bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart failure and major haemorrhage in people with atrial fibrillation
Authors: Jones Nicholas R , Smith Margaret , Lay-Flurrie Sarah , Yang Yaling , Hobbs FD Richard , Taylor Clare J 
Published: October 2024

BackgroundHeart failure (HF) is not included in atrial fibrillation (AF) bleeding risk prediction scores, reflecting uncertainty regarding its importance as a risk factor for major haemorrhage. We aimed to report the relative risk of first major haemorrhage in people with HF and AF compared with people with AF without HF (‘AF only’).MethodsEnglish primary care cohort study of 2 178 162 people aged ≥45 years in the Clinical Practice Research Datalink from January 2000 to December 2018, linked to secondary care and mortality databases. We used traditional survival analysis and competing risks methods, accounting for all-cause mortality and anticoagulation.ResultsOver 7.56 years median follow-up, 60 270 people were diagnosed with HF and AF of whom 4996 (8.3%) had a major haemorrhage and 36 170 died (60.0%), compared with 8256 (6.4%) and 34 375 (27.2%), respectively, among 126 251 people with AF only. Less than half those with AF were prescribed an anticoagulant (45.6% from 2014 onwards), although 75.7% were prescribed an antiplatelet or anticoagulant. In a fully adjusted Cox model, the HR for major haemorrhage was higher among people with HF and AF (2.52, 95% CI 2.44 to 2.61) than AF only (1.87, 95% CI 1.82 to 1.92), even in a subgroup analysis of people prescribed anticoagulation. However, in a Fine and Gray competing risk model, the HR of major haemorrhage was similar for people with AF only (1.82, 95% CI 1.77 to 1.87) or HF and AF (1.71, 95% CI 1.66 to 1.78).ConclusionsPeople with HF and AF are at increased risk of major haemorrhage compared with those with AF only and current prediction scores may underestimate the risk of haemorrhage in HF and AF. However, people with HF and AF are more likely to die than have a major haemorrhage and therefore an individual’s expected prognosis should be carefully considered when predicting future bleeding risk.
Coastal Synechococcus strains can exploit low-oxygen habitats
Authors: Śliwińska-Wilczewska Sylwia , Savoie Mireille , Campbell Douglas A. 
Published: October 2024

We found that Phycoerythrin-rich Synechococcus achieved faster growth rates (µ), across the spectral bandwidths from 405 to 730 nm, under 2.5 µmol/L [O2], characteristic of oxygen minimum zones (OMZs), than under 250 µmol/L [O2], whereas phycocyanin-rich strain showed generally similar µ under 2.5 and 250 µmol/L [O2]. For phycocyanin- and phycoerythrin-rich Synechococcus, µ showed also positive linear responses to both phycobiliproteins:chlorophyll a, and to cumulative diel PSII electron flux, although the relations vary across strain and [O2]. Electron transport downstream of Photosystem II was generally higher for both phycocyanin- and phycoerythrin-rich strains under 250 µmol/L [O2], since cyanobacteria show strong capacity for electron flow away from PSII to O2, particularly under excess excitation. Even though electron transport was faster under 250 µmol/L [O2], the phycoerythrin-rich strain showed a higher growth yield of electron transport under 2.5 µmol/L [O2]. Phycoerythrin-rich Synechococcus are currently typically found at greater depths, and lower light, than are phycocyanin-rich strains, but we suggest that the phycoerythrin-rich strains are actually limited to lower light by an interaction between light and full air-saturated [O2]. In expanding OMZs phycoerythrin-rich strains will likely exploit higher light niches, across a wider spectral range.
A Novel 3‐Dimensional Printed Nanoceramic Hybrid Resin Fixed Lingual Retainer: Characterization and Mechanical Tests
Authors: Alnuaimy Noor Salam , Alhuwaizi Akram Faisal 
Published: October 2024

