bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA Expression in Asymptomatic Welders: Implications for Biomarker Discovery for Environmentally-Linked Neurodegenerative Disorders
Authors: Bargues-Carot Alejandra , Prado-Rico Janina , Kawasawa Yuka Imamura , Cai Jiazhang , Yanosky Jeff D. , Zenitsky Gary , Jin Huajun , Lewis Mechelle , Ma Ping , Anantharam Vellareddy , Kanthasamy Arthi , Rico Andre Luis Garao , Hall Molly A. , Mailman Richard B. , Kanthasamy Anumantha G. , Huang Xuemei
Published: February 2025

Chronic occupational exposure to metals in welding fumes has been implicated in the etiology of neurodegenerative diseases (NDDs), including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Changes in microRNA (miRNA) expression have been associated with various neurodegenerative conditions. Circulating miRNAs, in particular, have emerged as promising, minimally invasive biomarkers for diagnosing and monitoring disease progression. This study was designed to characterize the expression of miRNAs in neuronally-enriched serum extracellular vesicles (EVs) among welders and non-welders to explore their potential link to metal concentrations and welding exposure measures and their potential as early diagnostic biomarkers for neurodegeneration. Serum samples from 39 welders and 27 healthy individuals were collected, and EV-enclosed miRNAs were extracted and analyzed. Also, whole blood metal concentrations and welding exposure measurements were obtained. Fifty miRNAs were found to be dysregulated in weldersvs.non-welders, of which three (miR-16-5p, miR-93-5p, miR-486-5p) showing reduced expression and two (miR-4281 and miR-4417) exhibiting positive correlations with blood metal concentrations as well as with long- and short-term welding exposure measures. The dysregulation of these miRNAs suggests that exposure to metals could disrupt important biological processes, possibly contributing to an elevated risk of NDDs. These findings highlight the need for further research to validate the causal relationship between exposure to metals in welding fumes, the dysregulation of circulating miRNAs, and their role in neurodegenerative disease development, with implications for miRNA-based biomarkers in early disease detection and prevention.
A novel virus vB_PshM_Y4 with low similarity to both cultured and uncultured viruses
Authors: Zheng Zhaobin , Zhao Lei , Wang Wei , Liu Yundan , Zheng Kaiyang , Chen Xin , Zhang Suqing , Sun Yue , Ma Zhe , Shao Hongbing , Sung Yeong Yik , Mok Wen Jye , Wong Li Lian , Gao Chen , Sun Libin , Liang Yantao tao
Published: February 2025

Viruses are the abundant and diverse biological entities on the Earth. During past decades, our knowledge about genomic diversity of viruses has been greatly expanded through high-throughput sequencing. However, whether traditional isolation method could detect virus that could not be identified by high-throughput sequencing is still unknown. In this study, a novel virus, vB_PshM_Y4, infecting Pseudoalteromonas shioyasakiensis, which is an opportunistic pathogen of economically important marine species, was isolated. After comparing vB_PshM_Y4 with the over 15 million genomes of both cultivated and uncultivated viruses in the NCBI and IMG/VR v4 datasets, no similar genome was identified. This suggests that viral isolation methods can detect novel viruses that may not be identified through high-throughput sequencing alone. Transmission electron microscopy showed that vB_PshM_Y4 exhibits the myoviral morphology. The virus possesses a double-stranded DNA genome that is 158,231 bp in length, with a G+C content of 30.92%, and contains 226 open reading frames (ORFs). Six ORFs were identified as putative auxiliary metabolic genes (AMGs). Phylogenetic tree and gene content-based network analyses indicated that vB_PshM_Y4 may represent a novel viral species within an unknown family of the Caudoviricetes class. Additionally, biogeographical distribution analysis showed that vB_PshM_Y4 were mainly detected in the Arctic and temperate and tropical epipelagic zones with low abundance.
Identification of the Inducible HIV reservoir in Tonsillar, Intestinal and Cervical Tissue Models of HIV Latency
Authors: Gallego-Cortés A. , Sánchez-Gaona N. , Mancebo-Pérez C. , Ruiz-Isant O. , Benítez-Martínez A. , Landolfi S. , Castellví J. , Pumarola F. , Ortiz N. , Llano I. , Lorente J. , Mañalich-Barrachina L. , Prado JG. , Martín-Gayo E. , Falcó V. , Genescà M. , Buzon MJ.
Published: February 2025

HIV persists in diverse tissues, with distinct cellular reservoirs presenting a major barrier to a cure and requiring targeted therapeutic strategies to address this heterogeneity. Here, we developed tissue models of HIV latency using human tonsillar, intestinal and cervicovaginal tissues. These models revealed differential HIV infection across CD4+T cell subpopulations, with ART partially restoring CD4+T cells and reducing intact HIV DNA. T follicular helper cells (TFH CD69+ CCR7-) were the primary inducible reservoir in tonsils, while tissue-resident memory cells (TRM CD69+ CD49a+) dominated in the intestine. Identification of markers for inducible reservoirs revealed that CD69, CD45RO, and PD-1 were shared across tissues, while CXCR5 in the tonsils and CD49a in the intestine served as tissue-specific markers. Furthermore, using different latency reversal agents (LRAs) we found that Histone Deacetylase Inhibitors (HDACis) failed to induce HIV in any tissue, the SMAC mimetic AZD5582 was effective only in a resident-memory CD4+T cell subpopulation in the intestine, and IL15 exhibited the broadest reactivation potential across tissues and CD4+T subsets. These models recapitulate key aspects of HIV infection providing insights into the inducible reservoir’s composition in different tissues and informing strategies for its elimination.
Exposure to rotenone triggers redox driven system-wide lipidome alterations and metabolic trade-offs linked to Parkinson’s disease
Authors: Tiwari Ashutosh Kumar , Rathor Priya , Patel Rajendra P , Jha Pawan Kumar , Birse Nick , Ratnasekhar CH
Published: February 2025

