bluuebunny/crossref_metadata_2025 huggingface dataset:
Ganglion Cyst in Zone 2 of Guyon's Canal Causing Ulnar Neuropathy With Claw Hand Deformity
Authors: Chiang Liang-Jui , Shieh Shyh-Jou
Published: February 2025

Guyon's canal, a fibro-osseous anatomical tunnel, sometimes harbors underlying pathologies such as a ganglion cyst, leading to symptoms including dysesthesia, paresthesia, and motor weakness in the ulnar nerve distribution. Surgical excision is often the recommended approach to restore normal hand function. Ulnar nerve palsy caused by mechanical compression can benefit from surgical decompression; however, a timely diagnosis is often difficult. In this report, we describe the successful tumor excision and nerve decompression of a ganglion cyst in Guyon's canal. The observed intraoperative findings challenge the conventional classification of compression zones. The processes of diagnosing and treating tumors within Guyon's canal were thoroughly explained and elaborated. A 40-year-old female patient presented with right-sided ulnar wrist pain, progressive weakness of the intrinsic muscles, and a claw hand deformity, typically suggestive of a zone 1 compression within Guyon's canal. Magnetic resonance imaging revealed a cystic mass at the ulnar side of the wrist, prompting a referral to the Department of Plastic and Reconstructive Surgery for further management. Intraoperatively, a transparent cystic tumor was identified in zone 2 of the Guyon's canal, causing significant compression of the motor branch, while displacing the superficial branch upward, which mimicked the clinical presentation of zone 1 compression. The tumor was excised, and the nerve was successfully decompressed. A pathological report confirmed the diagnosis of a ganglion cyst. At the 1-year follow-up, the patient showed no signs of complications or recurrence. Her initial symptoms, including pain and intrinsic muscle weakness, improved significantly. Complete resolution of claw hand deformity indicated successful functional recovery. Compression of the ulnar nerve within Guyon's canal due to a ganglion cyst is uncommon, and the significance of the resulting neuropathy in the wrist is underrated. Meticulous clinical assessments, a thorough anatomical understanding and appropriate tests, are essential for accurate diagnosis. Timely decompression and surgical removal of the ganglion can facilitate a promising postoperative recovery.
Clinicopathological Characteristics, Gene Mutations, and Treatment of Fibro-adipose Vascular Anomaly
Authors: Xiong Fei , Jin Cai-Jun , Wang Shi-Qi , Zhong Hai-Yan , Zheng Miao , Zou Ming-Li , Wang Qian , Yuan Si-Ming
Published: February 2025

Purpose

The objective of this study is to offer a thorough overview of the clinical and pathological characteristics, potential pathogenic genes, treatment modalities, and prognoses of a cohort of Chinese individuals diagnosed with Fibro-adipose Vascular Anomaly (FAVA). This study aims to advance the comprehension of this specific medical condition.

Methods

A total of 15 cases of FAVA patients admitted to our center between June 2015 and December 2023 were included in this study. Clinical symptoms, laboratory tests, imaging findings, and pathological data were systematically reviewed to outline the clinical and pathological features of FAVA. Furthermore, whole-exome sequencing was conducted on lesion samples from five patients to identify potential pathogenic genes. The treatment modalities encompassed sclerotherapy and surgical interventions, with treatment outcomes assessed based on clinical symptoms, imaging characteristics, and enhancement of limb functions.

Results

The FAVA lesions were predominantly located in the limbs in 14 patients and in the trunk in 1 patient. The clinical manifestations included pain (9/15, 60%), muscle contracture deformity (3/15, 20%), and joint dysfunction (3/15, 20%). Coagulation function assessments indicated that 3 patients exhibited localized intravascular coagulation (LIC). Magnetic resonance imaging (MRI) findings displayed mixed vascular malformation components and fibrofatty components within the muscles, showing isointense or hyperintense signals on T1-weighted images and heterogeneous hyperintense signals on T2-weighted images. Histopathological analysis revealed activation of the PI3K-AKT-mTOR signaling pathway. Whole-exome gene sequencing of 5 cases identified 10 genes potentially linked to pathogenicity. All patients underwent ethanol sclerotherapy. Surgical intervention was performed on five patients due to muscle contracture and joint dysfunction. Some patients reported pain relief following sclerotherapy, whereas those who underwent surgery demonstrated significant enhancement of joint function.

Conclusions

The Chinese patients diagnosed with FAVA in this study presented characteristic clinical symptoms, imaging features, and pathological traits. The lesion tissue showed activation of the PI3K-AKT-mTOR signaling pathway, with only one patient (1/5, 20%) exhibiting a PIK3CA mutation. This finding underscores the intricate nature of the pathogenic genes and pathogenesis of FAVA. Although sclerotherapy demonstrated restricted efficacy in alleviating pain symptoms, surgical intervention was deemed necessary for addressing joint dysfunction resulting from muscle contracture.
Facial Gender-Affirming Surgery: Facial Analysis and Procedures for Facial Masculinization
Authors: Hu Allison C. , Pang John H. , Satterwhite Thomas J.
Published: February 2025

