bluuebunny/crossref_metadata_2025 huggingface dataset:
The wages of investor power: shareholder exploitation in Europe
Authors: Soener Matthew , Norris Davon
Published: February 2025

Exploitation, or the ability of property owners to gain at worker’s expense, is a classic sociological explanation for inequality. However, it is a difficult process to identify and empirically show with most data sources. Using data on European corporations from 1995 to 2020, we ask if shareholder gains come at the expense of employee earnings in a process we call “shareholder exploitation.” Panel estimation results confirm a robust antagonistic pattern with shareholders experiencing cumulative advantages relative to employees over this period. We further explore moderating mechanisms in this process. These results show globalization effects and the importance of the profit rate over time. Antagonism between shareholders and workers increases when profitability declines but attenuates when profitability increases and workers can claim more of the surplus. By using ideas from critical political economy, this paper has important implications for the study of inequality.
The Use of Pattern Recognition to Augment Traditional Monitoring in the Prevention of Opioid Overdose Harm
Authors: Patel Rakesh , Hopkins Anne Marie , Matta Basil , Wilson William C. , Sayed Hoomai , Park Linus , Dilanji Gabriel E.
Published: February 2025

Objectives

The aim of the study was to investigate the correlation of a pattern recognition algorithm to the opioid overdose intervention activities of trained medical staff at a safe consumption site (SCS).

Methods

Continuous physiological data were collected using the Masimo Radius PPG pulse oximeter from volunteer users of nonprescribed, unregulated opioids at a SCS. The algorithm retrospectively calculated opioid-induced respiratory depression (OIRD) severity scores (Opioid Halo scores) were compared to interventions recorded by SCS staff.

Results

The study included data prospectively collected from 167 individuals, who underwent 370 sessions of intravenous injection of nonprescribed, unregulated opioids (Fentanyl). Interventions were documented for 150 sessions (~41%) by the SCS staff. The remaining 220 sessions had no interventions documented. The algorithm demonstrated a strong correlation with the intervention activities (Spearman ρ = 0.80, P < 0.001). The area under the receiver operating curve for the correlation with intervention activities (ie, supplemental oxygen or naloxone administration) was 0.94. The OIRD severity scores were significantly higher (P < 0.001) in sessions requiring interventions compared to nonintervention sessions.

Conclusions

In this study, the algorithm generated OIRD severity scores had a strong correlation with the intervention activities provided by SCS staff who were blinded to the study pulse oximeter and algorithm scores. This suggests that the algorithm may be useful in detecting severe opioid-induced respiratory depression for which intervention is needed.
The Orthopaedic Trauma Fellowship Application Process: An Analysis of the Applicant Experience
Authors: McKeeman Jonathan , Ramski David
Published: February 2025

Background:

Several studies have analyzed the fellowship application process from the perspective of the program director and few have analyzed the application process from the perspective of the applicant. There is no study that analyzes orthopaedic trauma fellowship applicant perspectives on the application process to fellowship.

Methods:

An anonymous electronic survey was distributed via the Orthopaedic Trauma Association directory to all current orthopaedic trauma surgery fellows and attending physicians one year post-fellowship in the United States who completed fellowship in 2021-2022 and 2022-2023. The survey contained a total of 24 questions: 10 questions regarding demographics and accomplishments, 13 questions regarding interview statistics, preferences and expenses, and a set of questions concerning how applicants formed impressions of programs.

Results:

47/180 surgeons (26.11%) completed the survey. 37 (78.7%) were male. There was no associations between sex, USMLE Step 1, Step 2, or AOA status and number of interviews (R<0.20). There was a moderate correlation between the number of applications and number of interviews (R=0.68). Respondents valued faculty interaction (average scoring of 3.91 out of 4) and case volume/complexity (3.83 out of 4) the most. Research was the least valued program factor (2.19 out of 4). The average cost of applying to fellowship was $3331.84.

Conclusions:

Orthopaedic trauma fellowship applicants value case volume/complexity and faculty interaction the most and least value research. The financial burden of applying to fellowship is significant with most applicants spending over $3000. This study provides insight into factors that applicants value; which may lead to improved applicant satisfaction and reduced financial burden.
Feasibility of a new L43K ultrasound probe attachment for intraoperative laparoscopic ultrasonography in robot-assisted partial nephrectomy
Authors: Kobayashi Satoshi , Nakadate Ryu , Miyata Shinichi , Tsukino Keiji , Mutaguchi Jun , Ueda Shohei , Matsumoto Takashi , Monji Keisuke , Shiota Masaki , Inokuchi Junichi , Eto Masatoshi
Published: February 2025

Background

We assessed the feasibility of a new probe attachment (PA) developed to improve the ease of holding the drop-in-type L43K ultrasound probe during robot-assisted partial nephrectomy.

Materials and methods

We retrospectively analyzed the outcomes of 58 patients after robot-assisted partial nephrectomy using the conventional grip and 13 patients after surgery using the PA between September 2019 and February 2021. Propensity score matching (1:1) was performed to adjust for potential baseline confounders. The usability of the PA was evaluated regarding (1) total procedure time for intraoperative laparoscopic ultrasound; (2) proportion rate of intraoperative laparoscopic ultrasound in console time; (3) total number of probe fin grips; (4) total number of grip failures; (5) intraoperative laparoscopic ultrasound procedure time per grip; and (6) rate of successful gripping.

