bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping polarization sensitive optical coherence tomography and ultra-high-field diffusion MRI in the macaque brain
Authors: Pisharady Pramod K , Yeatts Marilyn , Farooq Hamza , Johnson Matthew , Harel Noam , Moeller Steen , Zimmermann Jan , Yacoub Essa , Ugurbil Kamil , Heilbronner Sarah R. , Lenglet Christophe , Akkin Taner 
Published: April 2024

AbstractThis paper provides comparisons between microstructure and two-dimensional fiber orientations measured optically using polarization sensitive optical coherence tomography (PS-OCT) and those estimated from ultra-high-field diffusion MRI (dMRI) at 10.5T in the macaque brain. The PS-OCT imaging is done at an in-plane resolution of ∼10 microns in and around the thalamus. Whole brain dMRI is acquired at an isotropic resolution of 0.75 mm. We provide comparisons between cross-polarization and optical orientation from PS-OCT with the fractional anisotropy and two-dimensional orientations extracted from dMRI using a diffusion tensor model. The orientations from PS-OCT are also extracted computationally using a structure tensor. Additionally, we demonstrate the utility of mesoscale, PS-OCT imaging in improving the MRI resolution by learning the mapping between these contrasts using a super-resolution Generative Adversarial Network.
A deep intronic variant inMMEcauses autosomal recessive Charcot-Marie-Tooth neuropathy through aberrant splicing
Authors: Grosz Bianca R , Parmar Jevin M , Ellis Melina , Bryen Samantha , Simons Cas , Reis Andre L.M. , Stevanovski Igor , Deveson Ira W. , Nicholson Garth , Laing Nigel , Wallis Mathew , Ravenscroft Gianina , Kumar Kishore R. , Vucic Steve , Kennerson Marina L 
Published: April 2024

AbstractBackgroundLoss-of-function variants inMME(membrane metalloendopeptidase) are a known cause of recessive Charcot-Marie-Tooth Neuropathy (CMT). A deep intronic variant,MMEc.1188+428A>G (NM_000902.5), was identified through whole genome sequencing (WGS) of two Australian families with recessive inheritance of axonal CMT using the seqr platform.MMEc.1188+428A>G was detected in a homozygous state in Family 1, and in a compound heterozygous state with a known pathogenicMMEvariant (c.467del; p.Pro156Leufs*14) in Family 2.AimsWe aimed to determine the pathogenicity of theMMEc.1188+428A>G variant through segregation and splicing analysis.MethodsThe splicing impact of the deep intronicMMEvariant c.1188+428A>G was assessed using anin vitroexon-trapping assay.ResultsThe exon-trapping assay demonstrated that theMMEc.1188+428A>G variant created a novel splice donor site resulting in the inclusion of an 83 bp pseudoexon betweenMMEexons 12 and 13. The incorporation of the pseudoexon intoMMEtranscript is predicted to lead to a coding frameshift and premature termination codon (PTC) inMMEexon 14 (p.Ala397ProfsTer47). This PTC is likely to result in nonsense mediated decay (NMD) ofMMEtranscript leading to a pathogenic loss-of-function.InterpretationTo our knowledge, this is the first report of a pathogenic deep intronicMMEvariant causing CMT. This is of significance as deep intronic variants are missed using whole exome sequencing screening methods. Individuals with CMT should be reassessed for deep intronic variants, with splicing impacts being considered in relation to the potential pathogenicity of variants.
Characterization of age-associated inflammasome activation reveals tissue specific differences in transcriptional and post-translational inflammatory responses
Authors: Talley Sarah , Nguyen Tyler , Van Ye Lily , Valiauga Rasa , DeCarlo Jake , Mustafa Jabra , Cook Benjamin , White Fletcher A , Campbell Edward M. 
Published: April 2024