Feminine facial features may be a source of significant gender dysphoria in certain patients. A masculine appearance includes an M-shaped hairline, wider and taller forehead, supraorbital bossing, larger and wider nose with a large dorsal hump, broader chin, wider mandible with a sharper angle, thinner lips, presence of facial hair, and prominent thyroid cartilage. Given these critical differences between feminine and masculine facial features, a comprehensive and systematic way of evaluating these distinct structures is necessary before facial gender-affirmation surgery. While no single approach to facial masculinization surgery exists due phenotypic diversity of masculine features and unique individual preferences, select anatomic features can be augmented through nonsurgical and surgical techniques to create a harmonious face that better aligns with a patient’s identified gender. Here, the authors describe a standardized method for facial analysis and review anatomic sexual dimorphism and procedural and surgical facial masculinization.
Development and Validation of the Ileoanal Pouch Syndrome Distress Index
Authors: Cavallaro Paul , Olortegui Kinga S. , Steinhagen Randolph , Jeganathan Nimalan A. , Fearnhead Nicola , McKendry Susan , Kennedy Kevin , Bordeianou Liliana ,   On behalf of the PROPS Scientific Committee
Published: February 2025

Objective:

To design and validate a questionnaire-based scoring system that measures distress and quality of life implications related to specific bowel function symptoms and consequences.

Summary of Background Data:

The Patient Reported Outcomes after Pouch Surgery Delphi consensus study identified symptoms and consequences that were utilized to previously create a pouch severity score. The existing score does not specifically evaluate patients’ accommodations to pouch function or their perceived distress related to bowel-related quality of life over time.

Methods:

Pouch patients were recruited at inflammatory bowel disease centers and via patient advocacy websites. They were administered a questionnaire-based survey eliciting responses regarding the frequency of a variety of bowel symptoms identified in the prior Delphi consensus study. For each item, participants also responded to the question “How much does having this symptom (or consequence) bother you?”. Participants also reported on their quality of life. The responses were used to generate the Ileoanal Pouch Syndrome Distress index. Test-retest validity, convergent validity, and clinical validity were evaluated.

Results:

The distress index was calculated by adding the patient’s scores for all 16 items. The possible scores range from 0 to 64, ranked from least to most bothersome symptoms. With increasing distress index scores, a higher proportion of patients reported poor quality of life. The receiver operating characteristic area under the curve for the distress score prediction of poor quality of life was calculated at 0.871. The distress index showed excellent correlation with bowel function scores and measures of clinical validity.

Conclusions:

The distress index represents a step forward in the patient-centered management of ileoanal pouch function. When used in combination with the severity score and longitudinally over time, it will allow surgeons and gastroenterologists to take a nuanced approach to optimizing bowel function for a population of highly complex gastrointestinal patients, while accounting for symptom accommodation over time.
Pseudoalteromonas ardens sp. nov., Pseudoalteromonas obscura sp. nov. and Pseudoalteromonas umbrosa sp. nov. isolated from the coral Montipora capitata on a reef in Kāneʻohe Bay, Oʻahu, Hawaiʻi
Authors: Thomas Emily M. , Smith Emma M. , Papke Erin , Shlafstein Maximillian D. , Grant-Beurmann Silvia , Coelho Lívia C. , Trott Alison C. , Häse Claudia C. , Oline David K. , Videau Patrick , Saw Jimmy H. , Strangman Wendy K. , Ushijima Blake
Published: February 2025

Strains P94T, B95T and R96T were isolated from apparently healthy fragments of the coral Montipora capitata, which were resistant to Vibrio coralliilyticus infection, from the reef surrounding Moku o Loʻe in Kāne‘ohe Bay, O‘ahu, Hawai‘i, USA, and were taxonomically evaluated using a polyphasic approach. Phylogenetic and phylogenomic analyses placed strains P94T, B95T and R96T within the Pseudoalteromonas genus and most closely related to Pseudoalteromonas luteoviolacea and Pseudoalteromonas rubra. Following genome sequencing of strains P94T, B95T and R96T, the average nt identity and in silico DNA–DNA hybridization comparisons with closely related strains resulted in values that fell below species-level cutoffs. Based on a polyphasic characterization and differences in genomic and taxonomic data, strains P94T, B95T and R96T represent novel species, for which the names Pseudoalteromonas ardens sp. nov., Pseudoalteromonas obscura sp. nov. and Pseudoalteromonas umbrosa sp. nov. are proposed. The type strains are R96T (=DSM 114998T=LMG 32870T), P94T (=DSM 114996T=LMG 32871T) and B95T (=DSM 114997T=LMG 32872T), respectively.
Brain-wide mapping reveals temporal and sexually dimorphic opioid actions
Authors: Vasylieva Iaroslavna , Smith Megan C. , Aravind Eshan , He Kelin , Ling Tianhan , Kozel Jenesis , Puig Stephanie , Kedziora Katarzyna M , Scarlett Jessica J. , Joseph Paul N. , Lycas Matthew D. , Gether Ulrik , Logan Ryan W. , Freyberg Zachary , Watson Alan M.
Published: February 2025

