bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial/Ethnic Associations with Morbidity and Mortality in Adults with Acute Traumatic Cervical Spinal Cord Injury
Authors: Elsamadicy Aladine A. , Belkasim Selma , Serrato Paul , Sadeghzadeh Sina , Ghanekar Shaila D. , Khalid Syed I. , Lo Sheng-fu Larry , Sciubba Daniel M.
Published: January 2025

Study Design.

Retrospective cohort study

Objective.

This study aimed to investigate the association of race with morbidity and mortality in acute cervical spinal cord injury (cSCI) patients.

Summary of Background Data.

Racial disparities in spine surgery are associated with adverse outcomes, however, the impact of race on cSCI is understudied.

Methods.

We retrospectively reviewed the American College of Surgeons Trauma Quality Programs database to compare outcomes for acute cSCI patients between racial/ethnic identities: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic/Latino (HIS), and other (OTH). Demographics, comorbidities, injury type, treatment modality, and adverse events (AEs) were assessed. Multivariable logistic regression was used to identify independent predictors of AEs, non-routine discharge (NRD), and in-hospital mortality.

Results.

There were 71,048 patients stratified by race/ethnicity: 44,639 (62.8%) NHW, 13,555 (19.1%) NHB, 5,820 (8.2%) HIS, and 7,034 (9.9%) OTH. NHB and HIS-identifying patients had the greatest rates of any AE (NHW: 20.7% vs. NHB: 25.0% vs. HIS: 24.6% vs. OTH: 22.0%, P<0.001) and the longest mean length of stay (NHW: 11.3±13.5 d vs. NHB: 15.5±20.2 d vs. HIS: 15.0±20.5 d vs. OTH: 12.6±17.5 d, P<0.001). NRDs were lowest for HIS-identifying patients (NHW: 74.8% vs. NHB: 75.5% vs. HIS: 69.5% vs. OTH: 75.4%, P<0.001), while in-hospital mortality was lowest for NHB-identifying patients (NHW: 12.8% vs. NHB: 10.1% vs. HIS: 12.4% vs. OTH: 13.4%, P<0.001). On multivariable analyses, NHB (OR: 1.16, P<0.001), HIS (OR: 1.22, P<0.001), and OTH (OR: 1.14, P=0.004) cohorts had significantly increased odds of AEs. The NHB cohort had significantly increased odds (OR: 1.25, P<0.001), while the HIS cohort had significantly decreased odds (OR: 0.78, P=0.001) of NRD. Only the NHB cohort had significantly decreased odds of in-hospital mortality (OR: 0.69, P<0.001).

Conclusion.

Our study suggests racial disparities in outcomes and discharge disposition for acute cSCI patients.
Safety of acrylic intraocular lenses in patients with methyl methacrylate allergy
Authors: Khalil Rana , Lockington David
Published: January 2025

Introduction:

Increased rates of methyl methacrylate (MMA)-induced contact dermatitis correspond to widespread usage in biomedical, dental, and beauty industries. There have been no publications of acrylic intraocular lens (IOL)-related hypersensitivities.

Patient and Clinical Findings:

A patient with MMA allergy queried if acrylic IOLs were safe for her cataract surgeries. We performed a literature review to answer this question. Only 1 report described cataract surgery in known MMA allergy through avoidance strategies and silicone IOL use (currently unavailable in the United Kingdom). While acrylic monomers are responsible for MMA allergy, they are nonirritant and nonallergenic once polymerized (as with acrylic IOLs). IOL manufacturers advised extremely low likelihood of reactions, with taping IOLs to skin for reassurance proposed anecdotally.

Diagnosis, Intervention, and Outcomes:

After uneventful IOL patch testing and informed consent, our patient underwent sequential cataract surgeries (Rayner RAO800C and RAO200E), without any postoperative issues.

Conclusions:

Acrylic IOLs should not cause any adverse reaction in patients with MMA allergies. This was our clinical experience, which should reassure patients and clinicians.
Evaluative Research on Psychodynamic Therapy: Foundations and Recent Advances
Authors: Guénolé Fabian
Published: January 2025

Psychodynamic therapy (PDT), a technical adaptation of psychoanalysis, is one of the most widely practiced forms of psychotherapy, making evaluative research on it essential. Although research on PDT has been ongoing for several decades, theoretical and practical challenges initially hindered the adoption of evidence-based medicine standards in such research, a shift that has largely taken place over the past 20 years. This article reviews the evolution of evaluative research on PDT for mental disorders in adults, with a focus on those with complex conditions. Since the first prospective evaluative studies in the 1950s, an accumulating body of knowledge—including cohort studies, randomized controlled trials, and meta-analyses—has established PDT as an evidence-based treatment for common mental disorders such as depression, anxiety, somatic symptoms and related disorders, and personality disorders, as well as complex mental disorders involving combinations of these conditions. There is also evidence supporting PDT’s usefulness in treating anorexia nervosa and opioid dependence, along with some findings suggesting its potential use for schizophrenia spectrum disorders, bulimia nervosa, and posttraumatic stress disorder. Recent studies indicate that PDT can serve as a personalized treatment, promoting deep and lasting psychopathological changes in patients with severe, complex, and chronic mental disorders, involving specific technical features and mechanisms of change. These findings support the inclusion of PDT in mental health care policies and training, while ongoing research continues to explore its optimal treatment parameters.
Licensure Actions Against Psychiatric Clinicians: A Cohort Analysis of National Practitioner Database Reports
Authors: Dadlani Akanksha , Mills Jeffrey A. , Strawn Jeffrey R.
Published: January 2025

Objective:

To examine trends and predictors of administrative actions against psychiatric clinicians’ licenses between 2002 and 2022.