With the global rise in aging populations, the increasing incidence of neurodegenerative diseases underscores concerns about brain health, with pesticides like rotenone, emerging as key environmental hazardous. The precise mechanism by which chronic environmental concentration of rotenone exposure causes Parkinson-like phenotype is not understood. Previous studies showed that rotenone induces depletion of dopaminergic neurons by influencing mitochondrial functions. Mitochondrial dysfunction alters lipid homeostasis; therefore, brain lipids can be potential targets for the early risk assessment and prognosis of Parkinson’s disease (PD). However, the specific lipidome changes and associated biomarkers of chronic rotenone in vivo exposure causing PD are largely unknown. This study investigates the lipid profile disruptions and biomarkers induced by environmentally relevant concentrations of chronic rotenone exposure using the neuro-modelDrosophila melanogaster. An untargeted LC-HRAMS-based lipidomics identified that lipid classes, GP, SP, FA and GL were significantly altered. Furthermore, system-wide loss of cross talk of mitochondrial and peroxisome lipids by altering their redox homeostasis causing PD was observed. Additionally, lipid oxidative stress markers, and behavior abnormalities correlated with altered lipids linked to PD. The findings highlight the rotenone induced complex metabolic trade-offs, prioritizing brain’s neural integrity at the expense of peripheral lipid levels, leading to PD.

Environmental implication

This study highlights the environmental risks of chronic rotenone exposure, commonly used in agriculture. The findings show that even low concentrations of rotenone disrupt lipid metabolism, particularly in the brain, affecting mitochondrial and peroxisomal functions, contributing to depleting dopaminergic neurons, which are linked to neurodegenerative diseases like Parkinson’s. The study also identify lipid markers linked to rotenone induced PD and reveals metabolic trade-offs, where the brain prioritizes neural integrity over peripheral lipid balance. These lipidome changes and redox-driven shifts threaten both individual health and ecosystem stability, emphasizing the need for policies to regulate pesticide use and minimize exposure risks.

Graphical abstract
Protein degradation and growth dependent dilution substantially shape mammalian proteomes
Authors: Leduc Andrew , Slavov Nikolai
Published: February 2025

Cellular protein concentrations are maintained through a balance of synthesis and clearance. Clearance occurs through both protein degradation and growth-dependent dilution. At slow growth, clearance is dominated by degradation, which leads to the accumulation of long lived proteins. At fast growth, however, it is dominated by dilution, preventing this accumulation. Thus, the concentration of long lived proteins will be reduced unless cells compensate by preferentially increasing synthesis rates. To determine the dominant regulatory mechanisms, we quantified the degree of compensation between activated and resting human B cells and across mouse tissues. The results indicate that growth-dependent dilution is insufficiently compensated for by changes in protein synthesis, and it accounts for over a third of the concentration changes between high and low growth conditions. Furthermore, we find that about 25 % of the differences in protein concentration across all tissues are controlled by protein clearance. When comparing only slowly growing tissues such as the brain and pancreas, clearance differences explain as much as 42 %. Within a tissue or cell type, clearance variation is sufficient to account for 50 % of the abundance variation for all measured proteins at slow growth, contrasted with 7 % at fast growth. Thus, our model unifies previous observations with our new results and highlights a context-dependent and larger than previously appreciated contribution of protein degradation in shaping protein variation both across the proteome and across cell states.
Predictors of brain iron deposition in dementia and Parkinson’s disease-associated subcortical regions: genetic and observational analysis in UK Biobank
Authors: Casanova Francesco , Tian Qu , Williamson Daniel S , Lucas Mitchell R , Zweibaum David , Ding Jun , Atkins Janice L , Melzer David , Ferrucci Luigi , Pilling Luke C
Published: February 2025

Background

Brain iron in specific subcortical regions increases risk of dementia and Parkinson’s Disease (PD). Genetic and environmental factors affect iron deposition, but the underlying mechanisms are unclear.

Objective

Identify risk factors and diseases associated with brain iron, and assess causality using genetics.

Methods

41,581 UK Biobank participants had MRI-estimated brain iron in four dementia or PD-associated subcortical regions (Caudate, Putamen, Substantia Nigra, Thalamus). We investigated common risk factors (including adiposity, blood pressure, health behaviours, and inflammation) and diseases observationally, using covariate-adjusted regression models, and genetically, with Mendelian randomization.

Results

Participants diagnosed with Alzheimer’s disease, PD, or other diseases had higher brain iron. Anaemia, osteoporosis, and hyperparathyroidism were associated with lower brain iron. Higher BMI and blood pressure, history of smoking, and self-reported meat consumption, increased brain iron. Haematological parameters, inflammatory and kidney biomarkers, and calcium, were also associated.

