bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caregiver Perspectives on Provider Continuity During Prolonged PICU Hospitalizations: A Single-Center Qualitative Study, 2021–2022
Authors: Jiménez Patricia Peña , Phipps Wendy Leatherman , Jacob-Files Elizabeth , Lindo Elizabeth , Rakes Lauren C. , Roberts Joan S. , Clark Jonna D. , Berkman Emily R. , Nielsen Katie R. 
Published: December 2024

OBJECTIVES:
To improve continuity of care, some PICUs assign a continuity attending (CA) physician for children with prolonged hospitalizations. Little is known about how this intervention impacts familial caregivers’ experiences. The objective of this study was to provide in-depth descriptions of family perspectives about continuity of care during prolonged PICU hospitalizations for children with and without a PICU CA.

DESIGN:
Qualitative semi-structured interviews.

SETTING:
Single center cohort, from October 2021 to December 2022, at an academic PICU in the United States.

PARTICIPANTS:
Familial caregivers (n = 39) of critically ill children hospitalized in the PICU for greater than or equal to 14 days were purposively sampled, stratified by group: 18 with a PICU CA and 21 without a PICU CA.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Semi-structured interviews were audio recorded, transcribed, coded, and analyzed in the context of the continuity of care model using a realist thematic approach. Familial caregivers described six themes related to relational, informational, and management continuity: 1) familiar providers who demonstrate empathy for the child improve family members’ comfort and trust (Relational); 2) providers who know and use a child’s baseline health status to inform clinical decision-making alleviate family members’ stress (Relational, Management); 3) information loss during care team transitions frustrates families (Informational, Management); 4) known providers enhance caregiver communication (Informational); 5) familiar providers who value a family’s expertise about their child’s care (Relational, Management); and 6) take responsibility for the child’s long-term care plan (Management) decrease parental stress.

CONCLUSIONS:
As PICU patient medical complexity and length of stay increase, familial caregivers’ needs transition from understanding day-to-day management to navigating care team transitions and partnering with providers to develop long-term care plans. Targeted interventions to increase provider continuity that consider relational, informational, and management continuity are needed to optimize patient outcomes and family experiences.
Developing a Practice-Driven Taxonomy of Implementation Strategies for HIV Prevention
Authors: Golub Sarit A. , Wolfer Carly , Beacham Alexa , Lane Benjamin V. , Chastain Cody A. , Meyers Kathrine A. 
Published: December 2024

Background:
Effective implementation of evidence-based HIV prevention interventions continues to be a challenge in the United States, and the field is increasingly turning to implementation science for solutions. As such, it is critical to expand the current implementation science vocabulary—and its taxonomy of implementation strategies—to increase its relevance and utility for front-line implementers.

Setting:
Community-based health centers providing HIV prevention services in the southeastern United States.

Methods:
We conducted a collective case-study analysis, combining document review and qualitative interviews with program directors, clinicians, and other providers (N = 30) at 5 sites. We used an inductive and iterative analytic approach to specify and categorize strategies, and then conducted in-depth cross-case analysis to derive a practice-driven taxonomy of HIV prevention implementation strategies.

Results:
From an initial matrix of 264 activities, we identified 50 strategies common across sites. In contrast to existing implementation science frameworks, most (68%, n = 34) strategies were designed to affect implementation outcomes (eg, acceptability, adoption, feasibility) for patients. We present a practice-driven taxonomy of these strategies, operationalized according to implementation science literature, but with terminology that more directly relates to implementers.

Conclusions:
Findings demonstrate the feasibility and utility of this method for developing a practice-driven implementation science vocabulary for HIV prevention. Our evidence-based taxonomy provides a framework for implementers seeking data about the universe of strategies they might consider for their own programs, and increases researchers' ability to measure and evaluate the effectiveness of implementation strategies being enacted in practice settings.
A Novel Approach to Aplasia Cutis Congenita With PolyNovo BTM
Authors: Pollock Michaela , Leung Rachael , Low Nelson CK 
Published: December 2024

Aplasia cutis congenita (ACC) is a rare congenital condition characterized by the absence of skin and subcutaneous tissue, typically affecting the scalp. This case report presents a female infant born at 38+3 weeks with a posterior midline scalp defect measuring 15×12.5 mm, involving skin, subcutaneous tissue, and calvarium. The defect was managed with NovoSorb Biodegradable Temporising Matrix (BTM). Initially, the plan involved a subsequent skin graft; however, the defect epithelized without grafting. By 2 months, the wound had healed completely, and by 6 months, the underlying bone had ossified. ACC presents with significant variability, and management strategies range from conservative treatment to surgical intervention depending on defect size. This case demonstrates the successful use of a fully synthetic dermal substitute in managing full-thickness scalp defects, providing a novel, effective option for treating ACC without requiring grafting.
The human glucocorticoid receptor variant rs6190 promotes blood cholesterol and atherosclerosis
Authors: Durumutla Hima Bindu , Haller April , Noble Greta , Prabakaran Ashok Daniel , McFarland Kevin , Latimer Hannah , Akinborewa Olukunle , Namjou-Khales Bahram , Hui David Y. , Quattrocelli Mattia 
Published: December 2024

