bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the secretion of immunogenic gluten peptides in breast milk from celiac and non celiac mothers
Authors: Ruiz-Carnicer Ángela , Segura Verónica , de Lourdes Moreno María , Coronel-Rodríguez Cristóbal , Sousa Carolina , Comino Isabel 
Published: May 2024

AbstractBackgroundExposure to antigens is crucial for child immune system development, aiding disease prevention and promoting infant health. Some common food antigen proteins are found in human breast milk. However, it is unclear whether gluten antigens linked to celiac disease (CD) are transmitted through breast milk, potentially impacting the development of the infant’s immune system.ObjectiveThis study aimed to analyze the passage of gluten immunogenic peptides (GIP) into human breast milk. We evaluated the dynamics of GIP secretion after lactating mothers adopted a controlled gluten-rich diet.MethodsWe prospectively enrolled 96 non-CD and 23 CD lactating mothers, assessing total proteins and casein in breast milk, and GIP levels in breast milk and urine. Subsequently, a longitudinal study was conducted in a subgroup of 12 non-CD lactating mothers who adopted a controlled gluten-rich diet. GIP levels in breast milk and urine samples were assayed by multiple sample collections over 96 hours.ResultsAnalysis of a single sample revealed that 24% of non-CD lactating mothers on a regular unrestricted diet tested positive for GIP in breast milk, and 90% tested positive in urine, with significantly lower concentrations in breast milk. Nevertheless, on a controlled gluten-rich diet and the collection of multiple samples, GIP were detected in 75% and 100% of non-CD participants in breast milk and urine, respectively. The transfer dynamics in breast milk samples were long-enduring and GIP secretion persisted from 0 to 72 h. In contrast, GIP secretion in urine samples was limited to the first 24 h, with inter-individual variations. In the cohort of CD mothers, 82.6% and 87% tested negative for GIP in breast milk and urine, respectively.ConclusionsThis study definitively established the presence of GIP in breast milk, with substantial inter-individual variations in secretion dynamics. Our findings provide insights into distinct GIP kinetics observed in sequentially collected breast milk and urine samples, suggesting differential gluten metabolism patterns depending on the organ or system involved. Future research is essential to understand whether GIP functions as sensitizing or tolerogenic agents in the immune system of breastfed infants.
Neuroblastoma in Adults: A Scoping Review of Presentations, Genetics and Therapies
Authors: Alsaikhan Bader H. , Alwahhabi Basmah , Alshalan Abdullah , Koziarz Alex , Alkhayal Abdullah M. , Alrabeeah Khalid 
Published: May 2024

ABSTRACTPurposeAs a scoping review, evaluate the literature on the presentations, genetics, and therapies for neuroblastoma in adult patients.MethodsWe searched four databases for studies reporting adults with neuroblastoma. Cohort studies, case series, and case reports were synthesized qualitatively. Progression-free and overall survival were compared amongst cohort studies.ResultsOf 2287 unique records, 136 studies published in 141 articles were included. A total of 679 patients were included. On review of individual patient-level data, the adrenal gland and retroperitoneum were the most common primary site (47.3%).MYCNwas rarely amplified: seven studies reported zero patients with MYCN amplified, two studies with a single patient, and one study with 3/7 patients. Adult patients appear to show a high frequency of somatic mutations, specificallyALK(42%) andATRX(58%). Registry data of included studies showed 5- year overall survival to be 36.3% in adults aged ≥20 years.ConclusionOf nearly 700 cases of adult neuroblastoma published in the literature, the most common primary site is the adrenals or retroperitoneum. Relative to pediatric cases, adult cases demonstrate a considerable rate of somatic mutations such asALKandATRX. Registry data showed 5-year survival of 36%. Future studies evaluating targeted therapies in larger samples are needed.Take home messages679 cases of adult neuroblastoma have been published in the literature.Compared to pediatrics, adult cases have more somatic mutations (eg: ALK, ATRX).Registry data showed that adult neuroblastoma has a 5-year survival of 36%.
Prevalence, Concordance, and Related Factors of Four Cardiovascular Risk Calculators in the Peruvian Population: Analysis of a National Survey
Authors: Vera-Ponce Víctor Juan , Zuzunaga-Montoya Fiorella E. , Milagros Vásquez-Romero Luisa Erika , Loayza-Castro Joan A. , Vigil-Ventura Enrique , De Carrillo Carmen Inés Gutierrez 
Published: May 2024

