bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer
Authors: Foote Jeremy B. , Mattox Tyler E. , Keeton Adam B. , Chen Xi , Smith Forrest T. , Berry Kristy , Holmes Thomas W. , Wang Junwei , Huang Chung-hui , Ward Antonio , Mitra AMIT K. , Ramirez-Alcantara Veronica , Hardy Cherlene , Fleten Karianne G. , Flatmark Kjersti , Yoon Karina J. , Sarvesh Sujith , Nagaraju Ganji P. , Bandi Dhana Sekhar Reddy , Maxuitenko Yulia Y. , Valiyaveettil Jacaob , Carstens Julienne L. , Buchsbaum Donald J. , Yang Jennifer , Zhou Gang , Nurmemmedov Elmar , Babic Ivan , Gaponeko Vadim , Abdelkarim Hazem , Boyd Michael R. , Gorman Greg , Manne Upender , Bae Sejong , El-Rayes Bassel F. , Piazza Gary A. 
Published: December 2024

Abstract
RAS is a common driver of cancer that was considered undruggable for decades. Recent advances have enabled the development of RAS inhibitors, but the efficacy of these inhibitors remains limited by resistance. Here, we developed a pan-RAS inhibitor, ADT-007, that binds nucleotide-free RAS to block GTP activation of effector interactions and MAPK/AKT signaling, resulting in mitotic arrest and apoptosis. ADT-007 potently inhibited the growth of RAS mutant cancer cells irrespective of the RAS mutation or isozyme, and RASWT cancer cells with GTP-activated RAS from upstream mutations were equally sensitive. Conversely, RASWT cancer cells harboring downstream BRAF mutations and normal cells were essentially insensitive to ADT-007. Sensitivity of cancer cells to ADT-007 required activated RAS and dependence on RAS for proliferation, while insensitivity was attributed to metabolic deactivation by UDP-glucuronosyltransferases that were expressed in RASWT and normal cells but repressed in RAS mutant cancer cells. ADT-007 displayed unique advantages over KRAS mutant-specific, pan-KRAS, and pan-RAS inhibitors that could impact in vivo antitumor efficacy by escaping compensatory mechanisms that lead to resistance. Local administration of ADT-007 showed robust antitumor activity in syngeneic immune-competent and xenogeneic immune-deficient mouse models of colorectal and pancreatic cancer. The antitumor activity of ADT-007 was associated with the suppression of MAPK signaling and activation of innate and adaptive immunity in the tumor immune microenvironment. Oral administration of ADT-007 prodrug also inhibited tumor growth. Thus, ADT-007 has the potential to address the complex RAS mutational landscape of many human cancers and to improve treatment of RAS-driven tumors.
Lysosomal–Mitochondrial Interaction Promotes Tumor Growth in Squamous Cell Carcinoma of the Head and Neck
Authors: Gopalkrishnan Avani , Wang Nathaniel , Cruz-Rangel Silvia , Yassin-Kassab Abdul , Shiva Sruti , Kurukulasuriya Chareeni , Monga Satdarshan P. , DeBerardinis Ralph J. , Skinner Heath D. , Kiselyov Kirill , Duvvuri Umamaheswar 
Published: December 2024

Abstract
Communication between intracellular organelles including lysosomes and mitochondria has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other [lysosomal–mitochondrial interaction (LMI)] is emerging as a major determinant of tumor proliferation and growth. About 30% of squamous carcinomas [including squamous cell carcinoma of the head and neck (SCCHN)] overexpress transmembrane member 16A (TMEM16A), a calcium-activated chloride channel, which promotes cellular growth and negatively correlates with patient survival. We have recently shown that TMEM16A drives lysosomal biogenesis; however, its impact on mitochondrial function has not been explored. In this study, we show that in the context of high-TMEM16A SCCHN, (i) patients display increased mitochondrial content, specifically complex I; (ii) in vitro and in vivo models uniquely depend on mitochondrial complex I activity for growth and survival; (iii) NRF2 signaling is a critical linchpin that drives mitochondrial function, and (iv) mitochondrial complex I and lysosomal function are codependent for proliferation. Taken together, our data demonstrate that coordinated lysosomal and mitochondrial activity and biogenesis via LMI drive tumor proliferation and facilitate a functional interaction between lysosomal and mitochondrial networks. Therefore, inhibition of LMI instauration may serve as a therapeutic strategy for patients with SCCHN.
Implications: Intervention of LMI may serve as a therapeutic approach for patients with high TMEM16A–expressing SCCHN.
Heterogeneous Cardiac-Derived and Neural Crest–Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption
Authors: Ren Pengwei , Jiang Bo , Hassab Abdulrahman H.M. , Li Guangxin , Li Wei , Assi Roland , Tellides George 
Published: December 2024

BACKGROUND:
Smooth muscle cells (SMCs) of cardiac and neural crest origin contribute to the developing proximal aorta and are linked to disease propensity in adults.