Genetics support causal effects of depression, type-2 diabetes, and 7 other diseases with increased iron, but not Alzheimer’s disease. Evidence supports a causal effect of osteoporosis on lower iron in the substantia nigra. We found causal associations between adiposity and proteins (such as IL-6 receptor and transferrin receptor) on subcortical brain iron.

Conclusions

We identified causal effects for liability to type-2 diabetes, depression, and other conditions, on subcortical iron deposition, but not to Alzheimer’s disease, supportive of dementia as a consequence of brain iron deposition, not a cause. The role of adiposity reducing interventions on brain iron should be investigated. Relationships between brain iron, osteoporosis, calcium, and hyperparathyroidism warrant further investigation.
Wearable MEG data recorded during human stepping
Authors: Spedden Meaghan E. , O’Neill George C. , West Timothy O. , Tierney Tim M. , Mellor Stephanie , Alexander Nicholas A. , Seymour Robert , Lundbye-Jensen Jesper , Nielsen Jens Bo , Farmer Simon F. , Bestmann Sven , Barnes Gareth R.
Published: February 2025

Non-invasive spatiotemporal imaging of brain activity during large-scale, whole body movement is a significant methodological challenge for the field of movement neuroscience. Here, we present a dataset recorded using a new imaging modality – optically-pumped magnetoencephalography (OP-MEG) – to record brain activity during human stepping. Participants (n=3) performed a visually guided stepping task requiring precise foot placement while dual-axis and triaxial OP-MEG and leg muscle activity (electromyography, EMG) were recorded. The dataset also includes a structural MRI for each participant and foot kinematics. We validate the fidelity of the OPM data by showing movement-related beta band desynchronization source localised to the primary motor cortex. This multimodal dataset offers a resource for methodological development and testing for OPM data (e.g., movement-related interference rejection), within-subject analyses, and exploratory analyses to generate hypotheses for further work on the neural control of human stepping.
Rearing conditions bidirectionally modulate cognitive abilities and AP-1 signaling in hippocampal neurons in a cell type-specific manner
Authors: Alaiz-Noya Marta , Miozzo Federico , Fuentes-Ramos Miguel , Machnicka Magdalena , Kurowska Marcelina , Herrera Macarena L. , del Blanco Beatriz , Ninerola Sergio , Bustos-Martínez Isabel , Wilczynski Bartek , Barco Angel
Published: February 2025

Environmental conditions profoundly influence cognitive development, particularly during early life. Transcriptional and epigenetic mechanisms may serve as molecular substrates for the lasting effects of environmental enrichment (EE) and impoverishment (IE) on cognitive abilities and hippocampal function. However, the specific gene programs driving these changes remain largely unknown. In this study, EE and IE modulated the cognitive abilities of mice in opposing directions. By combining hippocampal microdissection and genetic tagging of neuronal nuclei with genome-wide analyses of gene expression, chromatin accessibility, histone acetylation, and DNA methylation, we uncovered profound differences in the transcriptional and epigenetic profiles of CA1 pyramidal neurons and dentate gyrus (DG) granule neurons. These analyses revealed cell type-specific genomic changes induced by EE and IE, highlighting distinct patterns of neuroadaptation within each population. This multiomic screen pinpointed the activity-regulated transcription factor AP-1 as a crucial mediator of neuroadaptation to conditions during early life in both cell types, albeit through distinct downstream mechanisms. Conditional deletion ofFos, a core AP-1 subunit, in excitatory neurons hampered EE-induced cognitive enhancement, further underscoring the pivotal role of this transcription factor in neuroadaptation.
AI-qualizing Science
Authors: Divakaruni Anantha , Bares Francois , Phalippou Ludovic
Published: February 2025

Researchers face significant disparities in accessing resources for high-impact research. Artificial Intelligence (AI) promises to bridge these gaps by offering capabilities previously unavailable to many institutions. This paper examines the effects on protein research of AlphaFold, an AI tool that won the 2024 Nobel Prize in Chemistry for accurately predicting protein structures. Using comprehensive publication data, we show that AlphaFold benefits researchers at lower-ranked universities as their share of top-journal publications increases significantly following its release. These findings suggest that AI tools can lower barriers to entry in resource-intensive scientific fields and challenge established knowledge production hierarchies. AI can lead to a more equitable distribution of opportunities, with broader implications for innovation, scientific discovery, and research policy.
Identifying Neurobiological Psychosis Biotypes Using Multi-Scale Functional Network Connectivity and its Latent Independent Subspace
Authors: Ballem Ram , Andrés-Camazón Pablo , Jensen Kyle M. , Bajracharya Prerana , Díaz-Caneja Covadonga M. , Bustillo Juan R , Turner Jessica A. , Pearlson Godfrey D. , Chen Jiayu , Calhoun Vince D. , Iraji Armin
Published: February 2025

