bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving beyond self-report in characterizing drug addiction: Using drug-biased behavior to prospectively inform treatment adherence in opioid use disorder
Authors: McClain Natalie , Ceceli Ahmet O. , Kronberg Greg , Alia-Klein Nelly , Goldstein Rita Z.
Published: January 2025

Drug addiction is accompanied by enhanced salience attributed to drug over nondrug cues. This objectively measured bias is reliable yet underutilized in informing clinical endpoints, as clinical trials largely employ subjective (i.e., self-report or interview-based drug use and craving) or simple categorical (e.g., drug in urine) measures, with limited success. Having previously demonstrated their utility in cocaine addiction, we investigated whether behavioral picture choice (a lab-simulated drug seeking measure) and verbal fluency similarly reveal drug bias in 59 abstinent, inpatient individuals with opioid use disorder (iOUD) compared to 29 healthy controls (HC). Using a hierarchical regression, and compared to subjective measures, we then tested whether these objective markers can better inform prospective treatment completion—a clinically relevant and measurable outcome. As expected, results showed that the iOUD exhibited higher simulated drug seeking (ps<0.036) and drug fluency (p=0.008) compared to the HC. Importantly, after dimensionality reduction, while the self-reported years of regular opioid use and cue-induced craving showed null results (|β|<0.47,p>0.290), and controlling for demographics, drug choice was associated with treatment completionβ=-0.75,p=0.036), explaining greater variability in its likelihood compared to the subjective measures (model comparison:ΔR2=0.102,p=0.027). Extending drug-biased choice and fluency from cocaine to opioid addiction, results further indicate that these objective measures of drug bias outperform the commonly employed subjective drug use and craving in informing a clinical outcome; unlike drug urine tests, they show important variability in abstinent iOUD. Results implicate these cognitive-behavioral tasks as powerful markers of drug bias and predictors of treatment outcome.
Identifying Psychiatric Manifestations in Outpatients with Depression and Anxiety: A Large Language Model-Based Approach
Authors: Xu Shihao , Yan Yiming , Ding Yanli , Li Feng , Zhang Shu , Tang Haoyun , Luo Chao , Li Yan , Liu Hao , Mei Yu , Gu Wenjie , Qiu Hong , Wang Yong , Qiu Jianyin , Yang Tao , Wang Zike , Zhang Qing , Geng Haiyang , Han Yunyun , Shao Jun , Opel Nils , Bing Lidong , Zhao Min , Xu Yifeng , Jiang Xun , Chen Jianhua
Published: January 2025

Purpose

Accurate psychiatric diagnosis and assessment are crucial for effective treatment. However, while current data-driven approaches emphasize diagnostic outcomes, the process of decoding the underlying symptom expressions in patients’ language and mapping them to well-defined psychiatric terminology has received relatively little attention. This study investigates the potential of Large Language Models (LLMs) to automate the identification of diagnostic categories and symptoms from psychiatrist-patient dialogues, to provide interpretable insights and support automatic diagnosis.

Methods

We analyzed audio recordings from 1160 psychiatric diagnostic interviews, primarily involving patients with depressive disorder and anxiety disorder. A clinical entities corpus was formed by leveraging clinical annotations in EMRs (e.g., chief complaints, mental status, elements in assessment scales) and widely used assessment scales. LLMs were utilized to identify clinical symptoms, rate assessment scales, and an ensemble learning pipeline was designed to classify diagnostic results and symptoms with 10-fold cross-validation.

Results

The system achieved 86.9% accuracy for identifying the appearance of clinical annotations and 74.7% (77.2%) accuracy for identifying anxiety (depression) symptoms. Patients with depression and anxiety, diagnosed using ICD-10 codes, were differentiated with an accuracy of 75.5%. Analysis of LLM-generated features shows that depression cases exhibited prominent markers of anhedonia and decreased volition, whereas anxiety disorders were characterized by tension and an inability to relax.

Conclusion

This study demonstrates the potential of integrating LLM technology with linguistic and acoustic features to enhance psychiatric diagnostics. The developed pipeline effectively predicts psychiatric diagnoses and provides interpretable insights, showcasing a valuable tool for clinicians in mental health assessment.
Ferritin-guided iron supplementation in whole blood donors (FORTE): results of a double-blind randomized controlled trial
Authors: Karregat Jan H M , Meulenbeld Amber , Quee Franke A , Novotny Vĕra M J , de Haas Masja , Swinkels Dorine , van den Born Bert-Jan H , Zaaijer Hans L , Twisk Jos W R , van den Hurk Katja
Published: January 2025

BACKGROUND

Regular blood donation is associated with an increased risk of iron deficiency (ID; ferritin <15 µg/L). Oral iron supplementation is known to shorten iron store recovery time and could serve as a more effective alternative to extended donation intervals. We aimed to determine the optimal ferritin-guided iron supplementation protocol in terms of donor health, side-effects, donor return, and treatment adherence.

