bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily Surveillance Blood Cultures in Children Supported With Extracorporeal Membrane Oxygenation: Single-Center, Retrospective Cohort Study, 2021–2023
Authors: Schmoke Nicholas , Clark Eunice , Nemeh Christopher , Vargas Chaves Diana , Saiman Lisa , Cheung Eva W. , Middlesworth William , Sen Anita I.
Published: February 2025

Objective:

Diagnosing bloodstream infections (BSIs) in patients on extracorporeal membrane oxygenation (ECMO) can be challenging due to circuit-controlled temperature, altered hemodynamics, and questionable reliability of inflammatory markers in critically ill patients. As a result, practice variability exists among ECMO centers regarding routine blood cultures for surveillance of BSI. Our study aimed to evaluate daily surveillance blood cultures in pediatric and neonatal ECMO patients.

Design:

Retrospective review of daily surveillance blood cultures from January 2021 to July 2023. We evaluated signs, symptoms, and laboratory results in patients with positive blood cultures.

Setting:

Academic children’s hospital, New York, NY.

Patients:

All pediatric and neonatal patients supported on ECMO.

Interventions:

None.

Measurements and Main Results:

We identified a cohort of 111 patients (39 neonates and 72 children) who were supported with ECMO. Daily blood cultures were obtained on 1059 (99%) of 1065 completed ECMO days. Overall, 3% (35/1059) of blood cultures were positive, affecting 6% (7/111) of patients. All seven patients had new evidence of infection on the day of their first positive blood culture; six had clinical signs of infection, including new-onset hypotension, hypothermia, or respiratory decline, and the remaining patients had newly elevated inflammatory markers.

Conclusions:

Daily surveillance blood cultures are low-yield in our practice with pediatric and neonatal ECMO patients. Our experience shows that changes in clinical status, including abnormal physical or laboratory findings consistent with infection, are associated with BSI, allowing for timely diagnosis. These criteria should prompt as-needed blood cultures, reducing blood draws and preventing costly and unnecessary daily surveillance cultures.
Cannabis use and HIV among Black sexually minoritized men: a systematic review and narrative analysis
Authors: Knox Justin , Magana Christopher , Duncan Dustin T. , Shrader Cho-Hee , Wilson Allison , Keedy Sarah , Pagkas-Bather Jade , Chen Yen-Tyng , Schneider John A.
Published: February 2025

Objective:

We conducted a systematic review evaluating the extant literature examining the impacts of cannabis use on HIV-related outcomes among Black sexual minoritized men (BSMM).

Design:

Systematic review

Methods:

We conducted a search in November 2024 of PubMed, EMBASE, CINAHL, PsycINFO, and Web of Science using keywords related to BSMM, HIV, and cannabis. Study quality was assessed utilizing a tool developed for observational studies. 108 unique articles were screened with 55 undergoing full-text review, and 20 met inclusion criteria. Results were synthesized and presented utilizing a narrative review process.

Results:

We identified 20 studies published between 1999–2024. Measures of cannabis use included any use (e.g., ever, past 30 days), daily/intermittent/heavy use, use before/during sex, and problematic use. Outcomes included: HIV positivity/seroconversion, HIV Continuum of Care (CoC), PrEP CoC, and sex behavior strengths, vulnerabilities, and assets. Study findings were generally mixed, however positive associations between cannabis use and HIV seroconversion, inconsistent condom use, being HIV-positive and unaware of one's serostatus, and suboptimal ART adherence were reported.

Conclusions:

This systematic review identified a growing literature on cannabis use and HIV among Black SMM. Conclusions that can be drawn from the evidence are limited. There is a critical need for studies that more rigorously measure cannabis use by considering contexts of cannabis use. In addition, there is a need for research that examines the pathways and mechanisms through which cannabis use may affect prevention and treatments outcomes related to HIV among Black SMM.
Comparison of 68Ga-FAPI and 18F-FDG PET/CT Findings in Oncocytic and Conventional Subtypes of Pediatric Adrenocortical Carcinoma
Authors: Jenabi Elnaz , Amini Hamidreza , Nikkholgh Bababk , Divband Ghasemali
Published: February 2025

Adrenocortical carcinoma, a poor prognosis cancer with a low survival rate, is a rare pediatric malignancy. We performed 18F-FDG PET/CT and 68Ga-FAPI PET/CT imaging in 2 children with different subtypes of adrenocortical carcinoma and compared the findings. FAPI PET/CT revealed superior performance in patient with conventional subtype and in detecting skeletal lesions. However, the recurrent lesions in the surgical bed had higher FDG uptake in both patients.
Women and People From Deprived Areas Are Less Likely to be Assessed for Liver Transplantation for Alcohol-related Liver Disease: Results From a National Study of Transplant Assessments
Authors: Oldroyd Christopher , Aluvihare Varuna , Holt Andrew , Chew Yun , Masson Steven , Parker Richard , Rajoriya Neil , Ryan Jennifer , Shepherd Liz , Simpson Kenneth , Wai Clare , Webzell Ian , Walton Sharon , Verne Julia , Allison Michael E.D.
Published: February 2025

Background.

Alcohol-related liver disease (ArLD) is the most common indication for liver transplantation in Europe and the United States. Few studies have examined the characteristics of patients with ArLD formally assessed for liver transplants.

Methods.