Psychotic disorders present a great amount of biological heterogeneity. We explore this by leveraging multiscale functional network connectivity (msFNC) to identify distinct neurobiological psychosis biotypes. Resting-state fMRI data from 2103 B-SNIP 1&2 participants (1127 with psychosis, 350 relatives, 626 controls) were analyzed to obtain subject-specific multiscale intrinsic connectivity networks (msICNs) and compute msFNCs. A low-dimensional neurobiological subspace of multiscale connectivity features termed Latent Network Connectivity (LNC) was identified, consisting of three components (cognitive-related, typical, psychosis-related). Projections of psychosis participants’ msFNC onto this subspace revealed three distinct biotypes through unsupervised learning. These biotypes, characterized by cognitive, clinical, and connectivity profiles, spanned all DSM diagnoses (Schizophrenia, Bipolar, Schizoaffective disorders), revealing their overlapping connectivity profiles. Biotype-1, the most cognitively impaired compared to other biotypes, showed Cerebellar-Subcortical and Visual-Sensorimotor hypoconnectivity, alongside Visual-Subcortical hyperconnectivity. Biotype-2 was most cognitively preserved and showed Visual-Subcortical, Subcortical-Sensorimotor, and Subcortical-Higher Cognition hypoconnectivity. Biotype-3 exhibited intermediate cognitive function, showing Cerebellar-Subcortical hypoconnectivity alongside Cerebellar-Sensorimotor and Subcortical-Sensorimotor hyperconnectivity. Notably, unaffected relatives displayed intermediate connectivity patterns, with 55% classified into the same biotype group as their affected family member—a significantly higher rate than random chance (p-valueRelatives-to-Biotype-1< 0.001, p-valueRelatives-to-Biotype-2< 0.05, p-valueRelatives-to-Biotype-3< 0.001) compared to a non-significant 37% alignment using DSM-based diagnosis. Cognitive performance reliably aligns with distinct brain connectivity patterns, which are also evident in unaffected relatives, supporting their construct validity. These findings underscore the limitations of DSM-based classifications in capturing the biological complexity of psychotic disorders and highlight the potential of neurobiological biotypes to enhance our understanding of their spectrum.
Evaluating Variants of Uncertain Significance in Adult Knock-in Zebrafish: A Proof of Concept with aCOL1A2Variant
Authors: Vanhooydonck Michiel , Debaenst Sophie , Vanbelleghem Eva , De Saffel Hanna , Syx Delfien , Sips Patrick , Coucke Paul J. , Willaert Andy , Callewaert Bert
Published: February 2025

Genomic variants of uncertain significance (VUS) impede clinical decision-making. In this study, we use a knock-in strategy in zebrafish to evaluate theCOL1A2c.2123G>A VUS, identified in a 59-year-old female with recurrent fractures. Using prime editing, we obtained different zebrafish lines respectively harboring the VUS, a known pathogenic variant, or a known benign variant. Comprehensive skeletal phenotyping revealed no significant abnormalities in the zebrafish modeling the benign variant and the VUS, while zebrafish modeling the pathogenic variant showed scoliosis of the vertebral column, vertebral fusions, vertebral compressions, fractures, and increased mineralization of the notochord and intervertebral ligament. Our findings demonstrate for the first time, thatCOL1A2variant modeling in zebrafish models informs functional validation and shows potential for elucidating associated pathogenic mechanisms. This approach can be extended to study VUS in other genes.
Ankyrins are essential for synaptic integrity of photoreceptors in the mouse outer retina
Authors: Perez Ross M , Campbell Jay , Goswami-Sewell Debalina , Venkatraman Rajashree , Gomez Cesiah C , Bagnetto Caitlin , Lee Audrey , Mattos Marlon F , Hoon Mrinalini , Zuniga-Sanchez Elizabeth
Published: February 2025

The mammalian visual system consists of two distinct pathways: rod- and cone-driven vision. The rod pathway is responsible for dim light vision whereas the cone pathway mediates daylight vision and color perception. The distinct processing of visual information begins at the first synapse of rod and cone photoreceptors. The unique composition and organization of the rod and cone synapse is what allows information to be parsed into the different visual pathways. Although this is a critical process for vision, little is known about the key molecules responsible for establishing and maintaining the distinct synaptic architecture of the rod and cone synapse. In the present study, we uncovered a new role for Ankyrins in maintaining the synaptic integrity of the rod and cone synapse. Loss of Ankyrin-B and Ankyrin-G results in connectivity defects between photoreceptors and their synaptic partners. Ultrastructure analysis of the rod and cone synapse revealed impaired synaptic innervation, abnormal terminal morphology, and disruption of synaptic connections. Consistent with these findings, functional studies revealed impairedin vivoretinal responses in animals with loss of Ankyrin-B and Ankyrin-G. Taken together, our data supports a new role for Ankyrins in maintaining synaptic integrity and organization of photoreceptor synapses in the mouse outer retina.

SIGNFICANCE STATEMENT

The first synapse in the outer retina begins to process visual information into two distinct pathways. This is largely attributed to the different composition and organization of the rod and cone synapse. Although the structural integrity of the rod and cone synapse is critical for normal vision, little is known about the key molecules responsible for maintaining the unique structure of the different photoreceptor synapses. In this study, we demonstrate a new function for the cytoskeletal scaffolding proteins, Ankryin-B and Ankyrin-G in the mouse outer retina. We found Ankyrin-B and Ankyrin-G are both required for proper retinal connectivity, where loss of these molecules leads to synaptic defects and impaired retinal responses.
Mutations in TAC1B drive CDR1 and MDR1 expression and azole resistance in C. auris
Authors: Barker Katherine S , Santana Darian J , Zhang Qing , Peters Tracy L , Rybak Jeffrey , Morschhauser Joachim , Cuomo Christina A , Rogers P David
Published: February 2025