METHODS

In this prospective randomized placebo-controlled trial donors with ferritin levels ≤30 µg/L were enrolled in the study and randomly assigned to one of six groups, stratified for sex and age. Depending on the study arm, donors were asked to adhere to a ferrous bisglycinate supplementation protocol for 56 days, taking capsules containing 0 mg (i.e. placebo), 30 mg or 60 mg of elemental iron, either on alternate days or daily. The primary outcome was iron deficiency (ID) at 56 days follow-up, while secondary outcomes included low ferritin (≤30 µg/L), low Hb (≤135 g/L for men and ≤125 g/L for women), iron deficiency-related symptoms, side effects, treatment adherence, and evaluations of all outcomes at 122 and 180 days follow-up. This trial is registered in the Dutch trial registry (NL73283.018.20).

FINDINGS

Of the 2,052 donors who provided their informed consent, 830 donors (464 women) had ferritin levels ≤30 µg/L and were included in the trial. Compared to placebo, all iron supplementation groups exhibited similar significantly lower odds of ID at 56 days, with odds ratios (OR) ranging from 0.60 (95% CI [0.55–0.66]) to 0.65 (95% CI [0.59–0.72]). Similarly, for low Hb, the OR’s ranged from 0.74 (95% CI [0.64–0.86]) to 0.80 (95% CI [0.68–0.93]) For low ferritin, 60 mg of daily iron supplementation yielded an OR of 0.52 (95% CI [0.47–0.57]), markedly lower than those of other protocols, which ranged from 0.61 (95% CI [0.55–0.68]) to 0.82 (95% CI [0.74–0.91]). Iron supplementation did not result in any significant differences compared to placebo in ID-related symptoms, gastrointestinal side effects, intention to return to donate, or treatment adherence.

INTERPRETATION

In regular donors, 60 mg iron supplements taken daily was shown to be the most effective strategy for mitigating ID, low Hb, and especially low ferritin without introducing gastrointestinal discomfort or changes in the donors intention to return to donate. Ferritin-guided iron supplementation is an effective iron management strategy as an alternative or supplement to extended donation intervals.
Primary open angle glaucoma is associated with cortico-cortical receptive fields changes in early visual cortex
Authors: Invernizzi Azzurra , Carvalho Joana C. , Martins Joana , Jansonius Nomdo M. , Renken Remco J. , Cornelissen Frans W.
Published: January 2025

PURPOSE

Primary open angle glaucoma (POAG, hereafter referred to as glaucoma) is a neuro-ophthalmic disease characterized by progressive degeneration of the retinal ganglion cells and nerve fibers. However, the exact pathogenesis of this disease remains unresolved, notably including its effect on the neural circuits of the visual pathway and cortex.

METHODS

We used both resting state (RS) and stimulus-driven functional MRI and applied a novel analysis technique (Bayesian Connective Field Modelling) to investigate the intra-cortical functional connective organization of the early visual cortex of patients with POAG. Analogous to population receptive field modelling for stimulus-driven activity, our connective field approach models how the activity in one cortical area (e.g. V2) can be explained based on that of another (e.g. V1).

RESULTS

We compared the CF parameters obtained for the early visual cortical areas in glaucoma to those of control participants. Our results show that in both RS and stimulus-driven conditions, CF sizes in early visual areas are smaller in glaucoma compared to control participants. To assess if these differences could be related to the ocular damage altering the visual input to the visual cortex, the control participants also observed the visual stimuli with a simulated scotoma (SS), designed to match the visual sensitivity of a participant affected by glaucoma as assessed using standard automated perimetry (SAP). In this condition, no differences in CF size were observed. Moreover, we found that CF size did not correlate with glaucoma severity, as assessed using both SAP and optical coherence tomography (OCT).

CONCLUSION

The observed differences in CF metrics may be the result of local reorganization or neurodegeneration of the early visual cortex that must have developed already at an early disease stage.
Regulation of the lncRNAmalat1/Egr1 Axis by Wnt, Notch and TGF-β signaling: A Key Mechanism in Retina Regeneration
Authors: Premraj Sharanya , Sharma Poonam , Chaudhary Mansi , Shukla Pooja , Yadav Kshitiz , Desai Omkar Mahadeo , Ramachandran Rajesh
Published: January 2025

Adult zebrafish retinas rely on the resident Müller glia to maintain homeostasis and enable regeneration. Retina regeneration remains incomplete in mammals despite extensive efforts to emulate zebrafish regenerative conditions. Many studies have examined the reprogramming of zebrafish Müller glia cells, which is necessary for regeneration driven by regeneration-associated gene expression. Here, we show that the lncRNAmalat1, crucial for many biological functions, plays essential roles during retina regeneration. We demonstrate thatmalat1functions through an Egr-dependent axis, modulated by Wnt, Notch, and TGF-β signaling pathways, and is necessary for effective retina regeneration. Moreover, we uncover that the antisense lncRNAtalam1, which regulatesmalat1availability, is differentially regulated in zebrafish and mice, highlighting species-specific gene regulatory mechanisms after retinal injury. Cells with active TGF-β signaling stabilize Malat1 in mice while the same signaling destabilizesmalat1in zebrafish. Taken together, our work uncovers a new role for themalat1/Egr1 axis in necessitating retina regeneration, which may have important implications for differential regenerative ability in vertebrates.
Effects of Sudarshan Kriya Yoga (SKY) Breath Meditation on Heart Rate Variability, Sleep and Mental Health in Healthy Individuals : A Pilot and Feasibility Randomized Controlled Trial
Authors: Ganesan Vinitha , Fowler Lauren A , Bajaj Sahil , Qu Haiyan , Singh Priyam , Krishnan Snehaa D , McGregor Keith M , Nolan Timiya S , Baidwan Navneet , Mehta Tapan S , Aneja Ritu
Published: January 2025