AbstractElevated cholesterol poses a significant cardiovascular risk, particularly in older women. The glucocorticoid receptor (GR), a crucial nuclear transcription factor that regulates the metabolism of virtually all major nutrients, harbors a still undefined role in cholesterol regulation. Here, we report that a coding single nucleotide polymorphism (SNP) in the gene encoding the GR,rs6190, associated with increased cholesterol levels in women according to UK Biobank and All Of Us datasets. In SNP-genocopying transgenic mice, we found that the rs6190 SNP enhanced hepatic GR activity to transactivatePcsk9andBhlhe40, negative regulators of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptors in liver respectively. Accordingly, in mice the rs6190 SNP was sufficient to elevate circulating cholesterol levels across all lipoprotein fractions and the risk and severity of atherosclerotic lesions on the pro-atherogenichAPOE*2/*2background. The SNP effect on atherosclerosis was blocked by in vivo knockdown of Pcsk9 and Bhlhe40 in liver. Remarkably, we found that this mechanism was conserved in human hepatocyte-like cells using CRISPR-engineered, SNP-genocopying human induced pluripotent stem cells (hiPSCs). Taken together, our study leverages a non-rare human variant to uncover a novel GR-dependent mechanism contributing to atherogenic risk, particularly in women.Abstract FigureGraphical Abstract
Genome size estimation from long read overlaps
Authors: Hall Michael B , Coin Lachlan J M 
Published: December 2024

AbstractSummaryAccurate genome size estimation is an important component of genomic analyses, though existing tools are primarily optimised for short-read data. We present LRGE, a novel tool that uses read-to-read overlap information to estimate genome size in a reference-free manner. LRGE calculates per-read genome size estimates by analysing the expected number of overlaps for each read, considering read lengths and a minimum overlap threshold. The final size is taken as the median of these estimates, ensuring robustness to outliers such as reads with no overlaps. Additionally, LRGE provides an expected confidence range for the estimate. LRGE outperformsk-mer-based methods in both accuracy and computational efficiency and produces genome size estimates comparable to those from assembly-based approaches, like Raven, while using significantly less computational resources. We validate LRGE on a large, diverse bacterial dataset and confirm it generalises to eukaryotic datasets.Availability and implementationOur method, LRGE (LongRead-basedGenome sizeEstimation from overlaps), is implemented in Rust and is available as a precompiled binary for most architectures, a Bioconda package, a prebuilt container image, and a crates.io package as a binary (lrge) or library (liblrge). The source code is available athttps://github.com/mbhall88/lrgeunder an MIT license.
Reevaluating the Association Between Epstein-Barr Virus (EBV) and Breast Cancer in the United States
Authors: Hu Clarence C. , Kamtam Devanish N. , Cardona Juan J. 
Published: December 2024

AbstractThe World Health Organization estimates 9.9% of cancers are attributable to viruses. Notably, human papillomavirus causes roughly 90% of cervical cancers, while Epstein-Barr virus (EBV) is linked to nearly 10% of gastric carcinomas. Regarding breast cancer, the association with EBV is inconclusive. While studies in some nations report an association, those in the United States largely do not. We reviewed studies from 2003 to 2023 and identified seven that analyzed EBV association with breast cancer in American patients. We observed a potential risk of not investigating novel EBV variants. Detection protocols utilized only lymphoma-derived strains, despite the current knowledge suggesting that genotype variation can influence pathogenic potential and cell tropism. Certain EBV strains, for instance, may preferentially infect epithelial cells and increase the risk of nasopharyngeal carcinoma (NPC) by up to 11 times. Stated simply, the optimal EBV detection protocol for breast cancer cells may differ from lymphoma cells. Reliance on lymphoma-derived strains assumes a level of sequence conservation among EBV genomes. Mounting evidence demonstrates greater variation than previously believed, especially in key coding and non-coding regions. Our analysis reveals that 5/7 (71%) studies used at least one assay sequence that did not exactly match more than 50% of EBV genomes in NCBI GenBank. Moreover, 98% of these GenBank entries became available after assay sequences were selected. Overall, it is possible the current understanding may be incomplete. Should breast cancer mirror gastric carcinoma and exhibit EBV influence in certain subtypes, these insights could enable targeted therapies and screening programs.ObjectivesThis study examines potential limitations of prior investigations into the association between Epstein-Barr Virus (EBV) and breast cancer in the United States. Specifically, our aims are to:Assess the cellular origin and pathogenicity of EBV strains employed in detection protocols.This objective stems from the background section’s discussion on EBV genotype variations and their potential influence on tissue tropism and pathogenic mechanisms.Evaluate the sequence similarity between assay sequences and available EBV genomic data.This objective addresses the concern raised in the background section regarding the potential for newfound sequence variation among EBV strains and the implications for accurate detection.Determine the extent to which detection protocols incorporate the latest EBV genomic data.
Soft, 3D printed muscle ultrasound phantom with structurally tunable B-mode echo intensity
Authors: Gillespie Samuel D , Collins Caralyn P , Perreault Eric J , Sun Cheng , Balogun Oluwaseyi , Murray Wendy M 
Published: December 2024

