bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrater reliability of chart-based assessment of functional impairment after pediatric injury using the functional status scale
Authors: Melhado Caroline G. , Kao Emily , Hogan-Schlientz Jacqueline , Crane Debbie , Shui Amy M. , Stephens Caroline Q. , Evans Lauren , Burd Randall S. , Jensen Aaron R. 
Published: April 2023

BACKGROUND
Functional impairment has been proposed as an alternative outcome for quality improvement in pediatric trauma. The functional status scale (FSS) has been used in studies of injured children, but has only been validated with resource-intensive in-person assessment. Implementation with retrospective chart-based FSS assessment would offer a simplified and scalable alternative. The purpose of this study was to evaluate interrater reliability of retrospective FSS assessment and to identify factors associated with unreliable assessment.

METHODS
A retrospective cohort of admissions to a Level I pediatric trauma center between July 2020 and June 2021 was analyzed. Two physicians and two nurse registrars reviewed charts to obtain measures of six FSS domains (mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status) at discharge. Functional impairment was categorized by total FSS scores as good (6,7), mild impairment (8,9), moderate impairment (10–15), severe impairment (16–21), or very severe impairment (>21). Interrater reliability was assessed using intraclass correlation (ICC). Predictors of rater disagreement were evaluated using multivariable logistic regression.

RESULTS
The cohort included 443 children with a mean age of 7.4 years (standard deviation, 5.4 years) and median Injury Severity Score of 9 (interquartile range, 5–12). The median time per chart to assess FSS was 2 minutes (interquartile range, 1–2). Thirty-seven patients (8%) had functional impairment at discharge. Interrater reliability was excellent for total FSS score (ICC = 0.87) and good for FSS impairment categorization (ICC = 0.80). Rater disagreement of functional impairment categorization occurred in 14% of cases overall. Higher level of functional impairment and use of therapies (occupational and speech language therapy) were independently associated with more frequent rater disagreement.

CONCLUSION
Chart-based FSS assessment is feasible and reliable, but may require more detailed review for patients with higher level of impairment that require allied health therapy. Validation of chart-based assessment is needed before widespread implementation.

LEVEL OF EVIDENCE
Prognostic/Epidemiological, Level III.
Utility of computed tomography reconstructed thoracolumbar spinal imaging in blunt trauma
Authors: Swarup Abhishek , Amro Chris , Choron Rachel L. , Cong Alexander , Park John , Butts Christopher A. , Goswami Julie , Teichman Amanda L. 
Published: April 2023

OBJECTIVES
Fractures of the thoracolumbar (TL) spine are common and may cause neurologic damage, pain, and reduced quality of life. Computed tomography (CT) TL reconstructions from CT chest, abdomen, and pelvis (CAP) are used to identify TL fractures; however, their benefit over CAP imaging is unclear. We hypothesized that reformatted TL images do not identify additional clinically significant injuries or change outcomes.

METHODS
Retrospective data were collected 2016 to 2021 from trauma patients at a level 1 trauma center. All patients 18 years or older with TL fractures on CT CAP with/without CT TL reformats were included. Clinically significant TL fractures were defined as requiring operative fixation, brace, or spinal rehabilitation. A binary classification model was created to assess the diagnostic utility of CTCAP compared with CTTL in predicting clinically significant fractures in patients who underwent CT CAP/TL.

RESULTS
There were 828 patients with TL fractures, 634 had both CT CAP/CT TL (CAPTL) and 194 CTCAP only (CAP). There were 134 clinically significant TL fractures (16%) (14 [7.2%] CT CAP vs. 120 [18.9%] CT CAPTL, p < 0.001). There were no differences among unstable fractures, fractures on magnetic resonance imaging (MRI) only, mortality, or neurologic deficits on discharge between CAPTL and CAP (p > 0.05). Among clinically significant fractures, CAPTL was not associated with increased MRI utilization, surgery, spinal brace, or spinal cord rehabilitation (p > 0.05). Among clinically insignificant fractures, CAPTL was associated with increased MRIs, length of stay (LOS), and intensive care unit LOS (p < 0.05). CAPTL was also an independent predictor of increased MRIs (odds ratio, 5.79; 95% confidence interval, 2.29–14.65; p < 0.01) and spine consultation (odds ratio, 2.39; 95% confidence interval, 1.64–3.67; p < 0.01). More CT CAP/TL were performed in those with clinically significant fractures; however, CTCAP was equivalent to CTTL for detection of fractures (p > 0.05).