Objective: Candida auris has emerged as a fungal pathogen of particular concern owing in part to its propensity to exhibit antifungal resistance, especially to the commonly prescribed antifungal fluconazole. In this work we aimed to determine how mutations in the transcription factor gene TAC1B, which are common among resistant isolates and confer fluconazole resistance, exert this effect. Methods: Selected TAC1B mutations from clinical isolates were introduced into a susceptible isolate and reverted to the wild-type sequence in select clinical isolates using CRISPR Cas9 gene editing. Disruption mutants were likewise generated for select genes of interest. TAC1B mutants were subjected to transcriptional profiling by RNA-seq, and relative expression of specific genes of interest was determined by qRT-PCR. Antifungal susceptibilities were determined by modified CLSI broth microdilution. Results: TAC1B mutations leading to A640V, A657V, and F862_N866del conferred fluconazole resistance, as well as increased resistance to other triazoles, when introduced into a susceptible isolate. RNA-seq revealed that the ATP-Binding Cassette (ABC) transporter gene CDR1 as well as the Major Facilitator Superfamily (MFS) transporter gene MDR1 were both upregulated by these TAC1B mutations. Disruption of CDR1 greatly abrogated resistance in strains with TAC1B mutations whereas disruption of MDR1 had little to no effect. However, disruption of both CDR1 and MDR1 resulted in an additional reduction in resistance as compared to disruption of either gene alone. Conclusion: TAC1B mutations leading to A640V, A657V, and F862_N866del all result in increased resistance to fluconazole and other triazole antifungals, and increased expression of both CDR1 and MDR1 in C. auris. CDR1 is the primary driver of resistance conferred by these TAC1B mutations.
The minor antennae of photosystem II contribute to qH-energy dissipation inArabidopsis
Authors: Bru Pierrick , Crepin Aurélie , Provot Yolande , Guardini Zeno , Bassi Roberto , Dall’Osto Luca , Malnoë Alizée
Published: February 2025

Photosynthesis is a biological process that converts light energy into chemical energy. Excessive light can damage the photosynthetic machinery, so plants have evolved photoprotective mechanisms such as non-photochemical quenching (NPQ). Among the NPQ mechanisms, qH is a form of sustained quenching, dependent on LIPOCALIN IN THE PLASTID (LCNP) and repressed by SUPPRESSOR OF QUENCHING 1 (SOQ1), protecting against abiotic stress. Recently, we showed inArabidopsis thalianathat qH can occur in the major light-harvesting complexes (Lhcb1, Lhcb2, Lhcb3) but independently of any specific major antenna. Interestingly, in mutants with little or no accumulation of major antennae (koLHCII, lhcb1, cpsrp43), qH can still be induced. Here, we show that the minor antennae can be quenched by qH and remain quenched once isolated. To investigate the role of minor antennae in qH, we combined thesoq1mutant, which displays high qH, with mutations in each minor antenna type (Lhcb4, Lhcb5, or Lhcb6), or with a mutant lacking all minor antennae. None are strictly required for qH to occur. Still, the absence of Lhcb6 decreases qH induction likely due to an indirect effect from the slower electron transport rate and/or a different macro-organization of photosynthetic complexes in the thylakoids. Overall, this work demonstrates that the minor antennae are a secondary target for qH and could serve as an additional safety valve for photoprotective energy dissipation during prolonged stress.
Charting standard model duality and its signatures
Authors: Cacciapaglia Giacomo , Sannino Francesco
Published: February 2025

We investigate high and low energy implications of a gauge dual description of the Standard Model. The high energy electric theory features gauge dynamics involving only fermionic matter fields, while the low energy magnetic description features a quasisupersymmetric spectrum testable at colliders. The flavor theory is constructed via operators generated at the Planck scale, possibly by gravitational global symmetry breaking interactions. We further show that duality opens novel avenues for theories of grand unification.

Published by the American Physical Society
2025
Three-body exchanges with primordial black holes
Authors: Bhalla Badal , Lehmann Benjamin V. , Sinha Kuver , Xu Tao
Published: February 2025

The abundance of massive primordial black holes has historically been constrained by dynamical probes. Since these objects can participate in hard few-body scattering processes, they can readily transfer energy to stellar systems and, in particular, disrupt wide binaries. However, disruption is not the only possible outcome of such few-body processes. Primordial black holes could also participate in exchange processes, in which one component of a binary system is ejected and replaced by the black hole itself. In this case, the remaining object in the binary would dynamically appear to have an invisible companion. We study the rate of exchange processes for primordial black holes as a component of dark matter and evaluate possible mechanisms for detecting such binaries. We find that many such binaries plausibly exist in the Solar neighborhood and show that this process can account for observed binary systems whose properties run counter to the predictions of isolated binary evolution.

Published by the American Physical Society
2025
Stochastic model for the turbulent ocean heat flux under Arctic sea ice
Authors: Toppaladoddi S. , Wells A. J.
Published: February 2025

The physics of planetary climate features a variety of complex systems that are challenging to model as they feature turbulent flows. A key example is the heat flux from the upper ocean to the underside of sea ice which provides a key contribution to the evolution of the Arctic sea ice cover. Here, we develop a model of the turbulent ice-ocean heat flux using coupled ordinary stochastic differential equations to model fluctuations in the vertical velocity and temperature in the Arctic mixed layer. All the parameters in the model are determined from observational data. A detailed comparison between the model results and measurements made during the Surface Heat Budget of the Arctic Ocean (SHEBA) project reveals that the model is able to capture the probability density functions (PDFs) of velocity, temperature, and heat flux fluctuations. Furthermore, we show that the temperature in the upper layer of the Arctic Ocean can be treated as a passive scalar during the whole year of SHEBA measurements. The stochastic model developed here provides a computationally inexpensive way to compute an observationally consistent PDF of this heat flux and has implications for its parametrization in regional and global climate models.

