bluuebunny/crossref_metadata_2025_split huggingface dataset:
How not to defend aesthetic autonomism
Authors: Eker Bahadir 
Published: January 2025

ABSTRACT
Aesthetic autonomism is standardly defined as the view that the aesthetic value of an artwork in no way depends on its moral value, and hence that considerations about the latter are irrelevant to aesthetic evaluation. However, it has recently been argued that definitions along these lines involve certain flaws and that autonomism should be characterized instead as the view that it is rationally permissible not to adjust one’s initial aesthetic judgment about a work in light of how one evaluates it morally. This paper argues that this proposal is seriously misguided in three central respects: its focus on evaluative adjustments is objectionably narrow and ignores other forms of evaluative conduct; its appeal to rationality misconstrues the core commitments of non-autonomists; and its permissivist character results in a distortion of what is at stake in the debate about the autonomy of the aesthetic.
High GRWD1 expression may predict clinically aggressive lower grade glioma, skin cutaneous melanoma, and kidney renal clear cell carcinoma carrying wild-type p53: a systematic study based on TCGA data analysis
Authors: Kayama Kota , Ooga Akihiro , Hasetsu Kouji , Kokubo Ryoma , Sugimoto Nozomi , Fujita Masatoshi 
Published: January 2025

Abstract
Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a novel oncogene/oncoprotein that downregulates the p53 tumour suppressor protein through several mechanisms. One important mechanism involves binding of GRWD1 to RPL11, which competitively inhibits the RPL11–MDM2 interaction and releases RPL11-mediated suppression of MDM2 ubiquitin ligase activity towards p53. Here, we mined the TCGA (The Cancer Genome Atlas) database to gain in-depth insight into the clinical relevance of GRWD1. We found that high expression of GRWD1 is associated with a poor prognosis for lower grade glioma (LGG) of the brain, skin cutaneous melanoma (SKCM), and kidney renal clear cell carcinoma (KIRC) carrying wild-type p53. Further investigations revealed that copy number alterations in the GRWD1 gene are one determinant of GRWD1 expression level. By contrast, even in patients with a diploid GRWD1 gene, high GRWD1 expression was associated with a poor prognosis for LGG, SKCM, and KIRC carrying wild-type p53. Additional studies suggest that some transcriptional factors may be involved in regulation of GRWD1 in cancers with a diploid GRWD1 gene. Taken together, the data presented herein suggest that high expression of GRWD1 may contribute to malignant behaviour, and predict a clinically unfavourable prognosis for LGG, SKCM, and KIRC carrying wild-type p53.
Parathyroid hormone-related protein levels and treatment outcomes in hypercalcemia of malignancy: a retrospective cohort study
Authors: Kato Kazuhiko , Nakashima Akio , Kimura Ai , Maruyama Yukio , Ohkido Ichiro , Miyazaki Yoichi , Yokoo Takashi 
Published: January 2025

Abstract
The challenge of managing acute hypercalcemia in patients diagnosed with hypercalcemia of malignancy (HCM) merits further attention. Elevated levels of PTHrP may be a risk factor for treatment resistance in acute hypercalcemia; however, few studies have tested this hypothesis. This study aimed to investigate whether high PTHrP levels represent an independent risk factor that impedes the treatment of acute hypercalcemia. This retrospective cohort study recruited 159 patients aged 20-80 years with diagnosed malignancies who had been hospitalized for hypercalcemia with PTHrP levels above the reference value (1.1 pmol/L). The median (25%-75%) patient age was 69 (61-76) years, and the median PTHrP level was 6.3 (3.3-11.1) pmol/L. The corrected calcium levels decreased from 12.8 mg/dL (11.9-14.1 mg/dL) to 10.6 mg/dL (9.8-11.7 mg/dL) following treatments, such as bisphosphonates and saline solution. Multivariate linear regression analysis showed less significant decreases in the corrected calcium levels as natural logarithm-transformed PTHrP levels increased (β coefficient [95% CI]: 0.569 [0.225-0.914]; p = .001 for Model 3). Multivariate logistic regression analysis showed an association between high natural logarithm-transformed PTHrP levels and lack of treatment response, defined as a corrected calcium level of ≤10.4 mg/dL in the last blood test conducted within 2 wk of treatment initiation (odds ratio [95% CI]: 0.504 [0.312-0.814]; p = .005). Therefore, elevated PTHrP levels are a potential risk factor for treatment resistance in hypercalcemia in HCM patients, complicating management regardless of calcium levels.
Detection of new gamma-ray AGN candidates using SIMEFIC III and DBSCAN in Fermi-LAT data
Authors: Soor M , Akhondi F , Hedayati Kh H 
Published: January 2025