Methods:

Data from the National Practitioner Data Bank (NPDB) identified 6400 disciplinary actions against psychiatric clinicians’ licenses. Linear trend models assessed the trends of disciplinary actions across mental/physical health, licensing/legal issues, and unprofessional conduct. A first-order autoregressive model with a time indicator interaction term evaluated structural breaks (ie, a sudden or gradual change in the characteristics of data in a time series). Predictors of claims were assessed using logistic regression.

Results:

Since 2002, disciplinary actions related to clinicians’ mental/physical health (P=0.004) and licensure/legal issues (P=0.018) have decreased, while actions related to unprofessional conduct remained unchanged (P=0.358). Declines emerged in 2012 for mental/physical health (break coefficient −0.367; P=0.026) and in 2009 for unprofessional conduct (break coefficient −0.199; P=0.013). Clinicians facing disciplinary actions related to physical/mental health were significantly younger than those with legal/licensure issues (P<0.001). While the average age remained stable for mental/physical health-related actions, the average age increased for actions related to licensure/legal claims and unprofessional conduct.

Conclusions:

The decrease in disciplinary actions related to physical/mental health may reflect better access and acceptance of treatment of clinicians, while the reduction in licensure/legal actions may indicate policy shifts. Findings regarding age underscore the need for enhanced support for mid and late-career clinicians to promote lifelong learning and practice.
How Quickly Multiple Medication Use Can Start: A Medication for Every Complaint on the First Visit Compromising the Ability to Determine Cause and Effect
Authors: Preskorn Sheldon H. , Terry Amy
Published: January 2025

This article presents a case demonstrating that multiple medication use can begin on the first outpatient visit if the prescriber makes multiple psychiatric diagnoses and then feels the need to treat each diagnosis with a different central nervous system active medication labeled for each indication. This approach poses potential problems. First, a single drug or perhaps 2 drugs, in this case, may have been sufficient as initial and perhaps final treatment. Second, the prescriber cannot tell which drug(s) is/are producing either a beneficial or an ﻿adverse effect. This approach may stem from prescribers thinking that if they have made a diagnosis then they need to treat it with a drug labeled for or clinically used to treat that indication rather than taking a more conservative approach. However, such an approach adversely affects the ability to determine cause-and-effect relationships and hence adversely affects the ability to determine the best way to revise the treatment going forward.
Because of γ-Aminobutyric Acid-Glutamate Imbalance, Gut Microbiota, or Both? Delirious Mania Induced by Ciprofloxacin Use: A Case Report and Review of the Literature
Authors: Sakalli Kani Ayşe , Süleyman Ayşe
Published: January 2025

Ciprofloxacin is an antibiotic from the fluoroquinolone group that is frequently used in many clinical practices. In addition to its peripheral neuropathic side effects, it is an antibiotic that can pass through the blood-brain barrier due to its lipophilic features and cause rare central nervous system symptoms. Although cases of neuropsychiatric symptoms developing after treatment with ciprofloxacin have been reported in the literature, the number of reports of manic episodes after ciprofloxacin use is limited, and there have been no reports of delirious mania developing after ciprofloxacin use until the case presented in this report. Here we report the case of a 52-year-old woman who developed manic symptoms after receiving ciprofloxacin, which evolved into delirious mania. Clinical factors that may predispose to neurotoxicity are discussed and compared with features of the mania cases in the literature. The underlying neurobiological mechanisms are also reviewed.
Antifungal potential of silver nanoparticles stabilized with the flavonoid naringenin
Authors: Luiz Correa Jakeline , Kikuchi Larissa , Ferreira Deisiany Gomes , Gomes da Silva Fabiana , de Oliveira Kelly Mari P. , de Souza Monique , Baesso Mauro Luciano , Yamanishi Gustavo , Urbano Alexandre , Negri Melyssa
Published: January 2025

Graphical abstract

Biosynthesis and antifungal activity of silver nanoparticles stabilized with naringenin.
Seo1p, a high affinity, plasma membrane transporter of the γ-Glu-met dipeptide in yeasts and fungi
Authors: Dubey Pratiksha , Ahmad Md Shabbir , Laxman Sunil , Bachhawat Anand K
Published: January 2025

γ-Glu dipeptides are ubiquitous in nature, and yet their metabolism and transport are poorly understood. Here we investigate this using the dipeptide γ-Glu-met inSaccharomyces cerevisiae. γ-Glu-met was efficiently utilized byS. cerevisiaeand its degradation was dependent on both the glutathione degrading cytosolic Dug2p/Dug3p complex, and the vacuolar Ecm38p. Using a transcriptomics approach, followed by a genetic screen, we identified Seo1p, an orphan transporter of yeast, as the transporter of γ-Glu-met. Uptake studies confirmed Seo1p as a high affinity (Km =48uM), highly specific transporter of γ-Glu-met since other analogs like n-Glu-met, γ-Glu-leu, γ-Glu-cys, γ-Glu-met-gly, methionine and methionine sulfoxide were not transported by Seo1p. Candida spp. also encoded a functional Seo1p. A second transporter, Opt2p, identified in the screen, was also investigated. However, Opt2p was not primarily involved in γ-Glu-met uptake. Its deletion affected vacuolar morphology, that interfered with the degradation of the peptide through Ecm38p. These studies demonstrate how organisms have evolved dedicated pathways for the uptake of these unusual peptides.
Evidence for evolution of a new sex chromosome within the Marchantiales haploid-dominant plant lineage
Authors: Fu Yuan , Zhang Xiaoxia , Zhang Tian , Sun Wenjing , Yang Wenjun , Shi Yajing , Zhang Jian , He Qiang , Charlesworth Deborah , Jiao Yuannian , Chen Zhiduan , Xu Bo
Published: January 2025