CONCLUSION
CTCAP alone is sufficient to identify clinically significant TL fractures. While the addition of TL reformatted imaging minimizes missed injuries, it is associated with increased hospital LOS and MRI resource utilization. Therefore, careful consideration is needed for appropriate CT TL patient selection.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
A novel machine-learning tool to identify community risk for firearm violence: The Firearm Violence Vulnerability Index
Authors: Polcari Ann M. , Hoefer Lea E. , Zakrison Tanya L. , Cone Jennifer T. , Henry Marion C. W. , Rogers Selwyn O. , Slidell Mark B. , Benjamin Andrew J. 
Published: April 2023

BACKGROUND
Firearm violence in the United States is a public health crisis, but accessing accurate firearm assault data to inform prevention strategies is a challenge. Vulnerability indices have been used in other fields to better characterize and identify at-risk populations during crises, but no tool currently exists to predict where rates of firearm violence are highest. We sought to develop and validate a novel machine-learning algorithm, the Firearm Violence Vulnerability Index (FVVI), to forecast community risk for shooting incidents, fill data gaps, and enhance prevention efforts.

METHODS
Open-access 2015 to 2022 fatal and nonfatal shooting incident data from Baltimore, Boston, Chicago, Cincinnati, Los Angeles, New York City, Philadelphia, and Rochester were merged on census tract with 30 population characteristics derived from the 2020 American Community Survey. The data set was split into training (80%) and validation (20%) sets; Chicago data were withheld for an unseen test set. XGBoost, a decision tree-based machine-learning algorithm, was used to construct the FVVI model, which predicts shooting incident rates within urban census tracts.

RESULTS
A total of 64,909 shooting incidents in 3,962 census tracts were used to build the model; 14,898 shooting incidents in 766 census tracts were in the test set. Historical third grade math scores and having a parent jailed during childhood were population characteristics exhibiting the greatest impact on FVVI’s decision making. The model had strong predictive power in the test set, with a goodness of fit (D
2) of 0.77.

CONCLUSION
The Firearm Violence Vulnerability Index accurately predicts firearm violence in urban communities at a granular geographic level based solely on population characteristics. The Firearm Violence Vulnerability Index can fill gaps in currently available firearm violence data while helping to geographically target and identify social or environmental areas of focus for prevention programs. Dissemination of this standardized risk tool could also enhance firearm violence research and resource allocation.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system developmentin vitro
Authors: Rockel Anna F. , Wagner Nicole , Ergün Süleyman , Wörsdörfer Philipp 
Published: April 2023

AbstractHere we describe a novel neuro-mesodermal assembloid model which recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC) induction, delamination, migration and sensory as well as sympathetic ganglion formation. The ganglia send neuronal projections to the mesodermal as well as the neural compartment. Axons in the mesodermal part are associated with Schwann cells. In addition, peripheral ganglia as well as nerve fibers interact with the co-developing vascular plexus, forming a neurovascular niche. Finally, developing sensory ganglia show response to capsaicin treatment indicating their functionality.The presented assembloid model could help to uncover mechanisms of NCC delamination, migration and PNS development in the human tissue context. Moreover, the model could be used for toxicity screenings or drug testing. The co-development of mesodermal and neuroectodermal tissues and of a well-organized vascular plexus along with a peripheral nervous system allows to investigate the crosstalk between neuroectoderm and mesoderm and between peripheral neurons/neuroblasts and endothelial cells. Such interactions influence NCC delamination and migration, sensory neuron differentiation and rearrangement of the primitive vascular plexus in the embryo.
Towards robust clinical genome interpretation: developing a consistent terminology to characterize disease-gene relationships - allelic requirement, inheritance modes and disease mechanisms
Authors: Roberts Angharad M , DiStefano Marina T. , Riggs Erin Rooney , Josephs Katherine S , Alkuraya Fowzan S , Amberger Joanna , Amin Mutaz , Berg Jonathan S. , Cunningham Fiona , Eilbeck Karen , Firth Helen V. , Foreman Julia , Hamosh Ada , Hay Eleanor , Leigh Sarah , Martin Christa L. , McDonagh Ellen M. , Perrett Daniel , Ramos Erin M. , Robinson Peter N. , Rath Ana , van Sant David , Stark Zornitza , Whiffin Nicola , Rehm Heidi L. , Ware James S. 
Published: April 2023