AbstractAging is associated with systemic chronic, low-grade inflammation, termed ‘inflammaging’. This pattern of inflammation is multifactorial and is driven by numerous inflammatory pathways, including the inflammasome. However, most studies to date have examined changes in the transcriptomes that are associated with aging and inflammaging, despite the fact that inflammasome activation is driven by a series of post-translational activation steps, culminating in the cleavage and activation of caspase-1. Here, we utilized transgenic mice expressing a caspase-1 biosensor to examine age-associated inflammasome activation in various organs and tissues to define these post-translational manifestations of inflammaging. Consistent with other studies, we observe increased inflammation, including inflammasome activation, in tissues. However, we note that the degree of inflammasome activation is not uniformly correlated with transcriptional changes commonly used as a surrogate for inflammasome activation in tissues. Furthermore, we used a skull thinning technique to monitor central nervous system inflammasome activationin vivoin aged mice and found that neuroinflammation is significantly amplified in aged mice in response to endotoxin challenge. Together, these data reveal that inflammaging is associated with both transcriptional and post-translational inflammatory pathways that are not uniform between tissues and establish new methodologies for measuring age-associated inflammasome activationin vivoandex vivo.
Holistic AI analysis of hybrid cardiac perfusion images for mortality prediction
Authors: Michalowska Anna M , Zhang Wenhao , Shanbhag Aakash , Miller Robert JH , Lemley Mark , Ramirez Giselle , Buchwald Mikolaj , Killekar Aditya , Kavanagh Paul B , Feher Attila , Miller Edward J , Einstein Andrew J , Ruddy Terrence D , Liang Joanna X , Builoff Valerie , Ouyang David , Berman Daniel S , Dey Damini , Slomka Piotr J 
Published: April 2024

AbstractBackgroundWhile low-dose computed tomography scans are traditionally used for attenuation correction in hybrid myocardial perfusion imaging (MPI), they also contain additional anatomic and pathologic information not utilized in clinical assessment. We seek to uncover the full potential of these scans utilizing a holistic artificial intelligence (AI)-driven image framework for image assessment.MethodsPatients with SPECT/CT MPI from 4 REFINE SPECT registry sites were studied. A multi-structure model segmented 33 structures and quantified 15 radiomics features for each on CT attenuation correction (CTAC) scans. Coronary artery calcium and epicardial adipose tissue scores were obtained from separate deep-learning models. Normal standard quantitative MPI features were derived by clinical software. Extreme Gradient Boosting derived all-cause mortality risk scores from SPECT, CT, stress test, and clinical features utilizing a 10-fold cross-validation regimen to separate training from testing data. The performance of the models for the prediction of all-cause mortality was evaluated using area under the receiver-operating characteristic curves (AUCs).ResultsOf 10,480 patients, 5,745 (54.8%) were male, and median age was 65 (interquartile range [IQR] 57-73) years. During the median follow-up of 2.9 years (1.6-4.0), 651 (6.2%) patients died. The AUC for mortality prediction of the model (combining CTAC, MPI, and clinical data) was 0.80 (95% confidence interval [0.74-0.87]), which was higher than that of an AI CTAC model (0.78 [0.71-0.85]), and AI hybrid model (0.79 [0.72-0.86]) incorporating CTAC and MPI data (p<0.001 for all).ConclusionIn patients with normal perfusion, the comprehensive model (0.76 [0.65-0.86]) had significantly better performance than the AI CTAC (0.72 [0.61-0.83]) and AI hybrid (0.73 [0.62-0.84]) models (p<0.001, for all).CTAC significantly enhances AI risk stratification with MPI SPECT/CT beyond its primary role - attenuation correction. A comprehensive multimodality approach can significantly improve mortality prediction compared to MPI information alone in patients undergoing cardiac SPECT/CT.
A Generative Model For Evaluating Missing Data Methods in Large Epidemiological Cohorts
Authors: Radosavljević Lav , Smith Stephen M. , Nichols Thomas E. 
Published: April 2024

AbstractBackgroundThe potential value of large scale datasets is constrained by the ubiquitous problem of missing data, arising in either a structured or unstructured fashion. When imputation methods are proposed for large scale data, one limitation is the simplicity of existing evaluation methods. Specifically, most evaluations create synthetic data with only a simple, unstructured missing data mechanism which does not resemble the missing data patterns found in real data. For example, in the UK Biobank missing data tends to appear in blocks, because non-participation in one of the sub-studies leads to missingness for all sub-study variables.MethodsWe propose a method for generating mixed type missing data mimicking key properties of a given real large scale epidemiological data set with both structured and unstructured missingness while accounting for informative missingness. The process involves identifying sub-studies using hierarchical clustering of missingness patterns and modelling the dependence of inter-variable correlation and co-missingness patterns.ResultsOn the UK Biobank brain imaging cohort, we identify several large blocks of missing data. We demonstrate the use of our method for evaluating several imputation methods, showing modest accuracy of imputation overall, with iterative imputation having the best performance. We compare our evaluations based on synthetic data to an exemplar study which includes variable selection on a single real imputed dataset, finding only small differences between the imputation methods though with iterative imputation leading to the most informative selection of variables.ConclusionsWe have created a framework for simulating large scale data with that captures the complexities of the inter-variable dependence as well as structured and unstructured informative missingness. Evaluations using this framework highlight the immense challenge of data imputation in this setting and the need for improved missing data methods.
A Qualitative Interview Study of General Practitioners’ Experiences of Managing Post-COVID-19 Syndrome
Authors: Schulze Josefine , Lind Lennart , Rojas Alina , Lüdtke Laura , Hensen Jens , Bergelt Corinna , Härter Martin , Pohontsch Nadine Janis 
Published: April 2024