While the molecular and cellular effects of opioids have been extensively studied, the precise mechanisms by which these drugs target specific brain regions over time remain unclear. Similarly, despite well-documented sex differences in opioid responses, the anatomical basis for this sexual dimorphism is not well characterized. To address these questions, we developed an automated, scalable, and unbiased approach for whole-brain anatomical mapping of the neuronal activity marker c-Fos in response to acute morphine exposure. Using ribbon scanning confocal microscopy, we imaged whole cleared brains from male and female wild-type mice at 1 hour and 4 hours post-morphine administration. Our whole-brain analysis of c-Fos expression revealed distinct patterns of morphine-induced regional brain activation across time and sex. Notably, we observed a greater number of structures with significant activity differences at 4 hours compared to 1 hour. In male mice, significant changes were primarily localized to regions within the dopamine system, whereas in female mice, they were concentrated in cortical regions. By combining high-throughput imaging with whole-brain expression analysis, particularly in the context of opioid actions, our approach provides a more comprehensive understanding of how drugs of abuse affect the brain.
Mouse sensorimotor cortex reflects complex kinematic details during reaching and grasping
Authors: Grier Harrison , Salimian Sohrab , Kaufman Matthew
Published: February 2025

Coordinated forelimb actions, such as reaching and grasping, rely on motor commands that span a spectrum from abstract target specification to detailed instantaneous muscle control. The sensorimotor cortex is central to controlling these complex movements, yet how the detailed command signals are distributed across its numerous subregions remains unclear. In particular, in mice it is unknown if the primary motor (M1) and somatosensory (S1) cortices represent low-level joint angle details in addition to high-level signals like movement direction. Here, we combine high quality markerless tracking and two-photon imaging during a reach-to-grasp task to quantify movement-related activity in the mouse caudal forelimb area (CFA) and forelimb S1 (fS1). Linear decoding models reveal a strong representation of proximal and distal joint angles in both areas, and both areas support joint angle decoding with comparable fidelity. Despite shared low-level encoding, the time course of high-level target-specific information varied across areas. CFA exhibited early onset and sustained encoding of target-specific signals while fS1 was more transiently modulated around lift onset. These results reveal both shared and unique contributions of CFA and fS1 to reaching and grasping, implicating a more distributed cortical circuit for mouse forelimb control than has been previously considered.
β-Hydroxybutyrate enhances brain metabolism in normoglycemia and hyperglycemia, providing cerebroprotection in a mouse stroke model
Authors: Holstein Deborah M , Saliba Afaf , Lozano Damian , Kim Jiwan , Sharma Kumar , Lechleiter James D
Published: February 2025

Hyperglycemia in poorly controlled diabetes is widely recognized as detrimental to organ dysfunction. However, the acute effects of hyperglycemia on brain metabolism and function are not fully understood. The potential protective benefit of ketone bodies on mitochondrial function in the brain has also not been well characterized. Here, we evaluated the acute effects of hyperglycemia and β-hydroxybutyrate (BHB) on brain metabolism by employing a novel approach leveraging adenosine triphosphate (ATP)-dependence of bioluminescence originating from luciferin-luciferase activity. Oxygen consumption rate was measured inex vivolive brain punches to further evaluate mitochondrial function. Additionally, we investigated the functional relevance of BHB using anin vivophotothrombotic stroke model to assess its cerebroprotective effects. Our data demonstrate that brain metabolism in mice is affected by acute exposure to high glucose, at a level similar to consuming food or a beverage with high sucrose. This short-term effect of glucose exposure was reduced by co-administration with the ketone body BHB. Moreover, BHB significantly reduced infarct size in the brain stroke model, providing evidence for its functional protective role in the brain. These findings suggest that BHB may effectively mitigate the adverse effects of metabolic stress and ischemic events on brain metabolism and function.
GRPhIN: Graphlet Characterization of Regulatory and Physical Interaction Networks
Authors: Barelvi Altaf , Anderson Oliver , Ritz Anna
Published: February 2025

Graphs are powerful tools for modeling and analyzing molecular interaction networks. Graphs typically represent either undirected physical interactions or directed regulatory relationships, which can obscure a particular protein's functional context. Graphlets can describe local topologies and patterns within graphs, and combining physical and regulatory interactions offer new graphlet configurations that can provide biological insights. We present GRPhIN, a tool for characterizing graphlets and protein roles within graphlets in mixed physical and regulatory interaction networks. We describe the graphlets of mixed networks in B. subtilis, C. elegans, D. melanogaster, D. rerio, and S. cerevisiae and examine local topologies of proteins and subnetworks related to the oxidative stress response pathway. We found a number of graphlets that were abundant in all species, specific node positions (orbits) within graphlets that were over-represented in stress-associated proteins, and rarely-occurring graphlets that were enriched in stress subnetworks. These results showcase the potential for using graphlets in mixed physical and regulatory interaction networks to identify new patterns beyond a single interaction type.
Ketogenic Diet Enhances Cognitive-Behavioral Function and Hippocampal Neurogenesis While Attenuating Amyloid Pathology in Tg-SwDI Mice
Authors: Pulido-Correa Victoria E. , Hernandez Ariana , Wind Eleanor J. , Zhu YingYing , Vogel Chana , Binu Shaina , Jeneske Mikayla , Kuni Dylan , Chiduruppa Vedika , Echeverria Bianca , Rosenberg Lauren , Robison Lisa S.
Published: February 2025