Effective interventions are needed to address increasing mental health challenges that affect wellbeing. Sudarshan Kriya Yoga (SKY), a breath-based meditation, has previously shown to improve mental health. We conducted a pilot randomized controlled trial (RCT) in healthy individuals, to evaluate the feasibility of SKY intervention with an eight-week followup for studying its immediate and sustained effects on psychophysiological outcomes in real-world settings. 187 healthy individuals (>21 years old) were assessed for eligibility through telephone interviews and 45 consented individuals were randomized (2:1) to either receive three-day SKY intervention with eight-week followup or waitlist control group. The mean age was 40.9 years (SD = 11.3), and 35 (77.8%) were female. Adherence (≥ three-times/week) to 30-minute daily (75.9%) and (≥ six-times/week) 75-minute (89.7%) SKY practice were high. Compared to controls, SKY participants exhibited significantly higher resting heart rate variability (mean difference = 6.47 ([95% CI [0.95, 11.98]) at the end of three-days, and at eight-week followup (mean difference = 5.55 (90% CI [0.46, 10.64]) relative to baseline. At eight-week followup, SKY participants had significant improvements in resting heart rate, overall sleep score, anxiety and social connectedness compared to controls. These results demonstrate feasibility that consistent SKY practice can impact physiology. ClinicalTrials.gov,NCT05523414.
RNA denaturation underlies circular RNA separation
Authors: Jiang Yanyi , Kjems Jorgen
Published: January 2025

In vitro synthesized circular RNAs (circRNAs) have emerged as a promising drug modality for RNA therapeutics due to their improved stability and reduced immunogenicity. However, effective analysis and purification of circRNAs pose critical challenges arising from the insufficient separation of circRNAs and linear RNA byproducts. In this study, we systematically evaluate the effectiveness of gel electrophoresis and high-performance liquid chromatography - size exclusion chromatography (HPLC-SEC) for separating circRNAs synthesized through ligase- or ribozyme-based strategies. While the synthesis strategy dictates the purification complexity, we demonstrate that both techniques rely on RNA denaturation to successfully separate circRNAs. Additionally, when using HPLC-SEC, we show that even a trace amount of magnesium ions in RNA samples can significantly compromise circRNA separation. Under optimized denaturing conditions, HPLC-SEC enables circRNA purification directly from diluted crude in vitro transcription products, thus streamlining the purification process. Our study provides mechanistic insights into circRNA separation, advancing the purity and scalability of circRNA-based therapeutics.
Thermodynamic uncertainty relation constraints information transmission through cell signaling systems
Authors: Verma Shreyansh , Saravanan R Vishva , Ghosh Bhaswar
Published: January 2025

Biological systems in general operates out of equilibrium which demands the requirement for constant supply of energy due to non-equilibrium entropy production. The thermodynamic uncertainty relation (TUR) essentially imposes a bound on minimum current fluctuation the system can have given a entropy production rate. The fluctuation eventually impacts the signal to noise ratio imposing an upper bound on information transmission accuracy. In this study, we explored the role of TUR on the information transmission capacity of a set of cellular signaling systems using a coupled mathematical and machine learning approaches to experimental data in yeast under several stress conditions. Cell signaling systems are involved in sensing the changes in environment by activating a set of transcription factors which typically diffuse inside the nucleus to trigger transcription of the required genes. However, the inherent stochasticity of the biochemical pathways associated with signaling processes severely limits the accuracy of estimating the environmental input by the transcription factors. Application of TUR reveals a general picture about the working principle of the transcription factors. We found that the the activation followed by biased diffusion of transcription factors (TF) towards the nucleus triggers entropy production which amplifies magnitude of the overall TF currents towards the nucleus as well as reduces the fluctuations. These outcomes significantly improve the accuracy of information transmission carried out by the transcription factors following the bound imposed by TUR. Thus, experimental observations coupled with TUR based theoretical models demonstrate the role of thermodynamic fluctuation and entropy production on cellular information processing.
Rational engineering of lipid-binding probes via high-throughput protein-lipid interaction screening
Authors: Nishimura Taki , Tsuboyama Kotaro , Nakagaki Yuki , Yamamoto Eiji , Mizushima Noboru
Published: January 2025

Lipid-binding domains, originally isolated from natural proteins, are useful tools essential for analyzing membrane lipids in cells, and their applications are varied. Yet, there is no general strategy for engineering lipid-binding domains. Here, we present a robust method for monitoring protein-lipid interactions, named the Cell surface Liposome Binding (CLiB) assay. Using this technique, we isolated high-affinity lipid-binding domains and nanobodies that preferentially bind to phosphatidylinositol phosphates. Furthermore, by combining the CLiB assay with next-generation sequencing, allowing the analysis of more than 10,000 clones in parallel, we identified novel variants with enhanced binding to phosphatidylinositol phosphates and uncovered a common structural feature: a positively charged pocket necessary for binding, formed by the three loop regions. This study opens a new avenue for the rational design and generation of lipid-binding probes on demand.
Lack of ADAP1/Centaurin-α1 Ameliorates Cognitive Impairment and Neuropathological Hallmarks in Mouse Alzheimer Model
Authors: Szatmari Erzsebet M. , Moran Corey , Cohen Sarah J. , Bashtovyy Denys , Jacob Amanda , Bunner Wyatt , Phipps Mary , Lora Joan Cristino , Stackman Robert W. , Yasuda Ryohei
Published: January 2025