Introduction: An innovative retention protocol was developed to create a new 3D‐printed fixed retainer employing SprintRay OnX nanoceramic hybrid resin. The feasibility and usability of the retainer were subsequently evaluated.Methods: Identification and characterization of SprintRay OnX was done using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy dispersive X‐ray (SEM‐EDX), field emission scanning electron microscope (FE‐SEM), X‐ray diffraction (XRD), and flexural strength. Load–deflection and pull‐out tests were conducted on the 3D‐printed straight wires, with three distinct cross‐sectional geometries: round (1 mm), oval (1 mm × 1.5 mm) and semielliptical (1 mm × 1.5 mm). Twisted G&H and coaxial Respond stainless steel multistrand retainers were used for comparison. In the load–deflection test, a three‐point bending test (3PBT) was employed. For the pull‐out test, the retainer wire was inserted into the composite, which was placed in a centrally located hole of an acrylic block; the retainer wire was subjected to a tensile force along its long axis.Results: Characteristic bands close to those of PMMA were observed in the FTIR spectra. SEM‐EDX and XRD revealed a crystalline material with homogeneously distributed Yb element signals (19.4%). On FE‐SEM micrographs, small clumps were displayed on smooth surfaces. The flexural strength and the flexural modulus were, respectively, 142.48 MPa and 7.842 GPa. All groups of 3D‐printed wires exhibited significantly higher load–deflection levels than the multistrand wires (MSWs). Concerning pull‐out forces, they fell in between twisted G&H (96 N) and coaxial Respond (48.09 N) retainer wires. The 3D‐printed wires fractured cohesively without detachment from the adhesive, suggesting that the chemical bond was adequate for satisfactory wire integration, yet the wire’s strength was compromised. Concerning the cross‐sectional geometry, the load–deflection and the pull‐out forces of 3D‐printed oval and semielliptical wires were significantly higher than that of 3D‐printed round wires, which was attributed to the larger cross‐sections of the wires.Conclusion: Oval and semielliptical 3D‐printed wires offered favorable features as lingual retainers.
Breast Cancer Disseminated Tumor Cells: Do They Stay and Fight or Run and Hide?
Authors: Cackowski Frank C. , Korkaya Hasan 
Published: October 2024

Many solid tumors including breast cancer can exhibit early dissemination and dormancy—in which cancer cells spread early in the disease process and survive long periods without detectable growth. These early disseminated tumor cells sometimes reactivate and lead to incurable metastatic disease years or even decades after curative-intent therapy for the primary tumor. We are just beginning to understand the role of the immune system in this process in part because of improvements in immunocompetent models as well as technological advances such as single-cell genomics and spatial transcriptomics. In this issue of Cancer Research, Bushnell and colleagues showed that NK cells are important in this context. The authors found that disseminated tumor cells and quiescent cells express higher levels of MHC 1 but are resistant to NK-cell–mediated immunity. The proposed mechanism involves the STING pathway and transcription factors Sox2 and Bach1. As other studies have highlighted the importance of T-cell immunity, this work reaffirms the importance and diversity of immune regulation of dormancy and suggests the need for future studies to flesh out mechanistic details and predict when each type of immunity is most important.See related article by Bushnell et al., p. 3337
Physical Activity during Adolescence and Early Adulthood and Breast Cancer Risk before Age 40 Years
Authors: Kehm Rebecca D. , Genkinger Jeanine M. , Knight Julia A. , MacInnis Robert J. , Liao Yuyan , Li Shuai , Weideman Prue C. , Chung Wendy K. , Kurian Allison W. , Colonna Sarah V. , Andrulis Irene L. , Buys Saundra S. , Daly Mary B. , John Esther M. , Hopper John L. , Terry Mary Beth 
Published: October 2024

Abstract

Background:
Breast cancer incidence is increasing in women under age 40, underscoring the need for research on breast cancer risk factors for younger women.

Methods:
We used data from an international family cohort (n = 26,348) to examine whether recreational physical activity (RPA) during adolescence and early adulthood is associated with breast cancer risk before age 40. The cohort includes 2,502 women diagnosed with breast cancer before age 40, including 2,408 diagnosed before study enrollment (68% within 5 years of enrollment). Women reported their average hours per week of moderate and strenuous RPA during adolescence (12–17 years) and early adulthood (25–34 years), which were converted to total age-adjusted metabolic equivalents per week and categorized into quartiles. We conducted attained age analyses until age 40 (follow-up time began at age 18) using Cox proportional hazards regression models adjusted for study center, race and ethnicity, and education.