Results

After matching, 12 patients were allocated to each group, and the tumor site was significantly different between the groups. Usability was significantly better in the PA group: (1) conventional versus PA: 6.8 versus 7.6, p = 0.53; (2) 5.6% versus 6.1%, p = 0.61; (3) 8 versus 10, p = 0.32; (4) 3 versus 0, p = 0.014; and (5) 1.5% versus 0.7%, p = 0.021; (6) 66% versus 100%, p = 0.002. In patients with complex renal tumors, completely endophytic tumors, and renal hilum tumors, nearly identical improvements in usability were observed: (1) 9.8 versus 7.8 min, p = 0.21; (2) 9.9% versus 4.7%, p = 0.001; (3) 7 versus 6, p = 0.025; (4) 3 versus 0, p = 0.048, (5) 2.9 versus 1.6 min, p = 0.89, and (6) 60% versus 100%, p = 0.003.

Conclusions

Our proposed L43K PA can enhance the usability of the probe for intraoperative laparoscopic ultrasonography during robot-assisted partial nephrectomy and increase the accuracy of ultrasonography for complex renal tumors.
Stroke-Related Factors Influencing Thrombolysis Eligibility and Outcomes
Authors: Giorelli Maurizio , Aniello Maria Stella , Liuzzi Daniele , De Liso Alfredo , Accavone Donatella , Negri Francesco
Published: February 2025

Objective:

Intravenous thrombolysis (IVT) improves outcomes of acute ischemic stroke (AIS) when timely administered. The aim of this study was to collect and analyze data of stroke-related factors which may influence the performance of stroke-related rescue chains, the use of IVT, and patients’ outcomes.

Methods:

This study enrolled patients with AIS admitted to our Stroke Unit (SU) between January 1, 2023, and December 31, 2023. We investigated whether age, occurrence of baseline disabling deficits, stroke severity, or stroke location influenced the median Onset-to-Door Time (ODT), the chance of receiving IVT, or the outcomes of AIS in our facility.

Results:

A total of 208 patients were enrolled. Patients who received IVT had higher baseline National Institute of Health Stroke Scale (NIHSS) scores (12.26±1.2) than those who did not (6.77±0.51) (P<0.0001). Patients with IVT further showed a greater strength deficit, less ataxia, and lower median ODT (108±20 min) than patients with NO IVT (720±67) (P<0.0001). Weakness of the lower limbs and higher total NIHSS predicted ODT≤ 3.5 hours and the use of IVT. Ataxia and Posterior Circulation Stroke slowed the rescue chain and were negatively correlated with the use of IVT.

Conclusions:

Stroke-related factors may slow the rescue chain and affect the application of IVT for AIS. New evaluation strategies are warranted to overcome the detrimental effects of these factors and to allow clinicians to effectively manage strokes of any severity and location.
Prophylactic antibiotic use in trauma patients with non-operative facial fractures: A prospective AAST multicenter trial
Authors: Mian Rabiya K. , Grossman Verner Heather M. , Villalta Cynthia I. , Farsakh Dana , Amos Joseph D. , Minoza Karen G. , Kozar Rosemary , Doben Andrew R. , Keric Natasha , Moore Ernest E. , Alvarez Claudia , Murry Jason , Cardenas Tatiana C.P. , Lewis Richard H. , Zebley James A. , Blades Caitlin M. , Tominaga Gail , Charles Michael , Cripps Michael W. , Dultz Linda A. , Bailey Justin , Egodage Tanya , Ra Jin H. ,   the AAST Facial Fracture Study Group
Published: February 2025

BACKGROUND

Craniofacial trauma affects approximately 3 million individuals in the United States annually. Historically, low overall data quality and inadequate sample size have limited the development of clinical practice guidelines for prophylactic antibiotic use in facial fractures. We sought to examine the current use patterns and effects of prophylactic antibiotics in non-operative facial fractures.

METHODS

A prospective analysis of adult patients with nonoperative facial fractures was conducted across 19 centers from January 2022 to December 2023. Kruskal-Wallis H, Mann-Whitney U, Pearson’s χ2, Fisher's exact tests, and logistic regression models were used to evaluate the association between antibiotic duration (no antibiotics, ≤24 hours, and >24 hours) and facial fracture-associated infectious complications.

RESULTS

Among 1,835 patients, 1,168 (63.7%) received no antibiotics and 667 (36.4%) received antibiotics (≤24 hours, n = 264 (14.4%); >24 hours, n = 403 (22.0%). Nineteen (1.0%) patients developed infectious complications (0.7% in the no antibiotic group vs. 1.7% with antibiotics). Most patients (99.0%) did not develop an infection despite the majority (63.7%) receiving no antibiotics. Injuries were predominately closed fractures (86.3%), without mucosal disruption (83.9%) or foreign bodies (97.7%). Antibiotic administration had a statistically significant association with the occurrence of infectious complications (p = 0.050). However, no significant association was seen between antibiotic duration and infectious complications following multivariable logistic regression, adjusting for confounders (≤24 hours: adjusted odds ratio, 1.24; 95% confidence interval, 0.30–5.14; p = 0.766; >24 hours: adjusted odds ratio, 1.32; 95% confidence interval, 0.37–4.69; p = 0.668).

