bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of an Overactive Bladder Care Pathway on Longitudinal Patient Management
Authors: Selle Jessica M. , Hanson Kristine T. , Habermann Elizabeth B. , Gebhart John B. , Trabuco Emanuel C. , Occhino John A. , Young Alexis D. , Linder Brian J. 
Published: March 2024

ImportanceImplementation of an overactive bladder (OAB) care pathway may affect treatment patterns and progression.ObjectivesThis study aimed to assess the effect of OAB care pathway implementation on treatment patterns for women with OAB.Study DesignThis retrospective cohort study evaluated women with OAB, before (January 1, 2015–December 31, 2017) and after (January 1, 2019–December 31, 2021) care pathway initiation. Care pathway use included standardized counseling, early introduction of therapy, and close follow-up. Primary outcomes included OAB medication use, follow-up visits, third-line therapy, and time to third-line therapy.ResultsA total of 1,349 women were included: 1,194 before care pathway implementation and 155 after. Patients after implementation were more likely to have diabetes mellitus (P= 0.04) and less likely to smoke (P= 0.01). Those managed via a care pathway were more likely to use any medication or third-line therapy within 1 year after consultation (61.3% vs 25.0%;P< 0.001). This included higher proportions receiving a medication (50.3% [95% confidence interval (CI), 41.8%–57.6%] vs 23.3% [95% CI, 20.9%–25.7%];P< 0.001) and progressing to third-line therapy (22.6% [95% CI, 15.7%–28.9%] vs 2.9% [95% CI, 2%–3.9%];P< 0.001). Among those who underwent third-line treatment, care pathway use was associated with shorter time to third-line therapy (median, 10 days [interquartile range, 1–56 days] vs 29 days [interquartile range, 7–191 days];P= 0.013). Those managed via a care pathway were less likely to have additional clinic visits for OAB within 1 year after initial consultation (12.3% vs 23.9%;P< 0.001).ConclusionsUse of an OAB care pathway was associated with higher rates of oral medication and third-line therapy yet decreased follow-up office visits. Use of an OAB care pathway may promote consistent and efficient care for women with OAB.
Predictors of Care-Seeking Behavior for Treatment of Urinary Incontinence in Women
Authors: LaPier Zoe , Jericevic Dora , Lang Diane , Gregg Steven , Brucker Benjamin , Escobar Christina 
Published: March 2024

Importance
Urinary incontinence (UI) is a common and treatable medical condition among women, but only approximately one third of women seek care.

Objective
The objective of this study was to determine factors associated with care-seeking behavior in women with UI.

Study Design
This was a cross-sectional study using patient-reported survey data collected by the National Association for Continence from November 2018 to January 2019. This survey included 60 questions and was conducted using SurveyMonkey. Descriptive statistics were used for baseline characteristics, the χ2 test was used for categorical variables, and multivariate logistic regression was used to determine predictors of care-seeking behavior.

Results
Four hundred eighty-five women completed the survey, 30.7% were not care seeking, and 69.3% were care seeking for UI. Most women were 55 years or older and had UI for more than 4 years. Care-seeking women had more overactive bladder symptoms. Women who sought care were more likely to report feelings of anger, depression, hopelessness, isolation, and report greater social effects from UI than non–care-seeking women. Less than 10% of women who sought care were asked about their UI by a medical professional. In the multivariate logistic regression expenditure of $5 or more on monthly incontinence maintenance, daily UI and older age were associated with seeking care.

Conclusions
Most women in our study population sought care for UI. Factors associated with seeking care were expenditure greater than $5 per month on incontinence, daily UI, and age. This information demonstrates the need for effective implementation of screening interventions to increase treatment access.
Integration of medical legal services into a hospital-based violence intervention program: A survey and interview-based provider needs assessment
Authors: Sonnenberg Jake , Metchick Ariana , Schille Caitlin , Bhatnagar Prashasti , Kessler Lisa , Perry Deborah , Girard Vicki , Taylor Belinda , Hall Erin 
Published: March 2024

BACKGROUND
Violent injury among trauma surgery patients is strongly associated with exposure to harmful social determinants of health and negative long-term health outcomes. Medical-legal partnerships in other settings successfully provide patients with legal services to address similar health-harming legal needs and may offer a promising model for the care of violently injured patients.