We collected prospective data on every patient with ArLD formally assessed for liver transplantation in the United Kingdom during a 12-mo period.

Results.

Five hundred forty-nine patients with ArLD were assessed for liver transplantation. The median Model for End-Stage Liver Disease (MELD) score was 15 and the UK MELD score was 54. 24% were women. The median duration of abstinence was 12 mo. Listing outcomes were 59% listed, 4% deferred, and 37% not listed. The reasons for not listing were medical comorbidities (29%), too early for transplantation (20%), potential recoverability (18%), recent alcohol use (12%), and other (21%). Patients listed for transplant had a higher median MELD (16 versus 13; P < 0.001) and UK MELD scores (55 versus 53; P < 0.001), longer duration of abstinence (median 12 versus 10 mo; P = 0.026), and no differences in sex (P = 0.258), age distribution (P = 0.53), or deprivation deciles compared with those not listed. Comparing patients assessed for transplantation to national data on deaths from ArLD revealed a lower proportion of female patients (24% assessed versus 36% deaths; P < 0.001) and patients from areas of high deprivation (assessments: deaths, most deprived decile 1:20 versus least deprived decile 1:9).

Conclusions.

This study provides the first complete national profile of evaluations for liver transplantation for patients with ArLD. Women and patients from the most deprived deciles of the population may be relatively underrepresented.
Mental health and psychological processes associated with cognitive aging and dementia
Authors: Bartrés-Faz David , Marchant Natalie L.
Published: February 2025

Purpose of review

This review focuses on the role of psychological factors in cognitive aging and dementia, an area that has received less attention compared to other modifiable factors (e.g. sleep, physical activity, and so on) or reduction of disease risk.

Recent findings

A range of mental health and psychological aspects, including clinical symptoms, stable personality traits, and more specific constructs or processes (e.g. repetitive negative thinking, purpose in life), are associated with cognitive aging and dementia risk. Psychological factors can either serve as protective or risk elements, influencing brain health through general mechanisms, including stress regulation and impact on several biological systems, as well as modulate brain resistance and cognitive resilience to Alzheimer's disease and age-related brain changes. Protective psychological traits are linked to healthier lifestyle habits, while risk factors are associated with negative behaviors, and may impact cognitive function across the lifespan, suggesting benefits for psychological education from early life.

The review emphasizes the need for greater focus on optimizing psychological well being, particularly in at-risk populations, and suggests that interventions should be tailored to individuals’ values and life purposes. Additionally, further research is needed to explore the neurobiological mechanisms through which psychologically focused interventions may influence cognitive decline and dementia.
Numerical solutions of fixed points in two-dimensional Kuramoto–Stravinsky equation expedited by reinforcement learning
Authors: Jiang Juncheng , Wan Dongdong , Zhang Mengqi
Published: February 2025

This article presents a combined approach to enhancing the effectiveness of the Jacobianfree Newton–Krylov (JFNK) method by deep reinforcement learning (DRL) in identifying fixed points within the two-dimensional Kuramoto– Stravinsky equation (KSE). The JFNK approach entails a good initial guess for improved convergence when searching for fixed points. With a properly defined reward function, we utilize DRL as a preliminary step to enhance the initial guess in the converging process. The main advantage brought about by the reward function in DRL is to identify potential initial guess candidates with similar spectral structures over time, which facilitates the search of fixed points. We report new results of fixed points in the two-dimensional KSE that have not been reported in the literature. Additionally, we explored control optimization for the two-dimensional KSE to navigate the system trajectories between known fixed points, based on parallel reinforcement learning techniques. This combined method underscores the improved JFNK approach to finding new fixed-point solutions within the context of two-dimensional KSE, which may be instructive for other high-dimensional dynamical systems.
Streptococcus wuxiensis sp. nov., Streptococcus jiangnanensis sp. nov. and Streptococcus fermentans sp. nov.: three novel species of genus Streptococcus isolated from human breast milk
Authors: Zhou Ye , Zhao Jianxin , Ross Paul , Stanton Catherine , Chen Wei , Yang Bo
Published: February 2025

Three novel coccoid-shaped strains, designated 21WXBC0057M1T, 21WXBC0044M1T and BJSWXB5TM5T, were isolated from human breast milk in Wuxi, Jiangsu Province, China. These strains were facultative anaerobes, catalase-negative and Gram-positive. Through a comprehensive analysis of rRNA genes, protein-coding housekeeping genes and genomic phylogeny, we identified these strains as belonging to the genus Streptococcus. Specifically, strain 21WXBC0057M1T was phylogenetically most closely related to Streptococcus infantis, strain 21WXBC0044M1T was most closely related to Streptococcus oralis and strain BJSWXB5TM5T displayed similarities to Streptococcus australis, Streptococcus peroris and S. infantis. The pairwise average nucleotide identity and digital DNA–DNA hybridization values for these three strains were below 95 and 70%, respectively, indicating that they occupied evolutionary branches distinct from all previously validly published Streptococcus species. Distinctive phenotypic characteristics discriminated these novel species from the type strains of their most closely related species. The major cellular fatty acids in the three strains were C16 : 0 and C18 : 0. Genome annotation and a thorough examination of carbohydrate-active enzyme distribution highlighted the observation that all strains possessed extensive capabilities for carbohydrate metabolism, particularly human milk oligosaccharides utilization. Thus, based on these findings, we proposed the classification of the strains as representing three novel species within the genus Streptococcus: Streptococcus wuxiensis sp. nov. (type strain 21WXBC0057M1T=GDMCC 1.4126T=KCTC 25760T), Streptococcus jiangnanensis sp. nov. (type strain 21WXBC0044M1T= GDMCC 1.4127T=KCTC 25762T) and Streptococcus fermentans sp. nov. (type strain BJSWXB5TM5T=GDMCC 1.4130T=KCTC 25759T).
RNAseq-Based Machine Learning Models for Prognostication of Multiple Myeloma
Authors: Shah Krish U. , Millan Kaina A. , Pula Anna E. , Kubicki Tadeusz F. , Cannova Joseph , Wu Sulin , Bhagwat Manoj , Guenther Quincy C. , Cooperrider Jennifer , Roloff Gregory , Venkat Aarti , Derman Benjamin A. , Jakubowiak Andrzej J. , Drazer Michael W.
Published: February 2025