ABSTRACT
We present the detection of new high-energy gamma-ray active galactic nucleus candidates using the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) clustering algorithm on two-dimensional gamma-ray data from Fermi Large Area Telescope. Our approach involves iterative applications of the SIeving MEthod for FInding Core (SIMEFIC III) algorithm, designed to enhance point source detection. By integrating DBSCAN at each denoising step, we track and evaluate the significance of potential sources across iterations. Our findings indicate that source significance increases to a specific threshold, beyond which further denoising may remove genuine sources. At the optimal denoising stage, we identified 18 sources not listed in the Fermi catalogue, with several of these sources potentially matching entries in the the Candidate Gamma-Ray Blazar Survey (CRATES) and Roma-BZCAT (Roma-BZCAT Multi-Frequency Catalog of Blazars) catalogues.
Galaxy evolution in the Post-Merger Regime – I. Most merger-induced in situ stellar mass growth happens post-coalescence
Authors: Ferreira Leonardo , Ellison Sara L , Patton David R , Byrne-Mamahit Shoshannah , Wilkinson Scott , Bickley Robert , Conselice Christopher J , Bottrell Connor 
Published: January 2025

ABSTRACT
Galaxy mergers can enhance star formation rates throughout the merger sequence, with this effect peaking around the time of coalescence. However, owing to a lack of information about their time of coalescence, post-mergers could only previously be studied as a single, time-averaged population. We use time-scale predictions of post-coalescence galaxies in the UNIONS survey, based on the Multi Model Merger Identifier deep learning framework (mummi) that predicts the time elapsed since the last merging event. For the first time, we capture a complete timeline of star formation enhancements due to galaxy mergers by combining these post-merger predictions with data from pre-coalescence galaxy pairs in SDSS. Using a sample of 564 galaxies with $M_* \ge 10^{10}\mathrm{ M}_\odot$ at $0.005 \lt z \lt 0.3$ we demonstrate that: (1) galaxy mergers enhance star formation by, on average, up to a factor of two; (2) this enhancement peaks within 500 Myr of coalescence; (3) enhancements continue for up to 1 Gyr after coalescence; and (4) merger-induced star formation significantly contributes to galaxy mass assembly, with galaxies increasing their final stellar masses by, 10 per cent to 20 per cent per merging event, producing on average $\log (M_*/\mathrm{ M}_\odot) = {9.56_{-0.19}^{+0.13}}$ more mass than non-interacting star-forming galaxies solely due to the excess star formation.
Persistent, Private, and Mobile Genes: A Model for Gene Dynamics in Evolving Pangenomes
Authors: Gamblin Jasmine , Lambert Amaury , Blanquart François 
Published: January 2025

Abstract
The pangenome of a species is the set of all genes carried by at least one member of the species. In bacteria, pangenomes can be much larger than the set of genes carried by a single organism. Many questions remain unanswered regarding the evolutionary forces shaping the patterns of the presence/absence of genes in pangenomes of a given species. We introduce a new model for bacterial pangenome evolution along a species phylogeny that explicitly describes the timing of appearance of each gene in the species and accounts for three generic types of gene evolutionary dynamics: persistent genes that are present in the ancestral genome, private genes that are specific to a given clade, and mobile genes that are imported once into the gene pool and then undergo frequent horizontal gene transfers. We call this model the Persistent-Private-Mobile (PPM) model. We develop an algorithm fitting the PPM model and apply it to a dataset of 902 Salmonella enterica genomes. We show that the best fitting model is able to reproduce the global pattern of some multivariate statistics like the gene frequency spectrum and the parsimony vs. frequency plot. Moreover, the gene classification induced by the PPM model allows us to study the position of accessory genes on the chromosome depending on their category, as well as the gene functions that are most present in each category. This work paves the way for a mechanistic understanding of pangenome evolution, and the PPM model developed here could be used for dynamics-aware gene classification.
Transcription factors induce differential splicing of duplicated ribosomal protein genes during meiosis
Authors: Petibon Cyrielle , Catala Mathieu , Morales Danna , Panchapakesan Shanker Shyam , Unrau Peter J , Abou Elela Sherif 
Published: January 2025