ArfGAP, with dual PH domain-containing protein 1/Centaurin-α1 (ADAP1CentA1), is a brain-enriched and highly conserved Arf6 GTPase-activating and Ras-anchoring protein. ADAP1 is involved in dendritic outgrowth and arborization, synaptogenesis, and axonal polarization by regulating the dynamics of the actin cytoskeleton. An increased level of ADAP1 and its association with amyloid plaques in the human Alzheimer’s disease (AD) brain suggest a role for this protein in AD progression. To understand the role of ADAP1/CentA1 in neurodegeneration, we crossbred CentA1 KO mice with the hAPP-J20 mouse model of AD (J20 x CentA1 KO). We then evaluated the gene expression profile and the behavioral and neuropathological hallmarks of AD to determine the impact of eliminating ADAP1/CentA1 expression on AD-related phenotypes. Spatial memory assessed by the Morris Water Maze test showed significant impairment in J20 mice, which was rescued by the deletion of CentA1. Neuropathological hallmarks of AD, such as deposits of amyloid plaques and neuroinflammation, were significantly reduced in the AD model mice with CentA1 KO background. To identify potential mediators of AD phenotype rescue, we analyzed differentially expressed genes (DEGs) between genotypes, by employing transcriptome profiling with Nanostring nCounter Neuropathology and Neuroinflammation panels. We found significant upregulation of genes associated with apoptosis and gliosis in the brain of J20 mice. However, many of these genes, including the pro-apoptotic gene,Bid, were restored in the brains of J20 x CentA1 KO mice compared to J20 mice. In summary, our data indicate that CentA1 is required for the progression of AD phenotypes and that targeting CentA1 signaling at mitochondria might have therapeutic potential for AD prevention or treatment.

SIGNIFICANCE STATEMENT

ADAP1/Centaurin-α1 (CentA1) is highly enriched in the brain and increased CentA1 level has been linked to Alzheimer’s disease (AD). However, the precise role of ADAP1 in the pathogenesis of AD is poorly understood. We found that genetic deletion of CentA1 in the AD model mice rescues the pathological hallmarks of AD, including loss of dendritic spines in the hippocampus, amyloid plaque deposition, neuroinflammation and spatial memory deficits. Transcriptome analysis of forebrain samples using NanoString nCounter panels for 880 genes, identified the pro-apoptotic protein, Bid, with significantly reduced expression in the J20 mice on ADAP1 KO background. These findings point towards a role of ADAP1 in the activation of the mitochondrial pathways of death associated with the progression of neurodegeneration.
Changes in free-roaming dog population demographics and health associated with a catch-neuter-vaccinate-release program in Jamshedpur, India
Authors: Smith Lauren , Kartal Tamara , Rawat Sanjay , Chaudhari Amit , Kumar Ashok , Pandey Rajesh Kumar , Quinnell Rupert J. , Collins Lisa
Published: January 2025

India’s large free-roaming dog populations contribute to significant human health, environmental, and social challenges. Population management strategies, such as capture-neuter-vaccinate-return (CNVR), aim to reduce dog numbers, improve their welfare, and reduce human-animal conflict. The Humane Society International, in partnership with the Animal Health Foundation, implemented a CNVR program in Jamshedpur, neutering and vaccinating over 20,000 dogs. This study evaluates the impact of this program on dog health, population structure and size. The study areas encompassed 10 sites within the Jamshedpur Metropolitan Region, including both intervention sites where CNVR was directly applied and sites without direct intervention. Data was collected from May 2014 until December 2018, including bi-annual street surveys, as well as clinical data from the dogs captured and treated. We fit logistic regression, negative binomial, and binomial mixed effects models to assess changes in dog population characteristics, health, and reproductive conditions over time in relation to the CNVR intervention. We found that, over time, the CNVR program significantly reduced the probability of dogs entering the clinic with mange, transmissible venereal tumours, and pregnant. Street surveys showed an increase in sterilised dogs, with higher proportions observed in CNVR-treated sites, although the counts of dogs observed increased overall. The age-structure of free-roaming dogs remained stable over time. In CNVR-treated areas, the probability of observing lactating female dogs decreased, whereas it increased in untreated sites. This work contributes to the growing body of knowledge investigating the impact of dog population management interventions. Continued monitoring and evaluation of CNVR programs are required to identify optimal coverage required to reduce population size effectively.
Populations of the Australian saltmarsh mosquitoAedes vigilaxvary between panmixia and temporally stable local genetic structure
Authors: Schmidt Thomas L , Endersby-Harshman Nancy , Mills Toby , Rane Rahul , Pandey Gunjan , Hardy Chris , Court Leon , Webb Cameron , Trewin Brendan , Neilan Brett , Hoffmann Ary A
Published: January 2025

