bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular detection of a cryptic salamander: Development of an eDNA assay for the detection of the mud salamander (Pseudotriton montanus)
Authors: Brammell Ben F. , Brewer Sara A. , Hoogerheide Ethan A. , Johnson Mary R.
Published: January 2025

The mud salamander (Pseudotriton montanus) is a notoriously cryptic semi-aquatic Plethodontid found throughout much of the eastern United States, reports of decades passing between observations of this species in areas of known occurrence are common. Although it is listed as imperiled or in need of conservation throughout much of its range, with extirpation suspected in many areas, relatively little is known of its current distribution due to its secretive nature. We developed a species-specific qPCR assay for use in eDNA detection ofPseudotriton montanus. Primers and probe were designed based on cytochrome b sequences obtained from specimens collected in central and eastern KY, compared to published sequences throughout the species’ range, and screenedin silico(twenty-seven species) andin vitro(seventeen species) for specificity against sympatric salamander species. The developed assay was field tested via the collection of water samples at sites known or suspected to containP.montanusin Kentucky, Ohio, and Tennessee. Of the 68 samples collected,P. montanuseDNA was detected in eight, including all sites (six) in whichP. montanuslarvae were observed in the field. Sequencing of each environmentally-obtained amplicon confirmed detection ofP. montanus diastictus. This work provides thoroughly vetted tools that should prove useful for future monitoring and range delineation of this threatened and cryptic species.
Towards AI-based Precision Rehabilitation via Contextual Model-based Reinforcement Learning
Authors: Ye Dongze , Luo Haipeng , Winstein Carolee , Schweighofer Nicolas
Published: January 2025

Background

Stroke is a condition marked by considerable variability in lesions, recovery trajectories, and responses to therapy. Consequently, precision medicine in rehabilitation post-stroke, which aims to deliver the “right intervention, at the right time, in the right setting, for the right person,” is essential for optimizing stroke recovery. Although Artificial Intelligence (AI) has been effectively utilized in other medical fields, such as cancer and sepsis treatments, no current AI system is designed to tailor and continuously refine rehabilitation plans post-stroke.

Methods

We propose a novel AI-based decision-support system for precision rehabilitation that uses Reinforcement Learning (RL) to personalize the treatment plan. Specifically, our system iteratively adjusts the sequential treatment plan—timing, dosage, and intensity— to maximize long-term outcomes based on a patient model that includes covariate data (the context). The system collaborates with clinicians and people with stroke to customize the recommended plan based on clinical judgment, constraints, and preferences. To achieve this goal, we proposea Contextual Markov Decision Process (CMDP)framework and a novel hierarchical Bayesian model-based RL algorithm, namedPosterior Sampling for Contextual RL(PSCRL), that discovers and continuously adjusts near-optimal sequential treatments by efficiently balancing exploitation and exploration while respecting constraints and preferences.

Results

We implemented and validated our precision rehabilitation system in simulations with a sequence of 100 diverse, synthetic patients. Simulation results showed the system ability to continuously learn from both upcoming data from the current patient and a database of past patients via Bayesian hierarchical modeling. Specifically, the algorithm’s sequential treatment recommendations became increasingly more effective in improving functional gains for each patient over time and across the synthetic patient population.

Conclusions

Our novel AI-based precision rehabilitation system based on contextual model-based reinforcement learning has the potential to play a key role in novel learning health systems in rehabilitation.
Contaminating manufacturing plasmids and disrupted vector genomes present in liver tissue following adeno-associated virus gene therapy
Authors: Buddle Sarah , Brown Li-An K , Morfopoulou Sofia , Torres Montaguth Oscar Enrique , Scoto Mariacristina , Herder Vanessa , Dhawan Anil , Brown Julianne R , Atkinson Laura , Kopec Angelika , Davis Dee , Storey Nathaniel , Campos Luis , Sebire Neil , Macpherson Hannah , Lee Jasmaine , Orton Richard , Baranello Giovanni , Asamaphan Patawee , Ilia Georgios , Karda Rajvinder , Belfield Holly ,   ISARIC 4C Investigators, Semple Malcolm Gracie , Baillie J Kenneth , Counsell John , Waddington Simon , Thomson Emma C , Muntoni Francesco , Breuer Judith
Published: January 2025

Adeno-associated viruses (AAVs) are the most used vectors in gene therapy but can frequently cause liver complications in patients. The mechanisms underlying AAV-related liver toxicity remain poorly understood, posing challenges for effective prevention and intervention. We undertook long and short read metagenomic sequencing of liver tissue from a child with spinal muscular atrophy type 1 experiencing significant hepatitis after receiving onasemnogene abeparvovec. We identified manufacturing plasmid sequences, with evidence of complex structures and recombination. Vector genomes had extensive disruption and concatemerisation. We also identified the presence of human betaherpesvirus 6B in the liver. It is possible that presence of the manufacturing plasmid sequences or helper viruses allow replication of the vector within cells, contributing to the development of complex concatemeric structures and associated hepatitis.
Double-stranded RNA responses, neoantigen presentation and suppression of hepatocellular carcinoma through NMD inhibition via endonuclease SMG6
Authors: Arpa Enes S. , Ricci Virginie , Shapiro Ilja E. , Jokic Marija , Gonzalez-Menendez Irene , Quintanilla-Martinez Leticia , Bénéchet Alexandre P. , Rehwinkel Jan , Luther Sanjiv A. , Bassani-Sternberg Michal , Gatfield David
Published: January 2025