Abstract
In baker’s yeast, genes encoding ribosomal proteins often exist as duplicate pairs, typically with one ‘major’ paralog highly expressed and a ‘minor’ less expressed paralog that undergoes controlled expression through reduced splicing efficiency. In this study, we investigate the regulatory mechanisms controlling splicing of the minor paralog of the uS4 protein gene (RPS9A), demonstrating that its splicing is repressed during vegetative growth but upregulated during meiosis. This differential splicing of RPS9A is mediated by two transcription factors, Rim101 and Taf14. Deletion of either RIM101 or TAF14 not only induces the splicing and expression of RPS9A with little effect on the major paralog RPS9B, but also differentially alters the splicing of reporter constructs containing only the RPS9 introns. Both Rim101 and Taf14 co-immunoprecipitate with the chromatin and RNA of the RPS9 genes, indicating that these transcription factors may affect splicing co-transcriptionally. Deletion of the RPS9A intron, RIM101 or TAF14 dysregulates RPS9A expression, impairing the timely expression of RPS9 during meiosis. Complete deletion of RPS9A impairs the expression pattern of meiotic genes and inhibits sporulation in yeast. These findings suggest a regulatory strategy whereby transcription factors modulate the splicing of duplicated ribosomal protein genes to fine-tune their expression in different cellular states.
Control of cortical slow oscillations and epileptiform discharges with photoswitchable type 1 muscarinic ligands
Authors: Sanchez-Sanchez Jose M , Riefolo Fabio , Barbero-Castillo Almudena , Sortino Rosalba , Agnetta Luca , Manasanch Arnau , Matera Carlo , Bosch Miquel , Forcella Marta , Decker Michael , Gorostiza Pau , Sanchez-Vives Maria V 
Published: January 2025

Abstract
Acetylcholine and the cholinergic system are crucial to brain function, including functions such as consciousness and cognition. Dysregulation of this system is implicated in the pathophysiology of neurological conditions such as Alzheimer's disease. For this reason, cholinergic neuromodulation is relevant in both basic neuroscience and clinical neurology. In this study, we used photopharmacology to modulate neuronal activity using the novel selective type-1 muscarinic (M1) photoswitchable drugs: the agonist benzyl quinolone carboxylic acid-azo-iperoxo (BAI) and the antagonist cryptozepine-2. Our aim was to investigate the control over these cholinergic receptors using light and to investigate the effects of these drugs on physiological spontaneous slow waves and on epileptic activity in the cerebral cortex. First, we used transfected HEK cell cultures and demonstrated BAI’s preferential activation of M1 muscarinic acetylcholine receptors (mAChRs) compared with M2 mAChRs. Next, we found that white-light illumination of BAI increased the frequency of spontaneous slow-wave activity in brain cortical networks of both active slices and anesthetized mice, through M1-mAChRs activation. Illumination of cryptozepine-2 with UV light effectively suppressed not only the muscarinic-induced increase in slow-wave frequency, but also muscarinic-induced epileptiform discharges. These findings not only shed light on the role of M1 acetylcholine receptors in the cortical network dynamics but also lay the groundwork for developing advanced light-based pharmacological therapies. Photopharmacology offers the potential for high-precision spatiotemporal control of brain networks with high pharmacological specificity in both healthy and pathological conditions.
Senescence accelerated mouse-prone 8: a model of neuroinflammation and aging with features of sporadic Alzheimer’s disease
Authors: Ong Jun , Sasaki Kazunori , Ferdousi Farhana , Suresh Megalakshmi , Isoda Hiroko , Szele Francis G 
Published: January 2025