Pest management programs can operate more effectively when movement patterns of target species are known. As individual insects are difficult to track, genomic data can instead be used to infer movement patterns based on pest population structure and connectivity. These data can also provide critical information about cryptic taxa relevant to management. Here we present the first genomic investigation ofAedes vigilax, the Australian saltmarsh mosquito, a major arbovirus vector across Australasia. We used a ddRAD pool-seq approach and a draft genome assembly to investigate genetic variation in 60Ae. vigilaxpools from across Australia but with a focus on urban Newcastle and Sydney, NSW. There was strong genetic structure between samples from the west and east coasts of Australia, and additional structure that differentiated east coast populations. Within Newcastle and Sydney, contrasting patterns of genetic structure were evident. In Newcastle, there was no differentiation among subregions up to 60 km apart. In Sydney, samples from one urban subregion were differentiated from others < 3 km apart, and this structure was stable across sampling years. Heterozygosity and Tajima’s D indicated no bottlenecks in Newcastle or Sydney populations, suggesting this structure represents a gene flow barrier. Nuclear differentiation patterns contrast with previous mtDNA data indicating two COI clades in the east coast, one of which was also present in Western Australia. The panmixia over 60 km across the Newcastle region corroborates previous field observations of high dispersal capacity in this mosquito. These findings indicate specific challenges that may hinder local suppression strategies for this species.
Spectral acoustic contributions to musical pleasure are dynamically shaped by autonomic neural inputs
Authors: Cheung Vincent K.M. , Harada Tamaka , Sakamoto Shu , Furuya Shinichi
Published: January 2025

Most people enjoy music and often use music to regulate their emotions. Although pleasure derived from music-listening has been shown to be mediated by dopaminergic signals in the mesolimbic reward network, its relationship with physiology is still poorly understood. Here, we introducedtime-warped representational similarity analysis(twRSA) to directly map dynamic representations of multiple modalities across variable-duration stimuli. Our method revealed that although time-varying spectral and tonal acoustic features predicted changes in autonomic neural responses (measured via cardiac, pupil, and respiratory activity) during music-listening, only a small subset was in fact relevant to listeners’ on-line pleasure ratings. Despite that, we identified a weak mediation effect of physiology on shaping musical pleasure. Our results thus indicate that whilst musical pleasure may be embodied in bodily responses, the mapping between subjective experience and physiology is likely one-to-many—in line with psychological construction theories of emotion—and not one-to-one as is commonly assumed in classical basic emotion theories.
Design of an exclusive obligate symbiosis for organism-based biological containment
Authors: Forti Amanda M. , Jones Michaela A. , Elbeyli Defne N. , Butler Neil D. , Kunjapur Aditya M.
Published: January 2025

Biological containment is a critical safeguard for genetically engineered microbes prior to their environmental release to prevent proliferation in unintended regions. However, few biocontainment strategies can support the longer-term microbial survival that may be desired in a target environment without repeated human intervention. Here, we introduce the concept of an orthogonal obligate commensalism for the autonomous creation of environments that are permissive for survival of a biocontained microbe. We engineer one microbe to produce a non-standard amino acid (nsAA), and we engineer synthetic auxotrophy in a second microbe via reliance on this nsAA for growth. We show that this obligate commensalism is highly effective, with the survival of our commensal organism during co-culture dependent on the presence of our producer strain. We also show that this commensalism is orthogonal to a small microbial consortium isolated from maize roots, with survival of the synthetic auxotroph conditional upon the presence of the nsAA-producing strain in the consortium. Overall, our study demonstrates a transition from a chemical to a biological dependence for biocontained organisms that could lay the groundwork for biocontained synthetic ecologies.
Gait Adaptations in Step Length and Push-off Force during Walking with Functional Asymmetry
Authors: Baček Tomislav , Xu Yufan , Peng Liuhua , Oetomo Denny , Tan Ying
Published: January 2025

Human walking is remarkably adaptable, allowing individuals to maintain efficiency and stability across diverse conditions. This study investigates how healthy young adults adapt step length and push-off force to varying speeds and cadences under functional asymmetry induced by a unilateral knee constraint, simulating hemiparetic gait. A dataset of 19 participants walking across 30 conditions was used to examine these adaptations in both absolute terms and symmetry metrics. Results reveal that functional asymmetry disproportionately impacts propulsion, with constrained-leg force decreasing significantly at higher speeds. Step length symmetry remains stable, suggesting a prioritisation of spatial over kinetic symmetry, likely to optimise walking energetics and maintain anterior-posterior balance. Statistical models demonstrated good within-dataset performance but limited generalisability in cross-dataset predictions, where differences in population cohorts and experimental designs reduced accuracy. These findings provide insights into the mechanisms driving gait adaptations and highlight critical limitations in applying statistical models to patient populations, underscoring the importance of representative datasets and caution when extrapolating findings across populations.
A High Sensitivity Assay of UBE3A Ubiquitin Ligase Activity
Authors: Han Linna , Yagci Z. Begum , Keung Albert J.
Published: January 2025