METHODS:
We analyzed single-cell transcriptomes of aortic SMCs from adult mice to determine basal states and changes after disrupting TGFβ (transforming growth factor-β) signaling necessary for aortic homeostasis.

RESULTS:
A minority of Myh11 lineage-marked SMCs differentially expressed genes suggestive of embryological origin. Additional analyses in Nkx2-5 and Wnt1 lineage-marked SMCs derived from cardiac and neural crest progenitors, respectively, showed both lineages contributed to a major common cluster and each lineage to a minor distinct cluster. Common cluster SMCs extended from root to arch, cardiac subset cluster SMCs from root to ascending, and neural crest subset cluster SMCs were restricted to the arch. The neural crest subset cluster had greater expression of a subgroup of TGFβ-dependent genes. Nonetheless, conditional deletion of TGFβ receptors resulted in similar transcriptional changes among all SMC clusters. Several disease-associated transcriptional responses were comparable among SMC clusters in a mouse model of Marfan syndrome aortopathy, while many embryological markers of murine aortic SMCs were not detected in adult human aortas.

CONCLUSIONS:
There are multiple subtypes of cardiac-derived and neural crest–derived SMCs with shared or distinctive transcriptional profiles; neural crest subset cluster SMCs with increased expression of certain TGFβ-inducible genes are not spatially linked to the aortic root predisposed to aneurysms from aberrant TGFβ signaling; and loss of TGFβ responses after receptor deletion is uniform among SMC clusters.
Nurse-Led Multicomponent Behavioral Activation Intervention for Patients With Atrial Fibrillation: A Randomized Controlled Trial
Authors: Li Polly W.C. , Yu Doris S.F. , Yan Bryan P. 
Published: December 2024

BACKGROUND:
Patients with atrial fibrillation (AF) are often ill-equipped for shared decision-making. This study investigated the effects of a patient empowerment care model on patient-reported health outcomes and treatment decision-making in patients with AF.

METHODS:
This randomized controlled trial prospectively randomized patients with AF to receive standard care (n=194) or a 13-week nurse-led multicomponent behavioral activation intervention (n=198). The intervention consisted of risk profile assessments, empowered shared decision-making regarding the use of oral anticoagulants (OACs), empowered AF self-management, and increased access to professional advice. The primary outcome was health-related quality of life measured after the completion of the intervention (T1), while the secondary outcomes were patient-physician decision concordance regarding OAC use, actual OAC use, AF knowledge, medication adherence, anxiety, and depression.

RESULTS:

The intervention group showed significantly greater improvements in health-related quality of life (β, −6.702 [95% CI, −9.556 to −3.847];
P
<0.001), AF knowledge (β, −1.989 [95% CI, −2.342 to −1.635];
P
<0.001), and medication adherence (β, 0.340 [95% CI, 0.148–0.532];
P
<0.001) at immediate post-intervention compared with the control group, and the improvements were sustained at 6 months for all outcomes. A higher proportion of patients in the intervention group were prescribed an OAC compared with the control group at 6 months (odds ratio, 5.870 [95% CI, 1.957–12.331];
P
=0.012). No significant between-group differences were detected for patient-physician decision concordance regarding OAC use, anxiety, or depression at both time points.

CONCLUSIONS:
The nurse-led multicomponent behavioral activation intervention improved patient-reported outcomes and increased OAC prescription among patients with AF.
Cervical Artery Tortuosity Is Associated With Dissection Occurrence and Late Recurrence: A Nested Case-Control Study
Authors: Mayer-Suess Lukas , Knoflach Michael , Peball Tamara , Mangesius Stephanie , Steiger Ruth , Pereverzyev Sergiy , Lerchner Hannes , Blache Ludovic , Mayr Manuel , Ratzinger Gudrun , Kiechl Stefan , Gizewski Elke R. , Pechlaner Raimund 
Published: December 2024

BACKGROUND:
The pathogenesis of spontaneous cervical artery dissection remains unclear, and no established predictors of recurrence exist. Our goal was to investigate the potential association between cervical artery tortuosity, a characteristic of patients with connective tissue disorder, and spontaneous cervical artery dissection.