Nonsense-mediated mRNA decay (NMD) eliminates transcripts with premature termination codons, often resulting from mutations or RNA processing errors. While both pro-and anti-tumor NMD activities have been proposed, mechanistic and therapeutic insights into NMD inhibition in cancer have been hindered by the lack of a suitablein vivomodel. We address this by combining a liver-specific, conditionalSmg6mutation – disabling the endonuclease that cleaves NMD-regulated transcripts – with a genetic hepatocellular carcinoma (HCC) model. SMG6 inhibition elevates NMD-sensitive mRNA abundance and translation, promotes MHC presentation of unique immunopeptides, and enhances T-cell infiltration. Additionally, mutant SMG6 specifically activates type-I interferon signaling via double-stranded RNA (dsRNA) accumulation and dsRNA-sensor MDA5, boosting innate immune responses. These pathways converge to halt HCC at an inflammatory stage. Our findings establish SMG6 as a key regulator of dsRNA homeostasis and immune activation, offering therapeutic potential and advancing our understanding of NMD in immune regulation.
A general framework for cycles in ecology
Authors: Moura Rafael O. , Calleja-Solanas Violeta , Langa José A. , Godoy Oscar
Published: January 2025

Understanding the mechanisms that promote cyclic dynamics among species is critical for predicting biodiversity patterns and community assembly. Here, we present a general framework for studying cycles in ecological systems. Using invasion graphs derived from the Lotka-Volterra equations, we discovered that cycles are primarily driven by the antisymmetric component of the interaction matrix, which captures directional imbalances in interaction strength and promotes non-hierarchical dynamics. We also generalized the concept of cycles to include multi-species equilibria and transitions between states with varying species compositions. Additionally, we found that intrinsic growth rates modulate the likelihood of cycles: homogeneous growth rates promote cycles, while greater variability, particularly with negative growth rates, inhibits them. Our results suggest that cycles are constrained to ecological systems with pronounced interaction asymmetries and relatively uniform growth rates, providing a theoretical basis for their absence in natural communities.
Eco-evolutionary dynamics between multiple competitors reduce phytoplankton coexistence but have limited impacts on community productivity
Authors: Briddon Charlotte L. , García Aurora Menéndez , Ghedini Giulia
Published: January 2025

Species can evolve rapidly in response to competition but how evolution within communities affects community properties is unclear. To test this, we grew three marine phytoplankton species in monoculture (alone) or polyculture (together) for 17 weeks. We then combined them in communities based on their competition history (monoculture or polyculture isolates) and tracked their composition and productivity over time. We found that species dominance was unaffected, but coexistence was reduced when species evolved together (polyculture isolates). Total biovolume was robust to changes in species relative abundances. However, polyculture isolates had greater oxygen fluxes during exponential phase and were less robust to the addition of an invader. Our results suggest that evolution within communities can strengthen competitive differences between species with uneven effects on different aspects of community functioning. Thus, we should be cautious in extrapolating the consequences of evolution on community biomass to other aspects of productivity or stability.
Evolution ofWolbachiamale-killing mechanism within a host species
Authors: Arai Hiroshi , Wijonarko Arman , Katsuma Susumu , Naka Hideshi , Kageyama Daisuke , Hornett Emily A. , Hurst Gregory D. D.
Published: January 2025

Male-killing bacterial symbionts, prevalent in arthropods, skew population sex ratios by selectively killing male progeny, profoundly impacting ecology and evolution of their hosts. Male-killing is a convergently evolved trait, with microbes evolving diverse male-killing mechanisms across host species with widely divergent sex determination pathways. A common evolutionary response to MK presence is the spread of suppressor mutations that restore male survival. In this study, we demonstrate evolution of a novel male-killing mechanism that is insensitive to an existing male-killing suppressor.Hypolimnas bolinabutterflies from Yogyakarta, Indonesia, showed extreme female biased population sex ratio associated with high prevalence of a male-killingWolbachia. This strain,wBol1Y, shared a very recent common ancestor with the previously characterized ‘suppressed’ male-killing strain in the species,wBol1, but retained its male-killing ability in the presence of the male-killing suppressor. The genome ofwBol1Y differed from the suppressedwBol1 in carrying an additional prophage that included strong candidate genes for male-killing.In vitroandin vivodata demonstrated thatwBol1Y feminized splicing and expression of lepidopteran sex determination pathway genes, and that the geneHb-oscar– present onwBol1Y’s unique prophage insert – was sufficient to disrupt the male sex determination pathway. Our study demonstrates the diversity of male-killing mechanisms is a product both of interaction with varying insect sex determination systems and evolution of male-killing within a host species. Our data indicate male-killer and host may be involved in escalating arms races, where spread male-killing suppression drives evolution of additional systems that reestablish male killing by the symbiont.
Infant RSV infection desensitizes β2-adrenergic receptor via CXCL11-CXCR7 signaling in airway smooth muscle
Authors: Zhao Caiqi , Taliento Alice E. , Belkin Elise M , Fearns Rachel , Lerou Paul H. , Ai Xingbin , Bai Yan
Published: January 2025

Rationale

Airflow obstruction refractory to β2 adrenergic receptor (β2AR) agonists is an important clinical feature of infant respiratory syncytial virus (RSV) bronchiolitis, with limited treatment options. This resistance is often linked to poor drug delivery and potential viral infection of airway smooth muscle cells (ASMCs). Whether RSV inflammation causes β2AR desensitization in infant ASMCs is unknown.