UBE3A is an E3 ubiquitin ligase associated with several neurodevelopmental disorders. The development of several preclinical therapeutic approaches involving UBE3A, such as gene therapy, enzyme replacement therapy, and epigenetic reactivation, require the detection of its ubiquitin ligase activity. Prior commercial assays leveraged Western Blotting to detect shifts in substrate size due to ubiquitination, but these suffered from long assay times and have also been discontinued. Here we develop a new assay that quantifies UBE3A activity. It measures the fluorescence intensity of ubiquitinated p53 substrates with a microplate reader, eliminating the need for Western Blot antibodies and instruments, and enables detection in just 1 hour. The assay is fast, cost-effective, low noise, and uses components with long shelf lives. Importantly, it is also highly sensitive, detecting UBE3A levels as low as 1nM, similar to that observed in human and mouse cerebrospinal fluid. It also differentiates the activity of wild-type UBE3A and catalytic mutants. We also design a p53 substrate with a triple-epitope tag HIS-HA-CMYC on the N terminus, which allows for versatile detection of UBE3A activity from diverse natural and engineered sources. This new assay provides a timely solution for growing needs in preclinical validation, quality control, endpoint measurements for clinical trials, and downstream manufacturing testing and validation.
Non-invasive characterization of oocyte deformability in micro-constrictions
Authors: Barbier Lucie , Bulteau Rose , Rezaei Behnam , panier Thomas , Labrune Elsa , Verlhac Marie-Hélène , Vernerey Franck , Campillo Clement , Terret Marie-Emilie
Published: January 2025

Oocytes naturally present mechanical defects that hinder their development after fertilization. Thus, in the context of assisted reproduction, oocyte selection based on their mechanical properties has great potential to improve the quality of the resulting embryos and the success rate of these procedures. However, the use of mechanical properties as a quantifiable selective criterion requires robust and non-destructive measurement tools. This study developed a constriction-based microfluidic device that monitors the deformation of mouse oocytes under controlled pressure. The device can distinguish mechanically aberrant oocyte groups from healthy control ones. Based on a mathematical model, we propose that deformability measurements infer both oocyte tension and elasticity, elasticity being the most discriminating factor in our geometry. Despite force transmission during oocyte deformation, no long-term damage was observed. This non-invasive characterization of mouse oocyte deformability in micro-constrictions allows for a significant advance in assessing the mechanical properties of mammalian oocytes and has potential application as a quantifiable selective criterion in medically assisted reproduction.

Teaser

A measurement method for translating advances in oocyte mechanics into selection criteria for improving medically assisted reproduction.
High genetic diversity and no detectable founder effects following a rapid range expansion of a long-distance migrant (Acrocephalus scirpaceus)
Authors: Bergman Nora M. , Lehikoinen Petteri , Kluen Edward , Bensch Staffan , Lo Cascio Sætre Camilla , Eroukhmanoff Fabrice , Fossøy Frode , Procházka Petr , Smith William J. , Stokke Bård G. , Primmer Craig R. , Thorogood Rose , Rönkä Katja
Published: January 2025

Many species are currently experiencing range shifts in response to climate change. The colonisation of new regions can have serious genetic consequences for the shifting population, given that repeated founder events and strong genetic drift are expected to erode genetic variation along the expansion axis. Such a loss of genetic diversity could reduce adaptive potential, slowing or even halting the expansion. These genetic consequences are known to be particularly acute in species with low dispersal capabilities and therefore low levels of gene flow. Whether highly mobile species experience similar genetic bottlenecks as they undergo environment-driven range shifts is, however, less clear. Here we combined ecological and genomic evidence to (1) infer the origin and (2) quantify the genetic consequences of a recent and rapid northward range expansion of the common reed warbler (Acrocephalus scirpaceus), a philopatric long-distance migratory passerine capable of high dispersal. Together, historical observations, ringing data, and genomic RAD-seq data covering the species’ European breeding range support an expansion origin from southwest. There were no reductions in levels of nucleotide diversity or allelic richness along the colonisation route, and no detectable allele frequency clines persisting from potential past founder effects. The genomic dataset confirmed the occurrence of low but significant levels of geographically continuous population structure across the European range. These results suggest that high dispersal capabilities can help even strongly philopatric species to escape the genetic costs of rapid range expansions. The lack of genetic patterns also highlights the value of combining multiple lines of evidence to reveal range shifts as genomic data alone was not sufficient to detect the occurrence of this large-scale range expansion.
Coherent feedback control for cavity optomechanical systems with a frequency-dependent mirror
Authors: Du Lei , Monsel Juliette , Wieczorek Witlef , Splettstoesser Janine
Published: January 2025

Ground-state cooling of mechanical resonators is a prerequisite for the observation of various quantum effects in optomechanical systems and thus has always been a crucial task in quantum optomechanics. In this paper, we study how to realize ground-state cooling of the mechanical mode in a Fano-mirror optomechanical setup, which allows for enhanced effective optomechanical interaction but typically works in the (deeply) unresolved-sideband regime. We reveal that for such a two-sided cavity geometry with very different decay rates at the two cavity mirrors, it is possible to cool the mechanical mode down to its ground state within a broad range of parameters by using an appropriate single-sided coherent feedback. This is possible even if the total optical loss is more than seven orders of magnitude larger than the mechanical frequency and the feedback efficiency is relatively low. Importantly, we show that a more standard double-sided feedback scheme is not appropriate to cooperate with a Fano-mirror system.