Results:
Being in the highest versus lowest quartile of RPA during adolescence and early adulthood were respectively associated with 12% [HR (95% confidence interval, or CI), 0.88 (0.78–0.98)] and 16% [HR (95% CI), 0.84 (0.74–0.95) lower breast cancer risks before age 40. Being in the highest quartile of RPA during both adolescence and early adulthood (Pearson correlation = 0.52) versus neither time point was associated with a 22% lower risk [HR (95% CI), 0.78 (0.68–0.89)].

Conclusions:
Findings suggest that RPA during adolescence and early adulthood may lower breast cancer risk before age 40.

Impact:
Policies promoting physical activity during adolescence and early adulthood may be important for reducing the growing burden of breast cancer in younger women.
Tissue-Resident T Cells in Clinical Response and Immune-Related Adverse Events of Immune Checkpoint Blockade
Authors: Zhao Ye , Wucherpfennig Kai W. 
Published: October 2024

Abstract
T-cell surveillance of tissues is spatially organized: circulating memory T cells perform surveillance of secondary lymphoid organs, whereas tissue-resident memory T cells act as sentinels in barrier tissues. In the context of infection, tissue-resident memory T cells survive long term in barrier tissues and are poised to respond to re-encounter of infectious agents. The activity of such tissue-resident T cells is regulated by the PD-1 and cytotoxic T-lymphocyte–associated protein 4 inhibitory receptors targeted by cancer immunotherapies. This review investigates the hypothesis that T cells with a tissue residency program play an important role in both protective antitumor immunity and immune-related adverse events (irAE) of immune checkpoint blockade (ICB). A series of translational studies have demonstrated that a higher density of tissue-resident T cells within tumors is associated with favorable survival outcomes in a diverse range of cancer types. Tissue-resident T cells have also been implicated in clinical response to ICB, and dynamic tracking of T-cell populations in pre- and on-treatment tumor samples demonstrated that T cells with a tissue residency program responded early to ICB. Investigation of colitis and dermatitis as examples of irAEs demonstrated that tissue-resident memory T cells were reactivated at these epithelial sites, resulting in a highly cytotoxic state and secretion of inflammatory cytokines IFNγ and TNFα. It will therefore be important to consider how a tissue residency program can be enhanced to promote T-cell–mediated tumor immunity while preventing the development of irAEs.
T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H. 
Published: October 2024

Abstract
Resistance to immune checkpoint inhibitors (ICI) is common, even in tumors with T-cell infiltration. We thus investigated consequences of ICI-induced T-cell infiltration in the microenvironment of resistant tumors. T cells and neutrophil numbers increased in ICI-resistant tumors following treatment, in contrast to ICI-responsive tumors. Resistant tumors were distinguished by high expression of IL1 receptor 1, enabling a synergistic response to IL1 and TNFα to induce G-CSF, CXCL1, and CXCL2 via NF-κB signaling, supporting immunosuppressive neutrophil accumulation in tumor. Perturbation of this inflammatory resistance circuit sensitized tumors to ICIs. Paradoxically, T cells drove this resistance circuit via TNFα both in vitro and in vivo. Evidence of this inflammatory resistance circuit and its impact also translated to human cancers. These data support a mechanism of ICI resistance, wherein treatment-induced T-cell activity can drive resistance in tumors responsive to IL1 and TNFα, with important therapeutic implications.
Cathepsin L Promotes Pulmonary Hypertension via BMPR2/GSDME-Mediated Pyroptosis
Authors: Peng Zhouyangfan , Luo Xue-Yang , Li Xinyi , Li Yapei , Wu Yusi , Tian Yuyang , Pan Bingjie , Petrovic Aleksandar , Kosanovic Djuro , Schermuly Ralph Theo , Ruppert Clemens , Günther Andreas , Zhang Zhen , Qiu Chengfeng , Li Ying , Pu Jun , Li Xiaohui , Chen Alex F. 
Published: October 2024

