bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve is a Therapeutic Strategy for Pancreatic Cancer
Authors: DeLiberty Jonathan M. , Roach Mallory K. , Stalnecker Clint A. , Robb Ryan , Schechter Elyse G. , Pieper Noah L. , Taylor Khalilah E. , Pita Lily M. , Yang Runying , Bang Scott , Drizyte-Miller Kristina , Ackermann Sarah E. , Nicewarner Peña Sheila R. , Baldelli Elisa , Min Sophia M. , Drewry David H. , Petricoin Emanuel F. , Morris John P. , Der Channing J. , Cox Adrienne D. , Bryant Kirsten L. 
Published: February 2025

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent growth. Inhibition of the KRAS-RAF-MEK-ERK pathway enhances autophagic flux and dependency, and concurrent treatment with the nonspecific autophagy inhibitor chloroquine (CQ) and ERK-MAPK pathway inhibitors can synergistically block PDAC growth. However, CQ is limited in terms of specificity and potency. To find alternative anti-autophagy strategies, here we performed a CRISPR-Cas9 loss-of-function screen in PDAC cell lines that identified the lipid kinase PIKfyve as a growth-promoting gene. PIKfyve inhibition by the small molecule apilimod resulted in durable growth suppression, with much greater potency than CQ treatment. PIKfyve inhibition caused lysosomal dysfunction, reduced autophagic flux, and led to the accumulation of autophagy-related proteins. Furthermore, PIKfyve inhibition blocked the compensatory increases in autophagic flux associated both with MEK inhibition and with direct RAS inhibition. Accordingly, combined inhibition of PIKfyve and the RAS-MAPK pathway showed robust growth suppression across a panel of KRAS-mutant PDAC models. Growth suppression was due, in part, to potentiated cell cycle arrest and induction of apoptosis following loss of IAP proteins. These findings indicate that concurrent inhibition of RAS and PIKfyve is a synergistic, cytotoxic combination that may represent a therapeutic strategy for PDAC.
The Brain-Penetrant Pan ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases
Authors: Ippolitov Danyyl , Lin Yi-Han , Spence Jeremy , Glogowska Aleksandra , Thanasupawat Thatchawan , Beiko Jason , Del Bigio Marc R. , Xu Xin , Wang Amy Q. , Williams Darian , Calvo Raul , Kapoor Abhijeet , Marugan Juan J. , Henderson Mark J. , Klonisch Thomas , Hombach-Klonisch Sabine 
Published: February 2025

Abstract
Brain metastasis occurs in about 50% of all women with metastatic HER2+ breast cancer and confers poor prognosis for patients. Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with trastuzumab and HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM). The scarcity of suitable patient-derived in vivo models for HER2+ BCBM has curtailed the study of molecular mechanisms that promote growth and therapeutic resistance in brain metastasis. Here, we generated and characterized a luminal B HER2+ BCBM cell model (BCBM94) isolated from a patient HER2+ brain metastasis. Repeated hematogenic xenografting of BCBM94 consistently generated BCBM in mice. The clinical receptor tyrosine kinase inhibitor (RTKi) lapatinib blocked phosphorylation of all ErbB receptors (ErbB1-4) and induced the intrinsic apoptosis pathway in BCBM94. Neuregulin-1 (NRG1), an ErbB3/ErbB4 ligand that is abundantly expressed in the brain, abrogated lapatinib-induced apoptosis in HER2+ BCBM94 and BT474 models. ErbB3 signaling pathways that involved PI3K-AKT and the phosphorylation of BAD at serine 136 to prevent apoptosis were essential for NRG1-induced survival. High throughput RTKi screening identified the brain-penetrant pan-ErbB inhibitor poziotinib as a highly potent compound that reduced cell viability in HER2+ BCBM in the presence of NRG1. Two weeks of poziotinib treatment successfully ablated BCBM94 and BT474 HER2+ brain tumors in vivo. In conclusion, this study established a patient-derived HER2+ BCBM model and identified poziotinib as highly efficacious RTKi with excellent brain penetrability that eliminated HER2+ BCBM.
Distinct states of Nuclear Speckles emerge as new predictors of cancer prognosis
Authors: Martina Lisa , Małszycki Michał , Aktaş Tuğçe 
Published: February 2025