Background

Multiple myeloma (MM) is characterized by abnormal plasma cell proliferation in the bone marrow, leading to symptoms like osteolytic lesions, anemia, hypercalcemia, and elevated serum creatinine. RNA-sequencing-based prognostic indicators for MM have shown promise in stratifying risk and assessing first-line treatment options. This study uses machine learning techniques and leverages RNA-sequencing, clinical, and biochemical data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass cohort to predict patient prognosis.

Methods

RNAseq data of 60,623 genes from bone marrow samples of 708 MM patients were pre-processed for batch effect correction and split into training (70%) and testing (30%) sets. Feature selection involved MAD, mRMR, and iterative permutation importance filtering for predicting PFS and OS. Machine learning survival models like Random Survival Forest (RSF), Gradient Boosted (GB), and Component-wise Gradient Boosted (CGB) were developed and optimized. Performance was evaluated using C-index and integrated Brier score (IBS).

Results

The RSF and GB models showed the highest performance for predicting progression-free survival (PFS) and overall survival (OS) on the testing dataset. Significant features for PFS included stem cell transplant status, serum β2-microglobulin levels, germline mutational status, and expression ofC12orf75and ENSG00000256006. For OS, stem cell transplant status, age, serum β2-microglobulin levels, germline mutational status, and expression ofNUTM2B-AS1and ENSG00000287022 were prominent. Gene ontology analyses confirmed the biological relevance of enriched pathways related to cell division, protein localization, and cancer.

Conclusion

Integrating RNAseq and clinical data with advanced machine learning models presents a robust approach for predicting MM prognosis, highlighting gene expression programs, germline mutational status, and clinical markers as significant features. Future research should focus on independent validation to confirm findings and explore additional genomic data for enhanced prognostication.
Developing a model to implement marker-assisted selection for root-knot nematode resistance in common bean
Authors: de Oliveira Floriani Talissa , Gama Henrique Castro , Moreno Bruna Marques , Luz Costa Guilherme Alexandre , Giordani Willian , Chiorato Alisson Fernando , Bibiano Líllian , Parker Travis A. , Camargo Luis Eduardo Aranha , Vieira Maria Lucia Carneiro , Garcia Antonio Augusto Franco
Published: February 2025

Common bean (Phaseolus vulgarisL.) is a vital crop for direct human consumption, with essential nutrients and valuable protein that provides food security in developing countries. However, its cultivation faces significant threats fromMeloidogyne incognita, a root-knot nematode (RKN), resulting in considerable yield loss. Developing crop resistance remains a key strategy for mitigating nematode infections. To investigate the genetic architecture of common bean responses to RKN (specifically, race 3 ofM. incognita), we performed controlled crosses between the genotypes ‘IAC-Tybatã’ and ‘Branquinho’ with contrasting resistance. The resulting segregating population (F2) of 333 individuals was genotyped using GBS (genotyping-by-sequencing). We used a phenotyping approach, already optimized in the lab, to collect trait data for a subset of 200 F2:3families. Evaluations of egg mass (EM), root-galling index (GI), and root dry mass (RM) were conducted 30 days after RKN inoculation under greenhouse conditions, in a completely randomized design with ten replicates. Linkage and quantitative trait loci (QTL) mapping were performed, while functional mapping of associated regions facilitated identification of candidate genes. A linkage map encompassing 954 SNPs assigned to 11 linkage groups totaling 1,687 cM formed the basis for Interval Mapping (IM), Composite Interval Mapping (CIM), and Multiple Interval Mapping (MIM), revealing four major QTLs (on Pv03, Pv05, Pv08, and Pv10) and epistasis between QTL on Pv08 and on Pv10 associated with the GI trait. No significant QTL were identified for EM and RM. The model enabled calculation of genotypic values through marker-assisted selection (MAS). The high correlation between observed and predicted values (0.72) underscores the model’s significance. Candidate genes previously associated with nematode resistance were also identified within the QTL interval on chromosome Pv10. Our results will be valuable for future selection of varieties resistant to this important crop disease.
Differentiating unirradiated mice from those exposed to conventional or FLASH radiotherapy using MRI
Authors: Jansen Jeannette , Kimbler Adam , Drayson Olivia , Lanz Bernard , Mosso Jessie , Grilj Veljko , Petit Benoit , Franco-Perez Javier , Simon Aaron , Limoli Charles L. , Vozenin Marie-Catherine , Stark Craig , Ballesteros-Zebadua Paola
Published: February 2025

Background and purpose

The FLASH effect expands the therapeutic ratio of tumor control to normal tissue toxicity observed after delivery of ultra-high (>100 Gy/s FLASH-RT) vs. conventional dose rate radiation (CONV-RT). In this first exploratory study, we assessed whether ex-vivo Magnetic Resonance Imaging (MRI) could reveal long-term differences after FLASH-RT and CONV-RT whole-brain irradiation.