Sex chromosomes have evolved independently in numerous lineages across the tree of life, in both diploid-dominant species, including many animals and plants, and the less studied haploid-dominant plants and algae. Strict genetic sex determination ensures that individuals reproduce by outcrossing. However, species with separate sexes (termed dioecy in diploid plants, and dioicy in haploid plants) may sometimes evolve different sex systems, and become monoicous, with the ability to self-fertilize. Here, we study dioicy-monoicy transitions in the ancient liverwort haploid plant lineage, using three telomere-to-telomere gapless chromosome-scale reference genome assemblies from the Ricciaceae group of Marchantiales. Ancestral liverworts are believed to have been dioicous, with U and V chromosomes (chromosome 9) determining femaleness and maleness, respectively. We confirm the finding that monoicy inRicciocarpos natansevolved from a dioicous ancestor, and most ancestrally U chromosomal genes have been retained on autosomes in this species. We also describe evidence suggesting the possible re-evolution of dioicy in the genusRiccia, with probablede novoestablishment of a sex chromosome from an autosome (chromosome 5), and further translocations of genes from the new sex chromosome to autosomes. Our results also indicated that m-chromosomes are consistent genomic features, and may have evolved independently from sex chromosomes inRicciocarposandRiccialineages.
Role ofN-glycosylation as a determinant of ATG9A conformations and activity
Authors: Lambrughi Matteo , Utichi Mattia , Borg Christian B. , Marjault Henri-Baptiste , Echeverría Sergio Esteban , Maeda Kenji , Taylor Nicholas M.I. , Fadda Elisa , Jäättelä Marja , Papaleo Elena
Published: January 2025

This study investigates the effects of N99 glycosylation on the structural dynamics and lipid scrambling activity of ATG9A, a key autophagy protein, using microsecond all-atom molecular dynamics (MD) simulations. ATG9A is an integral membrane protein involved in autophagosome biogenesis, and its N-glycosylation at N99 plays a critical, yet poorly understood role in its function. The simulations revealed that the hydrophilic central cavity of ATG9A supports lipid reorientation and partial transbilayer movements, consistent with its lipid scrambling activity observed experimentally. N-glycosylation at N99 was found to enhance cooperative interactions between protomers, facilitating lipid insertion and traversal within the central cavity. These findings align with the proposed mechanism of ATG9A’s role in lipid redistribution across the phagophore membrane during autophagy. However, mutagenesis experiments that abolished N-glycosylation in ATG9A (ATG9AN99Aand ATG9AN99Dmutants) did not show a marked change in autophagy flux, suggesting that further experimental approaches, such as lipid scramblase assays, may be needed to more clearly define the glycosylation’s impact. The study also observed asymmetric protomer conformations in ATG9A, contrasting with symmetric structures seen in cryo-EM, suggesting that the structural heterogeneity of the protein could be further explored in cryo-EM datasets. Overall, the study highlights the importance of incorporating glycosylation in computational studies of membrane proteins and offers valuable insights into the molecular mechanisms of lipid transport in autophagy, with potential implications for other lipid scramblases and flippases.
Tryptophan metabolism reprogramming contributes to the prothrombotic milieu in mice and humans infected with SARS-CoV-2
Authors: Subramaniam Saravanan , Napoleon Marc Arthur , Lotfollahzadeh Saran , Kamal Mohamed Hassan , Kurniawan Helena , Elsadawi Murad , Kenney Devin , Douam Florian , Bosmann Markus , Whelan Stephen , Cabral Howard , Burks Eric J , Zhao Grace , Kolachalama Vijay , Ravid Katya , Chitalia Vipul C.
Published: January 2025

SARS-CoV-2 infection disturbs the coagulation balance in the blood, triggering thrombosis and contributing to organ failure. The role of prothrombotic metabolites in COVID-19-associated coagulopathy remains elusive. Leveraging K18-hACE2 mice infected with SARS-CoV-2, we observed higher levels of the tryptophan metabolite, kynurenine, compared to controls. SARS-CoV-2 infected mice showed a significant upregulation of enzymes controlling Kynurenine biogenesis, such as indoleamine 2,3-dioxygenase (IDO-1) and tryptophan 2,3-dioxygenase levels in kidneys and liver, respectively, as well as changes in the enzymes involved in kynurenine catabolism, including kynurenine monooxygenase and kynurinase. Consistent with the agonistic role of these metabolites in Aryl Hydrocarbon Receptor (AHR) signaling, AHR activation and its downstream mediator, tissue factor (TF), a highly potent procoagulant factor, was observed in endothelial cells (ECs) of lungs and kidneys of infected mice. These findings were validated in humans, where compared to controls, sera of COVID-19 patients showed increased levels of Kynurenine, kynurenic acid, anthranilic acid, and quinolinic acid. Activation of the AHR-TF axis was noted in the kidneys and lungs of COVID-19 patients, and COVID-19 sera showed higher IDO-1 activity than controls. Levels of Kyn in COVID-19 patients correlated strongly with the TF-inducing activity of COVID-19 sera on ECs. A specific IDO-1 inhibitor or AHR inhibitor separately or in combination suppressed COVID-19 sera-induced TF activity in ECs. Together, we identified IDO-1 as upregulated by SARS-CoV-2 infection, resulting in augmented Kyn and its prothrombotic catabolites, thereby suggesting the Kyn-AHR-TF axis as possibly a new diagnostic and/or therapeutic target.