Published by the American Physical Society
2025
Two-scale effective model for defect-induced localization transitions in non-Hermitian systems
Authors: Davies B. , Barandun S. , Hiltunen E. O. , Craster R. V. , Ammari H.
Published: January 2025

We illuminate the fundamental mechanism responsible for the transition between the non-Hermitian skin effect and defect-induced localization in the bulk. We study a Hamiltonian with nonreciprocal couplings that exhibits the skin effect (the localization of all eigenvectors at one edge) and add an on-site defect in the center. Using a two-scale asymptotic method, we characterize the long-scale growth and decay of the eigenvectors and derive a simple and intuitive effective model for the transition that occurs when the defect is sufficiently large that one of the modes is localized at the defect site, rather than at the edge of the system.

Published by the American Physical Society
2025
Heavy ion collisions from
sNN
of 62.4 GeV down to 7.7 GeV in the EPOS4 framework
Authors: Werner K. , Jahan J. , Karpenko I. , Pierog T. , Stefaniak M. , Vintache D.
Published: January 2025

The EPOS4 project is an attempt to construct a realistic model for describing relativistic collisions of different systems, from proton-proton (pp) to nucleus-nucleus (AA), at energies from several TeV per nucleon down to several GeV. We argue that a parallel scattering formalism (as in EPOS4) is relevant for primary scatterings in AA collisions above 4 GeV, whereas sequential scattering (cascade) is appropriate below. We present briefly the basic elements of EPOS4, and then investigate heavy ion collisions from 62.4 GeV down to 7.7 GeV, to understand how physics changes with energy, studying in particular the disappearance of the fluid component at low energies.

Published by the American Physical Society
2025
Unified description of corpuscular and fuzzy bosonic dark matter. II. Dissipation and stochastic forces
Authors: Proukakis Nick P. , Rigopoulos Gerasimos , Soto Alex
Published: January 2025

We extend our previous work [Proukakis , Unified description of corpuscular and fuzzy bosonic dark matter, ] on the dynamics of bosonic, nonrelativistic and self-interacting dark matter that simultaneously contains both a “fuzzy” low-momentum component and one with higher momenta that may be well approximated as a collection of distinct particles and described by a corresponding phase-space distribution. Starting from the nonrelativistic Schwinger-Keldysh action and working beyond leading-order in the Keldysh basis fields, encoding stochastic fluctuations of the slow modes and all fluctuations of the fast modes, we obtain stochastic self-consistently coupled Gross-Pitaevskii, collisional Boltzmann kinetic and Poisson equations. Our final set of equations, which feature various collisional (dissipative and scattering) contributions and two corresponding independent stochastic force terms, are consistent with generalized fluctuation-dissipation type relations in the limit of thermal equilibrium between the particles.

Published by the American Physical Society
2025
Active particles in a tube: A generalized entropy potential approach
Authors: Zhao Yongfeng
Published: January 2025

We study the transport of self-propelled noninteracting active Brownian particles and run-and-tumble particles in long tubes of varying widths. Using a moment expansion, we construct a generalized Fick-Jacobs framework for the active particles when the tube width is large and slowly varying. We show that the variation of the particle density along the tube is well described by a one-dimensional generalized entropy potential. This potential resembles its passive counterpart, albeit with an effective temperature and an effective tube width that are renormalized by the activity. Our generalized entropy potential approach allows us to predict the steady-state density distribution along the tube as well as the mean-escape time out of a spindle chamber. Finally, we show how to account for the emergence of spontaneous ratchet flows in asymmetric channels by including higher-order corrections neglected in the effective entropy potential approach.

Published by the American Physical Society
2025
Investigation of the effect of interactive art activity program on repetitive behaviors, social skills and parents’ emotions in children with autism spectrum disorder
Authors: İnci Ramazan , Sağlam Mehmet
Published: January 2025

Purpose

The purpose of this study was to examine the effects of an interactive art activity program on repetitive behaviors, social skills and parents’ emotions in children with autism spectrum disorder.

Design/methodology/approach

The research was carried out in autism classes and special education and rehabilitation centers of children diagnosed with autism in Batman city center between September 2021 and March 2022. The study was concluded with 28 children with Autism spectrum disorder (5–17 years old) and their mothers (13 experiments, 15 controls). Data were collected using the Personal Information Form, the ASSP-T Form, the Quality of Life in Autism Questionnaire-Parent Edition and the Social Impact Form of the Repetitive Behaviors in Children with Autism Scale. In the analysis, in the comparison of the pretest, posttest and retention data in the application group, repeated measures ANOVA was used if the data were suitable for normal distribution, and Friedman analysis was used if not. In the comparison of the data in the control group, the Paired T test was used if the data were suitable for normal distribution, and the Wilcoxon test was used if it was not.

Findings

After the training, it was concluded that there was a significant difference p < 0.05 on social skills, repetitive behaviors and quality of life of the children and mothers in the experimental group, and there was no significant difference in the control group in general.

Research limitations/implications

It was determined that the interactive art activity program of children with autism had a positive effect on repetitive behaviors, social skills and parents’ emotions.

Originality/value

Considering the positive effect of art activities on children’s social skills and repetitive behaviors, educational programs for children with autism can be integrated with art and sports activities, and the use of different areas of art and sports can be expanded, taking into account the interests and readiness of the children.
Impact of corporate reputation on market risk: Indian evidence
Authors: Kaur Amanpreet , Joshi Mahesh , Singh GaganDeep
Published: January 2025

Purpose

The study aims to examine the relation between corporate reputation and a firm’s systematic risk for top performing Indian companies.