Materials and methods

Female C57BL/6 mice were divided into three groups: control (non-irradiated), conventional (CONV-RT 0.1 Gy/s), and ultra-high dose rates (FLASH-RT 1 pulse, 5.5 x 10˄6 Gy/s), and received 10 Gy of whole-brain irradiation in a single fraction at 10 weeks of age. Mice were evaluated by Novel Object Recognition cognitive testing at 10 months post-irradiation and were sampled at 13 months post-irradiation. Ex-vivo brains were imaged with a 14.1 Tesla/26 cm magnet with a multimodal MRI protocol, including T2-weighted TurboRare (T2W) and diffusion-weighted imaging (DWI) sequences.

Results

In accordance with previous results, cognitive tests indicated that animals receiving CONV-RT exhibited a decline in cognitive function, while FLASH-RT performed similarly to the controls. MRI showed decreased hippocampal mean intensity in the CONV-RT mice compared to controls but not in the FLASH-RT group. Comparing CONV-RT to control, we found significant changes in multiple whole-brain diffusion metrics, including the mean Apparent Diffusion Coefficient (ADC) and Mean Apparent Propagator (MAP) metrics. By contrast, no significant diffusion changes were found between the FLASH-RT and control groups. In an exploratory analysis compared to controls, regional diffusion metrics were primarily altered in the basal forebrain and the insular cortex after CONV-RT, and after FLASH-RT, a trend reduction was also observed.

Conclusion

This study presents initial evidence that MRI can uncover clear changes in the brain after CONV-RT but not after FLASH-RT. The MRI results aligned with the observed cognitive protection after FLASH-RT, indicating the potential use of MRI to analyze the FLASH response.
Neuro-behavioral impact of Tourette-related striatal disinhibition in rats
Authors: Loayza Joanna , Taylor Charlotte , Renstrom Jacco , Allen Rachel Grasmeder , Jackson Stephen , Bast Tobias
Published: February 2025

Tourette syndrome has been linked to reduced GABAergic inhibition, so called neural disinhibition, in the dorsal striatum. Dorsal-striatal neural disinhibition in animal models, caused by local microinfusion of GABA-A-receptor antagonists, produces striatal local field potential (LFP) spike-wave discharges and tic-like movements resembling motor tics. Here, we characterized further the neuro-behavioral impact of striatal disinhibition, by unilateral picrotoxin infusion into the anterior dorsal striatum, in adult male Lister hooded rats. In vivo electrophysiology under anesthesia revealed enhanced neuronal burst firing in the striatum, alongside spike-wave LFP discharges. In freely moving rats, striatal picrotoxin reliably induced tic-like movements, which mainly involved lifting of the contralateral forelimb and concomitant rotational movements of head and torso, as well as occasional rotations of the whole body around its long axis. Prepulse inhibition (PPI) of the acoustic startle response was not affected, but startle reactivity tended to be reduced. Both locomotor and non-ambulatory movements, measured in photo-beam cages, were increased. Our findings suggest that, apart from generating tic-like movements, dorsal striatal disinhibition may contribute to hyperactivity, which is often comorbid with Tourette syndrome. Enhanced striatal burst firing may be important for these behavioral effects. Our findings do not support that striatal disinhibition contributes to PPI disruption, which has been associated with Tourette syndrome and suggested to contribute to tic generation.

Significance Statement

Striatal disinhibition has been implicated in tic generation. Using a rat model, we show that a key neural effect of striatal disinhibition is enhanced firing of striatal neurons in bursts. We also characterized further the tic-like movements caused by unilateral disinhibition of the anterior dorsal striatum. These mainly involved lifting of the contralateral forelimb and concomitant rotational movements of head and torso, as well as occasional rotations of the whole body around its long axis. Striatal disinhibition did not affect prepulse inhibition (PPI) but caused locomotor hyperactivity. This suggests that striatal disinhibition may contribute to the general hyperactivity often comorbid with Tourette syndrome, but that other brain mechanisms underlie the PPI deficits that have been reported in the condition.
The impact of systematized generation, evaluation, and incorporation of machine learning algorithms for clinical variant classification
Authors: Fresard Laure , Facio Flavia M , Chen Elaine , Colavin Alexandre , Johnson Britt , Araya Carlos , Manders Toby , Wahl Alexander , Metz Hillery , Nicoludis Jack , Ouyang Karen , Padigepati Samskruthi , Kobayashi Yuya , Reuter Jason , Nykamp Keith
Published: February 2025

Variants of uncertain significance (VUS) pose a significant challenge for those undergoing genetic testing, leading to prolonged uncertainty and inappropriate medical care. VUS rate reduction is critical to fully realize the utility of genetic testing for all populations. With the growth of large-scale biological data sources and modern Machine Learning (ML) techniques, predictive modeling has enormous potential for VUS reduction.

