bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applications of Machine Learning in Prognostication of Mild Traumatic Brain Injury
Authors: Yao Patrick F. , Gandhi Pranjan A. , McMullen Eric P. , Manka Marlin , Liang Jason 
Published: June 2024

Objective
The aim of the study is to review the literature regarding the current state and clinical applicability of machine learning models in prognosticating the outcomes of patients with mild traumatic brain injury in the early clinical presentation.

Design
Databases were searched for studies including machine learning and mild traumatic brain injury from inception to March 10, 2023. Included studies had a primary outcome of predicting post-mild traumatic brain injury prognosis or sequelae. The Prediction model study Risk of Bias for Predictive Models assessment tool was used for assessing the risk of bias and applicability of included studies.

Results
Out of 1235 articles, 10 met the inclusion criteria, including data from 127,929 patients. The most frequently used modeling techniques were support vector machine and artificial neural network and area under the curve ranged from 0.66 to 0.889. Despite promise, several limitations to studies exist such as low sample sizes, database restrictions, inconsistencies in patient presentation definitions, and lack of comparison to traditional clinical judgment or tools.

Conclusions
Machine learning models show potential in early stage mild traumatic brain injury prognostication, but to achieve widespread adoption, future clinical studies prognosticating mild traumatic brain injury using machine learning need to reduce bias, provide clarity and consistency in defining patient populations targeted and validate against established benchmarks.
Does Primary Cleft Palate Repair by Furlow Z-Plasty Technique With a Buccinator Myomucosal Flap Change Speech and Middle Ear Outcomes?
Authors: Elrouby Iman Mohamed , Aboulhassan Mamdouh Ahmed , Abdel Fattah Hassan Tarek , Refahee Shaimaa Mohsen 
Published: June 2024

Background:
Children with repaired cleft lip and palate may present with middle ear effusion and disturbed speech due to velopharyngeal (VP) insufficiency. Furlow Z-palatoplasty with a buccinator myomucosal flap is one of the effective surgical techniques for primary cleft palate repair and lengthening of the palate.

Purpose of the study:
This study aimed to evaluate the effect of Furlow Z-palatoplasty with buccal myomucosal flap as a primary cleft palate repair technique on the VP function during speech and the Eustachian tube function.

Materials and methods:
Forty patients with non-syndromic cleft lip and palate aged 3 to 7 years surgically repaired with Furlow palatoplasty with a buccinator myomucosal flap were assessed. Perceptual speech assessment, nasopharyngoscopic examination, otoscopic examination, and tympanometry were done for all patients to assess the speech and middle ear function.

Results:
The percentage of mild hypernasality was significant in 22.5% of children with repaired cleft lip and palate, while 77.5% showed no hypernasality. Speech intelligibility was normal in 77.5% and mildly affected in 22.5% of children with repaired cleft palate. Compensatory misarticulations were recorded in 12.5% of children. Nasopharyngoscopic examination revealed adequate VP closure in 75% of children with repaired cleft palate. Twenty-five percent of children with repaired cleft lip and palate had middle ear effusion and required myringotomy with insertion of tympanostomy tubes.

Conclusion:
Primary cleft palate repair with Furlow Z-palatoplasty with buccal myomucosal flap had beneficial effects on speech outcomes. It was associated with a low prevalence of middle ear effusion, and a low number of tympanostomy tubes were needed.
Associations between gas stove usage and childhood asthma symptoms, attacks, and ED visits among children in the 2020 Asthma Call-back Survey
Authors: LeSon Sydney , Rosenthal Samantha 
Published: June 2024