Objectives

To investigate the interaction of RSV inflammation with the β2AR signaling pathway in infant ASMCs

Methods

Infant precision-cut lung slices (PCLSs) and mouse pup models of RSV infection were subjected to airway physiological assays. Virus-free, conditioned media from RSV-infected infant bronchial epithelial cells in air-liquid interface (ALI) culture and nasopharyngeal aspirates (NPA) from infants with severe RSV bronchiolitis were collected and applied to infant PCLSs and ASMCs. Cytokines in these samples were profiled and assessed for the effects on β2AR expression, cell surface distribution, and relaxant function in ASMCs.

Measurements and Main Results

Conditioned media and NPA induced similar resistance to β2AR agonists in ASMCs as RSV infection. Cytokine profiling identified CXCL11 as one of the most elevated signals following RSV infection. CXCL11 activated its receptor CXCR7 in a complex with β2AR in ASMCs to promote β2AR phosphorylation, internalization, and degradation. Blockade of CXCR7 partially restored airway relaxation in response to β2AR agonists in infant PCLSs and mouse pup models of RSV infection.

Conclusions

The CXCL11-CXCR7 pathway plays a critical role in β2AR desensitization in ASMCs during RSV infection and represents a potential therapeutic target in alleviating airflow obstruction in infant RSV bronchiolitis.
Real-time fMRI neurofeedback modulates auditory cortex activity and connectivity in schizophrenia patients with auditory hallucinations: A controlled study
Authors: Bauer Clemens C.C. , Zhang Jiahe , Morfini Francesca , Hinds Oliver , Wighton Paul , Lee Yoonji , Stone Lena , Awad Angelina , Okano Kana , Hwang Melissa , Hammoud Jude , Nestor Paul , Whitfield-Gabrieli Susan , Shinn Ann K. , Niznikiewicz Margaret A.
Published: January 2025

Background and Hypothesis

We have reported previously a reduction in superior temporal gyrus (STG) activation and in auditory verbal hallucinations (AHs) after real-time fMRI neurofeedback (NFB) in schizophrenia patients with AHs.

Study Design

With this randomized, participant-blinded, sham-controlled trial, we expanded our previous results. Specifically, we examined neurofeedback effects from the STG, an area associated with auditory hallucinations. The effects were compared to Sham-NFB from the motor cortex, a region unrelated to hallucinations. Twenty-three adults with schizophrenia or schizoaffective disorder and frequent medication-resistant hallucinations performed mindfulness meditation to ignore pre-recorded stranger’s voices while receiving neurofeedback either from the STG (n=10, Real-NFB) or motor cortex (n=13 Sham-NFB). Individuals randomized to Sham-NFB received Real-NFB in a subsequent visit, providing a within-subject ’Real-after-Sham-NFB’ comparison.

Study Results

Both groups showed reduced AHs after NFB, with no group differences. Compared to the Sham-NFB group, the Real-NFB group showed more reduced activation in secondary auditory cortex (AC) and more reduced connectivity between AC and cognitive control regions including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate. The connectivity reduction was also observed in the Real-after-Sham-NFB condition. Secondary AC-DLPFC connectivity reduction correlated with hallucination reduction in the Real-NFB group. Replicating prior results, both groups showed reduced primary auditory cortex activation, suggesting mindfulness meditation may regulate bottom-up processes involved in hallucinations.

Conclusions

Our findings emphasize delivering NFB from brain regions involved in medication-resistant AHs. They provide insights into auditory cortex and cognitive control network interactions, highlighting complex processing dynamics and top-down modulation of sensory information.
The nucleocytoplasmic translocation of HINT1 regulates the maturation of cell density
Authors: Zhang Xiaofang , Nakamura Fumihiko
Published: January 2025

Cell contact inhibition progresses through three stages: (i) increasing cell density leads to reduced movement while mitosis continues; (ii) a rapid shift to epithelial morphology; and (iii) ongoing division with decreased cell size. This transition involves reorganizing the actin cytoskeleton from stress fibers to a cortical network, stabilizing cell shape, and strengthening cell-cell connections. However, the signaling pathways regulating the final stage remain unclear. We identified histidine triad nucleotide-binding protein 1 (HINT1), also known as protein kinase C inhibitor 1 (PKCI-1), as essential for monolayer maturation. At low density, HINT1 is located in the nucleus, binding to open chromatin. As density increases, exportin-1 relocates HINT1 to the cytoplasm, where it inhibits PKC and remodels the actin cytoskeleton. While monolayer formation can occur without HINT1, its presence is necessary for fully confining cells and achieving a mature monolayer. Additionally, MARCKS phosphorylation decreases in high-density cells, and loss of HINT1 leads to increased cell area, similar to hypertrophic conditions in patients with low HINT1 levels.