For this purpose, we developed the Invitae Evidence Modeling™ Platform (EMP), with key features designed to maximize the utility and confidence of predictive algorithms for variant classification. First, input data for a new model is curated to correspond to a single major evidence category within a variant classification framework. Second, gene-specific training and/or validation is performed for each model type. Third, accuracy thresholds are set to filter out gene-specific models that do not meet stringent accuracy metrics. Finally, prediction scores for variant pathogenicity are calibrated to ensure internally consistent evidence weighting within the classification framework.

The EMP has accelerated the development of ML algorithms and greatly expanded the amount of evidence available for variant classification. EMP evidence has been applied to more than 800,000 variants across 1 million individuals, 42% of which would have been VUS without this evidence. Importantly, definitive classifications (P, LP, LB, B) made with EMP evidence have high prospective concordance (>99%) with ClinVar submissions. Finally, we demonstrate that further use and development of EMP evidence for variant classification has the potential to reduce the VUS disparity across race/ethnicity/ancestry (REA) groups.
Radiation exposure induced blood-brain barrier injury via mitochondria-mediated sterile inflammation
Authors: Wang Peng , Liu Jiayue , Zhang Min , Yang Juan , Lian Peihan , Cheng Xiu , Qin Jianhua
Published: February 2025

Radiation-induced brain injury (RIBI) is caused by exposure to high doses of ionizing radiation and characterized by severe cognitive dysfunction and brain necrosis. The widespread application of radiotherapy and rapid development of deep space exploration have substantially increased the risk of RIBI. However, the pathogenesis of RIBI is not fully understood, and no effective intervention is available. This work described a blood-brain barrier (BBB) microphysiological system (MPS), that allowed to explore the responses of BBB and distinct brain cells to radiation exposure. This BBB MPS can recapitulate the interface structure and function of BBB in brain microenvironment, including brain endothelial cells, astrocytes, pericytes and microglia co-cultured under flow condition. Following acute exposure to radiation of X-ray or γ-ray, characteristic RIBI-associated pathological responses were observed, including BBB compromise, DNA breaks, inhibited cell proliferation, cell hypertrophy and pro-inflammatory cytokine release. Among the distinctive types of cells, brain endothelial cells showed the highest radiosensitivity as compared to other cells in the MPS. Intriguingly, X-ray and γ-ray radiation consistently induced prominent sterile inflammation responses, especially type I interferon response, in the BBB MPS. These responses were mediated by radiation-induced mitochondrial DNA release and subsequent activation of cGAS-STING signaling pathway. Furthermore, we found abrocitinib (JAK1 inhibitor) and idebenone (mitochondrial protectant) can attenuate radiation-induced inflammation and ameliorate BBB injury. These findings revealed the involvement of mitochondria-mediated inflammation in RIBI pathogenesis, identifying mitochondria as a potential target for new radioprotective measures.
Psilocybin as a Treatment for Repetitive Mild Head Injury: Evidence from Neuroradiology and Molecular Biology
Authors: Brengel Eric K. , Axe Bryce , Maheswari Ashwath , Abeer Muhammad I. , Ortiz Richard J. , Woodward Taylor J. , Walhof Reagan , Utama Rachel , Sawada Courtney , Balaji Shreyas , Kulkarni Praveen P. , Bradshaw Heather B. , Gitcho Michael A. , Ferris Craig F.
Published: February 2025

Repetitive mild head injuries incurred while playing organized sports, during car accidents and falls, or in active military service are a major health problem. These head injuries induce cognitive, motor, and behavioral deficits that can last for months and even years with an increased risk of dementia, Parkinson’s disease, and chronic traumatic encephalopathy. There is no approved medical treatment for these types of head injuries. To this end, we tested the healing effects of the psychedelic psilocybin, as it is known to reduce neuroinflammation and enhance neuroplasticity. Using a model of mild repetitive head injury in adult female rats, we provide unprecedented data that psilocybin can reduce vasogenic edema, restore normal vascular reactivity and functional connectivity, reduce phosphorylated tau buildup, enhance levels of brain-derived neurotrophic factor and its receptor TrkB, and modulate lipid signaling molecules.
Sphingosine-1-phosphate signaling through Müller glia regulates neuroprotection and the accumulation of immune cells in the rodent retina
Authors: Taylor Olivia , Kelly Lisa , El-Hodiri Heithem , Fischer Andy J.
Published: February 2025

The purpose of this study was to investigate how Sphingosine-1-phosphate (S1P) signaling regulates glial phenotype, neuroprotection, and reprogramming of Müller glia (MG) into neurogenic MG-derived progenitor cells (MGPCs) in the adult mouse retina. We found that S1P-related genes were dynamically regulated following retinal damage.S1pr1(encoding S1P receptor 1) andSphk1(encoding sphingosine kinase 1) are expressed at low levels by resting MG and are rapidly upregulated following acute damage. Overexpression of the neurogenic bHLH transcription factor Ascl1 in MG downregulatesS1pr1, and inhibition of Sphk1 and S1pr1/3 enhances Ascl1-driven differentiation of bipolar-like cells and suppresses glial differentiation. Treatments that activate S1pr1 or increase retinal levels of S1P initiate pro-inflammatory NFκB-signaling in MG, whereas treatments that inhibit S1pr1 or decreased levels of S1P suppress NFκB-signaling in MG in damaged retinas. Conditional knock-out of NFκB-signaling in MG increases glial expression ofS1pr1but decreases levels ofS1pr3andSphk1. Conditional knock-out (cKO) ofS1pr1in MG, but notSphk1, enhances the accumulation of immune cells in acutely damaged retinas. cKO ofS1pr1 is neuroprotective to ganglion cells, whereas cKO ofSphk1is neuroprotective to amacrine cells in NMDA-damaged retinas. Consistent with these findings, pharmacological treatments that inhibit S1P receptors or inhibit Sphk1 had protective effects upon inner retinal neurons. We conclude that the S1P-signaling pathway is activated in MG after damage and this pathway acts secondarily to restrict the accumulation of immune cells, impairs neuron survival and suppresses the reprogramming of MG into neurogenic progenitors in the adult mouse retina.
Adolescents’ Use of Music for Pain Management
Authors: Lepping Rebecca J. , Black Lora L. , Kline Kymberly A. , Hanson-Abromeit Deanna , Chadwick Andrea L. , Wallace Dustin P. , Black William R.
Published: February 2025

