bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a shared decision making process for severe stroke-a mixed methods study
Authors: Visvanathan Akila , Morton Sarah , Macraild Allan , Black Polly , Gilbert Sophie , Barber Mark , Dennis Martin , O’Brien Richard , Mead Gillian 
Published: December 2024

AbstractBackgroundClinical decisions made early after stroke can make the difference between survival with disability or death. We aimed to develop, implement and evaluate a new Shared decision making (SDM) process for severe stroke into a regional 36 bedded stroke unit.MethodsWe developed the process through four coproduction workshops, attempted its implementation then its impact on death at 6 months, discharge destination and tube feeding. We also explored patients, families and staff views about SDM.ResultsEleven people (staff and people with lived experience of stroke) attended the first co-production workshop, eight the second, seven the third and six the fourth. The new SDM process incorporated Tailored Talks (a digital platform with information about stroke and its prognosis) and an implementation plan (including staff training). We implemented this process on 1stAugust 2022.Only 8/1020 patients received Tailored Talks (4 before and 4 after implementation). For the entire group there was no change tube feeding, discharge destination or death. The proportion of people with severe strokes dead at six months was higher before implementation. Twenty-one patients or family members provided views about SDM quality, but the sample size was too small to draw conclusions. Staff interviews suggested that insufficient time, lack of a ‘human touch’ and inadequate leadership explained the lack of implementation.ConclusionOur co-produced SDM was not effectively implemented into a stroke unit and there was no change in the use of tube feeding or death in 1020 patients.Key pointsShared decision making after severe stroke is complex.A co-produced new process for shared decision making after severe stroke was not effectively implemented into clinical practice.There was no change in tube feeding, death or institutionalisation.
Origin, pattern of bone metastasis and need for surgery in patients with Metastatic bone disease treated at tertiary hospital in Northern Tanzania. A hospital based cross sectional study
Authors: Ncheye Mathias , Maya Elifuraha , Serventi Furaha , Mandari Faiton , Temu Rogers , Magembe Peter , Massawe Honest 
Published: December 2024

AbstractBones are the third most common sites for cancer metastasis after lung and liver. Bone metastasis cause skeletal complications (SRE’s) that affect the quality of life of patients with bone metastasis. Management of these patients depend on the primary tumor and pattern of bone metastasis.The aim of this study was to describe the origin, distribution pattern of bone metastases, common SRE’s and proportion of patients with bone metastasis that need surgery.A cross sectional study was conducted among cancer patients with Metastatic bone disease attending KCMC Hospital from November 2022 to April 2023. Data was collected from patient’s files, histopathology and radiology reports by a structured extraction sheet. VAS, SINS and Mirel’s scores was used to document pain severity, spinal instability and fracture risk respectively. The ASIA impairment scale was used for documenting neurological deficits in patients with spine metastasis. Data was entered and analyzed in SPSS version 25.0A total of 72 participants were enrolled. Their mean age was 69 ± 11 years and (75%) were male. Prostate cancer (65.3%) was the leading cause of metastatic bone disease followed by breast cancer (18.1%). Most of patients with MBD have multiple lesions (91.7%) involving multiple sites but the spine (93.1%) was the mostly affected site. Osteoblastic lesions were the predominant radiological type by 59.7% followed by osteolytic lesions which accounted for 23.6% of the study participants. 30.6% had pathological fractures and half of these occurred in patients with osteolytics lesions. 36.1% of the study participants had an indication for surgical treatment of the bone metastasis.Most of MBD originate from Prostate and Breast cancer giving multiple lesions involving multiple sites but the spine remains to be the most affected site. Even though about a third of the patients had SRE’s that needed surgical intervention but few are expected to be operated considering the prognosis. This calls for more emphasis on prevention of SRE’s and use of appropriate less invasive therapies to prevent progression of the disease.
Survey of the Landscape of Society Practice Guidelines for Genetic Testing of Neurodevelopmental Disorders
Authors: Srivastava Siddharth , Cole Jordan J. , Cohen Julie S. , Chopra Maya , Smith Hadley Stevens , Deardorff Matthew A. , Pedapati Ernest , Corner Brian , Anixt Julia S. , Jeste Shafali , Sahin Mustafa , Gurnett Christina A. , Campbell Colleen A. 
Published: December 2024