Summary blurb

Histidine triad nucleotide-binding protein 1 shuttles between the nucleus and cytoplasm based on cell density, regulating gene expression in the nucleus and inhibiting protein kinase C in the cytoplasm to remodel actin.
Large-scale audiometric phenotyping identifies distinct genes and pathways involved in hearing loss subtypes
Authors: Ahmed Samah , Vaden Kenneth I. , Leitao Darren , Dubno Judy R. , Drögemöller Britt I.
Published: January 2025

Age-related hearing loss affects one-third of the population over 65 years. However, the diverse pathologies underlying these heterogenous phenotypes complicate genetic studies. To overcome challenges associated with accurate phenotyping for older adults with hearing loss, we applied computational phenotyping approaches based on audiometrically measured hearing loss. This novel phenotyping strategy uncovered distinct genetic variants associated with sensory and metabolic hearing loss. Sex-stratified analyses of these sexually dimorphic hearing loss phenotypes revealed a novel locus of relevance to sensory hearing loss in males, but not females. Enrichment analyses revealed that genes involved in frontotemporal dementia were implicated in metabolic hearing loss, while genes relating to sensory processing of sound by hair cells were implicated in sensory hearing loss. Our study has enhanced our understanding of these two distinct hearing loss phenotypes, representing the first step in the development of more precise treatments for these pathologically distinct hearing loss phenotypes.
Describing variability of intensively collected longitudinal ordinal data with latent spline models
Authors: Lunt Mark , Selby David A. , Dixon William G.
Published: January 2025

Population health studies increasingly collect longitudinal, patient-reported symptom data via mobile devices, offering unique insights into experiences outside clinical settings, such as pain, fatigue or mood. However, such data present challenges due to ordinal measurement scales, irregular sampling and temporal autocorrelation.

This paper introduces two novel summary measures for analysing ordinal outcomes: (1)the mean absolute deviation from the median(Madm) for cross-sectional analyses and (2) themean absolute deviation from expectation(Made) for longitudinal data. The latter is based on a latent cumulative model with penalized splines, enabling smooth transitions between irregular time points while accounting for the ordinal nature of the data. Unlike black-box machine learning approaches, this method is interpretable, computationally efficient and easy to implement in standard statistical software.

Through simulations, we demonstrate that the proposed measures outperform standard methods when the assumptions of normality or stationarity are violated. Application to real-world data from a national smartphone study,Cloudy with a Chance of Pain, highlights the utility of these measures in characterising symptom variability and trends over time.

The methods developed here provide intuitive tools for analysing patient-reported outcomes in longitudinal studies, with potential applications in prediction modelling, causal discovery and evaluation of interventions.
Adaptive Transfer Learning for Time-to-Event Modeling with Applications in Disease Risk Assessment
Authors: Lu Yuying , Gu Tian , Duan Rui
Published: January 2025

Objective

To address the challenges in for modeling time-to-event outcomes in small-sample settings by leveraging transfer learning techniques while accounting for potential covariate and concept shifts between source and target datasets.

Methods

We propose a novel transfer learning approach, termed CoxTL, for modeling time-to-event data based on the widely used Cox proportional hazards model. CoxTL utilizes a combination of density ratio weighting and importance weighting techniques to address multi-level data heterogeneity, including covariate and coefficient shifts between source and target datasets. Additionally, it accounts for potential model misspecification, ensuring robustness across a wide range of settings. We assess the performance of CoxTL through extensive simulation studies, considering data under various types of distributional shifts. Additionally, we apply CoxTL to predict End-Stage Renal Disease (ESRD) in the Hispanic population using electronic health record-derived features from the All of Us Research Program. Data from non-Hispanic White and non-Hispanic Black populations are leveraged as source cohorts. Model performance is evaluated using the C-index and Integrated Brier Score (IBS).

Results

In simulation studies, CoxTL demonstrates higher predictive accuracy, particularly in scenarios involving multi-level heterogeneity between target and source datasets. In other scenarios, CoxTL performs comparably to alternative methods specifically designed to address only a single type of distributional shift. For predicting the 2-year risk of ESRD in the Hispanic population, CoxTL achieves increase in C-index up to 6.76% compared to the model trained exclusively on target data. Furthermore, itdemonstrates up to 17.94% increase in the C-index compared to the state-of-the-art transfer learning method based on Cox model.