Design/methodology/approach

The paper uses Panel regression analysis of the data from the top 500 listed Indian companies constituting the BSE500 index over a 15-year period from 1 April 2002–31 March 2017. Firm age and shareholders’ return have been used as proxy of firm reputation. This paper use signalling theory to explain the impact of corporate reputation on market risk where proxy for the corporate reputation is seen as an information available to the market.

Findings

The findings show a significant positive impact of corporate reputation on systematic risk, indicating that a firm’s systematic risk increases with its reputation. Specifically, the findings suggest that reputed firms experience increased levels of market risk and scrutiny from stakeholders.

Practical implications

The results will help corporate managers from developing economies where corporate reputation plays an important role in determining the investment behaviour.

Originality/value

This study deploys two broad approaches to measure reputation and discern its impact on risk, such as reputation among financial stakeholders and reputation among public stakeholders on market risk, specifically on fast emerging Indian market.
Analysis of the perceived firm ethicality and brand loyalty through the lens of corporate social responsibility, green brand innovativeness and green marketing: evidence from an emerging economy
Authors: Budi Riharjo Ikhsan , Efendi David , Kurnia Kurnia , Respatia Wimba
Published: January 2025

Purpose

The aim of this study is to examine the relationship between the perceived firm ethicality and loyalty behaviour of consumers through the lens of corporate social responsibility (CSR), green brand innovativeness (GBI) and green marketing (GM).

Design/methodology/approach

The authors used questionnaires as a primary method of data collection. The authors selected four large malls in Jakarta, the capital of Indonesia and three large malls in Surabaya, the second-largest city in the country. These locations were chosen due to their high levels of consumer activity and the presence of numerous products from major companies.

Findings

The findings provide strong support for all proposed hypotheses, confirming that perceived firm ethicality plays a crucial role in significantly enhancing brand loyalty. This positive relationship however is mediated through distinct pathways, namely CSR, GBI and GM. Each of these factors contributes meaningfully to shaping consumer perceptions of a firm’s ethicality, which in turn drives greater loyalty to the brand. Collectively, these strategies synergise to amplify a firm’s perceived ethicality, further solidifying brand loyalty. Notably, CSR, perceived firm ethicality, GBI and GM together account for approximately 65.2% of the variance in customer brand loyalty.

Originality/value

The study offers important theoretical insights into attachment theory by extending it to consumer-brand relationships, demonstrating that perceived firm ethicality fosters emotional attachment, which enhances brand loyalty. Just as secure attachment in human relationships builds trust and loyalty, consumers develop emotional bonds with brands they perceive as ethical, supported by CSR practices, GBI and GM from the firms. These strategies reinforce consumer trust and loyalty, paralleling attachment theory’s secure base concept.
Affiliate eWOM: exploring in the purchase intention of beauty and personal care products
Authors: Ghorbanzadeh Davood , Chandra Teddy , Pallathadka Harikumar , Radie A. Abdalmmir , Sharipov Sharofiddin , Prasad KDV
Published: January 2025

Purpose

Particularly in the rapidly expanding beauty and personal care sector, affiliate electronic word of mouth (eWOM) from affiliates has grown to be a dependable and trustworthy source of information. Guided by Signaling Theory, this paper aims to conduct a comprehensive analysis to understand the intricate dynamics of affiliate eWOM within the context of Iranian beauty and personal care products.

Design/methodology/approach

The study polled 330 consumers who have purchased beauty and personal care products in Iran. Data were gathered using a convenience sample, and the partial least square structural equation modeling model was used to examine and assess the hypotheses.

Findings

The results demonstrated a significant impact of information quality, rating, helpfulness and number of reviews, along with user-generated videos and photos, on the customer’s actual purchase and intention to purchase the beauty and personal care products. However, the ranking and recency of reviews do not significantly contribute to the stated relationship.

Originality/value

This research is first of its kind to analyze affiliate eWOM cues in the case of cosmetics e-commerce.
Investigating the impact of multiple media use on performance in dispersed teams: unraveling the millefeuille effect
Authors: Boukef Nabila , Haas Aurore , Kalika Michel
Published: January 2025

Purpose

This paper aims to investigate the use of social media platforms compared to IT-enabled communication in the context of dispersed teams.

Design/methodology/approach

We draw on the millefeuille theory to develop a model that examines the impact of multiple media use (namely the millefeuille effect) on team performance. Data were collected from 70 dispersed teams.

Findings

We showed dispersed teams are more likely to improve their performance when relying on diverse media, including social media platforms and other IT-enabled communication. We provide empirical evidence that the millefeuille effect does not necessarily impede performance.

Originality/value

An increasing number of companies are implementing social media platforms as part of their media portfolio in addition to the already existing IT-enabled communication, such as email. However, we lack understanding of how the use of different media impacts team performance. Drawing on the millefeuille theory, this study investigates the use of social media platforms in dispersed teams by examining how their use with other IT-enabled communication can lead to team performance. This research introduces and differentiates two measures of the millefeuille effect to explain the different impacts of the millefeuille effect: millefeuille size (the number of non-overlapping media used) and millefeuille diversity (the variety of media used).