Key points

SARS-CoV-2-infection upregulates kynurenine biogenesis in the liver and diminishes kynurenine catabolism in the lungs and kidneys.

An increase in kynurenine stimulates the AHR-TF axis in the microvasculature in COVID-19 patients, which is inhibited by pharmacological manipulation.
ORAKLE: Optimal Risk prediction for mAke30 in patients with acute Kidney injury using deep Learning
Authors: Oh Wonsuk , Veshtaj Marinela , Sawant Ashwin , Agrawal Pulkit , Gomez Hernando , Suarez-Farinas Mayte , Oropello John , Kohli-Seth Roopa , Kashani Kianoush , Kellum John A. , Nadkarni Girish , Sakhuja Ankit
Published: January 2025

Background

Major Adverse Kidney Events within 30 days (MAKE30) is an important patient-centered outcome for assessing the impact of acute kidney injury (AKI). The existing prediction models for MAKE30 are static and overlook dynamic changes in clinical status. In this study, we introduce ORAKLE, a novel deep-learning model that utilizes evolving time-series data to predict MAKE30, enabling personalized, patient-centered approaches to AKI management and outcome improvement.

Methods

We conducted a retrospective study using three publicly available critical care databases: MIMIC-IV, SICdb, and eICU-CRD. Among these, MIMIC-IV was divided into 80% training and 20% internal test sets, whereas SiCdb and eICU-CRD were used as external validation cohorts. Patients with sepsis-3 criteria who developed AKI within 48 hours of intensive care unit admission were identified. Our primary outcome was MAKE30, defined as a composite of death, new dialysis or persistent kidney dysfunction within 30 days of ICU admission. We developed ORAKLE using Dynamic DeepHit framework for time-series survival analysis and its performance against Cox models using AUROC and AUPRC. We further assessed model calibration using Brier score.

Results

We analyzed 16,671 patients from MIMIC-IV, 2,665 from SICdb, and 11,447 from eICU-CRD. ORAKLE outperformed the Cox models in predicting MAKE30, achieving AUROCs of 0.84 (95% CI: 0.83–0.86) vs. in MIMIC-IV internal test set 0.80 (95% CI: 0.78–0.82), 0.83 (95% CI: 0.81–0.85) vs. 0.79 (95% CI: 0.77–0.81) in SICdb, and 0.85 (95% CI: 0.84–0.85) vs. 0.81 (95% CI: 0.80–0.82) in eICU-CRD. The AUPRC values for ORAKLE were also significantly better than that of Cox models. The Brier score for ORAKLE was 0.21 across the internal test set, SICdb, and eICU-CRD, suggesting good calibration.

Conclusions

ORAKLE is a robust deep-learning model for predicting MAKE30 in critically ill patients with AKI that utilizes evolving time series data. By incorporating dynamically changing time series features, the model captures the evolving nature of kidney injury, treatment effects, and patient trajectories more accurately. This innovation facilitates tailored risk assessments and identifies varying treatment responses, laying the groundwork for more personalized and effective management approaches.
Assessing Large Language Model Performance Related to Aging in Genetic Conditions
Authors: Othman Amna A. , Flaharty Kendall A. , Ledgister Hanchard Suzanna E. , Hu Ping , Duong Dat , Waikel Rebekah L. , Solomon Benjamin D.
Published: January 2025

Unlike some health conditions that have been extensively delineated throughout the lifespan, many genetic conditions are largely described in pediatric populations, with a focus on early manifestations like congenital anomalies and developmental delay. An apparent gap exists in understanding clinical features and optimal management as patients age. Generative artificial intelligence is transforming biomedical disciplines including through the introduction of large language models (LLMs). Motivated by these advances, we explored how LLMs handle age with respect to 282 genetic conditions selected based on prevalence. We divided these conditions into five categories: Disorders limited to childhood; Disorders limited to adulthood; Disorders with changes in presentation across ages; Disorders with changes in management across ages; Disorders with no changes across ages. We evaluated Llama-2-70b-chat (70b) and GPT-3.5 (GPT) capabilities at generating accurate medical vignettes for these conditions based on Correctness, Completeness, and Conciseness as graded by 3 clinicians. Using accurately generated vignettes as in-context prompts, we further generated and evaluated patient-geneticist dialogues and assessed LLM performance in answering specific questions regarding age-based management plans for a subset of conditions. Results revealed impressive performances of 70b with in-context prompting and GPT in generating vignettes. We overall did not observe age-based biases, though our experiments identified statistically significant differences in some areas related to LLM output. Despite impressive capabilities, LLMs still have limitations in clinical applications.
Endothelial Sphingosine-1-Phosphate Receptor (S1PR) 1, a Functional S1PR in the Human Cerebrovascular Endothelium, Limits Blood Brain Barrier Permeability and Neuronal Injury following Subarachnoid Hemorrhage in Mice
Authors: Ito Akira , Uchida Hiroki , Dash Sabyasachi , Aburakawa Daiki , Shingai Yuto , Liu Cathy , Avila-Gomez Paulo , Tominaga Keita , Kim Gab Seok , Faraco Giuseppe , Proia Richard L. , Niizuma Kuniyasu , Tominaga Teiji , Anrather Josef , Iadecola Costantino , Kluk Michael J. , Sanchez Teresa
Published: January 2025