The ketogenic diet (KD), characterized by high-fat, low-carbohydrate, and moderate protein intake, has gained attention for its therapeutic potential in patients with neurodegenerative diseases, including Alzheimer’s disease. Studies in Alzheimer’s rodent models report that KD and/or ketogenic supplements attenuate cognitive-behavioral impairments, neuroinflammation, amyloid-beta plaques and tau pathology. However, it is unknown whether KD can similarly benefit individuals with cerebral amyloid angiopathy (CAA), a prevalent condition in which amyloid accumulates in cerebral vessels. CAA is highly comorbid in patients with Alzheimer’s and, on its own, increases the risk of stroke, cognitive impairment, and dementia, yet no effective treatments currently exist. The objective of this study was to determine whether KD can improve cognitive-behavioral and neuropathological outcomes in a mouse model with CAA. Male Tg-SwDI mice were fed either a standard chow or KD from 3.5 to 7.5 months of age. Following ∼3 months of dietary intervention, glucose and ketone-body levels were assessed, then mice underwent a battery of behavioral tests to evaluate locomotor activity, anxiety-related behaviors, and cognition. Immunohistochemistry was performed to assess amyloid pathology, vascular density, neuroinflammation, white matter integrity, and hippocampal neurogenesis. In addition to KD inducing nutritional ketosis and achieving metabolic benefits, mice on KD exhibited increased activity, enhanced spatial learning and memory, and a trend toward improved spatial working memory. These cognitive benefits were accompanied by an attenuation of amyloid pathology and increased hippocampal neurogenesis. These findings suggest that a ketogenic diet may be safe and effective in Alzheimer’s and dementia patients with CAA.
Network properties constrain natural selection on gene expression inCaenorhabditis elegans
Authors: Inskeep Tyler R. , Groen Simon C.
Published: February 2025

Gene regulatory networks (GRNs) integrate genetic and environmental signals to coordinate complex phenotypes and evolve through a balance of selection and drift. Using publicly available datasets fromCaenorhabditis elegans, we investigated the extent of natural selection on transcript abundance by linking population-scale variation in gene expression to fecundity, a key fitness component. While the expression of most genes covaried only weakly with fitness, which is typical for polygenic traits, we identified seven transcripts under significant directional selection. These includednhr-114andfeh-1,implicating variation in nutrient-sensing and metabolic pathways as impacting fitness. Stronger directional selection on tissue-specific and older genes highlighted the germline and nervous system as focal points of adaptive change. Network position further constrained selection on gene expression; high-connectivity genes faced stronger stabilizing and directional selection, highlighting GRN architecture as a key factor in microevolutionary dynamics. The activity of transcription factors such aszip-3, which regulates mitochondrial stress responses, emerged as targets of selection, revealing potential links between energy homeostasis and fitness. Our findings demonstrate how GRNs mediate the interplay between selection and drift, shaping microevolutionary trajectories of gene expression and phenotypic diversity.
Brain stimulation preferentially influences long-range projections in primates
Authors: Vieira Pedro G. , Krause Matthew R. , Laamerad Pooya , Pack Christopher C.
Published: February 2025

Advances in brain stimulation have made it possible to target smaller and smaller regions for electromagnetic stimulation, in the hopes of producing increasingly focal neural effects. However, the brain is extensively interconnected, and the neurons comprising those connections may themselves be particularly susceptible to neurostimulation. Here, we test this hypothesis using single-unit recordings from alert non-human primates receiving transcranial electrical stimulation. We find that putative long-range projections (i.e., axons) are more strongly affected by stimulation than other cell types. These data suggest the need for alternate stimulation strategies that target the edges, rather than nodes, of neural networks.
Clofazimine treatment modulates key non-coding RNAs associated with tumor progression and drug resistance in lethal Prostate Cancer
Authors: Batten Sarah , Kumar Harish , Mazumder Suman , Ghosh Taraswi Mitra , Mitra Amit Kumar
Published: February 2025

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second-leading cause of cancer death among men in the United States, representing 24.3% of all new cancer cases in the US Metastatic castration-resistant prostate cancer (mCRPC) is a lethal variant of prostate cancer that is associated with increased aggressiveness, cancer stemness, morbidity, and the risk of developing into taxane drug-resistant PCa. As taxanes are currently the first-line chemotherapeutic agents for mCRPC, there is a critical need to develop novel agents for the treatment of mCRPC. Clofazimine (CLF) is a potential immunomodulator drug that is FDA-approved for the treatment of leprosy.

Recently, using a phenotype-based high-throughput drug screening, we demonstrated thein vitro(cell lines),in vivo(mouse xenograft models), andex vivo(patient-derived primary tumor cells) efficacy of CLF in drug-resistant forms of chronic myeloid leukemia and multiple myeloma.