METHODS:

The ReSect study (Risk Factors for Recurrent Cervical Artery Dissection) is an observational study that invited all spontaneous cervical artery dissection patients treated at the Innsbruck University Hospital between 1996 and 2018 for clinical and radiological follow-up. Internal carotid and vertebral artery tortuosity was assessed on magnetic resonance angiography using a validated 3-dimensional algorithm. Differences between patients and healthy controls as well as dependent on recurrence status were assessed by applying χ
2
, Mann-Whitney
U
test, and Kruskal-Wallis test where applicable, and confounders were established by bivariable Pearson correlation. Logistic regression was used to address the impact of tortuosity on dissection occurrence and recurrence as well as its association to extracellular matrix proteome data derived from skin biopsies in a subset of patients.

RESULTS:

Magnetic resonance angiography was performed a median of 6.5 years after dissection in the included dissection patients. Patients with dissection (n=125) had significantly increased values of internal carotid artery tortuosity compared with healthy controls (n=24; odds ratio, 2.65 [95% CI, 1.68–3.86], 1 SD increase;
P
<0.01). This was also true for patients with long-term dissection recurrence (n=7) when compared with those with single time-point dissection (n=118; odds ratio, 2.00 [95% CI, 1.47–3.99], 1 SD increase;
P
<0.01). In patients with dissection and available extracellular matrix protein data (n=37), 6 of 13 (46.2%) proteins previously found linked with dissection recurrence were also associated with increased tortuosity. All 3 proteins associated with both anterior and posterior circulation tortuosity belonged to the desmosome-related cluster.

CONCLUSIONS:
Internal carotid artery tortuosity is elevated in spontaneous cervical artery dissection patients compared with healthy controls, and this difference is most pronounced if individuals suffer from long-term dissection recurrence. Additionally, an association between tortuosity, being a readily measurable biomarker in routine magnetic resonance angiography, and proteomic markers of dissection recurrence exists, further enhancing the prospect of underlying subclinical connective tissue disease in dissection patients.
Learning or Boredom? Task Adaptation Effects in Sentence Processing Experiments
Authors: Chromý Jan , Tomaschek Fabian 
Published: December 2024

Abstract
Task adaptation, characterized by a progressive increase in speed throughout experimental trials, has been extensively observed across various paradigms. Yet, the underlying mechanisms driving this phenomenon remain unclear. According to the learning-based explanation, participants are implicitly learning, becoming more proficient over time. Conversely, a motivation-based view suggests that participants’ drive wanes gradually, prompting quicker pace and reduced task engagement. These explanations offer distinct predictions. The learning-based view anticipates not only accelerated speed but also improved response accuracy. In contrast, the motivation-based view assumes that participants lose their focus, their pace increases, but their response accuracy tends to decline. The present study tests these implications in a series of six self-paced reading experiments investigating the interplay between reaction times, immediate recall, and trial order. Robust learning effects are documented. Participants not only read progressively faster during the experiments, but they also get better in responding. Moreover, an analysis of recall accuracy reveals systematic differences between different types of information, with nouns yielding substantially higher recall accuracy than adjectives. These findings are explained through attentional mechanisms: prolonged processing of specific words correlates with improved recall. Furthermore, the differential recall patterns are modulated by the task’s question structure, with adjectives recalled more effectively in experiments with a higher proportion of adjective-targeting questions. This underscores participants’ strategic allocation of attention to sentence components deemed crucial for task performance, highlighting the dynamic interplay between learning, motivation, and attentional mechanisms in task adaptation.
Chromatics: Warm and Cool
Authors: Koenderink Jan J. , van Doorn Andrea J. , Braun Doris I. 
Published: December 2024