ABSTRACTOBJECTIVESImaging phantoms for training and validation are vital to improving the performance and adoption of ultrasound imaging modalities in clinical and pre-clinical applications, and the goal of this study was to assess the viability of 3D printed muscle ultrasound phantoms to meet this need.METHODSWe used a soft stereolithography resin to 3D print phantoms that mimicked the fascicle- and perimysium-scale structure of skeletal muscle and compared the long axis B-mode imaging quality and pattern of the phantom to that of healthy, adult Biceps brachii. We used a pulse-echo, time-of-flight method to measure the acoustic impedance of the resin for comparison to skeletal muscle and common soft tissue mimicking materials. We analyzed the echo intensity (EI) of muscle images to establish a physiological range and compared the EI of different phantom designs to assess the ability to control imaging brightness through structural modification.RESULTSA linear, striated hyper-/hypo-echoic B-mode imaging pattern mimicking long axis Biceps brachii muscle images was achieved with two 3D structure paradigms, rod and honeycomb. Acoustic impedance of Elastic 50A resin is higher than skeletal muscle in bulk, but appears suitable for use in a 3D structured phantom. EI measured in the Biceps images were found to vary both within and across images with an overall mean ± SD of 87 ±13 AU. EI measured in honeycomb phantoms (55 ±15 AU) was higher than in rod phantoms (42 ±13 AU), and a latticed honeycomb further increased EI (90 ±11 AU).CONCLUSIONSThis study serves as proof-of-concept for soft, 3D printed phantoms that replicate the characteristic muscle ultrasound imaging pattern with the ability to tune clinically relevant EI values via structural design.
Epigenetic study of the long-term effects of Gulf War illness
Authors: Jones B. C. , O’Callaghan J. P. , Ashbrook D. G. , Lu L. , Prins P. , Zhao W. , Mozhui K 
Published: December 2024

AbstractGulf war illness is a chronic multisymptom disorder that affects as many as many as 25-35% of the military personnel who were sent to the Persian Gulf war in 1991. The illness has many debilitating symptoms, including cognitive problems, gastrointestinal symptoms, and musculoskeletal pain. Those so afflicted have been sick for more than 30 years and, therefore, it has become imperative to understand the etiology and then produce treatments to ease the symptoms. We hypothesized that the length of the disease was reflected in epigenetic modification of possibly several genes related to the symptoms. We subjected male and female mice from 11 BXD strains to combined corticosterone and the sarin surrogate, diisopropylfluorophosphate, to emulate the physiological stress of war and the potential exposures to organophosphate pesticides and nerve agent in theater. Three hundred days after treatment, we analyzed the animals’ DNA for genome-wide methylation by MBD-seq. The analysis revealed 20 methylated genes, notablyEif2B5, that regulates myelin production. Loss of myelin with accompanying musculoskeletal pain is a major symptom of Gulf War illness. Our work demonstrates multiple genes were methylated by exposure to OPs and glucocorticoids. These genes point to biochemical mechanisms that may be targets for therapeutic intervention.
The proteome content of blood clots observed under different conditions: successful role in predicting clot amyloid(ogenicity)
Authors: Kell Douglas B. , Pretorius Etheresia 
Published: December 2024