ABSTRACTGenetic testing of patients with neurodevelopmental disabilities (NDDs) is critical for diagnosis, medical management, and access to precision therapies. Because genetic testing approaches evolve rapidly, professional society practice guidelines serve an essential role in guiding clinical care; however, several challenges exist regarding the creation and equitable implementation of these guidelines. In this scoping review, we assessed the current state of United States professional societies’ guidelines pertaining to genetic testing for unexplained global developmental delay, intellectual disability, autism spectrum disorder, and cerebral palsy. We describe several identified shortcomings and argue the need for a unified, frequently-updated and easily-accessible cross-specialty society guideline.
The Gut Metabolism is altered in patients withCRB1-associated inherited retinal degeneration
Authors: Moekotte Lude , de Boer Joke H. , Hiddingh Sanne , Gerritsen Bram , Lintelmann Jutta , Cecil Alexander , van den Born L. Ingeborgh , Nguyen Xuan-Thanh-An , Boon Camiel J.F. , van Genderen Maria M. , Kuiper Jonas J.W. 
Published: December 2024

AbstractPurposeTo compare the plasma metabolic profile of patients with aCRB1-associated inherited retinal degeneration (CRB1-IRD) with healthy controls (HCs).DesignA case-control study.MethodsPlasma concentration of 619 metabolites was measured with the MxP®Quant 500 Kit in 30 patients with aCRB1-IRD and 29 HCs. We fitted a linear regression model with adjustments for age and sex based on the concentration of metabolites in µM (µmol/L), or on the sums and ratios of metabolites, to determine differences between patients and controls.ResultsOver-representation of pathways among metabolites associated strongest toCRB1-IRDs (P< 0.05, n = 62) identified amino acid pathways (such as beta-alanine, histidine, and glycine/serine) and bile acid biosynthesis, driven by a decrease in deoxycholic acid derivatives produced by gut microbiota. Enrichment analysis of metabolic classes across the plasma metabolic profile further identified significant positive enrichment for lipid metabolites glycerophospholipids, cholesterol esters, and ceramides, and significant depletion for bile acid metabolites. Further investigation of the sums and ratios (i.e., metabolism indicators) ascertained a significant decrease in intestinal microbial-dependent secondary bile acid classes.ConclusionsLipid metabolic alterations and decreased microbiota-related secondary bile acid concentrations indicate significant alterations in gut metabolism in patients with aCRB1-IRD.
Prenatal ochratoxin A exposure, birth outcomes and infant growth in rural Burkina Faso: a human biomonitoring sub-study from the MISAME-III trial
Authors: Bastos-Moreira Yuri , Argaw Alemayehu , Dailey-Chwalibóg Trenton , El-Hafi Jasmin , Ouédraogo Lionel Olivier , Toe Laeticia Celine , De Saeger Sarah , Lachat Carl , De Boevre Marthe 
Published: December 2024

AbstractMycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth in low- and middle-income countries. We assessed multiple biomarkers and metabolites of exposure to mycotoxins during pregnancy and their associations with birth outcomes and infant growth in 305 pregnant participants, between 30 and 34 completed weeks of gestation, in rural Burkina Faso. In this study, whole blood microsamples were analyzed for mycotoxin concentrations using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Unadjusted and adjusted associations between mycotoxin exposure, and birth outcomes and infant growth at 6 months were estimated using linear regression models for continuous outcomes and linear probability models with robust variance estimation for binary outcomes. Infant growth trajectories from birth to 6 months were compared by exposure status using mixed-effects models with random intercept for the individual infant and random slope for the infant’s age. Ochratoxin A (OTA) exposure was detected in 50.8% of the study participants, with aflatoxin G1, aflatoxin M1, cyclopiazonic acid, deoxynivalenol and T-2-toxin being detected in the range of 0.33% and 2.31% of the population. We found no statistically significant (allp≥ 0.05) associations between OTA exposure, and birth outcomes and infant growth. Despite this, the findings indicate a significant presence of ochratoxin A among pregnant participants. Public health policies and nutrition-sensitive interventions must ensure that OTA exposure is reduced in Burkina Faso.
Zoonotic and environmental sources of infant enteric pathogen infections identified with longitudinal sampling
Authors: Paulos Abigail P. , Mboya John , Lowe Jeremy , Kim Daehyun Daniel , Wharton Hannah C. , Thuita Faith , Flax Valerie L. , Njenga Sammy M. , Harris Angela R. , Pickering Amy J. 
Published: December 2024