In this study, we demonstrate that CLF is effective as a single agent and in combination with docetaxel (DTX) in a panel of PCa cell lines representing the diversity of CRPC patients. The response to CLF in the PCa cell lines was quantified usingin vitrocytotoxicity assays, caspase 3/7 activity assay for apoptosis, cell cycle analysis, and aldehyde dehydrogenase activity assay for cancer stemness. We show that following CLF treatment, cellular pathways associated with apoptosis and ER stress were up-regulated, providing additional understanding of the mechanism of action of CLF in PCa cells. Further, we also found that CLF reduces ALDH activity, which is a marker for cancer cell stemness, a subtype of cancer cells that are associated with the aggressiveness of the cancer.

Finally, drug-induced changes were investigated using whole transcriptome (next-generation RNA sequencing) analysis, where CLF treatment was found to modulate the expression of several non-coding RNAs that are associated with tumor cell proliferation, cell migration, and PCa drug resistance. Western Blotting was performed to validate the dysregulation of proteins associated with cell death and apoptosis, as well as the top dysregulated pathways in mCRPC following treatment with CLF.

Our results support the preclinical development of CLF as a combination therapy candidate against aggressive forms of Prostate Cancer and provide additional insights into its mechanism of action.
Neurophysiological Correlates of Modifiable Dementia Risk Factors in Cognitively Unimpaired Older Adults
Authors: Levenstein Jacob M. , Treacy Ciara , Andrews Sophie C.
Published: February 2025

The 2024 Lancet Commission on Dementia estimates that up to 45% of dementia cases could be prevented by addressing modifiable risk factors, emphasising both prevention opportunities and the need to understand the biological mechanisms. This study investigated neurophysiological mechanisms underlying modifiable dementia risk factors in cognitively unimpaired older adults. Seventy-nine cognitively unimpaired older adults underwent MRI brain scans, with spectroscopy measurements taken from the sensorimotor cortex (SMC) and prefrontal cortex (PFC), using a Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence, optimised for measuring GABA+. Modifiable dementia risk scores were calculated using the Assessment for Cognitive Health and Dementia Risk (CogDrisk). Hierarchical linear regression analyses revealed a significant negative relationship within the SMC, with lower GABA+ (β = −0.249, p = 0.009) associated with higher risk scores. In the PFC, lower tNAA and tCho concentrations significantly predicted higher risk scores (β = −0.168 and −0.170, respectively). These findings suggest that GABAergic system alterations may underlie the pathophysiology of modifiable dementia risk in healthy ageing, whilst changes in tNAA and tCho may reflect early alterations in neuronal integrity. These region-specific neurochemical findings may help identify potential early biomarkers for dementia risk, and suggest new therapeutic pathways for preventive interventions.
Identification of QTLs linked to partial resistance to foot and root rot caused byFusarium avenaceumandFusarium oxysporumin faba bean (Vicia faba)
Authors: Webb Anne , Thomas Jane E. , Davis Huw , McAdam Simon , Angra Deepti , O’Sullivan Donal M. , Gostkiewicz Krystyna , Capozzi Martina , Wood Thomas A.
Published: February 2025

Foot and root rot, caused by a complex of soil-borne fungal and oomycete pathogens, including severalFusariumspp., can cause serious yield losses in faba bean. Current control strategies rely largely on agronomic practices and limited varietal resistance. Identifying novel sources of genetic resistance is of great potential value for breeding elite varieties with improved foot rot resistance. A partially resistantVicia fabaaccession ‘ig124213’ (NV490) was crossed with a moderately susceptible ‘ig124301’ (NV512) and a mapping population comprising 198 F3families was developed. This was screened for resistance to a mixture of seven UK field isolates ofFusarium avenaceumandFusarium oxysporumunder glasshouse conditions. Several F3families with moderate to high levels of resistance to bothFusariumspecies were identified, and a high-density linkage map of theV. fabagenome including 6755 SNP-markers in seven linkage groups (LG) was generated using the ‘Vfaba_v2’ Axiom SNP array. Quantitative trait loci associated with improved resistance toFusariumfoot and root rot were identified, including one major QTL on LG4, corresponding to the chromosome 4 ofV. faba.

Key message

The first QTL associated with partial resistance toFusariumfoot and root rot has been identified using a biparental mapping population ofVicia faba.
Locomotion selectively enhances visual speed encoding in mouse medial higher visual areas
Authors: Horrocks Edward A. B. , Saleem Aman B.
Published: February 2025

Mammalian visual systems are comprised of multiple brain areas with distinct functional roles. Whilst functional specialisations have been proposed in the mouse based on visual feature encoding, the extent to which these specialisations are contingent on ongoing behaviour is unknown. To address this we analysed neural encoding of visual motion stimuli by thousands of neurons recorded across six cortical and two thalamic mouse visual areas while mice were stationary or locomoting. We found locomotion selectively enhanced visual speed encoding in medial higher visual cortical areas, indicating that these areas may be specialised for the processing visual motion during locomotion. By contrast, encoding of drifting gratings direction was enhanced non-selectively across the mouse visual cortex during locomotion. Our results therefore reveal how a complex interplay of sensory input and ongoing behaviour differentially shapes the efficacy of sensory processing in mouse higher visual areas.
Deep Learning to Predict Future Cognitive Decline: A Multimodal Approach Using Brain MRI and Clinical Data
Authors: Chattopadhyay Tamoghna , Senthilkumar Pavithra , Ankarath Rahul H. , Patterson Christopher , Gleave Emma J. , Thomopoulos Sophia I. , Huang Heng , Shen Li , You Lei , Zhi Degui , Thompson Paul M.
Published: February 2025