Published by the American Physical Society
2025
Designs via Free Probability
Authors: Fava Michele , Kurchan Jorge , Pappalardi Silvia
Published: February 2025

Unitary designs have become a vital tool for investigating pseudorandomness, since they approximate the statistics of the uniform Haar ensemble. Despite their central role in quantum information, their relations to quantum chaotic evolution and, in particular, to the eigenstate thermalization hypothesis (ETH) are still largely debated issues. This work provides a bridge between the latter and k designs through free probability theory. First, by introducing the more general notion of k-freeness, we show that it can be used as an alternative probe to designs. In turn, free probability theory comes with several tools, useful, for instance, for the calculation of mixed moments or the so-called k-fold quantum channels. Our second result is the connection to quantum dynamics. Quantum ergodicity and, correspondingly, ETH apply to a restricted class of physical observables, as already discussed in the literature. In this spirit, we show that unitary evolution with generic Hamiltonians always leads to freeness at sufficiently long times but only when the operators considered are restricted within the ETH class. Our results provide a direct link between unitary designs, quantum chaos, and the eigenstate thermalization hypothesis and shed new light on the universality of late-time quantum dynamics.

Published by the American Physical Society
2025
Sustainable development practices in healthcare: a systematic review
Authors: Del Bene Luca , Leoni Giulia , Vermiglio Carlo , Zarone Vincenzo
Published: February 2025

Purpose

Healthcare organizations are rethinking their practices in response to the framework provided by the sustainable development goals (SDGs). The purpose of this paper is to explore whether, how and why sustainable development practices have been implemented in the healthcare sector.

Design/methodology/approach

The study is based on a systematic literature review, carried out using Scopus and Web of Science databases. The papers were analyzed according to the five activity-based theoretical framework categories: purpose, subject, community, object and practices.

Findings

Results reveal a lack of research regarding the integration of sustainable development and SDGs into managerial systems or functions. Moreover, they identify key areas of interest within sustainable development and healthcare practices, offering guidance for future research and strategies to better align healthcare with the SDGs.

Originality/value

To the best of the authors’ knowledge, this is the first paper that aims to summarize the scientific literature on this topic through the lens of the activity-based theoretical framework, allowing for an analysis of the literature that investigates how sustainable development practices shape organizational life.
Interplay of provider and customer factors for servitization success: a transaction cost theory approach
Authors: Lexutt Eva
Published: February 2025

Purpose

This study examine how provider- and customer-related factors interact to influence servitization success. It adopts the transaction cost theory along with a configurational approach and hypothesizes that different configurations of five key conditions—service offering, specific investments, perceived customer opportunism, willingness for integration and demand uncertainty—can lead to servitization success or failure.

Design/methodology/approach

The study applies fuzzy-set Qualitative Comparative Analysis (fsQCA) to a sample of 143 German manufacturers, addressing the complex causalities involved in servitization success.

Findings

The analysis identifies six sufficient configurations for servitization success and five for servitization failure. The findings reveal that servitization can succeed through various types of service offerings. While opportunism does not hinder success, the decision to offer an extensive service portfolio is influenced by anticipated opportunism and complex customer needs. Specific investments function primarily as drivers for success, particularly when combined with a limited service offering and complex customer needs. However, these investments can increase transaction costs when linked to an extensive service portfolio. Though not essential, customer integration emerges as a relevant success factor, acting as a safeguard against opportunism.

Practical implications

Servitization can be successful even with opportunism. Developing methods to assess customers’ readiness for integration can mitigate opportunistic behavior and foster successful servitization.

Originality/value

This study advances servitization research by addressing the often-overlooked interplay between provider- and customer-related factors. Applying the transaction cost theory and a cutting-edge fsQCA, it contributes to the theoretical and methodological plurality of the field.
Efficacy of granulocyte and monocyte adsorptive apheresis on skin and joint manifestations of palmoplantar pustulosis with pustulotic arthro‐osteitis: A multicentric, prospective, observational study
Authors: Abe Namiko , Higashi Yuko , Tateishi Chiharu , Kanekura Takuro , Tsuruta Daisuke , Kobayashi Tomoko , Okubo Yukari
Published: February 2025