CONCLUSION

Despite most patients not receiving antibiotics, infection rates remained low. This indicates prophylactic antibiotic use does not reduce the risk of fracture-associated infections for most injury patterns. While a randomized trial is optimal to validate these data, at this time, there is no evidence to support presumptive antibiotics for closed non-operative facial fractures.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
Examining Geographic Disparity: Variation in Cancer Outcomes within Appalachia
Authors: Burus Todd , Hull Pamela C , Lang Kuhs Krystle A , Gao Tianyan , Brainson Christine F , Evers B Mark
Published: February 2025

Background:

The Appalachian region of the United States (US) extends from the Mississippi delta to southern New York. Although disparities in Appalachian cancer outcomes have long been observed, recent rates and trends have not been assessed.

Study Design:

We calculated 5-year age-adjusted US cancer incidence and mortality rates for 2017–2021, stratified into Appalachian and non-Appalachian populations, as well as Appalachian subregions, using the US Cancer Statistics Incidence Analytics Database and National Center for Health Statistics mortality files. Annual rates for 2004–2021 were also calculated.

Results:

In 2017–2021, all-site cancer incidence (466.6; 95% confidence interval (CI), 465.5–467.6) and mortality rates (165.5; 95% CI, 164.9–166.1) among Appalachian residents were significantly higher (5.6% and 12.8%, respectively) than among non-Appalachian residents. Within Appalachia, the Central subregion—predominantly eastern Kentucky—had the highest rates of all-site cancer incidence (495.9) and mortality (201.9). In addition, the Central subregion had the highest rates of lung and colorectal cancer incidence, and the highest rates of lung, colorectal, and cervical cancer mortality. All-site cancer incidence and mortality rates among Appalachian individuals have decreased significantly since 2004 (-0.33%/year and -1.39%/year, respectively), with site-specific incidence rate decreases for late-stage lung (-2.19%/year), late-stage colorectal (-0.75%/year) and late-stage female breast (-0.35%/year) cancers in Appalachia.

Conclusion:

While cancer incidence and mortality rates are declining in Appalachia, they remain substantially higher and demonstrate slower progress than elsewhere in the US—particularly in the Central Appalachian subregion—indicating the need for targeted research to delineate and address the factors driving these cancer health disparities.
Multimodal AI-Based Risk Stratification for Distant Metastasis in Nasopharyngeal Carcinoma
Authors: Zhou Jiayu , Wibawa Made Satria , Wang Ruoyu , Deng Ying , Huang Haoyang , Luo Zhuoying , Xia Yue , Guo Xiang , Young Lawrence S. , Lo Kwok-Wai , Rajpoot Nasir , Lv Xing
Published: February 2025

Background

The TNM staging system is the primary tool for treatment decisions in nasopharyngeal carcinoma (NPC). However, therapeutic outcomes vary considerably between patients, and guidelines for the management of distant metastasis treatment remain limited. This study aimed to develop and validate a deep learning-based risk score to predict NPC survival.

Methods

We developed graph for nasopharyngeal carcinoma (GNPC) risk score, a multimodal deep learning based digital score incorporating signals from both Haematoxylin and Eosin (H&E)-stained tissue slides and clinical information. Digitised images of NPC tissue slides were represented as graphs to capture spatial context and tumour heterogeneity. The proposed GNPC score was developed and validated on 1,949 patients from two independent cohorts.

Results

The GNPC score successfully stratified patients in both cohorts, achieving statistically significant results for distant metastasis (p < 0.001), overall survival (p < 0.01) and local recurrence (p < 0.05). Further downstream analyses of morphological characteristics, molecular features, and genomic profiles identified several factors associated with GNPC score-based risk groups.

Conclusion

The proposed digital score demonstrates robust predictive performance for distant metastasis, overall survival, and local recurrence in NPC. These findings highlight its potential to assist with personalised treatment strategies and improve clinical management for NPC.
Early Imaging Identification of Osteoradionecrosis and Classification Using the Novel ClinRad System: Results from A Retrospective Observational Cohort
Authors:   MD Anderson Head and Neck Cancer Symptom Working Group; Collaborators, Rigert Jillian , Kaffey Zaphanlene , Belal Zayne , Tripuraneni Lavanya , Humbert-Vidan Laia , Sahli Ariana , Attia Serageldin , Hutcheson Katherine A. , Watson Erin , Hope Andrew , Dede Cem , Kiat-amnuay Sudarat , Walji Muhammad , Mohamed Abdallah S.R. , Sandulache Vlad C. , Fuller Clifton David , Lai Stephen Y. , Moreno Amy
Published: February 2025

Objective

Osteoradionecrosis of the jaw (ORNJ) is a chronic radiation-associated toxicity that lacks standardized classification criteria and treatment guidelines. Understanding early signs of tissue injury could help us better predict, prevent, and conservatively manage ORN. Our primary aims were to identify initial clinically-detected signs of ORN, determine the frequency of imaging-detected ORNJ, and validate the ability to classify cases using the novel system, ClinRad.

Study Design

A retrospective electronic health record review of 91 patients treated for head and neck cancer at The University of Texas MD Anderson Cancer Center with suspected ORN was performed by an Oral Medicine specialist to identify initial signs of ORN. Patients who received reirradiation to the head and neck or did not have enough evidence of ORN were excluded. A descriptive analysis was performed.

Results

51 patients met the inclusion criteria. Half (53%) presented with imaging findings and exposed bone. Imaging findings in the absence of bone exposure were identified in 37%, of which disease progression was observed in 26%. All cases were classifiable using ClinRad.

Conclusion

Subclinical signs of bony changes consistent with ORN may be evident on imaging without exposed bone, supporting the use of imaging surveillance. ClinRad provided a mechanism to classify all cases at early onset.