Predicting the trajectory of clinical decline in aging individuals is a pressing challenge, especially for people with mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, or vascular dementia. Accurate predictions can guide treatment decisions, identify risk factors, and optimize clinical trials. In this study, we compared two deep learning approaches for forecasting changes, over a 2-year interval, in the Clinical Dementia Rating scale ‘sum of boxes’ score (sobCDR). This is a key metric in dementia research, and scores range from 0 (no impairment) to 18 (severe impairment). To predict decline, we trained a hybrid convolutional neural network that integrates 3D T1-weighted brain MRI scans with tabular clinical and demographic features (including age, sex, body mass index (BMI), and baseline sobCDR). We benchmarked its performance against AutoGluon, an automated multimodal machine learning framework that selects an appropriate neural network architecture. Our results demonstrate the importance of combining image and tabular data in predictive modeling for clinical applications. Deep learning algorithms can fuse image-based brain signatures and tabular clinical data, with potential for personalized prognostics in aging and dementia.
Cortical thinning in temporal pole, a core region in Alzheimer’s disease, in non-demented, middle-agedAPOE-ε4 andPICALM-AA/AG carriers
Authors: Dzianok Patrycja , Wojciechowski Jakub , Wolak Tomasz , Kublik Ewa
Published: February 2025

The symptoms of Alzheimer’s disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal cortex. However, the influence of genetic risk on cortical thickness in non-demented individuals prior to disease onset remains unclear. This study aimed to explore the relationship between two AD risk genes (APOE/PICALM) and cortical thickness in selected regions of interest (ROIs) in non-demented, middle-aged individuals. Sixty-nine (N = 69) participants (34 females, 35 males; age: 55.45±3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their AD risk. Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred as “the cortical signature of AD” in previous studies.APOE-ε4 withPICALM-AA/AG carriers (A+P-) are characterized by a thinner cortex in the right temporal pole compared to non-carriers, controlling for sex. No other differences in cortical thickness were found in the selected ROIs. The direction of the findings aligns with existing literature reporting cortical thinning in amyloid-positive individuals, as well as in patients with mild cognitive impairment and Alzheimer’s disease when compared to control groups.
Layer connective fields from ultrafast resting-state fMRI differentiate feedforward from feedback signaling
Authors: Carvalho Joana , Fernandes Francisca F. , Valente Mafalda , Haak Koen V. , Shemesh Noam
Published: February 2025

Deciphering the directionality of information flow in cortical circuits is essential for understanding brain dynamics, learning, and neuroplasticity after injury. However, current non-invasive methods cannot distinguish feedforward (FF) from feedback (FB) signals across entire networks, including deep brain regions. Here, we present a novel approach combining ultrafast fMRI with a Layer-based Connective Field (lCF) model to disentangle FF from FB signaling. Our findings reveal that lCF size, an indicator of spatial information integration, differentiates FF and FB activity through distinct layer-specific connectivity patterns during spontaneous activity, challenging the notion that FF signals are solely stimulus-driven. FF connectivity follows an inverted U-shape, peaking in layer IV, while FB exhibits a U-shaped pattern, with peaks in layers I and VI. These profiles generalize across sensory pathways (visual, somatosensory, and motor) and reveal injury-induced network reorganization, such as LGN bypassing V1 to provide direct FF input to higher visual areas.
Astrocytic activation of EMMPRIN contributes to their pathological phenotype in ALS
Authors: Edozie Gloria Nwamaka , Bélanger Jasmine , Pigeyre Shanna , Gosselin Ariane , Boyer Marion , Godin Antoine G. , Pozzi Silvia
Published: February 2025

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterised by the degeneration of upper and lower motoneurons. Onset and progression of the disease are determined by both cell-autonomous neuronal dysfunctions and non-cell-autonomous factors, mainly due to activation of glial cells such as astrocytes and microglia.

The Extracellular Matrix Metalloproteinases INducer (EMMPRIN), a glycoprotein expressed by various cell types including neurons, is the major activator of matrix metalloproteinases (MMPs) synthesis and release. EMMPRIN activation can be induced by peptidyl-prolyl isomerase A (PPIA), a chaperone protein with cis/trans isomerase activity, that exhibits cytokine- and chemokine-like behaviour. Previous studies showed that PPIA is highly released in the cerebrospinal fluid (CSF) of ALS patients and animal models where, by activating EMMPRIN on motoneurons, induces neuronal death.

Here, we show that EMMPRIN is expressed also by astrocytes, suggesting this cell type as sensitive as motoneurons to PPIA-mediated EMMPRIN activation. We observed that that PPIA-mediated EMMPRIN activation prompt astrocytes toward a pro-inflammatory profile. Interestingly, we found that this pathogenic profile can be reverted by an anti-EMMPRIN antibody. Finally, we provide evidence that the activation of EMMPRIN is relevant for mutant SOD1 and TDP-43 conditions.