AbstractObjectiveTo examine whether the use of gas stoves in the home is associated with increased asthma severity among children and adolescents ages 0-17 in the US.MethodsUsing the 2020 CDC Asthma Call-Back Survey for children, the association between gas stove usage and childhood asthma symptoms, asthma attack or episode, and emergency department visit for asthma was assessed. With a cross-sectional study design, bivariate analyses and multivariable logistic regression were conducted. Survey weights were used in the analyses for US population-based estimates.ResultsChildren who live in a household that uses gas for cooking or has a gas stove had 1.133 (95% CI: 0.48, 2.68)) times the odds of having an asthma attack or episode within the past 12 months, 9.141 (95% CI: 1.99, 42.06) times the odds of having visited the emergency department or urgent care within the past 12 months, and 1.739 (95% CI: 1.02, 2.95) times the odds of recent symptoms of asthma compared to children who live in a household that does not use gas for cooking or does not have a gas stove, controlling for all confounders. There is an association between the usage of gas stoves and asthma symptoms, asthma attacks/episodes, and ED visits among asthmatic children. Reducing the exposure of gas stove usage should be a consideration in regards to existing and future interventions to prevent childhood asthma and reduce exacerbation of underlying childhood asthma.
Longitudinal risk prediction for pediatric glioma with temporal deep learning
Authors: Tak Divyanshu , Garomsa Biniam A. , Zapaishchykova Anna , Ye Zezhong , Vajapeyam Sri , Mahootiha Maryam , Climent Pardo Juan Carlos , Smith Ceilidh , Familiar Ariana M. , Chaunzwa Tafadzwa , Liu Kevin X. , Prabhu Sanjay , Bandopadhayay Pratiti , Nabavizadeh Ali , Mueller Sabine , Aerts Hugo JWL , Haas-Kogan Daphne , Poussaint Tina Y. , Kann Benjamin H. 
Published: June 2024

ABSTRACTPediatric glioma recurrence can cause morbidity and mortality; however, recurrence pattern and severity are heterogeneous and challenging to predict with established clinical and genomic markers. Resultingly, almost all children undergo frequent, long-term, magnetic resonance (MR) brain surveillance regardless of individual recurrence risk. Deep learning analysis of longitudinal MR may be an effective approach for improving individualized recurrence prediction in gliomas and other cancers but has thus far been infeasible with current frameworks. Here, we propose a self-supervised, deep learning approach to longitudinal medical imaging analysis, temporal learning, that models the spatiotemporal information from a patient’s current and prior brain MRs to predict future recurrence. We apply temporal learning to pediatric glioma surveillance imaging for 715 patients (3,994 scans) from four distinct clinical settings. We find that longitudinal imaging analysis with temporal learning improves recurrence prediction performance by up to 41% compared to traditional approaches, with improvements in performance in both low- and high-grade glioma. We find that recurrence prediction accuracy increases incrementally with the number of historical scans available per patient. Temporal deep learning may enable point-of-care decision-support for pediatric brain tumors and be adaptable more broadly to patients with other cancers and chronic diseases undergoing surveillance imaging.
MIAI: Maturation of Immunity Against Influenza - a German birth cohort study with focus on the development of immunity against respiratory viral infections
Authors: Hartmann Carina R. , Khan Robin , Schöning Jennifer , Richter Maximilian , Willers Maike , Pirr Sabine , Heckmann Julia , Dirks Johannes , Morbach Henner , Konrad Monika , Fries Elena , Winkler Magdalene , Büchel Johanna , Seidenspinner Silvia , Fischer Jonas , Vollmuth Claudia , Meinhardt Martin , Marissen Janina , Schmolke Mirco , Haid Sibylle , Pietschmann Thomas , Backes Simone , Dölken Lars , Löber Ulrike , Keil Thomas , Heuschmann Peter U. , Wöckel Achim , Sagar  , Ulas Thomas , Forslund-Startceva Sofia K. , Härtel Christoph , Viemann Dorothee 
Published: June 2024

AbstractRespiratory viral infections (RVIs) are a major global contributor to morbidity and mortality. The susceptibility and outcome of RVIs are strongly age-dependent and show considerable inter-population differences, pointing to genetically and/or environmentally driven developmental variability. The factors determining the age-dependency and shaping the age-related changes of human anti-RVI immunity after birth are still elusive. We are conducting a prospective birth cohort study aiming at identifying endogenous and environmental factors associated with the susceptibility to RVIs and their impact on cellular and humoral immune responses against the influenza A virus (IAV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MIAI birth cohort enrolls healthy, full-term neonates born at the University Hospital Würzburg, Germany, with follow-up at four defined time-points during the first year of life. At each study visit, clinical metadata including diet, lifestyle exposures, sociodemographic information, and physical examinations, are collected along with extensive biomaterial sampling. Biomaterials are used to generate comprehensive, integrated multi-omics datasets including transcriptomic, epigenomic, proteomic, metabolomic and microbiomic methods. The results are expected to capture a holistic picture of the variability of immune trajectories with a focus on cellular and humoral key players involved in the defense of RVIs and the impact of host and environmental factors thereon. Thereby, MIAI aims at providing insights that allow unraveling molecular mechanisms that can be targeted to promote the development of competent anti-RVI immunity in early life and prevent severe RVIs.Trial registration number:DRKS00034278
Genotype-first analysis in an unselected health system-based population reveals variable phenotypic severity ofCOL4A5variants
Authors: Zellers McKenzie , Solanki Kaushal , Kelly Melissa A , Murphy Karyn M , Retterer Kyle , Kirchner H. Les , Bucaloiu Ion Dan , Moore Bryn , Mirshahi Tooraj , Chang Alexander R 
Published: June 2024