AbstractEnteric pathogen infections in young children can result in diarrhea, malnutrition, and developmental impairments. Many enteric pathogens that infect young children can be zoonotic, yet the exposure risk of domestic animals living in close proximity to young children is poorly understood. We conducted a prospective cohort study with longitudinal microbiological sampling of child stool, animal feces, and the household environment to investigate pathogen transmission between animals and children under two years of age in pastoralist communities in rural Northern Kenya. We generated 28,743 pathogen-sample observations by measuring 33 bacterial, viral, protozoan, and helminth pathogens in the following types of samples (n=871) collected from households at four consecutive visits: child stool, caregiver stool, drinking water, food, child hands, household soil, and feces from ruminant, avian, and canine domesticated animals. Child enteric pathogen burden increased with age from a median of 1 pathogen among children under 3 months to 5 pathogens at 1-2 years old. Of the 20 unique pathogens detected in child stool, 85% were also detected in animal feces. New infections in children were associated with preceding household detection of the same pathogen in soil (Odds ratio: 8.8, 95% confidence interval: 3.3 – 23) and on child hands (Odds ratio: 5.0, 95% confidence interval 1.1 – 17). Network analysis revealed transmission of pathogens from poultry, dog, and ruminant feces to household soil, and between child hands and child stool. Our results indicate child hand contact with soil containing animal feces is a primary transmission route for first infections among children living in close proximity to animals. Our study provides new evidence that domestic animals in the household environment contribute to early-life enteric pathogen exposure, and that child hand hygiene could substantially prevent animal-human enteric pathogen exchange.
Scaling ecological niches from individuals to populations and beyond
Authors: Lu Muyang , Yanco Scott , Carlson Ben , Winner Kevin , Cohen Jeremy , Ellis-Soto Diego , Sharma Shubhi , Rogers Will , Jetz Walter 
Published: December 2024

AbstractThe niche is a key concept that unifies ecology and evolutionary biology. However, empirical and theoretical treatments of the niche are mostly performed at the species level, neglecting individuals as important units of ecological and evolutionary processes. So far, a formal mathematical link between individual-level niches and higher organismal-level niches has been lacking, hampering the unification of ecological theories and more accurate forecasts of biodiversity change. To fill in this gap, we propose a bottom-up approach to derive population and higher organismal-level niches from individual niches. We demonstrate the power of our framework by showing that 1) the statistical properties of higher organismal-level niches (e.g. niche breadth, skewness etc.) can be partitioned into individual contributions; 2) the species-level niche shifts can be estimated by tracing the responses of individuals. Our method paves the way for a unifying niche theory and enables mechanistic assessments of organism-environment relationships across organismal scales.
Loom response in mouse superior colliculus depends on sensorimotor context
Authors: Zucca Stefano , Schulz Auguste , Gonçalves Pedro J. , Macke Jakob H. , Saleem Aman B. , Solomon Samuel G. 
Published: December 2024