In conclusion, we demonstrate that EMMPRIN activation in ALS occurs also in astrocytes where it exacerbates their pathological phenotype possibly contributing to the progression of the disease. Furthermore, we suggest the potential use of an anti-EMMPRIN antibody to reduce astrocytic activation during the disease.
The glare illusion in individuals with schizophrenia
Authors: Tamura Hideki , Hoshino Aiko
Published: February 2025

Individuals with schizophrenia are known to demonstrate unique reactions to visual illusions, and prior research has indicated a potential link between their increased susceptibility to geometric illusions and specific symptom profiles. While various illusory experiences have been examined among individuals with schizophrenia, their responses to brightness-related illusions remain poorly understood. In this study, we investigated how individuals with schizophrenia perceive the glare illusion, in which the apparent brightness of the central region is increased. A total of 30 patients with schizophrenia and 34 control participants were recruited. During each trial, a glare or control image (standard stimulus) was presented alongside a control image (comparison stimulus) with one of seven luminance levels. In the glare condition, the standard stimulus was a glare image; in the control condition, two control images were presented, but only the luminance of the comparison stimulus varied. The participants were asked to judge which central region appeared brighter. The results revealed that the individuals with schizophrenia exhibited greater susceptibility to the glare illusion than did the control participants. However, no significant associations were found between susceptibility to the glare illusion and scores assessing symptom severity. These findings suggest that differences in visual processing in patients with schizophrenia may increase their susceptibility to brightness illusions, although this phenomenon is independent of symptom characteristics. Understanding these perceptual alterations may aid in the development of objective measures of visual cognition for patients with schizophrenia.
Bacterial sexually transmitted infections and related antibiotic use among individuals eligible for doxycycline post-exposure prophylaxis in the United States
Authors: Parker Anna M. , Chang Jennifer J. , Chen Ligong , King Laura M. , McCoy Sandra I. , Lewnard Joseph A. , Bruxvoort Katia J.
Published: February 2025

Background

Doxycycline postexposure prophylaxis (doxyPEP) can prevent bacterial sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women. However, concern surrounds the volume of tetracycline use needed to realize these benefits, and whether potential risks of increased tetracycline exposure outweigh benefits of doxyPEP for specific populations.

Methods

We estimated incidence rates of gonorrhea, chlamydia, and syphilis and related antibiotic prescribing among commercially-insured US males and transgender individuals using the Merative MarketScan® Research Databases during 2016-2019. We evaluated potential impacts of doxyPEP implementation under risk-based prioritization schemes focusing on HIV pre-exposure prophylaxis (PrEP) recipients, people living with HIV (PLWH), and people with prior STI diagnoses.

Results

Incidence rates of gonorrhea, chlamydia, and syphilis among PLWH and PrEP recipients with ≥1 STI diagnosis in the prior year totaled 33.3-35.5 episodes per 100 person-years. Direct effects of doxyPEP could prevent 7.4-9.6 gonorrhea diagnoses, 7.3-8.1 chlamydia diagnoses, and 3.1-5.9 syphilis diagnoses per 100 person-years within these populations. Expected increases in tetracycline consumption resulting from doxyPEP implementation were equivalent to 271.9-312.9 additional 7-day doxycycline treatment courses (resembling current standards for chlamydia treatment) per 100 person-years of use. This increase corresponded to the equivalent of 36.5-37.0, 37.0-38.7, and 46.1-100.2 additional 7-day doxycycline treatment courses for each prevented chlamydia, gonorrhea, and syphilis episode, respectively. These increases in doxycycline use exceeded anticipated reductions in STI-related prescribing of cephalosporins, macrolides, and penicillins by 16-69 fold margins.

Conclusions

Estimates of changes in antibiotic use and STI incidence resulting from doxyPEP implementation in differing populations may inform priority-setting for this intervention.
Routine immunization intensification, vaccination campaigns, and measles transmission in Southern Nigeria
Authors: Thakkar Niket , Oteri Avuwa Joseph , McCarthy Kevin
Published: February 2025

In this paper, we compare – in terms of their estimated effects on disease transmission – Southern Nigeria’s large-scale measles vaccination campaigns since 2010 to a unique, more targeted routine immunization intensification that happened in 2019. A main focus of the discussion throughout is that quantifying intervention impact in real epidemiologies requires us to disentangle competing, dynamic sources of immunity, including unreported infection. To address this inference challenge, we create a collection of state-level, stochastic transmission models capable of estimating underlying measles susceptibility based on surveillance and survey data. Leveraging these models, we find that the 2019 intensification, despite being restricted in scale to children under 2 years-old, had an effect on transmission comparable to the region’s larger vaccination campaigns targeting children up to 5. This implies that vaccines delivered in that effort were more than twice as likely to reach a susceptible child.
Transfer of Learned Object Manipulations between Two- and Five-Digit Grasps
Authors: Ulloa-Marquez Jordana , Gutterman Jennifer , Santello Marco , Gordon Andrew M.
Published: February 2025