AbstractPURPOSEThe terminology used for gene-disease curation and variant annotation to describe inheritance, allelic requirement, and both sequence and functional consequences of a variant is currently not standardized. There is considerable discrepancy in the literature and across clinical variant reporting in the derivation and application of terms. Here we standardize the terminology for the characterization of disease-gene relationships to facilitate harmonized global curation, and to support variant classification within the ACMG/AMP framework.METHODSTerminology for inheritance, allelic requirement, and both structural and functional consequences of a variant used by Gene Curation Coalition (GenCC) members and partner organizations was collated and reviewed. Harmonized terminology with definitions and use examples was created, reviewed, and validated.RESULTSWe present a standardized terminology to describe gene-disease relationships, and to support variant annotation. We demonstrate application of the terminology for classification of variation in the ACMG SF 2.0 genes recommended for reporting of secondary findings. Consensus terms were agreed and formalized in both sequence ontology (SO) and human phenotype ontology (HPO) ontologies. GenCC member groups intend to use or map to these terms in their respective resources.CONCLUSIONThe terminology standardization presented here will improve harmonization, facilitate the pooling of curation datasets across international curation efforts and, in turn, improve consistency in variant classification and genetic test interpretation.
Stochastic modeling of the dynamics ofSalmonellainfection of epithelial cells
Authors: Hannig Jennifer , Beygi Alireza , Ackermann Jörg , Amstein Leonie , Welsch Christoph , Ðikić Ivan , Koch Ina 
Published: April 2023

AbstractBacteria of theSalmonellagenus are intracellular pathogens, which cause gastroenteritis and typhoid fever in animals and humans, and are responsible for millions of infections and thousands of deaths across the world every year. Furthermore,Salmonellahas played the role of a model organism for studying host-pathogen interactions. Taking these two aspects into account, enormous efforts in the literature are devoted to study this intracellular pathogen. Within epithelial cells, there are two distinct subpopulations ofSalmonella: (i) a large fraction ofSalmonella, which are enclosed by vacuoles, and (ii) a small fraction of hyper-replicating cytosolicSalmonella. Here, by considering the infection of epithelial cells bySalmonellaas a discrete-state, continuous-time Markov process, we propose a stochastic model of infection, which includes the invasion ofSalmonellainto the epithelial cells by a cooperative strategy, the replication inside theSalmonella-containing vacuole, and the bacterial proliferation in the cytosol. The xenophagic degradation of cytosolic bacteria is considered, too. The stochastic approach provides important insights into stochastic variation and heterogeneity of the vacuolar and cytosolicSalmonellapopulations on a single-cell level over time. Specifically, we predict the percentage of infected human epithelial cells depending on the incubation time and the multiplicity of infection, an d the bacterial load of the infected cells at different post-infection times.
Reconstruction of Gene Regulatory Networks using sparse graph recovery models
Authors: Shrivastava Harsh 
Published: April 2023