Data availability statement

Anonymized data for the reported analyses is made publicly available on figshare at 10.6084/m9.figshare.28292186.

Reporting guideline compliance statement

In accordance with the EQUATOR Network (Enhancing the QUAlity and Transparency Of health Research) guidance, we have utilized the RECORD checklist, a guideline for the “REporting of studies Conducted using Observational Routinely-collected health data” (Benchimool El at al., 2015) The RECORD checklist is provided as a Supplementary file and available via 10.6084/m9.figshare.28292219.

Data was anonymized in accordance with the EQUATOR guideline “Preparing raw clinical data for publication: guidance for journal editors, authors, and peer reviewers” (Hrynaszkiewicz I et al., 2010).
Efficient protein structure generation with sparse denoising models
Authors: Jendrusch Michael , Korbel Jan O.
Published: February 2025

Generating designable protein backbones has become an integral part of machine learning-assisted approaches to protein design. Together with sequence design and structure predictor-based filtering, it forms the backbone of the computational protein design pipeline. However, current protein structure generators face important limitations for large proteins and require retraining for protein design tasks unseen during model training. To address the first issue, we introducesalad, a family ofsparseall-atomdenoising models for protein backbone generation. Our models are notably faster than the state-of-the-art while matching or improving designability and diversity, and generate designable structures for protein lengths up to 1,000 amino acids. To address the second issue, we combinesaladwith structure-editing, a strategy for expanding the capability of protein denoising models to unseen tasks. We apply our approach to a variety of protein design tasks, from motif-scaffolding to multi-state protein design, demonstrating the flexibility ofsaladand structure-editing.
Fatty Acid Transport Protein-2 (FATP2) Inhibition Enhances Glucose Tolerance through α-Cell-mediated GLP-1 Secretion
Authors: Khan Shenaz , Gaivin Robert J. , Liu Zhiyu , Li Vincent , Samuels Ivy , Son Jinsook , Osei-Owusu Patrick , Garvin Jeffrey L. , Accili Domenico , Schelling Jeffrey R.
Published: February 2025

Type 2 diabetes affects more than 30 million people in the US, and a major complication is kidney disease. During the analysis of lipotoxicity in diabetic kidney disease, global fatty acid transport protein-2 (FATP2) gene deletion was noted to markedly reduce plasma glucose in db/db mice due to sustained insulin secretion. To identify the mechanism, we observed that islet FATP2 expression was restricted to α-cells, and α-cell FATP2 was functional. Direct evidence of FATP2KO-induced α-cell-mediated GLP-1 secretion included increased GLP-1-positive α-cell mass in FATP2KO db/db mice, small molecule FATP2 inhibitor enhancement of GLP-1 secretion in αTC1-6 cells and human islets, and exendin[9-39]-inhibitable insulin secretion in FATP2 inhibitor-treated human islets. FATP2-dependent enteroendocrine GLP-1 secretion was excluded by demonstration of similar glucose tolerance and plasma GLP-1 concentrations in db/db FATP2KO mice following oral versus intraperitoneal glucose loading, non-overlapping FATP2 and preproglucagon mRNA expression, and lack of FATP2/GLP-1 co-immunolocalization in intestine. We conclude that FATP2 deletion or inhibition exerts glucose-lowering effects through α-cell-mediated GLP-1 secretion and paracrine β-cell insulin release.

Graphical abstract
Ancient human extinction risk: Implications from high-precision computation and fossil evidence
Authors: Zhou Sumei , Zhou Yiwen , Di Vincenzo Fabio , Manzi Giorgio , Hu Wangjie , Hao Ziqian , Pan Yi-Hsuan , Li Haipeng
Published: February 2025

Reconstructing ancient population size dynamics is essential for understanding human evolution. Using the fast infinitesimal time coalescent process (FitCoal), we identified a severe population bottleneck approximately 930,000 years ago, which pushed human ancestors to near extinction but left only subtle genomic traces in present-day humans. Detecting this signal requires precise computational methods. Compared withmushiand ten billion simulations performed usingmsprime, FitCoal provides the fastest and most accurate inference of expected branch lengths across site frequency spectrum categories. Independent fossil and paleoclimate records corroborate the timing and evolutionary impact of this bottleneck, highlighting the need to integrate genetic, paleontological, and environmental evidence. These findings refine our understanding of hominin evolution and the demographic events that shaped modern human ancestry.
A systematic review of the factors affecting sperm binding and release from the oviduct using in vitro experimental animal models
Authors: Sitali Muloongo C. , Chelenga Madalitso
Published: February 2025

Background

After insemination, spermatozoa bind to epithelial cells of the isthmic part of the oviduct to form a functional sperm reservoir responsible for regulating sperm viability and capacitation prior to the ovulation signal that triggers its release. Understanding this information is essential for improving outcomes of in-vitro fertilization programs and semen-sorting process.

Objective

This review aims to provide a comprehensive systematic assessment of the literature on the non-steroid hormone factors involved in sperm binding and release from the sperm reservoir in animal species in in-vitro experiments.

Methods

PubMed, Web of Science, and Google Scholar databases were searched, and eligible studies included articles published between 1stJanuary 1990 and 31stJuly 2024 reporting molecules involved in sperm binding and release from the oviduct, as well as the impact of released sperm on in-vitro fertilization.