Conclusion

The proposed method effectively utilizes source data to enhance time-to-event predictions in target populations with limited samples. Its ability to handle various sources and levels of data heterogeneity ensures robustness, making it particularly well-suited for real-world applications involving target populations with small sample sizes, where traditional Cox models often struggle.
Tau Progression Index (TPI): An individualized, clinically applicable, multimodally-derived score to predict AD progression
Authors: Hojjati Seyed Hani H , Chinag Gloria , Butler Tracy , Ghaderi Yazdi Bardiya , Ozoria Sindy , Chernek Peter , Calimag Jenseric , Stern Yaakov , Devanand Devangere , Blum Sonja , Pahlajani Silky , Habeck Christian , He Hengda , Foldi Nancy , Khalafi Mohammad , Razlighi Qolamreza
Published: January 2025

While amyloid-beta and tau are known to be the key neuropathological hallmarks of the Alzheimers disease (AD), imaging and postmortem studies highlight significant variability in disease severity and progression even in subjects with similar burdens of amyloid-beta; and tau accumulation. This uncertainty in the trajectory of disease progression results in substantial challenges for patients and their families in understanding disease prognosis, as well as the research community in understanding heterogeneity in the rate of Aβ and tau accumulation, cognitive decline, and likelihood of progressing to dementia. In this study, we developed and validated the Tau Progression Index (TPI); a multimodally derived score that leverages strongly supported hypotheses and models of tau spread, to serve as a reliable, and clinically applicable biomarker of AD progression. TPI has 4 components: 1) Remote interaction (TPI-ri) interactions between Aβ and tau pathologies in regions that spatially separate; 2) Local interaction (TPI-li) between co-localized Aβ and tau pathology; 3) Functional connectivity (TPI-fc) is based on functional magnetic resonance imaging (fMRI)-measured inter-regional functional connections facilitate the spread of tau in the brain; and 4) Structural connectivity (TPI-sc) based on diffusion MRI (dMRI)-measured inter-regional structural connectivity. Importantly, all prior models of tau spread in AD were based on group-averaged structural and functional connectivity, derived from healthy and often young subjects. However, brain connectivity patterns are extremely subject-specific, often referred to as a human connectome fingerprint, and are significantly altered by aging and neurodegenerative diseases. Therefore, we have shown that TPI computed by subject-specific connectomes is crucial to accurately model subject-specific trajectories of tau spread.
Extreme high-diversity barcoded HIV library enables single cell multi-omics analysis of viral expression and fate determination
Authors: Zhang Tian-hao , Sheng Li , Meng Xiangzhi , Lai Wenjin , Du Yushen , Shi Yuan , Wen Jing , Kamata Masakazu , Chanda Sumit K. , Chen Irvin SY. , Sun Ren
Published: January 2025

HIV-1 persists as a global health challenge due to its ability to establish latent reservoirs that evade eradication by antiretroviral therapy (ART). This study introduces a high-diversity barcoded HIV-1 library combined with a novel peptide barcode system to enable single-cell multi-dimensional analysis of viral integration, transcription, splicing, and translation of distinct viral mRNA isoform. Our method revealed over 80 distinct HIV-1 splicing isoforms and uncovered significant temporal variation in mRNA diversity, driven by integration site and chromatin context. By linking HIV-1 5’UTR with peptide barcoding, we quantified the translation efficiency of alternative 5′ UTRs and demonstrated correlations with abundance of each viral mRNA isoform. Additionally, we showed that latency reversal agents, such as SAHA and Bryostatin, selectively reactivate proviruses depending on their genomic and chromatin context and leads to distinct viral RNA splicing program. This platform revealed the diversity of HIV-infected cells at levels of transcripts as well as at proteins, and subsequently the fate determination. The detailed understanding of the stochastic diversity and dynamic nature of HIV-1 latency, inform the development of targeted therapies to eliminate latent reservoirs.
Pseudomonassuperinfection drives Pf phage transmission within airway infections in patients with cystic fibrosis
Authors: Pourtois Julie D. , Haddock Naomi L. , Gupta Aditi , Khosravi Arya , Martinez Hunter , Schmidt Amelia K. , Prakash Prema S. , Jain Ronit , Fleming Piper , Chang Tony H. , Milla Carlos , Secor Patrick R. , De Leo Giulio A. , Bollyky Paul L. , Burgener Elizabeth B.
Published: January 2025

Pf bacteriophages, lysogenic viruses that infectPseudomonas aeruginosa (Pa),are implicated in the pathogenesis of chronicPainfections; phage-infected (Pf+) strains are known to predominate in people with cystic fibrosis (pwCF) who are older and have more severe disease. However, the transmission patterns of Pf underlying the progressive dominance of Pf+ strains are unclear. In particular, it is unknown whether phage transmission commonly occurs horizontally between bacteria within the airway via viral particles or if Pf+ bacteria are mostly acquired via newPseudomonasinfections. Here, we have studiedPagenomic sequences from 3 patient cohorts totaling 663 clinical isolates from 105 pwCF. We identify Pf+ isolates and analyze transmission patterns of Pf within patients between genetically similar groups of bacteria called “clone types”. We find that Pf is predominantly passed down vertically withinPalineages and rarely via horizontal transfer between clone types within the airway. Conversely, we find extensive evidence ofPasuperinfection by a new, genetically distinctPathat is Pf+. Finally, we find that clinical isolates show reduced activity of the type IV pilus and reduced susceptibility to Pfin vitro.These results cast new light on the transmission of virulence-associated phages in the clinical setting.
Small or absent Visual Word Form Area is a trait of dyslexia
Authors: Mitchell Jamie L. , Yablonski Maya , Stone Hannah L. , Fuentes-Jimenez Mia , Takada Megumi E. , Tang Kenny A. , Tran Jasmine E. , Chou Clementine , Yeatman Jason D.
Published: January 2025