Abstract
The large majority of Alzheimer’s disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage of AD cases are familial, with known genetic causes. Paradoxically, there are only few validated mouse models of sporadic AD but many of familial AD. Senescence accelerated mouse-prone 8 (SAMP8) mice are a model of accelerated aging with features of sporadic AD. They exhibit a more complete suite of human AD-relevant pathologies than most familial models. SAMP8 brains are characterized by inflammation, glial activation, b-amyloid deposits, and hyperphosphorylated Tau. The excess amyloid deposits congregate around blood vessels leading to vascular impairment and leaky BBBs in these mice. SAMP8 mice also exhibit neuronal cell death, a feature not typically seen in models of familial AD. Additionally, adult hippocampal neurogenesis is decreased in SAMP8 mice and correspondingly, they have reduced cognitive ability. In line with this, hippocampal LTP is significantly compromised in SAMP8 mice. No model is perfect and SAMP8 mice are limited by the lack of clarity about their genomic differences from control Senescence Accelerated Mouse-Resistant 1 (SAMR1) mice although their transcriptomics changes are being revealed. To further complicate matters, multiple substrains of SAMP8 mice have emerged over the years, sometimes making comparisons of studies difficult. Despite these challenges, we argue that SAMP8 mice can be useful for studying AD-relevant symptoms and propose important experiments to strengthen this already useful model.
A noncanonical‐GPRC5A signaling regulates keratinocyte adhesion and migration by nuclear translocation
Authors: Chanteloube Sarah , Ya Choua , Le Provost Gabrielle , Berthier Aurore , Dieryckx Cindy , Vadon‐Le Goff Sandrine , Nadal Florence , Fromy Bérengère , Debret Romain 
Published: January 2025

AbstractG‐Protein Coupled Receptor, Class C, Group 5, Member A (GPRC5A) has been extensively studied in lung and various epithelial cancers. Nevertheless, its role in the skin remains to be elucidated. In this study, we sought to investigate the function of this receptor in skin biology. Our research demonstrated that its expression responds to mechanical substrate changes in human primary keratinocytes. Furthermore, we observed the reinduction of GPRC5A during wound healing at the leading edges in an ex vivo burn model, coinciding with the translocation of its C‐terminal region into the nucleus. We identified the cleavage site of GPRC5A by N‐TAILS analysis, and cathepsin G was characterized as the protease responsible for proteolysis in cultured cells. In order to gain a deeper understanding of the role of GPRC5A in keratinocytes, we performed a GPRC5A knockdown in N/TERT‐1 cells using short‐hairpin RNA. Our findings indicate a strong association between GPRC5A and adhesion regulation pathways. Additionally, our results demonstrate that GPRC5AKD enhances cell adhesion while reducing cell migration and differentiation. It is noteworthy that these effects were reversed by the addition of a recombinant polypeptide that mimics the C‐terminal region of GPRC5A. In conclusion, our study reveals that GPRC5A plays an unexpected role in regulating keratinocyte behavior, with implications for its C‐terminal region translocation into the nucleus. These results offer promising avenues for future research in the field of wound healing.
Bacterial components‐driven intrahepatic CXCR5hi B cells are important population for MASH progression through inducing inflammation
Authors: Kim Nam‐Hee , Kim Mi‐Yeon , Yang Yoon Mee , Jeong Won‐Il , Lee Hye Won , Kim Wooseob , Kang Seung Goo , Han Yong‐Hyun 
Published: January 2025

AbstractMetabolic dysfunction‐associated steatohepatitis (MASH) is characterized by severe liver inflammation and fibrosis due to an imbalanced immune response caused by enhanced bacterial components. The progression of MASH is closely linked to increased permeability of intestinal mucosal barrier facilitating enter of bacterial components into hepatic portal venous system. B cells are important immune cells for adaptive responses and enhance hepatic inflammation through cytokine production and T cell activation. B cells are influenced by gut microbiota, but the specific B cell populations in MASH and their pathologic mechanism remain obscure. Here, we found that the numbers of B cells highly expressing CXCR5, the receptor of CXCL13 chemokine, were increased in the livers of MASH. CXCR5 high B cells are non‐proliferating naive B cells with inflammatory features mainly residing in hepatic parenchyma to affect liver pathology. Importantly, we revealed that CXCR5 high B cells were induced by bacterial components stimulating TLRs. These bacterial stimulator‐induced CXCR5hi B cells highly express TNFα, CD80, and MHC class II, leading to T cell activation. Consistently, we confirmed that intravenous injection of CXCR5 high B cells enhanced hepatic inflammation in MASH model. Ultimately, this study elucidates the role and mechanisms of CXCR5 high B cells in advancing MASH progression.
A Modified Procedure to Improve Pancreatic Drainage in Chronic Pancreatitis with Pancreatic Head Dominant Disease
Authors: Shaaban Mohamed A. , Beilman Greg J. 
Published: January 2025