AbstractVisual motion is produced both by an organism’s movement through the world, and by objects moving in the world such as potential predators. Choosing appropriate behaviour therefore requires organisms to distinguish these sources of visual motion. Here we asked how mice integrate self-movement with looming visual motion by combining virtual reality and neural recordings from superior colliculus (SC), a brain area important in visually-guided approach and avoidance behaviours. We first measured locomotion behaviour and neural activity while animals approached an object in virtual reality, and while the same object loomed at them. In both cases, vision dominated activity in superficial layers (SCs), while locomotion had more influence on activity in intermediate layers (SCim). In addition, animals instinctively slowed their locomotion when nearing the object, or when the object neared them. To directly test animals’ ability to distinguish self-from object motion we replayed the visual images generated during object approach. Locomotion behaviour often changed during replay, showing animals are able to establish if visual motion is matched to their self-movement. Further, decoders trained on locomotion behaviour, or on population activity in SC, particularly in SCim, were able to reliably discriminate epochs of replay and object approach. We conclude that both mouse behaviour and SC activity encode whether looming visual motion arises from self-or object movement, with implications for understanding sensorimotor coordination in dynamic environments.HighlightsWe recorded from superficial (SCs) and intermediate (SCim) superior colliculus in VRVision dominated SCs, while SCim was modulated by both vision and locomotionMice altered behaviour when visual experience did not match that expected from their locomotionPopulation activity differed between matched and unmatched visual experiences, particularly in SCim
Efficient High-Throughput DNA Breathing Features Generation Using Jax-EPBD
Authors: Inan Toki Tahmid , Kabir Anowarul , Rasmussen Kim , Shehu Amarda , Usheva Anny , Bishop Alan , Alexandrov Boian , Bhattarai Manish 
Published: December 2024

AbstractDNA breathing dynamics—transient base-pair opening and closing due to thermal fluctuations—are vital for processes like transcription, replication, and repair. Traditional models, such as the Extended Peyrard-Bishop-Dauxois (EPBD), provide insights into these dynamics but are computationally limited for long sequences. We presentJAX-EPBD, a high-throughput Langevin molecular dynamics framework leveragingJAXfor GPU-accelerated simulations, achieving up to 30x speedup and superior scalability compared to the original C-based EPBD implementation.JAX-EPBDefficiently captures time-dependent behaviors, including bubble lifetimes and base flipping kinetics, enabling genome-scale analyses. Applying it to transcription factor (TF) binding affinity prediction using SELEX datasets, we observed consistent improvements inR2values when incorporating breathing features with sequence data. Validating on the 77-bp AAV P5 promoter,JAX-EPBDrevealed sequence-specific differences in bubble dynamics correlating with transcriptional activity. These findings establishJAX-EPBDas a powerful and scalable tool for understanding DNA breathing dynamics and their role in gene regulation and transcription factor binding.
inVAE: Conditionally invariant representation learning for generating multivariate single-cell reference maps
Authors: Aliee Hananeh , Kapl Ferdinand , Pham Duy , Cakir Batuhan , Jimba Takahiro , Cranley James , Teichmann Sarah A. , Meyer Kerstin B. , Vento-Tormo Roser , Theis Fabian J. 
Published: December 2024

AbstractSingle-cell data is driving new insights into the spatiotemporal dynamics of cells and individual disease susceptibility. However, accurately identifying cell states across diverse cohorts remains challenging, as both biological variation and technical biases cause distributional shifts in the data. Separating these effects is crucial for capturing cellular heterogeneity and ensuring interpretability. To address this, we developedinVAE, a conditionally invariant deep generative model based on variational autoencoders. inVAE models the latent space as a combination of invariant variables, encoding true biological signals, and spurious variables, capturing technical biases. By conditioning the prior distribution of cells on biological covariates, such as disease variants, inVAE identifies high-resolution cell states in the invariant representation. Enforcing independence between the two representations disentangles biological signals from noise, enabling a more interpretable and generalizable model with a causal semantic. inVAE outperformed existing methods across four human cellular atlases of the human heart and lung, while uncovering novel cell states. It precisely stratified cell atlas donors based on the genetic impact of pathogenic variants, and excelled in predicting cell types and disease in unseen data, proving its generalizability as a reference model for label transfer. Furthermore, inVAE accurately identified temporal cell states and trajectories from developmental datasets, and captured spatial cell states in a spatially-resolved atlas. In summary, inVAE provides a powerful method for integrating multivariate single-cell transcriptomics data. By leveraging prior knowledge such as metadata, it effectively accounts for biological variation and improves latent space interpretability by disentangling biological and technical sources of variation. These capabilities enable deeper insights into cellular heterogeneity and its role in disease progression.
Variant Set Distillation
Authors: Christ Ryan , Kang Chul Joo , Aslett Louis J.M. , Lam Daniel , Savitski Maria Faelth , Stitziel Nathan , Steinsaltz David , Hall Ira 
Published: December 2024