AbstractA recent analysis compared the proteome of (i) blood clots seen in two diseases – sepsis and long COVID – when blood was known to have clotted into an amyloid microclot form (as judged by staining with the fluorogenic amyloid stain thioflavin T) with (ii) that of those non-amy-loid clots considered to have formed normally. Such fibrinaloid microclots are also relatively resistant to fibrinolysis. The proteins that the amyloid microclots contained differed markedly both from the soluble proteome of typical plasma and that of normal clots, and also between the disease studies (an acute syndrome in the form of sepsis in an ITU and a chronic disease represented by Long COVID). Many proteins in the amyloid microclots were low in concentration in plasma and were effectively accumulated into the fibres, whereas many other abundant plasma proteins were excluded. The proteins found in the microclots associated with the diseases also tended to be themselves amyloidogenic. We here ask effectively the inverse question. This is: can the clot proteome tell us whether the clots associated with a particular disease contained proteins that are observed uniquely (or are highly over-represented) in known amyloid clots relative to normal clots, and thus were in fact amyloid in nature? The answer is in the affirmative in a variety of major coagulopathies, viz. venous thromboembolism, pulmonary embolism, deep vein thrombosis, various cardiac issues, and ischaemic stroke. Galectin-3-binding protein and thrombospondin-1 seem to be especially widely associated with amyloid-type clots, and the latter has indeed been shown to be incorporated into growing fibrin fibres. These may consequently provide useful biomarkers with a mechanistic basis.
Guidelines for alternative polyadenylation identification tools using single-cell and spatial transcriptomics data
Authors: Zhao Qian , Rattray Magnus 
Published: December 2024

AbstractBackgroundMany popular single-cell and spatial transcriptomics platforms exhibit 3’ bias, making it challenging to resolve all transcripts but potentially more feasible to resolve alternative polyadenylation (APA) events. Despite the development of several tools for identifying APA events in scRNA-seq data, a neutral benchmark is lacking, complicating the choice for biologists.ResultsWe categorized existing APA analysis tools into three main classes, with the alignment-based class being the largest and we further divided this category into four sub-types. We compared the performance of methods from each algorithmic subtype in terms of site identification, quantification, and differential expression analysis across four single-cell and spatial transcriptomic datasets, using matched nanopore data as ground truth. No single method showed absolute superiority in all comparisons. Therefore, we selected representative methods (Sierra, scAPAtrap, and SCAPE) to deeply analyze the impact of different algorithmic choices on performance. SCAPE which is based on the distance estimation demonstrated less sensitivity to changes in read length and sequencing depth. It identified the most sites and achieved high recall but does not account for the impact of alternative splicing on site identification, leading to a loss in precision. Sierra that fits a coverage distribution is sensitive to changes in sequencing depth and identifies relatively fewer sites, but it considers the impact of junction reads on site identification and this results in relatively high precision. scAPAtrap combines peak calling and soft clipping, both of which are sensitive to sequencing depth. Moreover, soft clipping is particularly sensitive to read length, with increased read length leading to more false positive sites. Quantification consistency was affected by Cell Ranger versions and parameters, influencing downstream analysis but having less effect on differential expression between cell types.ConclusionsEach method has unique strengths. SCAPE is recommended for low-coverage data, scAPAtrap for moderate read lengths including intergenic sites, and Sierra for high-depth data with alternative splicing considerations. Filtering low-confidence sites, choosing appropriate mapping tools, and optimizing window size can improve performance.
Elevated plasma pTau181 in a specialty neuropsychiatric clinic is associated with opioid use and guides medication titration on a clinically relevant short-time scale
Authors: Hanson Emily , Berner Karl , Berner Jon 
Published: December 2024

AbstractA combinatorial explosion of agents that delay neurodegeneration in animal models has created a crisis of abundance in human applications with too many combinations to try when time is short. Plasma biomarkers of premature neuronal aging, the amyloid-tau-neurodegeneration (ATN) profile, may provide a tool to rapidly optimize treatment in single-patient trials. We retrospectively analyzed plasma ATN profiles in patients with extensive neuropsychiatric polypharmacy and premature neuronal aging. ATN profiles were based on the biomarkers amyloid-β ratio, phosphorylated Tau 181 (pTau181), and neurofilament light chain (NfL). We investigated whether ATN profile biomarkers were associated with age, gender, metabolic syndrome markers, and medication use. Two case reports additionally provide examples of the application of ATN profiles in clinical settings. We found that in 80 patients with ATN profiles and complete clinical phenotypes, pTau181 was elevated in 31 (38.75%), amyloid-β ratio was below normal ranges in 11 (13.75%), and NfL was elevated in three (3.75%). The biomarkers correlated with age, as expected. Opioid use was significantly associated with pTau181 (p=0.004) and NfL (p=0.002), also after Bonferroni correction (both p <0.05), but not with amyloid-β ratio. No other medications were associated with the biomarkers. In conclusion, identifying the overlaps between complex behavioral phenotypes (pain and cognition), plasma endophenotypes (ATN profile), and medication-targeted components of age-related pathophysiology is now a technical problem rather than theoretical speculation. Rapid progress in single-patient trials for treatment optimization will require funding to promote using repurposed generic treatments, educate patients and providers regarding optimization principles, and continue developing sensitive biomarkers.