AbstractThere is a considerable body of work in the field of computer science on the topic of sparse graph recovery, particularly with regards to the innovative deep learning approaches that have been recently introduced. Despite this abundance of research, however, these methods are often not applied to the recovery of Gene Regulatory Networks (GRNs). This work aims to initiate this trend by highlighting the potential benefits of using these computational techniques in the recovery of GRNs from single cell RNA sequencing or bulk sequencing based gene expression data. GRNs are directed graphs that capture the direct dependence between transcription factors (TFs) and their target genes. Understanding these interactions is vital for studying the mechanisms in cell differentiation, growth and development. We categorize graph recovery methods into four main types based on the underlying formulations: Regression-based, Graphical Lasso, Markov Networks and Directed Acyclic Graphs. We selected representative methods from each category and made modifications to incorporate transcription factor information as a prior to ensure successful reconstruction of GRNs.
Musculoskeletal phenotypes in 3q29 deletion syndrome
Authors: Pollak Rebecca M , Tilmon Jacob C , Murphy Melissa M , Gambello Michael J , Sanchez Russo Rossana , Dormans John P , Mulle Jennifer G 
Published: April 2023

Abstract3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000–197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry (3q29deletion.org) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 minutes or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population, suggesting 3q29del impacts bone strength. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome.
Acute kidney injury-induced circulating TNFR1/2 elevations correlate with persistent kidney injury and progression to fibrosis
Authors: Arthanarisami Akshayakeerthi , Komaru Yohei , Katsouridi Charikleia , Schumacher Julian , Verges Deborah K. , Ning Liang , Abdelmageed Mai M. , Herrlich Andreas , Kefaloyianni Eirini 
Published: April 2023

AbstractBackgroundElevated levels of circulating Tumor-Necrosis-Factor-Receptors 1 and 2 (cTNFR1/2) predict CKD progression. Whether acute kidney injury drives cTNFR1/2 elevations and whether they predict disease outcomes after AKI remains unknown.MethodsWe used AKI patient serum and urine samples, mouse models of kidney injury (ischemic, obstructive, toxic) and progression to fibrosis, nephrectomy, and related single cell RNA-sequencing datasets.ResultsWe show that TNFR1/2 serum and urine levels are highly elevated in all mouse models of kidney injury tested, beginning within one-hour post-injury, and correlate with its severity. Consistent with this, serum and urine TNFR1/2 levels are increased in AKI patients and correlate with severity of kidney failure. Interestingly, the extracellular vesicle (EV)-bound forms of cTNFR1/2 correlate with renal function better than their soluble forms. TNF neutralization does not affect early cTNFR1/2 elevations, suggesting that cTNFR1/2 levels do not reflect injury-induced TNF activity. Kidney tissue expression of TNFR1/2 after AKI is only mildly increased and bilateral nephrectomies lead to strong cTNFR1/2 elevations, suggesting release of these receptors by extrarenal sources. cTNFR1/2 remain elevated for weeks after severe kidney injury and at these later timepoints cTNFR1/2 correlate to remaining kidney injury. During AKI-to-CKD transition, kidney expression of TNFR1/2 and cTNFR2 levels, correlate with development of fibrosis.ConclusionsOur data demonstrate that AKI drives acute increases in cTNFR1/2 serum levels which negatively correlate with kidney function, in particular their EV-bound forms. Sustained TNFR1/2 elevations after kidney injury during AKI-to-CKD transition correlate with persistent tissue injury and progression to kidney fibrosis.Significance StatementCirculating TNF-Receptor-1 and -2 (cTNFR1/2) elevations predict chronic kidney disease progression. It remains unknown whether kidney injury can drive cTNFR1/2 elevations, whether cTNFR1/2 levels predict disease outcomes after AKI, and which are their circulating molecular forms. This study shows that kidney injury strongly increases cTNFR1/2 levels and that their extracellular vesicle-bound forms better correlate with kidney function loss, compared to their soluble forms. Sustained cTNFR1/2 elevations correlate to remaining kidney injury, and cTNFR1/2 levels post injury predict progression to kidney fibrosis. This work, thus, points to novel mechanisms for the observed cTNFR1/2 elevations in kidney disease and identifies unique predictive and diagnostic value in cTNFR1/2 elevations in AKI or AKI-to-CKD transition.
Endosome dysfunction leads to gain-of-function TLR7 and human lupus
Authors: Mishra Harshita , Schlack-Leigers Claire , Lim Ee Lyn , Thieck Oliver , Magg Thomas , Raedler Johannes , Wolf Christine , Klein Christoph , Ewers Helge , Lee-Kirsch Min Ae , Meierhofer David , Hauck Fabian , Majer Olivia 
Published: April 2023