Hypoxia-induced blood-brain barrier (BBB) permeability has been identified as a key contributor to the progression of ischemic-hypoxic brain injury and neuronal dysfunction in stroke and other cerebrovascular diseases. Emerging clinical evidence highlights that the vasoprotective signaling properties of high-density lipoprotein (HDL), mediated through its bioactive lipid component sphingosine-1-phosphate (S1P), may be impaired in cardiovascular and inflammatory conditions. Nonetheless, the precise contributions and mechanistic roles of S1P signaling within the cerebral microvasculature remain insufficiently characterized.

In this study, we aimed to elucidate the role of S1P signaling via its endothelial receptor S1PR1 in the pathophysiology of early brain injury following subarachnoid hemorrhage (SAH), a particularly severe form of stroke. Additionally, we sought to evaluate the relevance of the endothelial S1PR1 pathway in the human cerebrovascular endothelium, its functional role in hypoxia-induced cerebral endothelial barrier dysfunction, and its underlying molecular mechanisms. To address these objectives, we utilized endothelial-specific S1PR1 knockout mice subjected to the endovascular rupture model of aneurysmal SAH, performed mechanistic studies in primary human cerebral microvascular endothelial cells, and characterized S1PR1 expression in human brain tissue using validated protocols.

Our findings reveal robust expression of S1PR1 in the cerebrovascular endothelium of both mice and humans. Functional analyses demonstrated that S1PR1 is critical for maintaining BBB integrity and mitigating neuronal injury in the context of SAH. Mechanisticin vitrostudies indicated that S1PR1 exerts a vasoprotective effect by limiting hypoxia-induced BBB dysfunction in human primary brain microvascular endothelial cells through inhibition of Rho-associated kinase (ROCK)-mediated phosphorylation of myosin light chain (MLC), suppression of stress fiber formation and caveolin-1-dependent endosomal trafficking.

These results highlight the pivotal role of endothelial S1PR1 signaling in preserving cerebral vascular integrity and provide a strong scientific foundation for developing novel therapeutic approaches targeting the S1P pathway in the endothelium to enhance neurovascular protection.
ESMAdam: a plug-and-play all-purpose protein ensemble generator
Authors: Yu Zongxin , Liu Yikai , Lin Guang , Jiang Wen , Chen Ming
Published: January 2025

Proteins often adopt multiple ensemble conformations to perform essential functions such as catalysis, transport, and signal transduction. Traditional physics-based methods for generating these conformations, including molecular dynamics and Monte Carlo simulations, are computationally expensive and time-consuming, limiting their practicality for high-throughput applications like screening. Recent advances in machine learning, particularly deep generative models, offer a promising alternative for protein conformation ensemble generation. However, these models are often task-specific or rely on strong assumptions to generalize. Here, we introduce ESMAdam, a versatile and efficient framework for protein conformation ensemble generation. Using the ESMFold protein language model ESMFold and ADAM stochastic optimization in the continuous protein embedding space, ESMAdam addresses a wide range of ensemble generation tasks. In this work, we demonstrate several basic applications of ESMAdam, including conditional ensemble generation and CG-to-all-atom backmapping. In addition, we showcase advanced applications, such as screening alternative binding modes of protein multimers and reconstructing 3D structures from cryo-EM images. Compared to traditional physics-based methods, ESMAdam significantly reduces computational time. Unlike deep-generative-model-based approaches, it requires no retraining and easily adapts to diverse ensemble restraint conditions, making it exceptionally suited for various structure prediction and screening tasks. This plug-and-play framework represents a step toward efficient and flexible protein ensemble generation for applications in structural biology and drug discovery.
Age and Gender-Dependent Comorbidities in UAE Population identifies Coronary Artery Disease with Gene-Environment Interactions
Authors: Iftikhar Hassa
Published: January 2025

This study investigated the age and sex-dependent comorbidities contributing to coronary artery disease (CAD) within the UAE population. A cohort of 3,000 individuals was analyzed by integrating genetic data, environmental stressors (e.g., PM2.5 exposure), and demographic profiles to identify CAD and nine other diseases with heterogeneous comorbidity patterns. Key genetic markers, including APOE rs429358, PCSK9, and LPA were significantly associated with CAD risk, amplified by environmental exposure and metabolic conditions such as diabetes and obesity. Notably, APOE rs429358 carriers exposed to high PM2.5 levels exhibited a 2.8-fold increase in CAD risk (p < 0.001), emphasizing the synergistic effects of gene-environment interactions. Monte Carlo and Markov Chain Monte Carlo simulations validated the results, enabling the identification of high-risk genetic profiles across various environmental and demographic conditions. Kaplan-Meier survival analyses revealed accelerated disease progression in high-risk groups, whereas Principal Component Analysis and hierarchical clustering identified distinct genetic clusters stratified by age and sex. This study further identified demographic-specific disease subtypes with implications for public health strategies, such as addressing higher environmental susceptibility in males and targeted management of metabolic comorbidities in females such as obesity, diabetes, and stroke. These findings support precision medicine strategies tailored to regional populations, promoting targeted interventions to mitigate CAD risk. This study synthesizes observational findings and computational simulations to establish a comprehensive framework for elucidating the pathogenesis of coronary artery disease (CAD) and enhancing public health interventions in the United Arab Emirates (UAE). The actionable outcomes include the development of sex-specific health interventions and environmental policies to reduce CAD risk in high-susceptibility groups.
High intensity exercise before sleep boosts memory encoding the next morning
Authors: Ramirez Butavand Daniela , Nagel Juliane , Feld Gordon B. , Steib Simon
Published: January 2025