AbstractIntroductionOur knowledge of X-linked Alport Syndrome [AS] comes mostly from selected cohorts with more severe disease.MethodsWe examined the phenotypic spectrum of X-linked AS in males and females with a genotype-based approach using data from the Geisinger MyCode DiscovEHR study, an unselected health system-based cohort with exome sequencing and electronic health records. Patients withCOL4A5variants reported as pathogenic (P) or likely pathogenic (LP) in ClinVar, or protein-truncating variants (PTVs), were each matched with up to 5 controls withoutCOL4A3/4/5variants by sociodemographics, diabetes diagnosis, and year of first outpatient encounter. AS-related phenotypes included dipstick hematuria, bilateral sensorineural hearing loss (BSHL), proteinuria, decreased eGFR, and ESKD.ResultsOut of 170,856 patients, there were 29 hemizygous males (mean age 52.0 y [SD 20.0]) and 55 heterozygous females (mean age 59.3 y [SD 18.8]) with aCOL4A5P/LP variant, including 48 with the hypomorphic variant p.Gly624Asp. Overall, penetrance (having any AS phenotypic feature) was highest for non-p.Gly624Asp P/LP variants (males: 94%, females: 85%), intermediate for p.Gly624Asp (males: 77%, females: 69%), compared to controls (males: 32%; females: 50%). The proportion with ESKD was highest for males with P/LP variants (44%), intermediate for males with p.Gly624Asp (15%) and females with P/LP variants (10%), compared to controls (males: 3%, females 2%). Only 47% of individuals withCOL4A5had completed albuminuria screening, and a minority were taking renin-angiotensin aldosterone system (RAAS) inhibitors. Only 38% of males and 16% of females had a known diagnosis of Alport syndrome or thin basement membrane disease.ConclusionIn an unselected cohort, we show increased risks of AS-related phenotypes in men and women compared to matched controls, while showing a wider spectrum of severity than has been described previously and variability by genotype. Future studies are needed to determine whether early genetic diagnosis can improve outcomes in Alport Syndrome.
Performance of a Protein Language Model for Variant Annotation in Cardiac Disease
Authors: Hochstadt Aviram , Barbhaiya Chirag , Aizer Anthony , Bernstein Scott , Cerrone Marina , Garber Leonid , Holmes Douglas , Knotts Robert J , Kushnir Alex , Martin Jacob , Park David , Spinelli Michael , Yang Felix , Chinitz Larry A , Jankelson Lior 
Published: June 2024

AbstractIntroductionGenetic testing is a cornerstone in the assessment of many cardiac diseases. However, variants are frequently classified as Variants of Unknown Significance (VUS), limiting the utility of testing.Recently, the DeepMind group (Google, USA) developed AlphaMissense, a unique Artificial Intelligence (AI) based model, based on language model principles for the prediction of missense variant pathogenicity.ObjectiveTo report on the performance of AlphaMissense, accessed by VarCardio, an open web-based variant annotation engine, in a real-world cardiovascular genetics center.MethodsAll genetic variants from an inherited arrhythmia program were examined using AlphaMissense via VarCard.io and compared to the ClinVar variant classification system, as well as another variant classification platform (Franklin by Genoox). The mutation reclassification rate and genotype phenotype concordance were examined for all variants in the study.ResultsWe included 266 patients with heritable cardiac diseases, harboring 339 missense variants. Of those, 230 (67.8%) were classified by ClinVar as either VUS or non-classified. Using VarCard.io, 198 VUSs (86.1%, CI 80.9-90.3%) were reclassified to either Likely Pathgenic (LP) or Likely benign (LB). The reclassification rate was significantly higher for VarCard.io than for Franklin (86.1% vs 34.8%, p<0.001).Genotype-Phenotype concordance was highly aligned using VarCard.io predictions, at 95.9% (CI 92.8-97.9%) concordance rate. For 109 variants classified as Pathogenic, LP, Benign or LB by ClinVar, concordance with VarCard.io was high (90.5%).ConclusionAlphaMissense, accessed via VarCard.io, may be a highly efficient tool for cardiac genetic variant interpretation. The engine’s notable performance in assessing variants that are classified as VUS in ClinVar, demonstrates its potential to enhance cardiac genetic testing.
Unravelling the Dynamics of Bacterial-Laden Respiratory Droplets: Epidemiological Transfer from Fomites to Susceptible Host
Authors: Rasheed Abdur , Parmar Kirti , Poopady Jason Joy , Jain Siddhant , Chakravortty Dipshikha , Basu Saptarshi 
Published: June 2024