To investigate the experiences of adolescents with chronic pain who participated in an intensive interdisciplinary pain treatment program, this secondary study analyzes the themes that emerged regarding the spontaneous utilization of music in coping strategies for chronic pain. During research interviews focused on coping skills and treatment engagement, participants spontaneously reported using music as an effective coping strategy for managing pain. A deductive thematic analysis revealed key themes related to their usage, including using music as a distractor, motivator and in other ways as coping strategies. Since participants indicated that music is essential to their experiences of coping with pain, incorporating these strategies could improve the effectiveness of treatment protocols. To this end, further investigation is necessary to assess the impact of music on adolescents with chronic pain, focusing on its role in enhancing interdisciplinary treatment.
Mild cognitive impairment cases affect the predictive power of Alzheimer’s disease diagnostic models using routine clinical variables
Authors: Finney Caitlin A. ,   Alzheimer’s Disease Neuroimaging Initiative, Shvetcov Artur
Published: February 2025

Diagnostic models using primary care routine clinical variables have been limited in their ability to identify Alzheimer’s disease (AD) patients. In this study we sought to better understand the effect of mild cognitive impairment (MCI) on the predictive performance of AD diagnostic models. We sourced data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. CatBoost was used to assess the utility of routine clinical variables that are accessible to primary care physicians, such as hematological and blood tests and medical history, in multiclass classification between healthy controls, MCI, and AD. Our results indicated that MCI indeed affected the predictive performance of AD diagnostic models. Of three subgroups of MCI that we found, this finding was driven by a subgroup of MCI patients that likely have prodromal AD. Future research should focus on distinguishing MCI from prodromal AD as the utmost priority for improving translational AD diagnostic models for primary care physicians.
On the metabolic basis and predictability of global epistasis.
Authors: Venkataraman Pavithra , Saini Supreet
Published: February 2025

Fitness effects of mutations are epistatic, i.e., they depend on the genetic background in which they occur. Despite microscopic idiosyncrasies of mutational effects, laboratory evolution experiments showed consistent patterns of declining adaptability, indicating some underlying 'rule' that dictates mutational effects. Recently, global epistasis showed that mutations become less beneficial as the fitness of the genetic background in which they occur increases, thus making epistasis predictable. However, there exists no mechanistic explanation of this fitness dependence of fitness effects. In this work, we use a prokaryotic cell growth and division model based on metabolic sizing to study the mechanistic basis, and predict the likelihood of global epistasis. We report two important results. One, although the average extent of global epistasis does not change with genetic variation, the likelihood of strong global epistasis decreases as genetic variation increases. Two, the fitness effects of mutations in the slow reaction modules are well predicted using the global epistasis approach. Therefore, when the fitness of the cell is contingent on a rate-limiting step, mutations in that step are well-predicted by the fitness of the background in which they occur. Thus, declining adaptability is a consequence of evolution acting in a step-wise fashion to improve the slowest modules in a cell. Overall, our work offers a first-principle explanation of global epistasis and declining adaptability.
Early life phthalate exposure impacts gray matter and white matter volume in infants and young children
Authors: Werder Emily J. , Lu Kun , Liu Chih-Wei , Thistle Jake E. , Rager Julia E. , Li Gang , Wu Zhengwang , Li Tengfei , Wang Li , Sandler Dale P. , Gilmore John H. , Piven Joseph , Zhu Hongtu , Lin Weili , Engel Stephanie M.
Published: February 2025

Objective

Prenatal phthalate exposure is associated with adverse neurodevelopmental outcomes, yet data on impacts of early life exposure remains limited. We investigated phthalate and replacement plasticizer exposures from 2 weeks to 7 years of age in relation to brain anatomical attributes, using serial structural magnetic resonance imaging (sMRI).

Material and Methods

Children were enrolled after birth into the UNC Baby Connectome Project, a longitudinal neuroimaging study. Urine samples (n=406) were collected at each visit and analyzed for 17 phthalate and replacement plasticizer metabolites. Among 157 children contributing 369 sMRIs, we calculated metabolite-specific average exposures across each individual’s urine samples and used linear mixed models to estimate longitudinal associations of log transformed, specific gravity-adjusted average metabolite concentrations with gray (GMV) and white matter (WMV), and cortical volume (CV), thickness (CT), and surface area (CSA). We examined sex-specific differences in these associations.