Results

Sperm and oviducts from bovine, porcine, canine, camelid, equine, hamster and ovine were used and different culture systems such as epithelial explants, monolayers, and ex-vivo oviducts were established. The behaviour of sperm in the oviductal epithelium was influenced by several factors such as carbohydrates and their derivatives, seminal plasma proteins, glycoproteins, tyrosine phosphorylation of sperm, endocannabinoids, sex-sorting and glycosaminoglycans. Further, the seminal plasma proteins increased the binding ability of epididymal sperm to the oviductal explants.

Conclusions

Future studies should focus on designing comparative research across various species. This may aid in identifying species-specific adaptations and conserved mechanisms in sperm-oviduct interactions, which may be helpful for conservation and breeding efforts.

Summary Sentence

Herein we review factors that affect sperm binding and release from the oviductal epithelial cells in-vitro that has a direct effect on the fertilizing potential of sperm
Genome-wide associations spanning 194 in-hospital drug dosage change phenotypes highlight diverse genetic backgrounds in concurrent drug therapy
Authors: Henriksen Alexander Pil , Leal Rodríguez Cristina , Currant Hannah , Louloudis Ioannis , Biel Jorge Hernansanz , Herrero-Zazo Maria , Birney Ewan , Hansen Thomas Folkmann , Mazzoni Gianluca , Haue Amalie Dahl , Bundgaard Henning , Erikstrup Christian , Dinh Khoa Manh , Quinn Liam , Bruun Mie Topholm , Hjalgrim Henrik , Sørensen Erik , Mikkelsen Christina , Schwinn Michael , Vestager Pedersen Ole Birger , Ullum Henrik , Ostrowski Sisse Rye ,   DBDS Genomic Consortium, Banasik Karina , Brunak Søren
Published: February 2025

As populations get older and medicine consumption rises, the rate of concurrent drug use and polypharmacy among patients is increasing. Polypharmacy is known to complicate therapy and increase the risk of drug-drug interactions, the individuality of which remain largely unexplored. Here, we perform a series of genome-wide association studies to identify variants associated with dosage changes during episodes of concurrent drug therapy. We extracted in-hospital drug prescription records from 847,537 patients in a population-wide Danish hospital cohort. Using imputed genotype data from the Copenhagen Hospital Biobank and the Danish Blood Donor Study we then performed a series of genome-wide association analyses across 194 drug pair phenotypes fulfilling selection criteria. We identified 51 genome-wide significant (p < 5e-08) loci, 49 so far unreported in any genome-wide association studies, associated with dosage changes across 42 different drug pair phenotypes. 49 of the identified loci were unique to the respective drug pairs. Through annotation of the identified loci, expression quantitative trait loci analyses, and gene-based tests we found links to 57 distinct genes, several of which have previously been associated with disease.

This study identifies genes that may modulate response to drug therapy in the context of polypharmacy. Our findings reveal distinct patterns of genetic variation across different drug pairs, suggesting a diverse set of genes involved in drug efficacy and drug response. This study may give a better understanding of the individuality of such mechanisms and may aid the development personalized treatment approaches.
Echocardiography can accurately estimate pulmonary artery wedge pressure without left atrial volume information – diagnostic and prognostic performance
Authors: Lindow Thomas , Manouras Aristomenis , Strange Geoff , Lindqvist Per , Playford David , Bech-Hanssen Odd , Ugander Martin
Published: February 2025

Background

A quantitative estimate of pulmonary artery wedge pressures (PAWP) can be obtained using echocardiography, but including left atrial (LA) volume (ePAWP-LA) in the estimation may be misleading. We aimed to derive and validate a new estimate without LA volume information (ePAWP-NOLA) and compare its performance to the ASE/EACVI algorithms for diastolic dysfunction.

Methods

ePAWP-NOLA was derived and validated in separate datasets of patients who had undergone right heart catheterization and echocardiography. Prognosis was assessed in the validation cohort and the National Echocardiography Database Australia (NEDA) using Cox regression adjusted for age, sex and left ventricular ejection fraction (LVEF).

Results

In the derivation cohort (60±15 years, 40% males, 31% with LVEF<50%), ePAWP-NOLA was derived from mitral (E), and pulmonary vein systolic (S) and diastolic (D) Doppler velocities (n=134, mean difference±SD vs PAWP: 0.0±5.5 mmHg). In the validation cohort (n=116, 51±14 years, 69% males, 89% with LVEF<50%), PAWP agreed with both ePAWP-NOLA and ePAWP-LA (difference 1.3±6.1, 3.2±6.3 mmHg). PAWP>15 mmHg was accurately detected by both ePAWP-NOLA and ePAWP-LA (area under the curve (AUC): 0.84 [0.76–0.92], 0.80 [0.72–0.88]). AUC for the ASE/EACVI algorithm was lower ([0.69 [0.61–0.77]). ePAWP-NOLA and ePAWP-LA correlated with right ventricular afterload, associated with death or implantation of left ventricular assist device (hazard ratio: 1.09 [1.02–1.16], 1.07 [1.02–1.14]), and with cardiovascular death in NEDA (n=38,844, hazard ratio: 1.08 [1.07–1.09], 1.08 [1.07–1.09]).