The importance of sleep for memory consolidation has been extensively studied, but its role for memory encoding remains less well characterized. At the molecular and cellular level, the renormalization of synaptic weights during sleep has received substantial support, which is thought to free capacity to encode new information at the behavioral level. However, at the systems level and behaviorally, support for this process playing a major role for memory function remains scarce. In the current study, we investigated the utility of moderate- and high-intensity evening exercise as a low-cost low-tech intervention to modulate sleep and its influence on subsequent encoding in the morning. Our findings indicate that high-intensity interval training (HIIT) improved post-sleep memory performance with effects lasting up to 24 hours after initial encoding. In addition, we show that especially the early parts of the encoding task were affected by the HIIT intervention, which is in line with increases in synaptic homeostasis being targeted by the exercise. Intriguingly, low-performing participants seemed to benefit more from the HIIT intervention suggesting it not only as a tool for basic research but also as a candidate for applications to boost memory performance in mental disorders or in the elderly. These results provide first evidence that acute exercise can affect learning processes even hours after it occurs.
Two stages of substrate discrimination dictate selectivity in theE. coliMetNI-Q ABC transporter system
Authors: Yang Janet G. , Chen Hulda Yuchun , Guardado John H. , Gardner Maile , Foronda Matthew S.
Published: January 2025

TheEscherichia coliMetNI-Q importer, an ATP-binding cassette (ABC) transporter, mediates the uptake of both L- and D-enantiomers of methionine. Originalin vivouptake studies show a strong preference for L-Met over D-Met, but the molecular basis of this selectivity is unclear. In this work, we systematically examine substrate discrimination by the MetNI transporter and MetQ substrate binding protein using an array of biophysical and biochemical techniques. Based on the kinetic and thermodynamic parameters of individual intermediates in the transport cycle, we uncover multiple steps in the transport cycle that confer substrate specificity. As in many other ABC importer systems, selectivity is applied at the level of binding to the substrate binding protein: MetQ dictates a 1,000-fold preference for L-Met over D-Met. However, beyond this initial level of selectivity, MetQ displays distinct binding preferences for the MetNI transporter depending on the substrate. We propose that the differences in binding affinities reflect the more favored release of L-Met into the permeation pathway when compared to D-Met. In support of this model, under saturating conditions, MetNI transports L-Met across the lipid bilayer at a faster rate than D-Met. Interestingly, the ATPase activity of the MetNI-Q complex is not modulated by the presence of substrate. Our studies reveal that the MetNI-Q system incorporates two separate steps in tuning methionine uptake to substrate chirality and availability. This method of discrimination ensures the import of the most biologically preferred substrate while also allowing for adaptability to more limiting nutrient conditions.
Electronic structure and properties of trapped holes in crystalline and amorphous
Ga2O3
Authors: Kaewmeechai Chaiyawat , Strand Jack , Shluger Alexander
Published: January 2025

Structure and electronic properties of self-trapped holes were studied in both crystalline and amorphous Ga2O3 using density functional theory (DFT) and the nonlocal PBE0-TC-LRC density functional. Amorphous (a) Ga2O3 structures were generated using classical molecular dynamics and the melt-quench technique and further optimized using DFT. They exhibit an average density of 4.84g/cm3 and band gap around 4.3 eV. Calculations predict deep hole trapping in crystalline and amorphous phases with the hole-trapping energies in the amorphous structures being deeper than those found in the crystalline structure. In a−Ga2O3, trapped holes are localized around low-coordinated oxygen atoms (two or three coordinated). We predict the formation of stable hole bipolarons in both the crystalline and amorphous phases facilitated by the formation of O–O bonds with binding energies about 0.2 eV.

Published by the American Physical Society
2025
Particle production in a toy model: Multiplicity distribution and entropy
Authors: Levin Eugene
Published: January 2025

In this paper we found the multiplicity distribution of the produced dipoles in the final state for dipole-dipole scattering in the zero dimension toy models. This distribution shows the great differences from the distributions of partons in the wave function of the projectile. However, in spite of this difference the entropy of the produced dipoles turns out to be the same as the entropy of the dipoles in the wave function. This fact is not surprising since in the parton approach only dipoles in the hadron wave function which can be produced at t=+∞ and measured by the detectors. We can also confirm the result of Kharzeev and Levin that this entropy is equal to SE=ln(xG(x)), where we denote by xG the mean multiplicity of the dipoles in the deep inelastic scattering. The evolution equations for σn are derived.