Results

Higher average metabolite concentration was associated with lower GMV (MCPP: (−1.73 cm3, 95% CI: −3.36, −0.10) and higher WMV (∑DEHP: 2.28 cm3, 95% CI: 0.08, 4.48). Among boys (n=72, 140 sMRIs), MEP (−2.97 cm3, 95% CI: −5.85, −0.09) and MiBP (−2.40 cm3, 95% CI: −4.64, −0.15) were also associated with lower GMV. Among girls (n=85, 229 MRIs), higher ∑DINCH exposure was associated with higher WMV (2.27 cm3, 95% CI: 0.29, 4.25). We observed significant sex interactions for ∑DEHP with GMV (p-interaction=0.03) and ∑DINCH with WMV (p-interaction=0.001).

Conclusion

Early life phthalate/plasticizer exposure may differentially impact various brain region volumes in early childhood, with potential downstream consequences on functional development.
Estimating prevalence of immunocompromising conditions in Canada in 2022 using an administrative hospital database
Authors: Finès Philippe
Published: February 2025

Background

Immunocompromising conditions (ICs) are conditions that may be present at different moments in a person’s life and affect their health. In individuals with ICs, the body’s ability to effectively fight infections or mount a robust response to vaccination is weakened. It is thus important to understand the burden of ICs in part to inform public health policies on the procurement of vaccines for this population. However, no estimates of prevalence rates of ICs exist in Canada.

Objective

Our objective was to address this gap.

Intervention

We defined our list of ICs using different published sources and expert opinion. Using diagnoses coded with ICD-10 over a period of 14 years in the Discharge Abstract Database, we were able to estimate prevalence rates of ICs.

Outcome

For all ICs combined and conservatively assuming a hospitalization rate of 0.1, general population prevalence rates is estimated at 1.8% for females and 1.9% for males. Inflammatory bowel disease, severe liver disease and severe cancers are among the most frequent ICs at all age groups and for both genders. Functional asplenia and Primary Immunodeficient conditions are mostly present at young ages. Transplantation and renal dialysis are also among the most frequent ICs.

Conclusion

The prevalence of ICs estimated using DAD aligns with estimates obtained using other methods from other countries (2.7–6.6%) under certain assumptions for hospitalization rates. This work serves as the foundation for future investigation into obtaining more precise estimates of prevalence rates of ICs in Canada.
Sex differences in progressive multiple sclerosis brain gene expression in oligodendrocytes and OPCs
Authors: LaBarre Brenna A. , King Devin , Ploumakis Athanasios , Pinzon Alfredo Morales , Guttmann Charles R.G. , Patsopoulos Nikolaos , Chitnis Tanuja
Published: February 2025

Multiple sclerosis is a neurological autoimmune disease with sex-imbalanced incidence; in the USA, the disease is more likely to effect females at a ratio of 3:1. In addition, males are more likely to have a more severe disease course at time of diagnosis. Questions about both causes and downstream effects of this disparity remain. We aim to investigate gene expression differences at a cellular level while considering sex to discover fine-scale sex disparities. These investigations could provide new avenues for treatment targeting, or treatment planning based on sex.

Public single-nuclei RNA-sequencing data from three publications of progressive MS including control brains were analysed using the Seurat R package. Differential gene and pathway expression was looked at both within a specific data set which has sub-lesion level sample dissection and across all studies to provide a broader lens. This allowed for the consideration of cell types and spatial positioning in relation to the interrogated lesion in some of the calculations.

Our analysis showed expression changes in the female MS oligodendrocytes and oligodendrocyte progenitor cells compared to healthy controls, which were not observed in the corresponding male affected cells. Differentially up-regulated genes in females include increased HLA-A in the oligodendrocytes, and increased clusterin in the oligodendrocyte progenitor cells. There are also several mitochondrial genes in both the oligodendrocytes and oligodendrocyte progenitors which are up-regulated in females, including several directly involved in electron transport and which have previously been associated with neurodegenerative diseases.

These results point to altered states in oligodendrocyte progenitors and oligodendrocytes that in combination with known physiological dissimilarities between sexes may denote different programming in males and females in response to the onset of demyelinating lesions. The potential for increased debris clearance mediated by clusterin and availability of oligodendrocyte progenitors in females may indicate an environment more primed for repair, potentially including remyelination. This could contribute to the disparity in etiology in females versus males.
Reproductive microbial diversity is associated with competitive phenotypes in socially polyandrous jacanas
Authors: Houtz Jennifer L , Acosta Kimberly A , Berlow Mae , Lipshutz Sara
Published: February 2025

The composition of host-associated microbial communities may reflect the overall status of the host, including physiology and reproductive success. New hypotheses suggest that reproductive microbiomes can mediate sexually selected phenotypes, which may be particularly important for species with mating systems that feature strong sexual selection. These dynamics have been particularly understudied in female animals. Using 16S rRNA sequencing, we compared the cloacal microbiome of females and males from two socially polyandrous bird species that vary in the strength of sexual selection, Jacana spinosa (Northern Jacana) and J. jacana (Wattled Jacana). We hypothesized that the strength of sexual selection would shape cloacal microbial diversity, such that the more polyandrous J. spinosa would have a more diverse microbiome, and that microbiomes would be more diverse in females than in males. If the reproductive microbiome is indicative of competitive status, we also hypothesized that cloacal microbial diversity would be associated with competitive traits, including plasma testosterone levels, body mass, or weaponry. We found a positive relationship between microbial alpha diversity and testosterone and weaponry in female J. spinosa. We found no differences in microbial alpha diversity between species or sexes, but we did find that microbial beta diversity significantly differed between species. Our results suggest that the cloacal microbiome may be a key component of the competitive phenotype in socially polyandrous jacanas, supporting the hypothesis that the interplay between sexual selection and microbial communities can shape the physiology and fitness of wild avian hosts.
In the brain of the beholder: whole brain dynamics shape the perception during ambiguous motion
Authors: Pizzuti Alessandra , Acero Pousa Irene , Gulban Omer Faruk , Peters Judith , Deco Gustavo , Goebel Rainer
Published: February 2025