Successful object manipulation involves integrating object properties into a motor plan and scaling fingertip forces through learning. This study investigated whether learned manipulations using a two-digit grip transfer to a five-digit grip and vice versa, focusing on the challenges posed by added degrees of freedom in force distribution. The goal of the task was to exert the necessary compensatory torque (Tcom) and vertical forces to minimize object roll on a visually symmetrical object that with an asymmetrical mass distribution. To examine this, subjects performed blocked consecutive learning trials before switching grip type. Our results support the learning transfer between two-digits and five-digit grasp configurations despite challenges in maintaining perfect stability during the grip switch. Subjects adapted their grip forces (GF), center of pressure (CoP), and Tcom to minimize object roll, with significant improvements observed from novel (1st) to transfer (11th) trials. These findings suggest high-level, effector-independent representations of object manipulation that enable generalization across grip types, though some limitations in force distribution and digit position arise during transfers.
Cluster replicability in single-cell and single-nucleus atlases of the mouse brain
Authors: French Leon , Suresh Hamsini , Gillis Jesse
Published: February 2025

Single-cell RNA sequencing has advanced our understanding of cellular heterogeneity. Ensuring the replicability of identified cell clusters across studies is essential for determining their biological robustness. We assess the replicability of cell clusters identified in two large mouse brain atlases, one generated using single-cell RNA sequencing and the other with single nuclei. Both profile over 4 million cells and group them into over 5000 clusters. Using transcriptome-wide neighbor voting, we identify 2009 reciprocally matched cluster pairs with consistent spatial localization and coordinated gene expression, which were also observed in datasets from multiple species. Reciprocal clusters are enriched in the cerebellum, where lower diversity aids replicability, while the hypothalamus's heterogeneity limits agreement. Distinguishing close clusters is much more challenging than differentiating a cluster from most others, especially when using marker genes. By incorporating replicability data, we provide a stronger foundation for investigating the newly identified clusters and their biological meaning.
Efficient elastic tissue motions indicate general motor skill
Authors: Namburi Praneeth , Pallarès-López Roger , Folgado Duarte , Magana-Salgado Uriel , Ryu Enya , Kappacher Armin , Gamboa Hugo , Anthony Brian W. , Daniel Luca
Published: February 2025

Insights into the general nature of motor skill could fundamentally change how we develop movement abilities, like how education develops thought. This would have far-reaching implications for enhancing musculoskeletal well-being and performance, reducing musculoskeletal injury risk, and promoting graceful ageing. Here, we sought to identify indicators of general motor skill–those shared by experts across disciplines (e.g., squash, ballet, volleyball, hip-hop) during non-specialized movements (e.g., reaching for water). Identifying such general indicators of motor skill has remained elusive. Using ultrasound imaging with deep learning and optical flow analysis, we tracked elastic tissues (muscles and associated connective tissues) during a simple reaching task performed similarly by world-class athletes and regional-level athletes drawn from diverse disciplines, as well as untrained non-experts. We analyzed previously unexamined inefficiencies: transverse elastic tissue motions orthogonal to muscle fiber direction and physiological tremors, which are oscillations that do not contribute to the net work done by muscles. We discovered that world-class experts minimize both these inefficient motions compared to regional level athletes and non-experts. While regional-level athletes surprisingly showed similar inefficiencies to non-experts, they used elastic tissues more effectively, achieving equivalent movements with smaller actuation-related tissue motions. We establish elastic tissue motion as a key indicator of general motor skill, expanding our understanding of elastic mechanisms and their role in general aspects of motor skill.
Astrocytic MAOB-GABA axis as a molecular brake on repair following spinal cord injury
Authors: Lee Hye Yeong , Lee Jung Moo , Lee Hye-Lan , Park Jiyeon , An Heeyoung , Park Eun Kyung , Hwang Sae Yeon , Hwang Gwang Yong , Kim Keung Nyun , Nam Min-Ho , Lee Seung Eun , Kang Hyunji , Won Joungha , Jang Bo Ko , Lee Elijah Hwejin , Choi SunYeong , Park Mingu Gordon , Kim Sang Wook , Park Ki Duk , Lee SeungHwan , Lee C. Justin , Ha Yoon
Published: February 2025

Neuroregeneration and remyelination rarely occur in the adult mammalian brain and spinal cord following central nervous system (CNS) injury. The glial scar has been proposed as a major contributor to this failure in the regenerative process. However, its underlying molecular and cellular mechanisms remain unclear. Here, we report that monoamine oxidase B (MAOB)-dependent excessive GABA release from reactive astrocytes suppresses CNS repair system by reducing BDNF and TrkB expression in severe spinal cord injury (SCI) animal models. Genetic deletion of MAOB in a mouse SCI model promotes both functional and tissue recovery. Notably, the selective MAOB inhibitor, KDS2010, facilitates recovery and regeneration by disinhibiting the BDNF-TrkB axis in a rat SCI model. Its dose-dependent effects were further validated in a monkey SCI model. Moreover, KDS2010 demonstrates a tolerable safety profile and dose-proportional pharmacokinetics in healthy humans during a phase 1 clinical trial. Our findings identify the astrocytic MAOB-GABA axis as a crucial molecular and cellular brake on CNS repair system following SCI and highlight translational potential of KDS2010 as a promising therapeutic candidate for SCI treatment.