AbstractBackgroundThe management of the long-term sequelae of COVID-19 infection, known as post-COVID-19 syndrome (PCS), continues to challenge the medical community, largely due to a significant gap in the understanding of its aetiology, diagnosis and effective treatment.AimTo examine general practitioners’ (GPs) experiences of caring for patients with PCS and to identify unmet care needs and opportunities for improvement.Design and settingThis study follows a qualitative design, using in-depth semi-structured telephone interviews with GPs (N=31) from across Germany.MethodInterviews were audio-recorded, transcribed verbatim and analysed using qualitative content analysis.ResultsPatients with persistent symptoms after SARS-CoV-2 infection often consult their GPs as the first point of contact, with symptoms typically resolving within weeks. While ongoing symptomatic COVID-19 is perceived to be more common, the relevance of PCS to GP practices is considerable given its severe impact on patients’ functioning, social participation, and the substantial time required for patient care. GPs coordinate diagnosis and treatment, but face difficulties because of the unclear definition of PCS and difficulties in attributing symptoms, resulting in a cautious approach to ICD-10 coding. Interviewees highlight lengthy diagnostic pathways and barriers to accessing specialist care.ConclusionThe findings confirm the high functional limitations and psychosocial burden of PCS on patients and the central role of GPs in their care. The study suggests a need for further research and health policy measures to support GPs in navigating diagnostic uncertainty, interprofessional communication and the limited evidence on effective treatments.How this fits inPost-COVID-19 syndrome has garnered attention in research and healthcare, but limited evidence on its causes and effective treatment challenges clinicians. This study illustrates the symptom-driven approaches to diagnosis and treatment adopted by general practitioners and their concerns about referring patients to specialist clinics. Greater collaboration and communication across sectors and disciplines is needed to meet the identified need for interprofessional care. Research should also focus on developing comprehensive differential diagnostic protocols, and health policy should address barriers to accessing specific outpatient services.
Mitochondrial genome variants associated with Amyotrophic Lateral Sclerosis and their haplogroup distribution
Authors: Briones Marcelo R. S. , Campos João H. , Ferreira Renata C. , Schneper Lisa , Santos Ilda M. , Antoneli Fernando M. ,   NYGC ALS Consortium, Broach James R. 
Published: April 2024

AbstractIntroduction/AimsAmyotrophic lateral sclerosis (ALS) may be familial or sporadic, and twin studies have revealed that even sporadic forms have a significant genetic component. Variants in 55 nuclear genes have been associated with ALS and although mitochondrial disfunction is observed in ALS, variants in mitochondrial genomes (mitogenomes) have not yet been tested for association with ALS.MethodsHere we conducted a genome wide association study (GWAS) in mitogenomes of 1,965 ALS patients and 2,547 controls to test the hypothesis that mitogenome variants are associated with ALS.ResultsWe identified 51 mitogenome variants withp-values <10−7of which 13 variants have odds ratios (OR)>1, in genesRNR1,ND1,CO1,CO3,ND5,ND6andCYB, while 38 variants have OR<1 in genesRNR1,RNA2,ND1,ND2,CO2,ATP8,ATP6,CO3,ND3,ND4,ND5,ND6andCYB. The frequencies of haplogroups H, U and L, the most frequent in our ALS dataset, are the same in different onset sites (bulbar, limb, spinal and axial). Also, intra-haplogroup GWAS revealed unique ALS-associated variants in haplogroups L and U.DiscussionOur study shows that mitogenome variants (SNVs) are associated with ALS and suggests that these SNVs could be included in routine genetic testing for ALS and that mitochondrial replacement therapy would have a potential basis for ALS treatment.
Race is not Associated with Medical Emergency Team Evaluation Prior to In-Hospital Cardiac Arrest
Authors: Gathers Cody-Aaron L. , Morgan Ryan W. , Alvey Jessica S. , Reeder Ron , Goldberger Zachary D. , Fowler Jessica , Naim Maryam Y. , O’Halloran Amanda , Merchant Raina M. , Kienzle Martha , Nadkarni Vinay , Berg Robert A. , Sutton Robert M. ,   the American Heart Association’s Get With The Guidelines®-Resuscitation Investigators
Published: April 2024