Objectives:
Chronic pancreatitis is a debilitating and progressive inflammatory disease with an altered quality of life due to severe abdominal pain. Pancreaticoduodenectomy is a surgical option for patients with bulky disease involving the head of the pancreas, especially when this disease has progressed to stricture of the bile duct, duodenum, or both. A long term issue associated with this procedure is stricture of the pancreatic anastomosis. Re-operative and endoscopic interventions are difficult related to difficulty in reaching the anastomosis endoscopically. We describe a variation of this procedure with potential to lead to longer term improvement in drainage of the residual pancreas.

Methods:
We reviewed electronic medical records of patients undergoing pancreaticoduodenectomy for chronic pancreatitis performed by one surgeon at the University of Minnesota Medical Center, Minneapolis, MN, between 2014 and 2023. Information gathered from the patients’ records included preoperative demographics, perioperative outcomes, and postoperative follow up information.

Results:
The described procedure was performed in eight patients between 2014 and 2023. Three patients have died since surgery at 1.5, 5.5, and 8 years postop, with no deaths related to pancreatitis or surgical complications. Of the remaining five patients, median time from surgery is 7.5 years.

Conclusions:
We describe a surgical technique which may reduce the risk of pancreaticojejunal stricture in patients undergoing pancreaticoduodenectomy for chronic pancreatitis. In a small series of patients, this procedure can be performed safely with acceptable results.
Factors associated with failure of humerus nonunion surgery in patients with initial nonoperative management
Authors: Hysong Alexander , Harrison Noah , Posey Samuel , Yu Ziqing , Chen Andrew T. , Pallitto Patrick , Hsu Joseph R. , Obremskey William ,   Evidence-Based Musculoskeletal Injury and Trauma Collaborative (EMIT)
Published: January 2025

Abstract

Objectives:
To describe operative results after humerus nonunion surgery in patients whose initial humerus shaft fracture (OTA/AO code 12) was treated nonoperatively and to identify risk factors of nonunion surgery failure in the same population.

Design:
Case series.

Setting:
Nine academic level 1 trauma centers.

Patients/Participants:
One hundred twenty patients with humerus nonunion whose initial fracture was treated nonoperatively.

Intervention:
Operative treatment of humerus nonunions.

Main Outcome Measurements:
Rate of recalcitrant nonunion after humerus nonunion surgery.

Results:
Of 108 humerus nonunions, 26 (24.07%) failed to unite after nonunion surgery. Moreover, 34 patients (31.48%) experienced 1 or more postoperative complications. Multivariate analysis found that the use of bone graft or bone graft substitute was not associated with successful nonunion surgery (95% odds ratio confidence interval [CI] [0.67–5.3], P = 0.23). Tobacco use was associated with an increased risk of persistent nonunion (P = 0.0041). Postoperative complications (P = 0.0001) were also associated with an increased risk of persistent nonunion. Diabetes and open fracture were not associated with differences in the nonunion repair success rate.

Conclusions:
As the largest and most generalizable to date, this multicenter study found that nearly 1 in 4 patients with a humeral nonunion after initial nonoperative management failed their nonunion surgical treatment. While postoperative complications were associated with recalcitrant nonunion, surgical adjuncts such as bone grafting and type did not seem to influence the success rate of nonunion surgery. Smoking is a modifiable risk factor suggesting that smoking cessation should be part of the intervention. These findings can be used to give patients and surgeons a realistic expectation of results and complications after humerus nonunion surgery.

Level of Evidence:
Therapeutic level III.