Visual perception is typically based on a one-to-one mapping between stimuli and conscious experiences. However, under bistable conditions, identical sensory inputs can elicit alternating perceptions, requiring the brain to resolve ambiguity. The mechanisms underlying transitions between distinct perceptual states and their sustained maintenance remain poorly understood. In this ultra-high-field (7T) fMRI study, we investigated the neural dynamics of perception using a bistable motion stimulus (ambiguous motion quartet) that evoked endogenous alternations between horizontal and vertical motion, compared to a control condition (physical motion quartet) with unambiguous sensory input. Consistent with previous findings, the human motion complex (hMT+) played a central role in processing both physical and ambiguous motion conditions. By dissociating neural activity during perceptual transitions from sustained perceptions, we found that hMT+ mostly interacts dynamically with area 46 in the frontal cortex and PF/PFm within the inferior parietal lobe during transitions and with subregions of the superior parietal lobe during sustained perceptions. Beyond local activity, computational modeling revealed an increase in hierarchical organization across cortical networks during the ambiguous condition. In particular, the same frontal and parietal regions exhibited ascension within the functional hierarchy, likely reflecting their specific role in coordinating computations for resolving ambiguity.
Size in the city: morphological differences between city and forest great tits have a genetic basis
Authors: Tomotani Barbara M. , Couweleers Mika , ten Brinke Bram , Walboom Anne , van Oers Kees , Visser Marcel E.
Published: February 2025

Animals living in cities are smaller than their conspecifics from rural areas but whether such differences are caused by genetic differences or food constraints remains untested. We performed a multi-generation common garden study where we raised great tits (Parus major), originating from eggs collected from multiple Dutch cities and forests under the same conditions for two generations. Offspring from city birds had a smaller tarsus than forest birds in both generations, demonstrating that these morphological differences are genetic. Next, we tested whether size differences are an adaptation to the low food abundance when offspring are raised in the city. Third generation birds of both origins were given food amounts mimicking being raised in forests or cities during the second part of their nestling development. While the treatment resulted in birds in the lower feeding frequency treatment to be smaller, city and forest birds responded the same way, suggesting that city birds do not cope better with reduced food availability. Our study shows that the smaller size of urban birds has a genetic basis and is not only caused by a plastic response to restricted resources in the urban environment. Our experiment does not provide evidence that these genetic differences have evolved as an adaptive response to a reduced food availability in cities.
Low levels of post-vaccination hemagglutination inhibition antibodies and their correlation with influenza protection among healthcare workers during the 2024/2025 A/H1N1 outbreak in Japan
Authors: Yamamoto Shohei , Mizoue Tetsuya , Ujiie Mugen , Horii Kumi , Takeuchi Junko S. , Konishi Maki , Sugiura Wataru , Ohmagari Norio
Published: February 2025

Background

After the prolonged COVID-19 pandemic, during which the seasonal influenza epidemic was suppressed, Japan experienced a record-breaking influenza A/H1N1 outbreak in the 2024/2025 season. This situation also raises a concern about the immunogenicity of the annual quadrivalent inactivated influenza vaccine (QIIV). This study evaluated post-vaccination hemagglutination inhibition (HI) antibody titers and their association with influenza infection risk among healthcare workers.

Methods

A serosurvey was conducted among staff at a national medical and research center in Tokyo in December 2024, one month after staff received the QIIV. HI antibody titers against vaccine strains were measured, and participants were followed for influenza infection until January 2025. Seroprotection was defined as an HI titer ≥40. A Cox proportional hazards model assessed the association between HI titers and infection risk among vaccinated participants.

Results

Among 1,507 vaccinated participants, only 12.7% had seroprotective HI titers against A/H1N1. Around 90% had no influenza history for at least four seasons and had received repeated vaccinations over two seasons. Participants with HI titers <40 had a 4-fold higher infection risk than those with titers ≥40. A dose-response association was observed, even within the range below the titer of 40. Relative to titers <10, titers of 10 and 20 conferred 47.3% and 57.9% protection, respectively.

Conclusions

After a prolonged period without a major influenza epidemic, HI titers against A/H1N1 were extremely low in vaccinated healthcare workers. Nonetheless, higher post-vaccination HI titers, even at relatively low levels, were associated with protection, supporting the benefit of vaccines.

Main points

During Japan’s record-breaking 2024/2025 influenza A/H1N1 outbreak, HI antibody titers against A/H1N1 were extremely low in vaccinated healthcare workers. Nonetheless, even relatively low post-vaccination HI titers conferred moderate protection, highlighting the benefits of vaccination despite reduced immunogenicity.