Understanding the balance between plastic and persistent traits in the dyslexic brain is critical for developing effective interventions. This longitudinal intervention study examines the Visual Word Form Area (VWFA) in dyslexic and typical readers, exploring how this key component of the brain’s reading circuitry changes with learning. We found that dyslexic readers show significant differences in VWFA presence, size, and tuning properties compared to typical readers. While reading intervention improved reading skills and increased VWFA size, disparities persisted, suggesting that VWFA abnormalities are an enduring trait of dyslexia. Notably, we found that even with sufficient intervention to close the reading skill gap, dyslexic readers are still expected to have smaller VWFAs. Our results reveal intervention-driven long-term neural and behavioral changes, while also elucidating stable differences in the functional architecture of the dyslexic brain. This provides new insights into the potential and limitations of learning-induced plasticity in the human visual cortex.
Design, Development and Validation of New Fluorescent Strains for Studying Oral Streptococci
Authors: Peters Daniel I. , Shin Iris J. , Deever Alyssa N. , Kaspar Justin R.
Published: January 2025

Bacterial strains that are genetically engineered to constitutively produce fluorescent proteins have aided our study of bacterial physiology, biofilm formation, and interspecies interactions. Here, we report on the construction and utilization of new strains that produce the blue fluorescent protein mTagBFP2, the green fluorescent protein sfGFP, and the red fluorescent protein mScarlet-I3 in speciesStreptococcus gordonii, Streptococcus mutans, andStreptococcus sanguinis. Gene fragments, developed to contain the constitutive promoter Pveg, the fluorescent gene of interest as well asaad9, providing resistance to the antibiotic spectinomycin, were inserted into selected open reading frames on the chromosome that were both transcriptionally silent and whose loss caused no measurable changes in fitness. All strains, except for sfGFP inS. sanguinis, were validated to produce a detectable and specific fluorescent signal. Individual stains, along with extracellular polymeric substances (EPS) within biofilms, were visualized and quantified through either widefield or super-resolution confocal microscopy approaches. Finally, to validate the ability to perform single cell-level analysis using the strains, we imaged and analyzed a triculture mixed-species biofilm ofS. gordonii, S. mutans, andS. sanguinisgrown with and without addition of human saliva. Quantification of the loss in membrane integrity using a SYTOX dye revealed that all strains had increased loss of membrane integrity with water or human saliva added to the growth media, but the proportion of the population stained by the SYTOX dye varied by species. In all, these fluorescent strains will be a valuable resource for the continued study of oral microbial ecology.
Integrated model of the protein molecular clock across mammalian species
Authors: Saini Anshul , Usmanova Dinara R. , Vitkup Dennis
Published: January 2025

One of the foundational concepts in molecular evolution is the protein molecular clock [1-3], encapsulating the observation that proteins tend to accumulate amino acid substitutions at approximately constant and protein-specific rates over long evolutionary timescales. According to the neutral theory of molecular evolution, the majority of protein substitutions have neutral or nearly neutral effects on species fitness. The neutral theory suggests the existence of a strong generation time effect, positing that species with shorter generation times should accumulate protein substitutions faster per unit time compared to species with longer generation times. However, earlier studies failed to detect a significant generation time effect for amino acid substitutions in vertebrates, raising questions about core tenets of the neutral theory. In this study, we take advantage of the recently accumulated evolutionary and genomics data to investigate the scaling of substitution rates with generation time among many dozens of mammalian species and thousands of proteins. Our findings reveal a strong generation time effect both for synonymous and non-synonymous substitutions. We demonstrate that the empirically observed generation time effect is fully consistent with several mechanisms, such as functional and mutation rate selection. Building on these results, we develop an integrated model of protein evolution that incorporates changes in substitution rates due to variation in species generation times throughout their evolutionary history. Overall, our analysis shows that protein evolution is consistent with neutral or nearly neutral theories and explains time-like behavior of the protein molecular clock across deep phylogenetic lineages.
Unintended bias in the pursuit of collinearity solutions in fMRI analysis
Authors: Mumford Jeanette A. , Demidenko Michael I. , Bjork James M. , Chaarani Bader , Feczko Eric J. , Garavan Hugh P. , Hagler Donald J. , Nelson Steven M. , Wager Tor D. , Poldrack Russell A.
Published: January 2025

In task functional magnetic resonance imaging (fMRI), collinearity between task regressors in a design matrix may impact power. Researchers often optimize task designs by assessing collinearity between task regressors to minimize downstream effects. However, some methods intended to reduce collinearity during optimization and data analysis may fail, in some cases introducing unintended bias into the parameter estimates. Although relevant to all task-based fMRI studies, we describe these issues and illustrate them using the Monetary Incentive Delay (MID) task fMRI data from the Adolescent Brain Cognitive Development (ABCD®) study. Specifically, we show that omitting regressors for certain task components, using impulse regressors for extended activations, and ignoring response time adjustments can bias common contrast estimates. We present a “Saturated” model that models all stimuli and response times, which minimizes bias in MID task simulations and validly estimates task-relevant whole brain activity, offering greater flexibility in studying contrasts that might otherwise be avoided due to potential biases.
HIV prevalence, risk factors for infection, use of prevention methods, and interventions among taxi drivers and commercial motorcyclists in sub-Saharan Africa: A scoping review
Authors: Asiimwe John Baptist , Betunga Benjamin , Birungi Lilian , Kabasindi Joy , Wankiiri Moses , Nuwabaine Lilian , Kawuki Joseph , Kumakech Edward
Published: January 2025