Granulocyte and monocyte adsorptive apheresis (GMA) selectively removes activated granulocytes and monocytes from the peripheral blood. In 2012, GMA was approved in Japan as a treatment for generalized pustular psoriasis and localized pustular psoriasis or palmoplantar pustulosis (PPP). Limited evidence from case reports and monocentric studies suggested that GMA is an effective treatment for skin and joint symptoms of PPP with pustulotic arthro‐osteitis (PAO). The present, prospective, observational study was performed at three dermatology departments in Japan to evaluate the efficacy and safety of GMA in patients with PPP with PAO. Between April 2017 and December 2020, two male and 12 female patients with PPP and PAO were enrolled. Their mean age, mean duration of skin manifestations, and mean duration of PAO symptoms was 52.8 years, 51.2 months, and 44.9 months, respectively. GMA was applied weekly over five sessions. The skin and joint symptoms were assessed at baseline, post‐GMA, and at the 3‐month follow‐up. A total of 12 patients completed five GMA sessions, and two patients discontinued the treatment because of adverse events. Thus, 12 patients were finally assessed post‐GMA, and 10 patients were assessed at the 3‐month follow‐up. The assessment of GMA efficacy demonstrated that the skin symptoms had remarkably improved and improved in 33.3% (4/12) and 70% (7/10) of the patients post‐GMA and at the 3‐month follow‐up, respectively. Furthermore, the joint symptoms had remarkably improved in 66.7% (8/12) and 60% (6/10) of the patients post‐GMA and at the 3‐month follow‐up, respectively. These results suggest that GMA is effective in treating the skin and joint symptoms of PPP with PAO.
What Alternative Do I Have?: Syrian Immigrant Entrepreneurs and Interest‐Based Financing in Norway
Authors: Tobin Sarah A.
Published: February 2025

Syrian refugee entrepreneurs in Norway navigate a financing and support system that they find largely exclusive and unaccepting when it comes to launching and operating a new business. Using a case study of a Syrian Muslim immigrant entrepreneur and a lecture on the topic by a religious leader in a major mosque in Oslo, this paper utilizes a theoretical framework on moral economies and entrepreneurship to argue that there is a “mismatch” between the interests and needs of Syrian entrepreneurs for financial and social support, with the extremely limited offerings available in Norway. This leaves the entrepreneurs challenged to navigate the financial and moral issues on their own. The paper explores four key policy implications along the way that would enhance the possibilities for Muslim immigrant entrepreneurs to access and utilize financial and social support for opening and running a business in Norway. The paper concludes by linking the financial exclusion experienced by the Syrian entrepreneurs to their broader experiences attempting to integrate and become a positive part of Norwegian society through entrepreneurship, which is challenged in this context of exclusion.
Aligning Sustainable Finance and Fintech to Promote an Integrated Approach to Refugee Finance
Authors: Aassouli Dalal , Hajian Atieh , Asutay Mehmet , Jureidini Rajai Ray
Published: February 2025

The paper aims to assess the global landscape of refugee finance with an overview of global refugee‐related financing mechanisms and instruments. Despite the growing refugee population worldwide, most refugee financing mechanisms are characterized by their post hoc, grant‐based, small‐scale, short‐term, and unpredictable nature. This study will analyze the quantum of refugee finance supplied by different donors and intermediary types, the instruments through which they deploy refugee finance, and to where this financing is directed. It will then evaluate their effectiveness in addressing refugee financial inclusion and empowerment. The paper finally suggests alternative instruments and financing mechanisms leveraging Islamic finance, sustainable finance, and fintech. Two key mechanisms are proposed: a Refugee Empowerment Sukuk and a blended finance structure adopting a results‐based financing approach. The study recommends developing a proactive approach using event‐based financing with early warning triggers, leveraging fintech solutions for traceability and efficiency, and scaling up result‐based financing in social impact and humanitarian financing.
Reduced Alcohol Consumption Following Ablation of Cholinergic Interneurons in the Nucleus Accumbens of Wistar Rats
Authors: Loftén Anna , Cadeddu Davide , Danielsson Klara , Stomberg Rosita , Adermark Louise , Söderpalm Bo , Ericson Mia
Published: February 2025

Alcohol use disorder is a severe mental health condition causing medical consequences and preterm death. Alcohol activates the mesolimbic dopamine system leading to an increase of extracellular dopamine (DA) in the nucleus accumbens, an event that is associated with the reinforcing effects of alcohol. Cholinergic interneurons (CIN) are important modulators of accumbal DA signalling, and depletion of accumbal CIN attenuates the alcohol‐induced increase in extracellular DA. The aim of this study was to explore the functional role of accumbal CIN in alcohol‐related behaviour. To this end, ablation of CIN was induced by local administration of anticholine acetyltransferase‐saporin bilaterally into the nucleus accumbens of male Wistar rats. Alcohol consumption in ablated and sham‐treated rats was studied using a two‐bottle‐choice intermittent alcohol consumption paradigm. Rats with depleted CIN consumed significantly less alcohol than sham‐treated controls. No differences in sucrose preference, motor activity, water intake or weight gain were noted between treatment groups, suggesting that the ablation selectively affected alcohol‐related behaviour. In conclusion, this study further supports a role for accumbal CIN in regulating alcohol‐consummatory behaviour.
First application of three‐dimensional light sheet fluorescence microscopy to human testicular tumors: New perspectives in histopathology
Authors: Pinkert‐Leetsch Diana , Kareem Ahmad , Merz Simon F. , Teckentrup Marc , Fichtner Alexander , Bremmer Felix , Missbach‐Guentner Jeannine
Published: February 2025

Background

Testicular tumors are among the most frequently diagnosed cancers in young men. The consequences of this diagnosis are orchiectomies, severely restricting fertility. For these young patients, a comprehensive diagnostics would be desirable, achieving a refined diagnosis and improved therapeutic patient stratification.

Objective

The aim of this study was to use three‐dimensional (3D) light sheet fluorescence microscopy (LSFM) to analyze a complete testicular tumor punch at subcellular resolution—allowing a detailed diagnostic assessment of the entire punch.