Abstract
Artistically, an important bipartition of hues is with respect to their warm–cool quality. What might this correspond to in colorimetric terms? Various interpretations have been suggested, mostly informally. We attempt to compare them quantitatively, using either diverse data available from the literature, or formal means. We conclude that it is not possible to differentiate between various ontologically distinct interpretations. The warm–cool axis is roughly aligned with the Orange–Teal axis of the color circle. Leeway is about two steps either way for a 24-step division. Within this margin, virtually all suggested meanings pertain. The dominance of this axis in nature is due to generic physical properties.
The Economic Power of Capital and the Spread of COVID-19 in the United States: An Empirical Study
Authors: Zhao Junfu 
Published: December 2024

This study proposes a Marxian explanation to account for the spread of COVID-19 in the United States in 2020. Capital opposed and resisted public non-pharmaceutical interventions because they interfered with short-term profitability. The economy was prematurely reopened under the structural economic power of capital at the expense of society. This empirical analysis exploits the variation in the local economic power of capital across counties, measured by the county-level employment share of employees of private for-profit companies. If the structural economic power of capital in a county was more substantial, then the cumulative COVID-19 death rate and the unemployment rate were larger, and social distancing behaviors were discouraged in that county. Workplace safety was not guaranteed during the pandemic, potentially contributing to the spread of COVID-19. JEL Classification: B51, I18, P17
A Painful Reality Check? Examining the Accuracy of Subjective Survival Probabilities by Pain Interference and Depression Status
Authors: Fennell Gillian , Andrasfay Theresa , Grol-Prokopczyk Hanna , Ailshire Jennifer 
Published: December 2024

Purpose Pain and depression are linked to higher mortality risk and lower subjective survival probabilities (SSPs). We examine if SSPs for individuals with pain and depression match their actual lifespans. Methods Using data on 12,745 Health and Retirement Study respondents aged 57-89 in 2000 with follow-up through 2018, we assessed whether respondents’ SSPs were “correct,” “underestimated,” or “overestimated” relative to their lifespans. Adjusted multinomial logistic regressions predicted SSP accuracy based on pain interference, depression, and their interaction. Results Severe or interfering pain (i.e., high impact pain) was associated with a 25% higher risk of underestimating SSPs (RRR = 1.25, p = .04), and depression increased the risk by 49% (RRR = 1.49, p < .001). High impact pain and depression also corresponded with lower average SSPs and higher mortality risk. Conclusion High impact pain and depression increase the risk of underestimating longevity. Future research should explore the impact on health and financial decisions in older adults.
Cardioprotective Potential of Bioactive Compound from Methanolic Extract of Asparagus racemosus: An In Silico Study Utilizing GC–MS Analysis
Authors: Sen Sandip , Roy Biswabara , Kannappan N. , Zoghebi Khalid , Albratty Mohammed , Alhazmi Hassan A. , Najmi Asim , Alam Md Shamsher 
Published: December 2024

Background Historical accounts suggest that, throughout antiquity, medicinal plants and their constituent parts have been used to treat a variety of ailments. Asparagus racemosus, this plant exhibits a wide range of potential uses in medicine. Purpose The purpose of this study is to identify any potentially bioactive ingredients in the methanolic extract of A. racemosus. Methods A variety of compounds were detected using gas chromatography, and their molecular structures were confirmed by Fourier transform infrared (FTIR) analysis and mass spectrometry. Using in silico approaches, the molecule’s potential as a therapeutic candidate, biological activity, and projected targets were carefully examined. Results The molecule 4-(((9-(5-(ethylcarbamoyl)-3,4-dihydroxy tetrahydrofuran-2-yl)-9 H-purin-6-yl)amino)methyl)benzoic acid was found in the highest concentration (27.37%). The identified molecule is purine alkaloid in nature. The promising drug-like properties and therapeutic efficacy for the investigated molecule. Conclusion It could serve as a viable therapeutic option for addressing cardiovascular disorders.
Assessment of Symptom Burden and Quality of Life in Patients With Primary Brain Tumours Attending Palliative Care in a Tertiary Cancer Care Centre
Authors: Padhi Pratyasa , Gupta Nishkarsh , Bharati Sachidanand Jee , Garg Rakesh , Mishra Seema , Bhatnagar Sushma , Haresh K. P. , Kumar Vinod 
Published: December 2024