Background

Transport workers, particularly taxi drivers and commercial motorcyclists, comprise a population at high risk for HIV and account for nearly one-third of new HIV infections in sub-Saharan Africa (SSA). Furthermore, transport workers bridge HIV infections from high-risk populations to the general population. This scoping review aimed to map the available evidence around HIV prevalence, risk factors for HIV infection, use of HIV prevention methods, and HIV interventions among taxi drivers and commercial motorcyclists in SSA.

Method

This scoping review used the Arksey and O’Malley framework. Published articles were retrieved from MEDLINE (via PubMed), CINAHL, African Index Medicus, Web of Science, Scopus, EMBASE, HINARI, and Google Scholar from inception to August 2024. Two authors screened the titles and abstracts of retrieved studies and examined the references of relevant articles for additional literature. Three authors independently extracted data from the included studies using a standard data extraction form. Data were analyzed using descriptive statistics and content analysis techniques. The themes were collated, and a descriptive summary of the findings was reported.

Results

This review included 24 studies. The HIV prevalence was 2.02%–9.9% among commercial motorcyclists, and reached 33.4% in samples comprising both motorcyclists and taxi drivers. The high HIV infection rate was attributable to numerous behavioral (e.g., multiple sex partners), psychosocial (e.g., stigma), and sociodemographic (e.g., age, income) risk factors. However, there was suboptimal use of HIV prevention methods such as safe male circumcision (20.7%–64.9%) and condoms (26%–45.7%). The two HIV interventional studies were conducted among commercial motorcyclists. Despite HIV testing being an entry point for chronic care, we found no study reporting the HIV cascade for commercial motorcyclists or taxi drivers who were diagnosed with HIV, including the use of antiretroviral therapy, pre-exposure prophylaxis (PREP), and post- exposure prophylaxis.

Conclusions

The numerous research gaps highlight the need for longitudinal research on HIV incidence and predictors in this key population, especially the structural determinants of HIV infection. There is also a need for interventional and observational research on new models of HIV testing (e.g., HIV oral testing), antiretroviral-based HIV prevention methods (e.g., PREP), and the role of peer-to- peer educator or group support/counseling models in reducing HIV infection and mitigating risky HIV-related sexual behavior. Such studies may provide evidence to inform better HIV prevention and control policies and programs among taxi drivers and commercial motorcyclists in SSA.
Genetic changes linked to two different syndromic forms of autism enhance reinforcement learning in adolescent male but not female mice
Authors: Chase Juliana , Li Jing-Jing , Lin Wan Chen , Tai Lung-Hao , Castro Fernanda , Collins Anne GE , Wilbrecht Linda
Published: January 2025

Autism Spectrum Disorder (ASD) is characterized by restricted and repetitive behaviors and social differences, both of which may manifest, in part, from underlying differences in corticostriatal circuits and reinforcement learning. Here, we investigated reinforcement learning in mice with mutations in eitherTsc2orShank3, both high-confidence ASD risk genes associated with major syndromic forms of ASD. Using an odor-based two-alternative forced choice (2AFC) task, we tested adolescent mice of both sexes and found maleTsc2andShank3Bheterozygote (Het) mice showed enhanced learning performance compared to their wild type (WT) siblings. No gain of function was observed in females. Using a novel reinforcement learning (RL) based computational model to infer learning rate as well as policy-level task engagement and disengagement, we found that the gain of function in males was driven by an enhanced positive learning rate in bothTsc2andShank3BHet mice. The gain of function in Het males was absent when mice were trained with a probabilistic reward schedule. These findings in two ASD mouse models reveal a convergent learning phenotype that shows similar sensitivity to sex and environmental uncertainty. These data can inform our understanding of both strengths and challenges associated with autism, while providing further evidence that sex and experience of uncertainty modulate autism-related phenotypes.

Significance Statement

Reinforcement learning is a foundational form of learning that is widely used in behavioral interventions for autism. Here, we measured reinforcement learning in adolescent mice carrying genetic mutations linked to two different syndromic forms of autism. We found that males showed strengths in reinforcement learning compared to their wild type siblings, while females showed no differences. This gain of function in males was no longer observed when uncertainty was introduced into the reward schedule for correct choices. These findings support a model in which diverse genetic changes interact with sex to generate common phenotypes underlying autism. Our data further support the idea that autism risk genes may produce strengths as well as challenges in behavioral function.
Political ideology drives the integration of country-of-origin and offshoring sustainability impact information toward globally prosocial product decisions
Authors: Maxwell-Smith Matthew , Rotman Jeff D. , Johnson Allison R.
Published: January 2025

Purpose

We investigate how white Western consumers make prosocial decisions on domestically branded products manufactured in countries with a developing economy (CDEs). Citizens in these countries manufacture products routinely sold in Western markets under Western companies and brands as part of an offshore supply chain.

