESULTS: Four investigators and their mentors have received the Mentor-Mentee Award (100% PhD, 75% female, 50% Assistant Professor, 75% ESI, 75% with mentors from the mainland United States). Their program’s evaluation will be presented. Thirty-two (32) researchers have participated in the courses in Health Disparity and Scientific Communication. Support for grant writing was offered through a three-pronged approach: a webinar series, a course in Grantsmanship and a grant’s bootcamp. Twenty-four (24) mentors were certified, and over 30 training activities were offered to supply knowledge in areas previously identified in the needs assessment. We will present the complete curriculum, courses offerings, participants’ profiles, and productivity outcomes. DISCUSSION/SIGNIFICANCE: Alliance educational and mentoring supportive network increased the diversity of CTR workforce and prepared qualified researchers to address the Hispanics health needs. Collaborations with mainland researchers have expanded the PDC program’s reach and contributed to the enhancement of the Hispanic contribution to the health research ecosystem.