Background: Patients with primary brain tumors navigate a distinct illness trajectory, characterized by an uncertain prognosis, a rapid decline in physical functioning, and a significant deterioration in the quality of life. These unique challenges underscore the importance of our research in understanding and addressing the needs of these patients. Methods: The EORTC QLQ C30 & EORTC BN 20 questionnaires assessed the quality of life and symptom burden in patients with primary brain tumors. The scores were analyzed using SPSS statistical software. Results: 100 patients - 61 males and 39 females—were included with radiological or histopathological diagnoses of primary brain tumours. Seizures (38%) was the most common presenting symptom, followed by headache (18%), loss of consciousness (13%), focal neurological deficit (9%), and blurring of vision (8%). The mean quality of life at baseline was 78.29, with a standard deviation of 9.67 on a scale of 0 to 100, and the brain tumor-specific symptom burden score was 46.9, with a standard deviation of 17.95 on a scale of 0 to 100. There was a significant difference in the global health status score between the first and third visits at 3 months ( P value = .03). Conclusion: Despite the aggressive and often incurable nature of primary brain tumors, there is hope in the form of palliative care. By addressing unmet symptoms, uncertainties about the future, and social functioning, palliative care can significantly improve the quality of life of these patients.
Driven by purpose, weary in pursuit: Exploring competitive employment for autistic adults
Authors: Erdal Kerstin , Gelléri Petra , Billstedt Eva 
Published: December 2024

Background:  Autistic adults are notably underrepresented in the mainstream job market, with only 20% of them worldwide engaged in competitive employment. This underrepresentation carries significant societal and welfare costs. In our study, we explore the impact of competitive employment on autistic adults. Objective:  We examine the dynamics of personal resources, job demands, resource losses, and resource gains within the context of adult autism and competitive employment. We seek to comprehend the motivating factors related to work and the prerequisites for its sustainment, joining the theoretical frameworks of Job Demands-Resources and Conservation of Resources. Methods:  We conducted in-depth interviews with eight adults with autism who are employed in competitive roles. Thematic analysis was employed to identify categories and themes, further analyzed using inductive coding. Results:  Competitive employment was associated with resource gains, including feeling of mastery, improved self-esteem, and enhanced social connectedness. However, participants also reported elevated post-work fatigue as a job demand. Managing post-work fatigue required personal resources, such as stress management strategies and adequate recovery time. Conclusion:  Our findings highlight the potential of competitive employment to enhance the well-being among autistic adults. To realize these effects, both personal resources and a supportive work environment are crucial.
Idiopathic epiretinal membrane surgery with internal limiting membrane peeling: An optical coherence tomography angiography analysis of macular capillary plexus changes
Authors: Caretti Luigi , Pillon Giulia , Verzola Giacomo , Angelini Edoardo , Monterosso Cristina , Bonfiglio Vincenza , Longo Antonio , Formisano Martina 
Published: December 2024

Purpose This study aims to assess retinal vascular changes following internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (ERM) treatment using optical coherence tomography angiography (OCT-A). Design A retrospective study was conducted. Methods A cohort of thirty-nine patients was enlisted for this study. Each participant underwent comprehensive ophthalmological evaluation and OCT-A imaging at baseline, as well as at 1-month and 6-month intervals post-pars plana vitrectomy with ERM and ILM peeling. Results Post-surgery, remarkable improvements were observed in best-corrected visual acuity (BCVA) (from 0.335 ± 0.173 to 0.096 ± 0.126 at 6 months), coupled with a notable reduction in central retinal thickness (CRT) (from 460 ± 87 µm to 395 ± 53 µm at 6 months). Additionally, there was a noticeable expansion in the foveal avascular zone (FAZ) perimeter (from 0.099 ± 0.060 mm² to 0.125 ± 0.056 mm² at 6 months). However, there was a decline in vessel density (VD) in the superficial capillary plexus (SCP) (from 46.7 ± 4.4 to 43.8 ± 3.5% at 6 months), contrasted by an elevation in the deep capillary plexus (DCP) (from 45.2 ± 5.5% to 43.6 ± 5.3% at 6 months. Noteworthy correlations were detected between CRT and BCVA, as well as CRT and vascular parameters. Conclusion ERM instigates a milieu of changes including SCP crowding and elevation, potentially leading to a falsely augmented density at OCT-A in affected patients. Subsequent surgery results in a release of ERM-induced forces, elucidating the observed decrease in SCP density. Conversely, the DCP appears to be less distorted by the ERM, facilitating gradual vessel reopening after its removal. OCTA provides valuable insights into optimal surgical timing.