Conclusions

ePAWP-NOLA has diagnostic and prognostic performance comparable to ePAWP-LA, and improved diagnostic performance compared to the ASE/EACVI diastolic dysfunction algorithm.
Nectriatides with no antifungal activity bind to ergosterol and potentiate the antifungal activity of amphotericin B againstCandida albicans
Authors: Kobayashi Keisuke , Miyake Ryosuke , Nagai Kenichiro , Sato Yukino , Seki Reiko , Sakai-Kato Kumiko , Nishimura Shinichi , Ohshiro Taichi , Tomoda Hiroshi
Published: February 2025

Fungal cyclotetrapeptide nectriatide and its synthetic linear derivatives (nectriatide-based compounds, NCTs), having no antifungal activity, potentiated antifungal activity of amphotericin B (AmB) againstCandida albicans. The mechanism of action was investigated using fluorescein-conjugated and biotin-tagged probes. Microscopy revealed fluorescent-probe localization at theC. albicanscell membrane. The biotinyl probe binding assay towards membrane lipids showed the highest affinity for ergosterol but no affinity for cholesterol. Ergosterol binding was confirmed by a liposome disruption assay. LC-MS quantification of AmB inC. albicansrevealed that NCTs increased AmB binding toC. albicans. These results indicate that NCTs bind to ergosterol on the fungal plasma membrane, subsequently localizing AmB, explaining the observed potentiation of AmB fungicidal activity.
Information Shielding Through Neural Deactivation: A Fundamental Mechanism of Human Information Processing
Authors: He Zhenhong , Du Yifan , Fu Ziqi , Zheng Youcun , Muhlert Nils , Sahakian Barbara , Elliott Rebecca
Published: February 2025

Information processing is a core issue in cognitive neuroscience. The brain can either accept or shield information. However, information shielding has traditionally been regarded as a byproduct of other cognitive processes that prepare brain areas for activation, with the accompanying brain deactivation seen as merely supportive. Here, we offer an alternative perspective, demonstrating that people can directly perform information shielding without engaging other cognitive processes. Using information shielding as a novel investigative lens, we provide direct evidence that deactivation serves as a primary mechanism in its own right. We found that information shielding was characterized by a deactivation-dominant neural dynamic, with initial executive control region activation giving way to increased sensory region deactivation, especially after a 3-second boundary. Neural decoding results further confirmed this deactivation trend. This deactivation pattern was consistent across both auditory and visual modalities. Furthermore, non-invasive brain stimulation demonstrated a causal relationship between the deactivation pattern and information shielding, and we found that this deactivation mechanism extended to general unnecessary information processing, regardless of whether the necessity was determined objectively or subjectively. This challenges the conventional emphasis on activation as the primary mode of information processing and opens new fundamental avenues for understanding inhibitory cognitive processes.
The conserved N-terminal SANT1-binding domain (SBD) of EZH2 Regulates PRC2 Activity
Authors: Patriotis Agata L. , Soto-Feliciano Yadira , Barrows Douglas W. , Khan Laiba , Leboeuf Marylene , Lund Peder J. , Marunde Matthew R , Djomo Annaelle , Keogh Michael-Christopher , Carroll Thomas S. , Garcia Benjamin A. , Soshnev Alexey A. , Allis C. David
Published: February 2025

Polycomb group proteins maintain gene expression patterns established during early development, with Polycomb Repressive Complex 2 (PRC2) methyltransferase a key regulator of cell differentiation, identity and plasticity. Consequently, extensive somatic mutations in PRC2, including gain- or loss- of function (GOF or LOF), are observed in human cancers. The regulation of chromatin structure by PRC2 is critically dependent on its EZH2 (Enhancer of Zeste Homolog 2) subunit, which catalyzes the methylation of histone H3 lysine 27 (H3K27). Recent structural studies of PRC2 revealed extensive conformational changes in the non-catalytic EZH2 N-terminal SANT-Binding Domain (SBD) during PRC2 activation, though the functional significance remains unclear. Here, we investigate how the SBD regulates PRC2 function. The domain is highly conserved in metazoans, dispensable for PRC2 assembly and chromatin localization, yet required for genome-wide histone H3K27 methylation. Further, we show that an intact SBD is necessary for the proliferation of EZH2- addicted lymphomas, and its deletion in the presence ofEZH2GOF mutations inhibits cancer cell growth. These observations provide new insights to the regulation of PRC2 activity in normal development and malignancy.
Diploidy confers genomic instability inSchizosaccharomyces pombe
Authors: Park Joshua M. , Pinski Daniel F. , Forsburg Susan L.
Published: February 2025

Whole genome duplication, or polyploidy, has been implicated in driving genome instability and tumorigenesis. Recent studies suggest that polyploidy in tumors promotes cancer genome evolution, progression, and chemoresistance resulting in worse prognosis of survival. The mechanisms by which whole genome duplications confer genome instability are not yet fully understood. In this study, we useSchizosaccharomyces pombe(fission yeast) diploids to investigate how whole genome duplication affects genome maintenance and response to stress. We find thatS. pombediploids are sensitive to replication stress and DNA damage, exhibit high levels of loss of heterozygosity, and become dependent on a group of ploidy-specific lethal genes for viability. These findings are observed in other eukaryotic models suggesting conserved consequences of polyploidy. We further investigate ploidy-specific lethal genes by depleting them using an auxin-inducible degron system to elucidate the mechanisms of genome maintenance in diploids. Overall, this work provides new insights on how whole genome duplications lead to genome instability.
The distribution of the number of mutations in the genealogy of a sample from a single population
Authors: Fu Yun-Xin
Published: February 2025