AbstractThis study provides the first comprehensive investigation into how pathogen-laden respiratory droplets transfer diseases via inanimate surfaces. Respiratory fluid ejections containing pathogens pose a significant health threat, especially in high-traffic areas like hospitals, public transport, restaurants, and schools. When these droplets dry on surfaces, they form deposits that can transfer pathogens to healthy individuals through contact and can be ingested via the oral or nasal route. The study examined the effects of varying salt and mucin concentrations in respiratory fluid droplets containingPseudomonas aeruginosa(PA). Results showed that PA viability increased tenfold at elevated mucin concentrations, while changes in salt concentration had minimal impact. Adhesive properties of the deposits were analysed using atomic force spectroscopy and scotch tape test. Pathogen transfer from the deposit to a fingerprint patterned model thumb at different relative humidity (RH) levels was assessed using confocal microscopy, showing significant pathogen transfer at elevated RH. Out of 106CFU/ml pathogens in deposits, 17% to 38% are potentially transferable, with most of the transfer occurring from the droplet’s edge deposits. The study also explored evaporation, internal flow, and precipitation dynamics, with deposit and pathogen distribution characterized by optical profilometry, scanning electron microscopy, and confocal microscopy.
Studies of infused megakaryocytes into mice support a “catch-and-release” model of pulmonary-centric thrombopoiesis
Authors: Kim Hyunjun , Jarocha Danuta , Johnson Ian , Ahn Hyunsook , Hlinka Nicholas , French Deborah L. , Rauova Lubica , Lee Kiwon , Poncz Mortimer 
Published: June 2024

AbstractMany aspects of thrombopoiesis, the release of platelets from megakaryocytes (Mks), remain under debate, including where this process occurs. Murine lungin situ-microscopy studies suggested that a significant fraction of circulating platelets were released from lung-entrapped, marrow-derived Mks. We now confirm thesein situstudies that endogenous mMks are entrapped in the lungs and show that intravenously infusedin vitro-differentiated, mature murine (m) and human (h) Mks are similarly entrapped followed by shedding of their cytoplasm over ∼30 minutes with a peak number of released platelets occurring 1.5-4 hours later. However, while infused Mks from both species shed large intrapulmonary cytoplasmic fragments that underwent further processing into platelet-sized fragments, the two differed: many mMks escaped from and then recycled back to the lungs, while most hMks were enucleated upon first intrapulmonary passage. Infused immature hMks, inflammatory hMks, umbilical cord-blood-derived hMks and immortalized Mk progenitor cell (imMKCL)-derived hMks were also entrapped in the lung of recipient mice, and released their cytoplasm, but did so to different degrees. Intraarterial infused hMks resulted in few Mks being entrapped in tissues other than the lungs and was accompanied by a blunted and delayed rise in circulating human platelets. These studies demonstrate that the lung entraps and processes both circulating Mks and released large cytoplasmic fragments consistent with a recent lung/heart murine study and support a pulmonary-centric “catch-and-release” model of thrombopoiesis. Thus, thrombopoiesis is a drawn-out process with the majority of cytoplasmic processing derived from Mks occurring in the pulmonary bed.Key PointsInfusedin vitro-differentiated megakaryocytes synchronously release cytoplasmic fragments highly selectively in the pulmonary bed.Large, released megakaryocyte fragments recycle to the lungs, undergo further fission, terminally form platelets.
Growth-induced physiological hypoxia correlates with growth deceleration during normal development
Authors: Zhao Yifan , Alexandre Cyrille , Kelly Gavin , Perez-Mockus Gantas , Vincent Jean-Paul 
Published: June 2024