AbstractBackgroundBlack patients have worse outcomes after in-hospital cardiac arrest (IHCA). Whether these racial disparities are associated with medical emergency team (MET) evaluation prior to IHCA remains unknown.MethodsA retrospective cohort study of adults age ≥ 18 years from the American Heart Association Get With The Guidelines® Resuscitation registry who had an IHCA between 2000 and 2021 with acute physiologic decline (modified early warning score [MEWS] ≥ 3) during the 24 hours prior to IHCA. A propensity-weighted cohort was constructed to balance confounders between Black and White patients. The association between race and MET evaluation was quantified with weighted multivariable logistic regression.ResultsAmong 354,480 patients, 88,507 met the initial inclusion criteria, of which 29,714 patients (median age 69 [IQR 58-79] years, 42.5% female, and 26.9% Black) had acute physiologic decline during the 24 hours prior to IHCA. Among patients with acute physiologic decline, 4102 (13.8%) patients had a preceding MET evaluation before IHCA. Rates of MET evaluation prior to cardiac arrest did not differ significantly between Black and White patients with acute physiologic decline (aOR 1.02, 95% CI 0.94-1.11, p = 0.62).ConclusionsThough racial disparities in IHCA outcomes exist, this study did not detect a difference in rates of MET evaluation prior to IHCA among patients with acute physiologic decline as a potential mechanism for these disparities.Clinical Perspective What Is New?With the goal to identify potential mechanisms leading to racial disparities in outcomes from adult in-hospital cardiac arrest (IHCA), this multicenter prospective observational study is the first study to analyze the association between race and medical emergency team (MET) evaluation among patients with evidence of clinical deterioration. IHCAWe found that rates of MET evaluation among patients with clinical deterioration (i.e., vital sign abnormalities) prior to IHCA did not differ between Black and White patients.What Are the Clinical Implications?These data demonstrate that race is not associated with MET evaluation prior to adult in-hospital cardiac arrest.Future studies should evaluate other links in the American Heart Association’s in-hospital chain of survival (e.g., resuscitation quality, post-arrest care) as potential targets to mitigate racial disparities in IHCA survival.
Hemato-Chemical Variations- A Diagnostic Tool for Babesia, Theileria and Anaplasma Infections in Captive Hog Deer (Axis Porcinus)
Authors: Azhar Muhammad , Saleem Muhammad Hassan , Safdar Ayesha , Khan Muhammad Rizwan , Khan Bushra Nisar , Fatima Rida , Awan Furqan , Khalid Muhammad Mujahid , Nadeem Junaid 
Published: April 2024

ABSTRACTHog deer are an essential component of Pakistan’s biodiversity. Their conservation helps maintain integrity of local ecosystems, contributing to overall stability and balance of region’s wildlife populations. In Pakistan, they are classified as an endangered species according to IUCN. Theileria, babesia and anaplasma are among most prevalent blood parasites in ruminants which require diagnosis at early stages of the infection so that treatment protocols can be followed and more severe pathological alterations can be prevented. The changes in hemato-chemical parameters caused by Theileria, babesia and anaplasma were recorded individually and then compared with healthy group of hog deer respectively. Alterations in hemato-chemical parameters produced by these parasite-infected hog deer were assessed as potential diagnostic tools for distinguishing between individual blood parasites. Total leukocyte count, monocytes and eosinophils were observed to be higher than normal in babesia infected hog deer while level was lower than normal hog deer in anaplasma and theileria infected hog deer. The main objective of this study is to promote early diagnosis of parasitic infections in hog deer to facilitate prompt treatment, pathological prevention and allocate resources for further research on hemato-chemical parameters as diagnostic tools, enhancing understanding and management of blood parasite infections in hog deer.
An imbalance between proliferation and differentiation underlies the development of microRNA-defective pineoblastoma
Authors: Fraire Claudette R. , Desai Kavita , Obalapuram Uma A. , Mendyka Lindsay K. , Rajaram Veena , Sebastian Teja , Wang Yemin , Onel Kenan , Lee Jeon , Skapek Stephen X. , Chen Kenneth S. 
Published: April 2024