The numberKof mutations in the genealogy of a sample ofnsequences from a single population is one essential summary statistics in molecular population genetics and is equal to the number of segregating sites in the sample under the infinitesites model. Although its expectation and variance are the most widely utilized properties, its sampling formula (i.e., probability distribution) is the foundation for all explorations related toK. Recently, it has been established thatKis subject to the Central Limit Theorem, and thus has asymptotic normality. However, due to its slow convergence to normality, the finite-sample distribution remains indispensable. Although an analytic sampling formula exists, its numerical application is limited due to susceptibility to error propagation. This paper presents a new sampling formula forKin a random sample of DNA sequences from a neutral locus without recombination, taken from a single population evolving according to the Wright-Fisher model with a constant effective population size, or the constant-in-state model, which allows the effective population size to vary across different coalescent states. The new sampling formula is expressed as the sum of the probabilities of the various ways mutations can manifest in the sample genealogy and achieves simplicity by partitioning mutations into hypothetical atomic clusters that cannot be further divided. Under the Wright-Fisher model with a constant effective population size, the new sampling formula is closely analogous to the celebrated Ewens’ sampling formula for the number of distinct alleles in a sample. Numerical computation using the new sampling formula is accurate and is limited only by the burden of enumerating a large number of partitions of a largeK. However, significant improvement in efficiency can be achieved by prioritizing the enumeration of partitions with a large number of parts.
Basin-scale dynamics and enrichment-enabled genomics of marine nitrifiers: seasonality, niches, interactions, and genomic uniqueness
Authors: Kim Sookyoung , D'Agostino Elisa , Needham David M
Published: February 2025

Nitrification occurs widely from the deep sea to animal holobionts, but the eco-evolutionary forces shaping the niches and dynamics of the lineages of the chemoautotrophic bacteria and archaea responsible remain largely unknown. To make strides towards this goal in a rapidly changing, exemplar marine ecosystem, the Baltic Sea, we studied basin-scale nitrifier spatio-temporal dynamics, coupled with enrichment-enabled comparative genomics. Based on metagenomes and rRNA gene sequencing, we found nitrifiers to be persistently relatively abundant throughout deep depths (>25 m), and from late-fall to spring in surface waters, as revealed by twice-weekly sampling across two years in the southwest Baltic Sea surface waters. In these surface waters, we observed time-lagged dynamics between ammonia- and nitrite-oxidizers, which were positively correlated with nitrite, nitrate, and diverse other prokaryotes, and negatively correlated with day length, light, and chlorophyll. For the dominant nitrifiers, ammonia-oxidizing archaea (AOA), we enriched five novel species including the dominant deep Baltic Sea species, and obtained genomes from all dominant AOA phylotypes. Among these genomes, which enabled fine-scale niche-differentiation, we observed a high degree of gene conservation, with most differences related to genes associated with interactions with the external environment, including genes involved in signal transduction, cell wall/membrane biogenesis, and inorganic ion transport, indicating these may be the primary drivers of strain-variability. We also observed differences in nitrogen and phosphorus metabolism between two dominant surface types. Together our study provides key insights into the niche of nitrifiers, and begins the process of understanding the mechanisms and functional implications of these patterns.
From strange-quark tagging to fragmentation tagging with machine learning
Authors: Kats Yevgeny , Ofir Edo
Published: February 2025

We apply advanced machine learning techniques to two challenging jet classification problems at the LHC. The first is strange-quark tagging, in particular distinguishing strange-quark jets from down-quark jets. The second, which we term fragmentation tagging, involves identifying the fragmentation channel of a quark. We exemplify the latter by training neural networks to differentiate between bottom jets containing a bottom baryon and those containing a bottom meson. The common challenge in these two problems is that neither quark lifetimes and masses nor parton showering provide discriminating tools, making it necessary to rely on differences in the distributions of the hadron types contained in each type of jet and their kinematics. For these classification tasks, we employ variations of graph attention networks and the Particle Transformer, which receive jet and all constituent properties as inputs. We compare their performance to a simple multilayer perceptron that uses simple variables. We find that the more sophisticated architectures do not improve s-quark versus d-quark jet differentiation by a significant amount, but they do lead to a significant gain in b-baryon versus b-meson jet differentiation.

Published by the American Physical Society
2025
Asymptotically conformal color-flavor-locked quark matter within a nonlocal chiral quark model
Authors: Ivanytskyi Oleksii
Published: February 2025

We propose a three-flavor nonlocal Nambu–Jona-Lasinio model of quark matter with the scalar attractive, vector repulsive and diquark pairing interaction channels. The model is treated within the separable approximation to obtain the equation of state of cold quark matter. The analysis of the high density asymptotics of the model allows us to conclude about its qualitative agreement with the perturbative quantum chromodynamics (QCD). Particularly, a color superconducting color-flavor-locked (CFL) state is found to be the ground one at asymptotically high densities. The conformal limit of speed of sound and dimensionless interaction measure are also shown to be reached from below and above, respectively. The model is applied to modeling neutron stars (NSs) within the scenario of early quark deconfinement triggered by the gravitational instability of the NS matter due to the Bose-Einstein coordinate of a spin-color-flavor singlet three-diquark bound state, the light sexaquark, stable against the weak and strong decays. A conservative estimate of the sexaquark mass based on the most up-to-date results from QCD sum rules and a constituent quark model implies an early quark deconfinement with the onset mass below 1M⊙. The scenario is shown to be consistent with the present observational constraints on the mass-radius relation and tidal deformability of NSs. Given the fact that the proposed model by construction exhibits an asymptotically conformal behavior, we consider the question about approximately conformal quark matter in NSs. We report a nonperturbative energy density range, which is inaccessible in NSs and where the speed of sound and dimensionless interaction measure of the CFL quark matter simultaneously attain the conformal values.