ABSTRACTGrowth deceleration is a universal feature of growth during development: most organs and tissues slow down their growth rate much before growth termination. Using transcriptomics analysis, we show that during their two-day period of growth deceleration, wing imaginal discs ofDrosophilaundergo a progressive metabolic shift away from oxidative phosphorylation and towards glycolysis. We then develop an ultra-sensitive reporter HIF-1α activity, which reveals that imaginal discs become increasingly hypoxic during development in normoxic conditions, suggesting that limiting oxygen supply could underlie growth deceleration. Growth is energetically expensive and thus expected to contribute, indirectly, to oxygen consumption. Indeed, excess TOR signalling, a key stimulator of growth, triggers hypoxia locally and systemically, highlighting the need to rein in growth when oxygen becomes limiting. This is achieved by a negative feedback loop whereby the classic TOR-inhibitory function of HIF-1α is deployed in response to developmental hypoxia. The absence of Sima/HIF-1α leads to cellular stress, which is alleviated by reduced TOR signalling. Conversely, a small increase in oxygen supply reduces the stress induced by excess TOR activity. We conclude that mild hypoxia is a normal feature of organ development and that Sima/HIF-1α prevents growth-induced oxygen demand from exceeding supply.
Heterogeneous shedding and susceptibility in aCaenorhabditis eleganstransmission model
Authors: Vega Nic M. 
Published: June 2024

AbstractVariation in transmission plays a crucial role in shaping the dynamics of infectious diseases. Population heterogeneity is known to contribute to this variation and is often represented in epidemiological models. However, it is not always cleara prioriwhat sources of variation should contribute meaningfully to a given scenario, and it can be challenging to infer distributions of underlying processes from data. In this study, we demonstrate the use ofCaenorhabditis elegansas a tractable system in which high-quality data can be produced for experimental epidemics. We show that distributions of shedding and susceptibility in this host can be experimentally decoupled to measure heterogeneity in transmission processes. We observe and quantify super-shedding and heterogeneous susceptibility, and we show that distributions of population heterogeneity and transmission outcomes have features conserved with real-world epidemics. Our results quantify sources of heterogeneity in bacterial transmission in this small model organism and establishC. elegansas a promising quantitative model for experimental epidemics.
A frameshift mutation in the murinePrkragene causes dystonia and exhibits abnormal cerebellar development and reduced eIF2α phosphorylation
Authors: Burnett Samuel B. , Culver Allison M. , Simon Tricia A. , Rowson Taylor , Frederick Kenneth , Palmer Kristina , Murray Stephen A , Davis Shannon W. , Patel Rekha C. 
Published: June 2024

ABSTRACTMutations inPrkragene, which encodes PACT/RAX cause early onset primary dystonia DYT-PRKRA, a movement disorder that disrupts coordinated muscle movements. PACT/RAX activates protein kinase R (PKR, aka EIF2AK2) by a direct interaction in response to cellular stressors to mediate phosphorylation of the α subunit of the eukaryotic translation initiation factor 2 (eIF2α). Mice homozygous for a naturally arisen, recessively inherited frameshift mutation,Prkralear-5Jexhibit progressive dystonia. In the present study, we investigate the biochemical and developmental consequences of thePrkralear-5Jmutation. Our results indicate that the truncated PACT/RAX protein retains its ability to interact with PKR, however, it inhibits PKR activation. Furthermore, mice homozygous for the mutation have abnormalities in the cerebellar development as well as a severe lack of dendritic arborization of Purkinje neurons. Additionally, reduced eIF2α phosphorylation is noted in the cerebellums and Purkinje neurons of the homozygousPrkralear-5Jmice. These results indicate that PACT/RAX mediated regulation of PKR activity and eIF2α phosphorylation plays a role in cerebellar development and contributes to the dystonia phenotype resulting from this mutation.Summary StatementThis study shows, for the first time, a role of reduced eIF2α phosphorylation in DYT-PRKRA and the cerebellum development in a mouse model.