STUDY DESIGN
An electronic survey tool was distributed to clinicians and staff affiliated with the hospital-based violence intervention program at a single urban level one trauma center. Semistructured follow-up interviews were conducted with participants, and interviews were coded using thematic analysis and grounded theory.

RESULTS
Participants reported many health-harming legal needs among their violently injured patients. The most commonly identified needs were: health insurance denials (62.5%); difficulty accessing crime victims compensation funds (56.3%); trouble accessing official documents (50%); and problems with non-SSDI public benefits (50%). Participants reported inconsistent methods for learning about and responding to patients' health-harming legal needs. The most common barriers to addressing these needs included the following: lack of awareness that a lawyer could help with the issue (68.8%); prioritization of other needs (68.8%); previous negative legal experiences (62.5%); and cost (62.5%). Identified needs encompass issues traditionally addressed by MLPs as well as more novel challenges faced by violent injury survivors.

CONCLUSION
This survey and interview-based study identifies complex health-harming legal needs present among violently injured trauma surgery patients. Medical-legal partnerships specially designed for the setting of violent injury appear well-suited to meet these needs, potentially reducing risk of violent reinjury, long-term negative health outcomes, and health care system costs.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Medically relevant tandem repeats in nanopore sequencing of control cohorts
Authors: De Coster Wouter , Höijer Ida , Bruggeman Inge , D'Hert Svenn , Melin Malin , Ameur Adam , Rademakers Rosa 
Published: March 2024

AbstractResearch and diagnostics for medically relevant tandem repeats and repeat expansions are hampered by the lack of population-scale databases. We attempt to fill this gap using our pathSTR web tool, which leverages long-read sequencing of large cohorts to determine repeat length and sequence composition in the general population. The current version includes 878 individuals of the 1000 Genomes Project cohort sequenced on the Oxford Nanopore Technologies PromethION. A comprehensive set of medically relevant tandem repeats were genotyped using STRdust to determine the tandem repeat length and sequence composition. PathSTR provides rich visualizations of this dataset, as well as the feature to upload one’s own data for comparison along the control cohort. We demonstrate the implementation of this application using data from targeted nanopore sequencing of a patient with Myotonic Dystrophy type 1. This resource will empower the genetics community to get a more complete overview of normal variation in tandem repeat length and sequence composition, and enable a better assessment of the pathogenic impact of tandem repeats observed in patients. PathSTR is available athttps://pathstr.bioinf.be
Mapping under-five mortality in Malawi: towards achieving sustainable development goals
Authors: Vellemu Ruth , Sakala Melody , Chisope Evetta Kuwala , Chirombo James 
Published: March 2024

AbstractAs many low- and middle-income countries continue making gains towards attaining sustainable development goals in under-five mortality, surveillance of mortality outcomes and indicators at the sub-district level will become important as national- and district-level estimates may mask areas with a high burden. Spatial statistical modelling techniques such as geostatistical prevalence mapping can play a role in identifying hotspots of relatively high under-five mortality. To achieve this objective, it is necessary to combine data from multiple sources with different spatial resolutions to produce maps that reveal these hotspot clusters. We pooled DHS, high-resolution census data, economic vulnerability, and malaria risk data to estimate under-five mortality at a sub-district level in Malawi. Using a Bayesian hierarchical modelling approach, we fitted a binomial generalized linear geostatistical model with local area effects to generate estimates of under-five mortality at a sub-district level in Malawi. Results, in general, showed low mortality rates across the country with pockets of locations mostly in northern Malawi showing elevated risk. Rural locations were associated with higher odds of under-five mortality compared to urban locations. Our study provides a better understanding of progress made after the Millennium Development Goals in 2015 and can help improve surveillance through the application of targeted interventions which can lead to the attainment of sustainable development goals by 2030.
Synthesis of geometrically realistic and watertight neuronal ultrastructure manifolds forin silicomodeling
Authors: Abdellah Marwan , Foni Alessandro , Cantero Juan José García , Guerrero Nadir Román , Boci Elvis , Fleury Adrien , Coggan Jay S. , Keller Daniel , Planas Judit , Courcol Jean-Denis , Khazen Georges 
Published: March 2024