Materials and methods

Tissue punches (3  and 5 mm diameter) were taken from paraffin blocks of four miscellaneous testicular tumors. After deparaffinization and clearing using benzoic acid/benzyl benzoate, a label‐free LSFM autofluorescence imaging was performed. In addition, TO‐PRO‐3 nuclear stain was applied to several punches. After the scan, the samples were embedded in paraffin again and physically sectioned for conventional planar histology.

Results

Based on the specific autofluorescence, not only the general morphology of the tumor tissue was identified in LSFM datasets, but also diagnostic features like infiltrations, papillary and pagetoid tumor cell formations, germ cell neoplasia in situ and azoospermia. Subcellular characteristics such as vacuolated cytoplasm and pleomorphic nuclei could be detected at maximum magnification. After nuclear staining, virtual H&E sections were reconstructed from the LSFM data and tomographically visualized across the entire punch. Subsequent histology and immunohistochemistry after LSFM analyses is possible.

Discussion

LSFM analysis of testicular tumors enables the detailed 2D/3D analysis of an entire tumor punch for assessment of relevant tumor characteristics due to its intrinsic fluorescence or with specific nuclear staining.

Conclusion

LSFM provides the technical basis for the analyses of complete testicular tumor biopsies, thus maximizing the spatial morphological and anatomical information. The subcellular 3D imaging of the tumor has the potential to identify new cancer imaging biomarkers that have additional diagnostic and prognostic value for patients.
Evaluation of a virtual multidisciplinary tracheostomy meeting for ward‐based patients
Authors: Tan Hannah B. , Yii Matthew , Prasad Jessica
Published: February 2025

Background

Tracheostomy is frequently performed in an intensive care unit setting to progress the care of intubated patients. A multidisciplinary team follows up tracheostomised patients once transferred to the ward. A virtual tracheostomy multidisciplinary meeting (MDM) was established with the aim to standardize care for these patients.

Methods

A retrospective review of ward‐based patients discussed in a Tracheostomy MDM was performed at The Alfred Hospital, a tertiary hospital providing a state‐wide trauma service. Two groups were compared; (i) Outreach group comprising patients who were managed prior to the establishment of the Tracheostomy MDM on the 26 July 2021; (ii) Virtual Tracheostomy MDM (V‐MDM) group who were managed after the establishment of the Virtual Tracheostomy MDM. Primary outcome was decannulation time from ICU discharge.

Results

There were 65 patients in the Outreach group over 134 weeks. There were 44 patients in the V‐MDM group over 94 weeks. There was a significant difference between groups in the median time to decannulation from ICU discharge (P = 0.007) and the overall time to decannulation (P = 0.029) with the V‐MDM group requiring a longer period with tracheostomy prior to decannulation. There were no significant differences in the overall hospital length of stay (LOS) or rate of adverse events.

Conclusion

Implementing a supplemental Tracheostomy MDM in a virtual format may not improve time to decannulation and can possibly delay decannulation compared to an established tracheostomy team led by ICU clinicians. Virtual Tracheostomy MDM may have a role in managing patients were a non‐virtual ICU‐led team is not feasible.
FGFR2/3 Gene Alterations and Clinical Outcomes in Advanced/Metastatic Urothelial Cancer in Japan: MONSTAR‐SCREEN Database Study
Authors: Matsubara Nobuaki , Osawa Takahiro , Abe Takashige , Oya Mototsugu , Nishimoto Koshiro , Iwahori Toshiyuki , Tsuchiya Hiroaki , Murota Maiko , Yoshida Masaki , Tatematsu Yohei , Nakano Yosuke , Eto Masatoshi , Nonomura Norio
Published: February 2025

Advanced/metastatic urothelial cancer (a/m UC) still has a poor prognosis despite the recent medical advances. Recent studies demonstrated that fibroblast growth factor receptor (FGFR) gene alterations (GAs) may be driver genes for UC; however, the proportion of UC genetic panel testing in Japan remains low. We clarified the proportion of patients with FGFR2/3 GAs, treatment patterns, and clinical outcomes in a/m UC patients in Japan. This study was a descriptive epidemiological study using the MONSTAR‐SCREEN database, and 138 patients with a/m UC were evaluated. The primary endpoint was the proportion of patients with FGFR2/3 GAs. The secondary endpoints included treatment patterns, clinical outcomes, genomic status before and after treatment, etc. The proportion of FGFR GA‐positive patients in a/m UC was 11.9%. The most common FGFR mutation variant and fusion gene were S249C (4.4%) and FGFR3‐TACC3 fusion (3.7%), respectively. Fifty‐one patients were tested two or more times; a few changes were observed in the FGFR GA status, regardless of the treatment regimen. Co‐occurrence association was observed in FGFR1 with TET2, and in FGFR3 with CHEK2 or MLL2. During the first‐, second‐, and third‐line treatment, median progression‐free survival (PFS) of GA‐positive patients was 7.3, 2.9, and 6.2 months, while for GA‐negative patients, 6.9, 3.1, and 6.9 months, respectively. This study revealed that one in eight a/m UC patients had FGFR2/3 GAs, and a few changes were observed in FGFR GA status before and after treatment. Genetic testing will be beneficial for the selection of appropriate treatments after a diagnosis of a/m UC.