Abstract
The complex environment of the mammalian nucleus is compartmentalized into functional units by membraneless organelles. Recent advancements have elevated nuclear speckles, one of the most prominent nuclear condensates, to a central role in gene expression regulation. In their recent paper, Alexander and colleagues provide insights into the involvement of nuclear speckles in cancer progression. They identify two signatures of speckle transcriptome that stratify human cancers and, in the case of the clear cell renal cell carcinoma (ccRC), strongly correlate with drug response and ultimately with patient’s survival. These signatures correspond to different morphological states of nuclear speckles and influence speckle-regulated gene expression. A deeper look into transcriptional regulation allowed the authors to identify an amino acid sequence which enables the central transcription factor responsible of ccRC oncogenesis to bring its chromatin target into nuclear speckle proximity. The findings provide new insights into the intricacies of nuclear speckle biology and offer new avenues for understanding cancer progression and developing targeted therapies.
UniASA: A Unified Generative Framework for Argument Structure Analysis
Authors: Bao Jianzhu , Jing Mohan , Dong Kuicai , Sun Aixin , Sun Yang , Xu Ruifeng 
Published: February 2025

Abstract
Argumentation is a fundamental human activity that involves reasoning and persuasion, which also serves as the basis for the development of AI systems capable of complex reasoning. In NLP, to better understand human argumentation, argument structure analysis aims to identify argument components, such as claims and premises, and their relations from free text. It encompasses a variety of divergent tasks, such as end-to-end argument mining, argument pair extraction, and argument quadruplet extraction. Existing methods are usually tailored to only one specific argument structure analysis task, overlooking the inherent connections among different tasks. We observe that the fundamental goal of these tasks is similar: identifying argument components and their interrelations. Motivated by this, we present a unified generative framework for argument structure analysis (UniASA). It can uniformly address multiple argument structure analysis tasks in a sequence-to-sequence manner. Further, we enhance UniASA with a multi-view learning strategy based on subtask decomposition. We conduct experiments on seven datasets across three tasks. The results indicate that UniASA can address these tasks uniformly and achieve performance that is either superior to or comparable with the previous state-of-the-art methods. Also, we show that UniASA can be effectively integrated with large language models, such as Llama, through fine-tuning or in-context learning.
The Astute and the Kindly Ones
Authors: Weber Marc Andree 
Published: February 2025

Abstract
Recently, epistemologists have been much concerned with the question of whether or not we have to revise our beliefs if there are people whose epistemic position is as good as ours and who disagree with us. The results of such considerations, whatever they are, are sometimes said to be restricted to domains in which, unlike in politics or law, the relevant agents are not under any pressure to act in accordance with their beliefs, have no deeply held ideological beliefs, or have no beliefs that stem from their particular aims or desires. In response to this, and with regard to the paradigmatic cases of politics and law, this article argues that there are no genuine political or legal disagreements: what we call a political or legal disagreement is either no disagreement at all but a mere clash of interest, or it is a an empirical, moral, or practical disagreement that is not genuinely political or legal. To the latter, epistemological insights apply; to the former, they do not.
Wittgenstein on Mathematics
Authors: Schroeder Severin 
Published: February 2025

Abstract
In response to Felix Mühlhölzer’s critical discussion of my book Wittgenstein on Mathematics (2021), I argue against his main objections, in particular his view that one shouldn’t even look for coherence in Wittgenstein’s philosophy of mathematics, and his claim that Wittgenstein’s insistence on the empirical applicability of mathematical concepts need not be taken seriously because in one passage it is prefaced by the words ‘I want to say’. I also correct a number of irksome misunderstandings in Mühlhölzer’s review. Repeatedly he ascribes to me a position that I merely present for discussion – and reject or qualify in the end. In particular, he wrongly ascribes to me the empiricist view that mathematical propositions are derived from experience. Some of Wittgenstein’s remarks seem to express such a view, so I discuss it but conclude that, some exceptions apart, it is untenable and also inconsistent with Wittgenstein’s key ideas about mathematical proof.
On Minimizing Risk and Harm in the Use of Psychedelics
Authors: Evans Jules , Aixalà Marc , Anderson Brian T. , Brennan William , Bremler Rebecka , Breeksema Joost J. , Burback Lisa , Calder Abigail E. , Carhart‐Harris Robin L. , Cheung Katherine , Devenot Neşe , Gorman Ingmar , Greń Jakub , Hendricks Peter S. , Holoyda Brian , Jacobs Edward , Krecké Joy , Kruger Daniel J. , Luke David , Majić Tomislav , McGuire Amy L. , Mehtani Nicky J. , Mathai David S. , Nash Kristin , Noorani Tehseen , Palitsky Roman , Robinson Oliver C. , Simonsson Otto , Stahre Elin , van Elk Michiel , Yaden David B. 
Published: February 2025