AbstractHyperactive Toll-like receptor (TLR) 7 signaling has long been appreciated as a driver of autoimmune disease by breaking tolerance to self-nucleic acids in mouse models1–5. Recently, mutations in TLR7 or its associated regulator UNC93B16, 7, were identified as monogenic causes of human lupus; the unifying feature of these mutations being TLR7 gain-of-function. TLR7 is an intracellular transmembrane receptor, sensing RNA breakdown products within late endosomes8, 9. Hence, its function depends on intricate transport mechanisms and membrane interactions within the endomembrane network. Whether perturbations of any of these endosome-related processes can give rise to TLR7 gain-of-function and facilitate self-reactivity has not been investigated. Here, we show that a dysregulated endosomal compartment leads to unrestricted TLR7 signaling and human lupus. The late endosomal BLOC-1-related protein complex (BORC) together with the small Arf1-like GTPase Arl8b controls TLR7 protein levels, and a direct interaction between Arl8b and Unc93b1 is required to regulate TLR7 turnover. We identified an amino acid insertion in UNC93B1 in a patient with childhood-onset lupus, which reduces the interaction with the BORC-Arl8b complex and leads to endosomal TLR7 accumulation. Therefore, a failure to control the proper progression of TLR7 through its endocytic life cycle is sufficient to break immunological tolerance to nucleic acids in humans. Our results highlight the importance of an intact endomembrane system to prevent autoimmune disease. As the cellular mechanisms restricting TLR7 signaling can be manifold, identifying and stratifying lupus patients based on a TLR7-driven pathogenesis could be a viable strategy towards a targeted therapy.
Biological characterization of an emergent virus infecting vegetables in diversified production systems: physostegia chlorotic mottle virus
Authors: Temple Coline , Blouin Arnaud G. , Boezen Dieke , Botermans Marleen , Durant Laurena , De Jonghe Kris , de Koning Pier , Goedefroit Thomas , Minet Laurent , Steyer Stephan , Verdin Eric , Zwart Mark , Massart Sebastien 
Published: April 2023

AbstractWith the emergence of high throughput sequencing (HTS) technologies, the discovery of new plant viruses has outpaced their biological characterization. However, it is crucial to understand the biology of these viruses to evaluate the risks they pose for the production of crops and natural ecosystems and to manage them properly. In 2018, Physostegia chlorotic mottle virus (PhCMoV) was detected in Austria in aPhysostegiaplant (Lamiaceae) using HTS, and subsequent prepublication data sharing associated the presence of the virus with severe fruit symptoms on important crops like tomato, eggplant, and cucumber across nine European countries. This discovery led to a collaborative effort to understand better the virus’s genetic diversity, host range, symptomatology, and distribution. Still, specific knowledge gaps remained. In this study, the authors address these gaps by examining the transmission mode, prevalence, and disease severity of PhCMoV. Bioassay and field survey confirmed the causal association between the presence of the virus and symptoms on tomato and eggplant. The investigation also mapped out the historical and geographic footprint of the virus, spanning back 30 years and including a new location, Switzerland. Based on field survey, PhCMoV was found to naturally infect 11 new host plant species across seven families, extending the host range of PhCMoV to 20 plant species across 14 plant families. Greenhouse assays with mechanical inoculation showed that yield losses could reach 100% depending on the phenological stage of the plant at the time of infection. The study also identified a polyphagous leafhopper species (Anaceratagalliasp.) as the natural vector of PhCMoV. PhCMoV was widespread in diversified vegetable farms in Belgium where tomato is grown in soil, occurring in approximately one-third of such farms. However, outbreaks were sporadic and it can be suggested that they were associated with specific cultural practices, such as the cultivation of perennial plants in tomato tunnels that can serve as a host for both the virus and its vector. To further explore this phenomenon and better manage the virus, studying the ecology of theAnaceratagalliaevector would be beneficial.