AbstractAllelic heterogeneity – the presence of multiple causal variants at a given locus – has been widely observed across human traits. Combining the association signals across these distinct causal variants at a given locus presents an opportunity for empowering gene discovery. This opportunity is growing with the increasing population diversity and sequencing depth of emerging genomic datasets. However, the rapidly increasing number of null (non-causal) variants within these datasets makes leveraging allelic heterogeneity increasingly difficult for existing testing approaches. We recently-proposed a general theoretical framework for sparse signal problems, Stable Distillation (SD). Here we present a SD-based methodvsdistill, which overcomes several major shortcomings in the simple SD procedures we initially proposed and introduces many innovations aimed at maximizing power in the context of genomics. We show via simulations thatvsdistillprovides a significant power boost over the popular STAAR method.vsdistillis available in our new R package gdistill, with core routines implemented in C. We also show our method scales readily to large datasets by performing an association analysis with height in the UK Biobank.
Hypocretin receptor 1 blockade early in abstinence reduces future demand for cocaine
Authors: Samels Shanna B. , Shaw Jessica K. , Alonso Pamela , Black Emily M. , España Rodrigo A. 
Published: December 2024

AbstractRelapse to cocaine use after abstinence remains a significant challenge for treating cocaine use disorder. While the mechanisms of relapse are still under investigation, adaptations in mesolimbic dopamine systems may contribute to cocaine craving and propensity for relapse. Current pharmacological treatments targeting dopamine systems are often intolerable and may have abuse potential. Therefore, identifying novel pharmacological targets for cocaine use disorder is crucial. The hypocretin/orexin system has been shown to regulate cocaine-associated behavior and dopamine transmission. Our previous studies indicated that the hypocretin receptor 1 antagonist, RTIOX-276, reduced motivation for cocaine and attenuated dopamine responses to cocaine. Importantly, the effects of RTIOX-276 on dopamine transmission persisted for at least 24 hours, suggesting lasting effects of hypocretin receptor antagonism. Here, we hypothesized that a single RTIOX-276 treatment would reduce motivation for cocaine and normalize dopamine transmission after abstinence. Rats were pre-assessed for cocaine consumption and motivation using a within-session threshold schedule before intermittent access exposure to cocaine. Rats were subsequently treated with RTIOX-276 on the first day of a 7-day abstinence period, after which they were reassessed for cocaine consumption and motivation or examined for dopamine transmission using fast-scan cyclic voltammetry in nucleus accumbens core slices. We found that a single treatment with RTIOX-276 on the first day of abstinence reduced motivation for cocaine and normalized aberrant dopamine uptake observed following intermittent access to cocaine. These findings suggest that hypocretin receptor 1 may be a viable target for reducing motivation for cocaine through alterations in dopamine transmission in the nucleus accumbens.
Small Extracellular Vesicles Isolated from Cardiac Tissue Matrix or Plasma Display Distinct Aging-Related Changes in Cargo Contributing to Chronic Cardiovascular Disease
Authors: Ronan George , Yang Jun , Zorlutuna Pinar 
Published: December 2024

AbstractAging is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and numerous other diseases, but the mechanisms of these aging-related effects remain elusive. Chronic changes in the microenvironment and paracrine signaling behaviors have been implicated, but remain understudied. Here, for the first time, we directly compare extracellular vesicles obtained from young and aged patients to identify therapeutic or disease-associated agents, and directly compare vesicles isolated from heart tissue matrix (TEVs) or plasma (PEVs). While young EVs showed notable overlap of miRNA cargo, aged EVs differed substantially, indicating differential age-related changes between TEVs and PEVs. TEVs overall were uniquely enriched in miRNAs which directly or indirectly demonstrate cardioprotective effects, with 45 potential therapeutic agents implicated in our analysis. Both populations also showed increased predisposition to disease with aging, though through different mechanisms. PEVs were largely correlated with chronic systemic inflammation, while TEVs were more related to cardiac homeostasis and local inflammation. From this, 17 protein targets unique to TEVs were implicated as aging-related changes which likely contribute to the development of cardiovascular disease.