ObjectiveThis article outlines recommendations from 30 psychedelic researchers on how to create a better psychedelic safety net.MethodsA survey of 30 psychedelic researchers asked them to identify key critical research gaps around psychedelic harm and safety.ResultsThe critical research gaps identified by the authors included defining the main types of psychedelic harm, the predictors of those harms, and the most effective way to treat those harms. They also call for better support for those experiencing post‐psychedelic difficulties, including better online information, peer support groups, affordable therapy, and psychiatric consultation and medication. Finally, the authors call for better funding to create a psychedelic safety net, and suggest psychedelic philanthropists, investors and companies could commit 1% of their investment in psychedelics into supporting safety measures such as research and support services.ConclusionsThe authors identify several practical steps to create a better psychedelic safety net and call for more funding to psychedelic safety measures such as research and support services.Relevance to clinical practiceThe authors outline important gaps in our knowledge around the safety and risk profile of psychedelic medicines and identify practical steps forward for researchers and clinical practitioners to make this promising field safer.
Are There Race‐Based Differences in Neuropsychological Test Performance and Psychological Symptom Endorsement Among Adults Diagnosed With ADHD?
Authors: Phillips Matthew S. , Leese Mira I. , Abalos Steven A. , Shapiro Greg , Bare Kailyn , Orleans Nevin A. , Durkin Nicole M. , Soble Jason R. 
Published: February 2025

ObjectivePrevalence rates of attention‐deficit/hyperactivity disorder (ADHD) vary by several demographic factors, including sex, socioeconomic status, geographic region, and race/ethnicity, with higher rates seen among non‐Hispanic White children and adults compared to racially/ethnically minoritized individuals. This study investigated if similar race‐based differences exist in neurocognitive test performance and psychiatric/ADHD symptom reporting among groups in a demographically diverse sample.MethodsData from 491 adults with a confirmed diagnosis of ADHD were analyzed to assess for differences in broad neurocognitive domains (i.e., learning and memory, attention/working memory, processing speed, and executive functions), as well as on measures of mood and ADHD‐related symptomatology.ResultsFindings largely demonstrated comparable neurocognitive test performance and ADHD and psychiatric symptom endorsement across racial groups with a known diagnosis of ADHD.ConclusionsAlthough prior research has consistently documented racial/ethnic disparities in rates of ADHD diagnosis, current results largely did not demonstrate neuropsychological performance‐based differences among demographically diverse patients diagnosed with ADHD.Relevance to clinical practiceADHD is one of the most prevalent neurodevelopmental disorders in the U.S. and constitutes a large number of referrals for diagnostic evaluation. Despite disparities in rates of diagnosis among broad racial/ethnic groups, neuropsychological outcomes remain largely consistent among these groups.
Cardiac function and quality of life improvement with fasudil hydrochloride in patients with diabetes post-PCI: a randomized controlled trial
Authors: Yang Xuejia , Li Qian , Liu Yaning , Chen Ran , Liu Yanjing , Sun Chenghui , Kong Licha , Dong Qiuli 
Published: February 2025