BACKGROUND:
Pulmonary hypertension (PH) is a fatal progressive disease characterized by pulmonary endothelial injury and occlusive pulmonary vascular remodeling. Lysosomal protease cathepsin L degrades essential molecules to participate in the human pathophysiological process. BMPR2 (bone morphogenetic protein type II receptor) deficiency, an important cause of PH, results from mutational inactivation or excessive lysosomal degradation and induces caspase-3-mediated cell death. Given recent evidence that pyroptosis, as a new form of programmed cell death, is induced by caspase-3-dependent GSDME (gasdermin E) cleavage, we hypothesized that cathepsin L might promote PH through BMPR2/caspase-3/GSDME axis-mediated pyroptosis.

METHODS:
Cathepsin L expression was evaluated in the lungs and plasma of patients with pulmonary arterial hypertension. The role of cathepsin L in the progression of PH and vascular remodeling was assessed in vivo. Small interfering RNA, specific inhibitors, and lentiviruses were used to explore the mechanisms of cathepsin L on human pulmonary arterial endothelial cell dysfunction.

RESULTS:
Cathepsin L expression is elevated in pulmonary artery endothelium from patients with idiopathic pulmonary arterial hypertension and experimental PH models. Genetic ablation of cathepsin L in PH rats relieved right ventricular systolic pressure, pulmonary vascular remodeling, and right ventricular hypertrophy, also restoring endothelial integrity. Mechanistically, cathepsin L promotes caspase-3/GSDME-mediated endothelial cell pyroptosis and represses BMPR2 signaling activity. Cathepsin L degrades BMPR2 via the lysosomal pathway, and restoring BMPR2 signaling prevents the pro-pyroptotic role of cathepsin L in PAECs and experimental PH models.

CONCLUSIONS:
These results show for the first time that cathepsin L promotes the development of PH by degrading BMPR2 to induce caspase-3/GSDME-mediated endothelial pyroptosis.
Exploring distinct and joint contributions of the locus coeruleus and the substantia nigra/ventral tegmental area complex to reward and valence processing using high-resolution fMRI
Authors: Hall Julie M. , Shahnazian Danesh , Krebs Ruth M. 
Published: October 2024

Abstract
Dopaminergic neurons in the substantia nigra and the ventral tegmental area (SN/VTA) are classically viewed as key mediators in reward processing, while noradrenergic cells in the locus coeruleus (LC) are thought to modulate (negative) saliency processing. However, this conventional distinction is being revised by more recent research in animals. To explore the respective contributions of both the LC and SN/VTA in reward and valence processing in humans, we assessed fMRI data during stimulus encoding and response phase of a rewarded emotion-discrimination task (n = 38). Participants responded significantly faster to reward predicting and negative valence stimuli compared with their non-salient counterparts. LC activity was overall higher during trials involving reward prospect, and in particular for reward trials featuring positive valence, demonstrating an additive effect of reward and positive valence in LC. Moreover, LC activity was differentially increased for negative compared with positive valence in the response phase, indexing its role in invigorating responses to negative events. The SN/VTA showed increased activity in the response phase of reward trials (neutral valence) and negative valence trials (no reward), which aligns with coding relative saliency of these events in their respective contexts. LC modulations were accompanied by covariations in occipital cortex, suggesting noradrenergic contributions to visual prioritization of salient events. The findings underscore the sensitivity of both LC and SN/VTA to reward prospects and negative valence, challenging the dominant view of SN/VTA’s involvement in merely positive events and emphasizing their essential role in action invigoration above and beyond mere stimulus encoding. The intricate roles of the DA and NA system in reward and emotional valence processing in humans warrant further exploration and validation, given the limitations inherent to neuroimaging of deep brain structures.
Prior probability biases perceptual choices by modulating the accumulation rate, rather than the baseline, of decision evidence
Authors: Diaz Jessica A. , Pisauro M. Andrea , Delis Ioannis , Philiastides Marios G. 
Published: October 2024