AbstractUnderstanding the intracellular dynamics of brain cells entails performing three-dimensional molecular simulations incorporating ultrastructural models that can capture cellular membrane geometries at nanometer scales. While there is an abundance of neuronal morphologies available online, e.g. fromNeuroMorpho.Org, converting those fairly abstract point-and-diameter representations into geometrically realistic and simulation-ready, i.e. watertight, manifolds is challenging. Many neuronal mesh reconstruction methods have been proposed, however, their resulting meshes are either biologically unplausible or non-watertight. We present an effective and unconditionally robust method capable of generating geometrically realistic and watertight surface manifolds of spiny cortical neurons from their morphological descriptions. The robustness of our method is assessed based on a mixed dataset of cortical neurons with a wide variety of morphological classes. The implementation is seamlessly extended and applied to synthetic astrocytic morphologies that are also plausibly biological in detail. Resulting meshes are ultimately used to create volumetric meshes with tetrahedral domains to perform scalablein silicoreaction-diffusion simulations for revealing cellular structure–function relationships.Availability and implementationOur method is implemented in NeuroMorphoVis, a neuroscience-specific open source Blender add-on, making it freely accessible for neuroscience researchers.Key pointsA plethora of neuronal morphologies is available in a point-and-diameter format, but there are no robust techniques capable of converting these morphologies into geometrically realistic models that can be used to conduct subcellular simulations.We present a scalable method capable of synthesizing high fidelity watertight ultrastructural manifolds of complete neuronal models from their one-dimensional descriptions using the synaptic data obtained from the digitally reconstructed neuronal circuits of the Blue Brain Project.Resulting manifold models comprise geometrically realistic somata and spine geometries, enabling accuratein silicoexperiments that can probe intricate structure-function relationships.Our method is extensible and can be seamlessly applied to other cellular structures such as astroglial morphologies and even large networks of cerebral vasculature.
Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure
Authors: Towner Trevor T. , Coleman Harper J. , Goyden Matthew A. , Vore Andrew S. , Papastrat Kimberly M. , Varlinskaya Elena I. , Werner David F. 
Published: March 2024

AbstractAdolescent intermittent ethanol (AIE) exposure in rats leads to social deficits. Parvalbumin (PV) expressing interneurons in the prelimbic cortex (PrL) contribute to social behavior, and perineuronal nets (PNNs) within the PrL preferentially encompass PV interneurons, acting as significant regulators of these cells. AIE exposure increases PNNs, however, it is unknown if this upregulation contributes to AIE-induced social impairments. The current study was designed to determine the effect of AIE exposure on PNN expression in the PrL and to assess whether PNN dysregulation contributes to social deficits elicited by AIE. cFos-LacZ male and female rats were exposed every other day to tap water or ethanol (4g/kg, 25% w/v) via intragastric gavage between postnatal day (P) 25-45. We evaluated neuronal activation by β-galactosidase expression and PNN levels either at the end of the exposure regimen on P45 and/or in adulthood on P70. In addition, we used Chondroitinase ABC (ChABC) to deplete PNNs following adolescent exposure (P48) and allowed for PNN restoration before social testing in adulthhod. AIE exposure increased PNN expressionin the PrL of adult males, whereas a decrease in PNNs was evident immediately following AIE. Vesicular glutamate transporter 2 (vGlut2) and vesicular GABA transporter (vGat) near PNNs were moderately downregulated only in AIE-exposed females. Gene expression of PNN components were largely unaffected by AIE exposure. Removal and reestablishment of PNNs in the PrL led to upregulation of PNNs and social impairments in males, regardless of adolescent exposure. These data suggest that AIE exposure in males produces an upregulation of PrL PNNs that likely contribute to social impairments induced by AIE.
Functional characterization of QT interval associatedSCN5Aenhancer variants identify combined additive effects
Authors: Gunamalai Lavanya , Singh Parul , Berg Brian , Shi Leilei , Sanchez Ernesto , Smith Alexa , Breton Ghislain , Bedford Mark T , Balciunas Darius , Kapoor Ashish 
Published: March 2024