Objective We assessed the efficacy of fasudil hydrochloride, a Rho-kinase inhibitor, as adjunct therapy for enhancing cardiac function, managing blood sugar, and improving quality of life in patients with diabetes who have coronary heart disease (CHD) and who underwent percutaneous coronary intervention (PCI). Methods We conducted a randomized controlled trial including 100 patients with diabetes and CHD who underwent PCI. Participants were randomly assigned to an experimental group receiving fasudil hydrochloride plus standard therapy or a control group receiving standard therapy alone. Treatment outcomes were evaluated over 3 months, focusing on cardiac function, blood sugar levels, and quality of life across physical, social, activities of daily living, and psychological domains. Results The experimental group showed significant improvement in cardiac function and blood sugar control, compared with the control group. Additionally, quality of life scores were markedly higher for the experimental group in all evaluated domains. Conclusions Fasudil hydrochloride effectively targets endothelial dysfunction and atherosclerosis, contributing to better cardiac performance and metabolic regulation. These effects translate into improved post-PCI quality of life for patients with diabetes and CHD. As an adjunct to standard PCI therapy, fasudil hydrochloride treatment offers a promising strategy for enhancing clinical outcomes in this high-risk patient population.
Effects of 0.01 mM strontium on human periodontal ligament stem cell osteogenic differentiation via the Wnt/β-catenin signaling pathway
Authors: Sun Tongke , Ma Dan , Song Yang , Hu Jing , Yang Ziqing , Wang Xu , Zhang Jun 
Published: February 2025

Objectives Strontium (Sr2+) is a crucial trace element in humans, mainly present in the bones. We investigated the effects of Sr2+ on human periodontal ligament stem cell (hPDLSC) proliferation and osteogenesis and the relevant pathways. Methods hPDLSCs were harvested from extracted premolars and characterized by flow cytometry, then cultured and treated with various Sr2+ concentrations. Cell-counting kit-8 (CCK-8) assays were used to assess hPDLSC proliferation, with alkaline phosphatase (ALP) staining, Alizarin red S staining, and ALP activity assays used to analyze their osteogenic capacity. Quantitative reverse transcription polymerase chain reaction and western blots were used to examine the expression levels of relevant factors, such as collagen I (COL-1), ALP, and Runx family transcription factor 2 (RUNX2). Moreover, tankyrase inhibitor XAV939 treatment was used to investigate the role of Sr2+ in the canonical Wnt/β-catenin signaling pathway. Results The hPDLSCs were successfully isolated and cultured in vitro. A 0.01 mM Sr2+ concentration significantly enhanced hPDLSC proliferation and osteogenic differentiation. However, XAV939-mediated inhibition of the canonical Wnt/β-catenin pathway could reverse the Sr2+-induced osteogenic effects. Conclusions Sr2+ can enhance hPDLSC proliferation and osteogenesis by stimulating canonical Wnt/β-catenin signaling, suggesting it may play a critical role in periodontal regeneration and has clinical application potential.
Adaptations in the workplace as a labor inclusion strategy for people with physical disabilities: an integrative review
Authors: Urrejola-Contreras Gabriela Paz , Pérez Miguel A. , Herrera-Miranda Felipe , López Bernardita , Gary Zambra Boris , Hernández Pérez Karla 
Published: February 2025

Background Based on the International Classification of Functioning, disability entails a problem in participation, and work activity is a pillar for inclusion. The success of labor inclusion will depend on the labor adaptations that are adopted. Discrimination in the workplace remains one of the biggest obstacles to effective inclusion. Objective Analyzing the evidence associated with workplace adaptations as an inclusion strategy for people with physical disabilities Methods Literature published between 2012 and 2023 in English and Spanish. The databases were examined: Science Direct, Scopus, Taylor & Francis and free search and 10 articles were included to prepare this integrative review. The methodological quality followed the recommendations of the Equator network. Results Most of the changes were organizational and accessibility related to flexible hours, the adoption of teleworking, the availability of elevators, preferential parking and adaptations in bathrooms. The main shortcomings reported were limitations in evaluating jobs, productivity costs and effectiveness of adjustments, redesigning tasks and managing disability in the work environment. Conclusions Although there are international efforts aimed at improving the inclusion of people with disabilities in the workplace, the results are asymmetrical between accessibility and support. The development of reasonable accommodations in the workplace in pursuit of employment rights is still in its early stages.
Association of gender-based discrimination and burnout among faculty in an urban academic medical center
Authors: Peccoralo Lauren A. , de Guillebon Eleonore , Clifton Elizabeth , He Celestine , Kaplan Sabrina , Deshpande Richa , Kaplan Carly , Pietrzak Robert H. , Charney Dennis , Ripp Jonathan A. 
Published: February 2025