Published by the American Physical Society
2025
Jet discrimination with a quantum complete graph neural network
Authors: Chen Yi-An , Chen Kai-Feng
Published: January 2025

Machine learning, particularly deep neural networks, has been widely used in high-energy physics, demonstrating remarkable results in various applications. Furthermore, the extension of machine learning to quantum computers has given rise to the emerging field of quantum machine learning. In this paper, we propose the quantum complete graph neural network (QCGNN), which is a variational quantum algorithm-based model designed for learning on complete graphs. The QCGNN with deep parametrized operators offers a polynomial speedup over its classical and quantum counterparts, leveraging the property of quantum parallelism. We investigate the application of the QCGNN with the challenging task of jet discrimination, where the jets are represented as complete graphs. Additionally, we conduct a comparative analysis with classical models to establish a performance benchmark.

Published by the American Physical Society
2025
Impact of antisymmetric contributions to signal multipoles in the measurement of black-hole spins
Authors: Kolitsidou Panagiota , Thompson Jonathan E. , Hannam Mark
Published: January 2025

Many current models for the gravitational-wave signal from precessing black-hole binaries neglect an asymmetry in the ±m multipoles. The asymmetry is weak, but is responsible for out-of-plane recoil, which for the final black hole can be several thousand km/s. In this work we show that the multipole asymmetry is also necessary to accurately measure the black-hole spins. We consider synthetic signals calculated from the numerical relativity surrogate model ur7dq4, which includes the multipole asymmetry, and measure the signal parameters using two versions of the same model, one with and one without the multipole asymmetry included. We find that in high signal-to-noise-ratio observations where the spin magnitude and direction can in principle be measured accurately, neglecting the multipole asymmetry can result in biased measurements of these quantities. Measurements of the black-hole masses and the standard aligned-spin combination χeff are not in general strongly affected. As an illustration of the impact of the multipole asymmetry on a real signal we consider the LIGO-Virgo-KAGRA observation GW200129_065458, and find that the inclusion of the multipole asymmetry is necessary to identify the binary as unequal mass and a high in-plane spin in the primary.

Published by the American Physical Society
2025
Modeling adhesion in stochastic and mean-field models of cell migration
Authors: Noureen Shahzeb Raja , Mort Richard L. , Yates Christian A.
Published: January 2025

Adhesion between cells plays an important role in many biological processes such as tissue morphogenesis and homeostasis, wound healing, and cancer cell metastasis. From a mathematical perspective, adhesion between multiple cell types has been previously analyzed using discrete and continuum models, including the cellular Potts models and partial differential equations (PDEs). While these models can represent certain biological situations well, cellular Potts models can be computationally expensive, and continuum models capture only the macroscopic behavior of a population of cells, ignoring stochasticity and the discrete nature of cell dynamics. Cellular automaton models allow us to address these problems and can be used for a wide variety of biological systems. In this paper we consider a cellular automaton approach and develop an on-lattice agent-based model (ABM) for cell migration and adhesion in a population composed of two cell types. By deriving and comparing the corresponding PDEs to the ABM, we demonstrate that cell aggregation and cell sorting are not possible in the PDE model. Therefore, we propose a set of discrete mean equations which better capture the behavior of the ABM in one and two dimensions.

Published by the American Physical Society
2025
Parallel remote state preparation for fully device-independent verifiable blind quantum computation
Authors: Adamson Sean A.
Published: January 2025

We introduce a device-independent two-prover scheme in which a classical verifier can use a simple untrusted quantum measurement device (the client device) to securely delegate a quantum computation to an untrusted quantum server. To do this, we construct a parallel self-testing protocol to perform device-independent remote state preparation of n qubits and compose this with the unconditionally secure universal verifiable blind quantum computation (VBQC) scheme of Fitzsimons and Kashefi []. Our self-test achieves a multitude of desirable properties for the application we consider, giving rise to practical and fully device-independent VBQC. It certifies parallel measurements of all cardinal and intercardinal directions in the XY plane as well as the computational basis, uses few input questions (of size logarithmic in n for the client and a constant number communicated to the server) and requires only single-qubit measurements to be performed by the client device.

Published by the American Physical Society
2025
Fast plasma production by intense femtosecond extreme ultraviolet and x-ray pulses
Authors: Fasolato C. , Stellino E. , Sacchetti F. , Petrillo C.
Published: January 2025

We develop a semiempirical model to describe the creation of an electron plasma in matter at extreme conditions, as excited by high-intensity, extreme ultraviolet (EUV) or x-ray radiation pulses currently available at free-electron laser (FEL) facilities. In typical FEL experiments, EUV and x-ray pulses are used to investigate highly excited states of matter produced by optical pump pulses. The pump pulses, promoting electrons from delocalized valence band states, excite the system often through multiphoton absorption processes and/or shock wave propagation. Instead, the use of FEL radiation as a pump allows triggering electron transitions from bound, core states to nearly free levels above the Fermi energy, promptly generating a highly excited state, toward the warm dense matter regime. We model such an excitation process starting from the optical properties of the analyzed materials and first-principle considerations, with the aim of motivating further studies in this scheme. We apply our model to predict the differences in the plasma creation process in insulators and metals, at varying exciting pulse wavelength and fluence, and we interpret the results in terms of the different nature of the investigated systems. Furthermore, we explore the effect of the finite core hole lifetime on the plasma formation and relaxation dynamics. We show the model is suited for the interpretation of real experimental data obtained from a prototypical insulating crystal (LiF) in a EUV FEL pump–optical transmission probe experiment.