Abstract
The prior probability of an upcoming stimulus has been shown to influence the formation of perceptual decisions. Computationally, these effects have typically been attributed to changes in the starting point (i.e., baseline) of evidence accumulation in sequential sampling models. More recently, it has also been proposed that prior probability might additionally lead to changes in the rate of evidence accumulation. Here, we introduce a neurally-informed behavioural modelling approach to understand whether prior probability influences the starting point, the rate of evidence accumulation or both. To this end, we employ a well-established visual object categorisation task for which two neural components underpinning participants’ choices have been characterised using single-trial analysis of the electroencephalogram. These components are reliable measures of trial-by-trial variability in the quality of the relevant decision evidence, which we use to constrain the estimation of a hierarchical drift diffusion model of perceptual choice. We find that, unlike previous computational accounts, constraining the model with the endogenous variability in the relevant decision evidence results in prior probability effects being explained primarily by changes in the rate of evidence accumulation rather than changes in the starting point or a combination of both. Ultimately, our neurally-informed modelling approach helps disambiguate the mechanistic effect of prior probability on perceptual decision formation, suggesting that prior probability biases primarily the interpretation of sensory evidence towards the most likely stimulus.
Is There a Domain of Linguistic Competence AI Cannot Grasp?
Authors: Mumbeck Marius 
Published: October 2024

Abstract
Linguistic competence is, among other things, the cognitive ability of using words appropriately. Following this notion, being a competent language user cannot be merely simulated because pretending to use words appropriately already is using words appropriately. Since current AI already can use words appropriately it may be that AI already has linguistic competence instead of merely simulating it. However, in this article I argue that there is at least one domain of linguistic competence that can be simulated: grasping lexical effects. Since grasping lexical effects presupposes an ability which AI lacks, namely feeling emotions, I argue that AI can only grasp the cognitive part of words but not their lexical effects. AI can only simulate to grasp lexical effects. Hence, lexical effects are a domain of linguistic competence AI cannot grasp.
Frege, Sentence-questions, Questions, and Thoughts
Authors: Davies Nathan William 
Published: October 2024

Abstract
Dummett, Hanks, Künne, and Bobzien have all stated or implied that when Frege wrote ‘Über Sinn und Bedeutung’, Frege believed that the sense of a sentence-question was not a thought. I present the passage of ‘Über Sinn und Bedeutung’ which is relevant to the evaluation of that proposition. I then present and evaluate an argument which I assume to be the best argument based on that passage for that proposition. I argue that the argument is likely to be unsound. I also address the question whether Frege believed that sentence-questions could be true or false and discuss what Frege did say and what he should have said about logical-alternative questions.
Semi-Automated Virtual Endoscopy of the Frontal Recess
Authors: Jafar Ali , Yao William , Citardi Martin 
Published: October 2024

Introduction: Virtual endoscopy (VE) is the computer-based reprocessing of diagnostic imaging to simulate endoscopy of an anatomic region of interest. VE of the Frontal Sinus Outflow Tract (FSOT) may assist surgical planning and education. Method: VE was performed on 16 normal sinus computed tomography (CT) scans for a total of 32 sides using the “path-to-target” tool on the TruDi surgical navigation system (ver. 2.3; Acclarent, Irving, CA, USA). To aid orientation during VE, planning points were placed on the middle turbinate, ethmoidal bulla, and skull base. The VE representation of anatomy and FSOT accuracy was manually confirmed by reviewing the corresponding orthogonal CT images and comparing them to the computed pathway. Results: Of the 32 sides, the software successfully calculated the FSOT in 22 sides (69%). Of those 22 sides, the calculated FSOT, depicted in the VE sequences accurately represented the FSOT. Among sides with an accurately calculated FSOT, the VE sequences depicted a “fly-through” from a starting point in the middle meatus around various frontal recess cells to the end point in the frontal sinus Conclusion: This pilot study demonstrates that software-generated VE of the FSOT is indeed feasible but requires confirmation by the surgeon for accuracy. Instances in which the software did not achieve its objective may drive further refinements of the protocol. VE of the FSOT should be explored as a tool for preoperative planning and surgical education.