Background Burnout in physician and scientist faculty threatens professional satisfaction, mental health, and work quality while impacting women more than men. Women experience gender mistreatment more often than men, which may impact burnout. Objective To determine the differences in burnout, discrimination and harassment by gender, and whether these variables were associated with burnout in physician and scientist faculty. Methods An anonymous cross-sectional survey from November 2018 through February 2019 was conducted in physician and scientist faculty at a large urban hospital. Survey instruments included MaslachBurnout Inventory-2, gender-based discrimination and harassment questions, and demographic and professional characteristics. Results Of 4156 faculty, 1497 (36%) provided gender identification and were included in analyses. Women experienced burnout at higher rates than men (30.9% vs. 23.3%, p = 0.002). Women also experienced gender discrimination and gender harassment at 11 (25.0% vs 2.3%, p < 0.001) and 5.7 (13.0% vs 2.3%, p < 0.001) times the rate of men, respectively. In a multivariable analysis, gender-based discrimination and harassment was associated with burnout among women (OR 1.65, p = 0.035) and overall (OR 1.65, p = 0.017), but not among men. In men, those aged 40–60 experienced increased burnout compared to those aged >60 (OR 2.67, p = 0.017). For all participants, burnout was associated with depression symptoms, poor work life integration, and lower leadership scores. Conclusion Burnout is prevalent in both men and women physicians and scientists, but correlates vary by gender. Findings suggest that interventions to reduce burnout should account for gender differences, target leadership behaviors and address gender bias and mistreatment.
Design and validation of a novel ergonomic backpack
Authors: Bouve Lyndsey K. , DiAngelo Denis J. 
Published: February 2025

Background BP are the most common means for carrying items and are used by a large population but transporting heavy loads (over extended periods of time) can lead to a variety of health-related problems. An ergonomic backpack (EBP) was designed as a potential solution to reduce the incidence of injuries associated with heavy backpack weight. Objective The objective of this study was to design a novel ergonomic offloading backpack that reduced loads on the shoulder and spine compared to a traditional modern day backpack (BP). Methods Strap tension and shoulder loads were measured in a common two strap style commuter BP and the EBP during quiet (vertical) stance conditions for five weight increments (0 kg to 11 kg) to confirm the offloading capabilities of the EBP. Portable luggage scales were attached directly to the shoulder straps and configured to measure strap tension. Load sensors placed underneath the shoulder straps provided an estimate of the total force acting on the shoulders and transferred to the spine. Results The EBP had a large effect size and significant reduction ( p < 0.05) in shoulder loads compared to a traditional BP for all bag weight conditions. Similarly, the EBP had a large effect size in reducing strap tension compared to the traditional modern day two strap BP. Conclusion A newly designed EBP was effective at transferring a significantly large portion of the shoulder and spine loads to the pelvic region.
Attitudes of nurses toward artificial intelligence: A multicenter comparison
Authors: Kaplan Mehmet , Uçar Mehmet 
Published: February 2025

Background Artificial intelligence (AI) is transforming medical practices with rapidly developing technologies and the innovative solutions it provides. In order for this transformation to be successfully integrated into healthcare services, healthcare professionals must have positive attitudes towards this technology. Objective The present study was conducted with the aim of comparing the attitudes of nurses working in different provinces towards artificial intelligence. Methods The study was planned in a descriptive cross-sectional design. The study population consisted of 1453 nurses working in 3 state hospitals (inpatient hospitals providing secondary health care services) located in the city centers of Muş, Bingöl and Adıyaman provinces in eastern Turkey. While the sample size was 698 nurses in total, the study was completed with 737 nurses. The data were collected through the Introductory Information Form and the General Attitudes toward Artificial Intelligence Scale (GAAIS). ANOVA test and multiple regression were used to analyse the data. Results It was found that the nurses had highly positive attitudes towards artificial intelligence. When the nurses’ scores from the Positive GAAIS sub-dimension were compared, it was determined that there was a significant difference (p < 0.05) between the provinces. A statistically significant difference (p < 0.01) was found between the provinces in the Negative GAAIS sub-dimension, as well. Demographic characteristics were found to be effective on both Positive GAAIS and Negative GAAIS. Conclusions Although there were differences between the provinces, the nurses generally had positive attitudes towards artificial intelligence technologies. The majority of the participants continue to use artificial intelligence technologies although they state that artificial intelligence will replace humans in the future. Longitudinal studies on the factors affecting attitudes towards artificial intelligence are recommended.