AbstractSeveral empirical and theoretical studies suggest presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual variability in gene expression. However, for vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored. Here, we have evaluated the combined effects from fiveSCN5Aenhancers and their regulatory variants that are known to collectively correlate withSCN5Acardiac expression and underlie QT interval association in the general population. Using small deletions centered at the regulatory variants in episomal reporter assays in a mouse cardiomyocyte cell line we demonstrate that the variants and their flanking sequences play critical role in individual enhancer activities, likely being a transcription factor (TF) binding site. By performing oligonucleotide-based pulldown assays on predicted TFs we identify the TFs likely driving allele-specific enhancer activities. Using all 32 possible allelic synthetic constructs in reporter assays, representing the five biallelic enhancers in tandem in their genomic order, we demonstrate combined additive effects on overall enhancer activities. Using transient enhancer assays in developing zebrafish embryos we demonstrate the four out the five enhancer elements act as enhancersin vivo. Together, these studies extend the previous findings to uncover the TFs driving the enhancer activities of QT interval associatedSCN5Aregulatory variants, reveal the additive effects from allelic combinations of these regulatory variants, and prove their potential to act as enhancersin vivo.
Drosophilaappear resistant to trans-synaptic tau propagation
Authors: Catterson James H , Mouofo Edmond N , Soler Inés López De Toledo , Lean Gillian , Dlamini Stella , Liddell Phoebe , Voong Graham , Katsinelos Taxiarchis , Wang Yu-Chun , Schoovaerts Nils , Verstreken Patrik , Spires-Jones Tara L , Durrant Claire S 
Published: March 2024

AbstractAlzheimer’s disease (AD) is the most common cause of dementia in the elderly, prompting extensive efforts to pinpoint novel therapeutic targets for effective intervention. Among the hallmark features of AD is the development of neurofibrillary tangles comprised of hyperphosphorylated tau protein, whose progressive spread throughout the brain is associated with neuronal death. Trans-synaptic propagation of tau has been observed in mouse models and indirect evidence for tau spread via synapses has been observed in human AD. Halting tau propagation is a promising therapeutic target for AD, thus a scalable model system to screen for modifiers of tau spread would be very useful for the field. To this end, we sought to emulate the trans-synaptic spread of human tau (hTau) inDrosophila melanogaster. Employing the trans-Tango circuit mapping technique, we investigated whether tau spreads between synaptically connected neurons. Immunohistochemistry and confocal imaging were used to look for tau propagation. Examination of hundreds of flies expressing 4 different human tau constructs in two distinct neuronal populations reveal a robust resistance inDrosophilato the trans-synaptic spread of hTau. This resistance persisted in lines with concurrent expression of amyloid-β, in lines with global hTau knock-in to provide a template for human tau in downstream neurons, and with manipulations of temperature. These negative data are important for the field as we establish thatDrosophilaexpressing human tau in subsets of neurons are unlikely to be useful to perform screens to find mechanisms to reduce the trans-synaptic spread of tau. The inherent resistance observed inDrosophilamay serve as a valuable clue, offering insights into strategies for impeding tau spread in future studies.
Coupling hydrodynamic drifting simulations and seasonal demographics to forecast the occurrence of jellyfish blooms
Authors: Cant James , Jones Owen R. , Ellingsen Ingrid , Laverick Jack H. , Majaneva Sanna , Dierking Jan , Aberle Nicole , Javidpour Jamileh 
Published: March 2024