ABSTRACTMutations in the microRNA processing genesDICER1andDROSHAdrive several cancers that resemble embryonic progenitors. To understand how microRNAs regulate tumorigenesis, we ablatedDroshaorDicer1in the developing pineal gland to emulate the pathogenesis of pineoblastoma, a brain tumor that resembles undifferentiated precursors of the pineal gland. Accordingly, these mice develop pineal tumors marked by loss of microRNAs, including the let-7/miR-98-5p family, and de-repression of microRNA target genes. Pineal tumors driven by loss ofDroshaorDicer1mimic tumors driven byRb1loss, as they exhibit upregulation of S-phase genes and homeobox transcription factors that regulate pineal development. Blocking proliferation of these tumors facilitates expression of pinealocyte maturation markers, with a concomitant reduction in embryonic markers. Select embryonic markers remain elevated, however, as the microRNAs that normally repress these target genes remain absent. One such microRNA target gene is the oncofetal transcription factorPlagl2, which regulates expression of pro-growth genes, and inhibiting their signaling impairs tumor growth. Thus, we demonstrate that tumors driven by loss of microRNA processing may be therapeutically targeted by inhibiting downstream drivers of proliferation.
Cardiorespiratory exercise and self-management early after stroke to increase daily physical activity: results from a stepped-wedge cluster randomized trial
Authors: Devasahayam Augustine J. , Tang Ada , Taylor Denise , Inness Elizabeth L. , Fleck Rebecca , French Esmé , Jagroop David , Danells Cynthia , Mansfield Avril 
Published: April 2024

ABSTRACTTrial designStepped-wedge cluster superiority randomized controlled trial.ObjectiveThis study aimed to determine if Promoting Optimal Physical Exercise for Life (PROPEL) program increases participation in physical activity up to six months post-discharge from stroke rehabilitation, compared to participation in group cardiorespiratory exercise (GCE) alone.MethodsPeople with sub-acute stroke participated in the PROPEL (n=107) or GCE (n=65) intervention phases. The primary outcome was adherence to physical activity guidelines over seven days at six months post-discharge from rehabilitation. Secondary outcomes were exercise self-efficacy (Short Self-Efficacy for Exercise scale), exercise-related beliefs and attitudes (Short Outcome Expectation for Exercise scale), and perceived barriers to physical activity (Barriers to Being Active Quiz).ResultsFifty seven participants (PROPEL, n=29; GCE, n=28) were included in the analysis. At six months post-discharge, 6/17 PROPEL participants and 9/22 GCE participants met the guidelines for intensity and duration of physical activity; the odds of meeting the physical activity guidelines did not differ between phases (p>0.84). PROPEL participants reported higher self-efficacy for exercise than GCE participants (p=0.0047).ConclusionsParticipation in the PROPEL increases self-efficacy for exercise compared to GCE alone after stroke. However, increased self-efficacy for exercise did not increase the odds of meeting physical activity guidelines.Trial registrationNCT02951338
Survey of vitamin D intake in the general population in the Democratic Republic of Congo: Multicentre cross-sectional study
Authors: Bihehe Dieudonne Masemo , Mbaz Jacques Musung , Isaga Bertin , Shamputi Willy David , Mulume Jean Luhaga , Selemani Jean Missel , Mbo Jean Mukonkole , Bwihangane Ahadi Birindwa , Etale Eric , Ngongo Paul Tshonda , Lwandiko Roland Cibenda , Katchunga Philippe Bianga 
Published: April 2024

AbstractAimData on vitamin D intake are not available for the Democratic Republic of Congo. The aim of this study was to determine the level of sun exposure and dietary intake of vitamin D in the general adult Congolese population.MethodsBetween January and March 2024, 14,750 respondents (age= 31.3±12.5 years, 53.5% male) completed a questionnaire on sun exposure and dietary vitamin D intake. The association between satisfactory vitamin D intake ≥ 15 µg/day and hypothesised determinants was modelled in a multiple logistic regression.ResultsOf the 14,750 participants, 1,238 (8.4%) had very fair skin, 4,601 (31.2%) had less than 15 minutes’ exposure to the sun, 5,281 (35.8%) had only their head exposed to the sun and 2,509 (17.0%) had a vitamin D test. Fish was the main source of vitamin D intake [3.0 (1.0-7.0) µg/100 gr/day]. Finally, satisfactory vitamin D intake was significantly more frequent in participants aged < 40 years (adjusted OR= 2.45; p=0.0007), in those with a low socio-economic level (adjusted OR= 1.23; p=0.01) and in one of the towns studied (adjusted OR= 1.64; p=0.0001).ConclusionA low level of sun exposure and dietary intake of vitamin D is observed in the general Congolese population. Vitamin D intake is influenced by age and socio-economic status. The introduction of a vitamin D programme integrated into funded programmes (TB, HIV) would make it possible, at a lower cost, to combat vitamin D deficiency by raising awareness, screening and treating the general Congolese population.