Published by the American Physical Society
2025
Few-photon SUPER: Quantum emitter inversion via two off-resonant photon modes
Authors: Richter Quentin W. , Kaspari Jan M. , Bracht Thomas K. , Yatsenko Leonid , Axt Vollrath Martin , Rauschenbeutel Arno , Reiter Doris E.
Published: January 2025

With the realization of controlled quantum systems, exploring excitations beyond the resonant case opens new possibilities. We investigate an extended Jaynes-Cummings model in which two nondegenerate photon modes are coupled off resonantly to a quantum emitter. This allows us to identify few-photon scattering mechanisms that lead to a full inversion of the emitter while transferring off-resonant photons from one mode to another. This behavior is connected to recent measurements of a two-level emitter scattering two off-resonant photons simultaneously. Furthermore, our results can be understood as a quantized analog of the recently developed off-resonant quantum control scheme known as swing-up of quantum emitter (SUPER). Our intuitive formalism gives deeper insight into the interaction of a two-level emitter with off-resonant light modes with the prospect of novel photonic applications.

Published by the American Physical Society
2025
Decoherence-free many-body Hamiltonians in nonlinear waveguide quantum electrodynamics
Authors: Karnieli Aviv , Tziperman Offek , Roques-Carmes Charles , Fan Shanhui
Published: January 2025

Enhancing interactions in many-body quantum systems, while protecting them from environmental decoherence, is at the heart of many quantum technologies. Waveguide quantum electrodynamics is a promising platform for achieving this, as it hosts infinite-range interactions and decoherence-free subspaces of quantum emitters. However, as coherent interactions between emitters are typically washed out in the wavelength-spacing regime hosting decoherence-free states, coherent control over the latter becomes limited, and many-body Hamiltonians in this important regime remain out of reach. Here we show that by incorporating emitter arrays with nonlinear waveguides hosting parametric gain, we obtain a unique class of many-body interaction Hamiltonians with coupling strengths that increase with emitter spacing, and persist even for wavelength-spaced arrays. We then propose to use these Hamiltonians to coherently generate decoherence-free states directly from the ground state, using only global squeezing drives, without the need for local addressing of individual emitters. Interestingly, we find that the dynamics approaches a unitary evolution in the limit of weak intrawaveguide squeezing, and we discuss potential experimental realizations of this effect. Our results pave the way towards coherent control protocols in waveguide quantum electrodynamics, with applications including quantum computing, simulation, memory, and nonclassical light generation.

Published by the American Physical Society
2025
Noise-tolerant Grover's algorithm via success-probability prediction
Authors: Leng Jian , Yang Fan , Wang Xiang-Bin
Published: January 2025

We present theoretical and experimental studies on efficient quantum search with noise. We propose a noise-tolerant method that significantly reduces the running time and exponentially improves the error threshold with number of qubits for Grover's search. Experiments are implemented on different quantum computing setups, with all results clearly confirming the advantage of our noise-tolerant method to the original Grover's search. In one setup, our method produces quantum advantages while the original Grover's search does not. In another setup with smaller noise, our method produces a larger quantum advantage than the original Grover's search does.

Published by the American Physical Society
2025
The right fit: how the alignment between customer orientation and service climate boosts employee commitment and customer loyalty
Authors: Tremblay Michel , Parent-Rocheleau Xavier
Published: January 2025

Purpose

Drawing on the need–supply fit perspective, this study aims to examine how (mis)alignment between customer orientation (CO) and the service climate (SC) influences the affective organizational commitment and indirectly impacts employees’ customer-oriented behavior (COB) and customers’ word-of-mouth (WOM).

Design/methodology/approach

This paper used data from three different sources. The data set comprises 1,420 time-lagged observations from 725 employees surveyed at multiple time points, a total of 19,630 customers from 34 retail stores across multiple time points and the managers of the 34 stores, surveyed multiple times.

Findings

Employees’ affective commitment was found to be higher when CO and SC were both high. In case of misalignment, commitment is higher when the SC is stronger than the CO (compared to when the CO is stronger than SC). Employees’ commitment was positively related to subsequent store-level COBs, which in turn boosted customers’ WOM.

Originality/value

Very few studies have looked for impact of (mis)alignment of frontline employee characteristics with business unit features and how it relates to employees and customers responses.
Feed-in tariff policy for microgrids: past and future a case study of the option value of complementary energy assets in turbulent conditions
Authors: Feleafel Hanaa , Leseure Michel
Published: January 2025

Purpose

The intermittence of renewable energy sources is a substantial barrier to investments. This issue has conventionally been addressed by governmental policies such as feed-in tariffs (FiT). The purpose of this paper is to assess the effectiveness of these policies and the implications for investments in renewable energy systems, with a specific focus on systems where hydrogen storage systems are emerging as a viable option.

Design/methodology/approach

A quantitative modelling approach is used to analyse a real-life case study considering renewable energy investments staging options versus an upfront investment.

Findings

The main finding of the paper is that FiT policy is of little importance when storage is used, as the storage hedges weather related risk for customers. If the microgrid does not have local storage, or still exports substantial amounts of power, then FiTs are still needed. This implies that policies need updating as the energy sector evolves and the type of support needed becomes more sensitive to microgrid design.

Research limitations/implications

Simplifications were made when modelling weather. Normal weather volatility is accounted for, but not large-scale unusual weather patterns.

Originality/value

The paper provides new insights about using real options theory in a context of increasing uncertainty when complementarity between assets exist. It also argues that the historical “one size fits all” design of FiTs policies is ineffective for the future.