Design/methodology/approach

We propose that prosocial decision-making about these products can be traced to an interactive effect between consumers’ perceptions of the social sustainability impact of offshoring on CDE nations and social dominance orientation (SDO)-Dominance (SDO-D), an ideological preference for higher-status groups to forcefully oppress lower-status groups. In three studies with white Western consumers, this paper measured SDO-D, measured or experimentally manipulated the harmful versus beneficial impact of offshoring on CDEs, and presented assessed participants’ willingness to purchase domestically branded and CDE-manufactured products across a series of decision trials.

Findings

White Western consumers with low SDO-D prosocially displayed weaker purchase intentions toward products with a domestic brand manufactured in a CDE (“DCDE products”) when offshoring was perceived as harming those countries, and stronger intentions when offshoring was perceived as beneficial. This effect was mediated by consumers’ trust in domestic firms to treat workforce issues appropriately. Conversely, high SDO-Ds’ intentions were unaffected by the perceived harmful or beneficial impact of offshoring.

Research limitations/implications

Future work in this area will ideally use field purchasing situations while testing for brand familiarity – as a covariate or moderator.

Practical implications

Firms that market or sell these products are advised to understand if their target segments have lower or higher levels of SDO-D, and how they evaluate the impact of the offshored supply chain on CDE citizens. Our research also suggests Western low SDO-Ds attributed the responsibility of foreign worker treatment to their own domestic companies, rather than foreign governments or offshoring agencies, when CDE workers were harmed by offshoring.

Originality/value

These findings have broad implications for the various markets and policies behind the sale and positioning of DCDE products and help identify the consumers who demand socially sustainable supply chains and offshore operations.
Enhancing chronic care pathways with Health Lean Management: a case study in a Spanish hospital
Authors: Tiso Anna , Pozzan Caterina , Morales Contreras Manuel Francisco , Verbano Chiara
Published: January 2025

Purpose

Facing the burden of chronic diseases has become a priority for health-care systems’ economic and social sustainability. To this end, this paper aims to focus on adopting Health Lean Management (HLM), a widely used managerial approach, to improve the performance and quality of care provided in chronic care pathways. HLM addresses not only efficiency and timeliness issues but also care effectiveness and integration. Indeed, the lack of continuity and co-ordination of care constitutes a major challenge for chronic pathways. This research provides an innovative contribution, by extending the implementation of HLM to chronic pathways developed across hospital and territorial care. Indeed, HLM scope typically regards hospital units and departments; hence, analysing the interaction between different levels of care represents a novelty from an academic and practical perspective.

Design/methodology/approach

With the aim of understanding how to extend the adoption of HLM towards the territory, an action research project has been developed. In particular, an improvement project focused on breast cancer care pathways has been launched in a Spanish hospital. The research investigates which HLM activities, tools and practices need to be accomplished in this kind of project, grasping insights into emerging wastes. To this end, the HLM project followed the Define, Measure, Analyse, Improve and Control (DMAIC) cycle, supporting the project team in effectively conducting a preliminary context analysis, qualitative and quantitative data collection, the current state analysis and the countermeasure proposals.

Findings

The analysis conducted on the breast cancer care pathway highlighted major criticalities in managing the diagnosis of new patients. In particular, waiting times to obtain diagnostic imaging and breast specialist consultations highly impacted the care pathway effectiveness and efficiency. Specific wastes that caused these delays have been investigated, leading to the definition of specific countermeasures that could minimise the inefficiencies: an 85% reduction of the staging process lead time was estimated.

Originality/value

The achieved results contribute to enhancing the quality of care delivered to breast cancer patients. This paper enriches the theoretical knowledge about HLM, extending its typical field of application; provides practical support to health-care providers, managers and leaders with a case demonstrating how to develop HLM projects adopting the DMAIC cycle; and finally, it has valuable social implications, addressing the global threat of chronic disease.
The family business in the digital era: advancing towards artificial intelligence
Authors: Atienza-Barba María , Álvarez-García José , Meseguer-Martínez Ángel , Barba-Sánchez Virginia
Published: January 2025

Purpose

This study aims to analyse the literature on the digital transformation of family businesses and the impact of artificial intelligence on this process, highlighting key areas of interest and future perspectives.

Design/methodology/approach

A bibliometric analysis is performed to explore the interconnection between variables and the relationships between authors, countries and journals in this research area. The Scopus database was used as of March 2024, and the data analysis was carried out with Bibliometrix for result analysis and VOSviewer for scientific mapping.

Findings

The analysis confirms the increasing relevance of the topic, with a high number of articles in 2023. Prominent journals are identified, and authors are mainly from China and Europe. Keywords “family business” and “family firms” are strongly linked, showing a connection to artificial intelligence and digital transformation. Family businesses are embracing the digital era, and research must respond accordingly.

Originality/value

This pioneering study offers a novel contribution, as no prior bibliometric analysis has addressed this topic. It lays the groundwork for future research, identifying emerging themes with significant future potential.