Published by the American Physical Society
2025
Implications of latest NICER data for the neutron star equation of state
Authors: Brandes Len , Weise Wolfram
Published: February 2025

As an update to our previously performed Bayesian inference analyses of the neutron star matter equation-of-state and related quantities, the additional impact of the recently published NICER data of PSR J0437-4751 is examined. Including the mass and radius distributions of this pulsar in our database results in modest shifts from previously inferred median posterior values of radii R and central densities nc for representative 1.4M⊙ and 2.1M⊙ neutron stars: radii are reduced by about 0.2–0.3 km to values of R1.4=12.1±0.5  km and R2.1=11.9−0.6+0.5  km (at the 68% level), and central densities increase slightly to values of nc(1.4M⊙)/n0=2.8±0.3 and nc(2.1M⊙)/n0=3.8−0.7+0.6 (in units of equilibrium nuclear matter density, n0=0.16  fm−3)—i.e., they still fall below five times nuclear saturation density at the 68% level. As a further significant result, the evidence established by analyzing Bayes factors for a trace anomaly measure, Δ=1/3−P/ϵ<0, inside heavy neutron stars is raised to .

Published by the American Physical Society
2025
Testing Bell inequalities and probing quantum entanglement at CEPC
Authors: Wu Youpeng , Jiang Ruobing , Ruzi Alim , Ban Yong , Yan Xueqing , Li Qiang
Published: February 2025

We study quantum entanglement and test violation of Bell-type inequality at the Circular Electron Positron Collider (CEPC), which is one of the most attractive future collides. It is a promising particle collider designed to search new physics, make Standard Model (SM) precision measurements, and serving as a Higgs factory. Our study is based on a fast simulation of the Z boson pair production from Higgs boson decay at s=250  GeV. The detector effects are also included in the simulation. The spin density matrix of the joint ZZ system is parametrized using irreducible tensor operators and reconstructed from the spherical coordinates of the decay leptons. To test Bell inequalities, we construct observable quantities for the H→ZZ* process in CEPC by using the Collins-Gisin-Linden-Massar-Popescu (CGLMP) inequality, whose value is determined from the density matrix of the Z boson pairs. The sensitivity of the Bell inequality violation is observed with more than 1σ and the presence of the quantum entanglement is probed with more than 2σ confidence level.

Published by the American Physical Society
2025
Deformation of matrix geometry via Landau level evolution
Authors: Hasebe Kazuki
Published: February 2025

We propose a scheme for the construction of deformed matrix geometries using Landau models. The Landau models are practically useful tools to extract matrix geometries. The level projection method however cannot be applied straightforwardly to the Landau models on deformed manifolds, as they do not generally exhibit degenerate energy levels. We overcome this problem by exploiting the idea of spectral flow. Taking a symmetric matrix geometry as a reference point of the spectral flow, we evolve the matrix geometry by deforming the Landau model. In this process, unitarity is automatically preserved. The explicit matrix realization of the coordinates is derived mechanically even for a nonperturbative deformation. We clarify basic properties of the deformed matrix geometries through a concrete analysis of the nonrelativistic and relativistic Landau models on expanding two-sphere and elongating ellipsoid. The obtained ellipsoidal matrix geometries show behaviors quantitatively different in each Landau level, but qualitatively similar to their classical counterpart. We also numerically investigate the differences between the ellipsoidal matrix geometry and the fuzzy ellipsoid.

Published by the American Physical Society
2025
Probing celestial energy and charge correlations through real-time quantum simulations: Insights from the Schwinger model
Authors: Barata João , Mukherjee Swagato
Published: February 2025

Motivated by recent developments in the application of light-ray operators (LROs) in high energy physics, we propose a new strategy to study correlation functions of LROs through real-time quantum simulations. We argue that quantum simulators provide an ideal laboratory to explore the properties LROs in lower-dimensional quantum field theories. This is exemplified in the 1+1-d Schwinger model, employing tensor network methods, focusing on the calculation of energy and charge correlators. Despite some challenges in extracting the necessary correlation functions from the lattice, the methodology used can be extended to real quantum devices.

Published by the American Physical Society
2025
Langdon effect in the realm of extreme ultraviolet source plasmas
Authors: Gonzalez J. , Sheil J.
Published: February 2025

Already some years ago, Langdon [] proposed that inverse bremsstrahlung absorption in plasmas drives free electrons into non-Maxwellian distributions. Radiation-hydrodynamic simulations of plasma-based light sources, however, often (implicitly) assume Maxwellian-distributed electrons. In this paper, we quantify the effect of non-Maxwellian distributions on laser absorption and thermal conduction in laser-driven plasma light sources. For irradiation conditions Ilasλlas2∈[1011,1013]Wcm−2µm2 and plasma parameters Zeff/Te∈[0.2,0.6]eV−1, the electron distributions are predicted to be super-Gaussian of order m≃2.2–2.4. As a result, laser absorption is calculated to be 10–20% lower than plasmas with Maxwellian-distributed electrons. A ∼10–30% reduction of the Spitzer-Härm thermal conduction coefficient is also predicted.

Published by the American Physical Society
2025