AbstractAlthough jellyfish are an important component of coastal marine communities, their public perception is often tainted by their proclivity for aggregating in vast numbers, known as jellyfish blooms. Jellyfish blooms occur worldwide and are associated with major economic ramifications, particularly throughout the fisheries, aquaculture, and tourism sectors.Forecasting jellyfish blooms is critical in order to manage and mitigate their ecological and economic impacts, but the complex life cycles and cryptic life stages exhibited by most jellyfish species largely precludes accurate predictions of their temporal and spatial occurrence.Here we introduce a predictive framework, combining state-of-the-art hydrodynamic simulations and periodic population modelling approaches, to forecast spatial and temporal patterns in the formation of jellyfish blooms. While this framework is sufficiently flexible for accommodating various bloom-forming jellyfish species and impacted coastal regions worldwide, we focus on moon jellyfish (Aurelia aurita) populations within the Baltic Sea as an illustrative example.We emphasise how, through the iterative process of forecasting and model validation, this framework can provide valuable insights for resolving key gaps in our understanding of the drivers of bloom events. Indeed, our framework offers an approach for identifying the, to date, unknown locations of polyp-beds; a crucial parameter in enhancing our capacity to accurately predict the occurrence of jellyfish blooms. Accordingly, our framework, represents a key decision-support tool for mitigating the socioeconomic impacts of bloom formation.
The Cyclin-Like Protein Spy1 Mediates Tumourigenic Potential of Triple Negative Breast Cancer
Authors: Fifield Bre-Anne , Pecoraro Claudia , Basilious Amy , Gramisteanu Catalin , Mailloux Emily , Ferraiuolo Rosa-Maria , Porter Lisa A. 
Published: March 2024

AbstractTriple negative breast cancer is an aggressive subtype of breast cancer that relies on systemic chemotherapy as its primary means of treatment. Cell cycle regulators are enriched in drug resistant forms of the disease supporting the potential of targeting cell cycle checkpoints as a therapeutic direction to re-sensitize patients to treatment. Spy1 is an atypical cyclin-like protein that can override cell cycle checkpoints and is elevated in triple negative breast cancer. We report for the first time the effects of CRISPR-Cas9 mediated knockout of Spy1 on functional characteristics of triple negative breast cancer cells and perform unbiased analysis of protein expression to assess global changes in expression which correlate with functional changes in cell properties. Loss of Spy1 reduced rates of proliferation, decreased metastatic potential, and led to a reduction in stemness properties of triple negative breast cancer cells. Importantly, knockout of Spy1 delayed tumour onset in anin vivomodel and significantly increased response to chemotherapy, pushing cells towards a senescent state. This data reveals that changes in expression of proteins that are not essential for proliferation and only transiently expressed can have significant impacts on cell dynamics and provides support for targeting the Spy1-CDK2 complex as a new therapeutic avenue in triple negative breast cancer.Statement of SignificanceTargeting the atypical cell cycle regulator Spy1 induces senescence and increases responsiveness of triple negative breast cancer to standard of care chemotherapy.
Single-Domain Antibody-Based Protein Degrader for Synucleinopathies
Authors: Jiang Yixiang , Lin Yan , Tetlow Amber M. , Pan Ruimin , Ji Changyi , Kong Xiang-Peng , Congdon Erin E. , Sigurdsson Einar M. 
Published: March 2024

AbstractSynucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of α-synuclein (α-syn) in the brain, leading to motor and neuropsychiatric symptoms. Currently, there are no known cures for synucleinopathies, and treatments mainly focus on symptom management. In this study, we developed a single-domain antibody (sdAb)-based protein degrader with features designed to enhance proteasomal degradation of α-syn. This sdAb derivative targets both α-syn and Cereblon (CRBN), a substrate-receptor for the E3-ubiquitin ligase CRL4CRBN, and thereby induces α-syn ubiquitination and proteasomal degradation. Our results indicate that this therapeutic candidate enhances proteasomal degradation of α-syn, in addition to the endogenous lysosomal degradation machinery. By promoting proteasomal degradation of α-syn, we improved clearance of α-syn in primary culture and mouse models of synucleinopathy. These findings indicate that our sdAb-based protein degrader is a promising therapeutic candidate for synucleinopathies. Considering that only a small percentage of antibodies enter the brain, more potent sdAbs with greater brain entry than whole antibodies could enhance clinical benefits of antibody-based therapies.