AbstractIntroductionCardiovascular risk calculators (CVR) are essential for effectively preventing and managing cardiovascular diseases.ObjectiveTo determine the prevalence, the concordance among different CVR calculators, and the factors associated with these in the Peruvian population.MethodsAnalysis of data collected by the Food and Nutritional Surveillance Survey by Life Stages. The CVR calculators used were the AHA/ASCVD, World Health Organization (WHO) laboratory-based and non-laboratory-based, and Framingham. The percentage of risk for each individual in the study was calculated, categorizing the CVR of each calculator into low (<10%) vs moderate/high (≥10%). Concordance was analyzed through the kappa index.ResultsThe level of moderate/high CVR risk according to the type of calculator used was 5.44%, 4.73%, 6.62%, and 23.88% for WHO laboratory-based, non-laboratory-based, AHA/ASCVD, and Framingham, respectively. Common related factors identified were male gender, age between 50–59 years, current smoker, hypertension, and diabetes. WHO laboratory-based and AHA/ASCVD showed higher concordance (kappa of 0.7289). In contrast, concordance between WHO laboratory-based and Framingham and between WHO non-laboratory-based and Framingham was relatively lower (kappa of 0.3098 and 0.2732, respectively).ConclusionsThere are discrepancies in CVR levels according to the different calculators evaluated, especially with Framingham, and common associated factors were identified. These variations suggest that prediction tools might not be universally applicable in their current form, making it essential to consider calibrating existing risk calculators or developing new tools that more accurately reflect the epidemiological and health profiles of the Peruvian population.
Universal Health Coverage – Exploring the What, How, and Why Using Realistic Review
Authors: Endalamaw Aklilu , Mengistu Tesfaye Setegn , Khatri Resham B. , Wolka Eskinder , Erku Daniel , Zewdie Anteneh , Assefa Yibeltal 
Published: May 2024

AbstractBackgroundUniversal health coverage (UHC) is a critical target in many health system strategies to achieve the ‘good health and wellbeing’. Evidence on the meaning and scope of UHC and the strategies required to achieve it are needed, as variations in its understanding and implementation have risen. We synthesised evidence on the meaning, components, significance, and strategies of UHC.MethodsA review of evidence was conducted based on realist synthesis. We searched PubMed, EMBASE, Scopus, and Web of Science for published materials and websites for grey literature. We have followed some steps: define the scope of the review and develop initial programme theory, search for evidence, data extraction, and synthesis of evidence.ResultsUniversal coverage, universal health, universal healthcare, universal access, and insurance coverage are used interchangeably with UHC. It is a legal notion that embodies a human rights-based and collaborative approach to ensure fair and comprehensive health care services. Universal health coverage is relevant for three macro reasons: first, it prevents and reduces the impact of diseases; second, it addresses inequality and promotes equity; and third, it is key for global health security. Various mechanisms involved to implement UHC, such as health insurance, social health protection, digital financing systems, value-based care, private sectors, civil societies, partnership, primary health care, and reciprocal health care systems.ConclusionsUniversal health coverage is a multifaceted concept that can be expressed by various terms in different contexts. Universal health coverage is a political and ethical imperative that aims to promote health equity and protect human dignity across different levels of society. It is essential in preventing diseases and serving a crucial role in global health security. Practically, UHC is not truly universal, as it does not include all services under its scheme and varies across countries. This requires consistent advocacy, strategic and operational research as well as political will to ensure UHC.
Red flags to screen for tumors in patients with neck pain: a scoping review protocol
Authors: Occhetto Beatrice , Ballesio Martina , Mourad Firas , Trucco Marco , Maselli Filippo , Chiarotto Alessandro , Feller Daniel 
Published: May 2024

ABSTRACTBackgroundPeople with malignant (primary or metastatic) or benign tumors may present in clinical practice with neck pain, with or without other symptoms (e.g., radicular pain or headache). When not presenting as an emergency, neck pain is most often assessed by primary care clinicians such as general practitioners, physiotherapists, chiropractors or osteopaths. Therefore, primary care clinicians must be able to screen for tumors when evaluating patients with neck pain.Despite clinical practice guidelines providing recommendations to triage serious conditions presenting as neck pain, there is a paucity of overviews on red flags for tumors in patients presenting with neck pain in primary care settings. The present scoping review aims to comprehensively map the existing literature on red flags for tumors in patients presenting with neck pain in primary care settings. Furthermore, we will aim to identify gaps in the literature to direct future research in this area.MethodsWe will search MEDLINE (via PubMed), Embase, CINHAL, and Scopus. In addition, we will use Web of Science to implement backward and forward citation tracking strategies. We will consider any primary study design written in English or Italian. No time or geographical restrictions will be applied to the search. Studies with a focus on the diagnostic pathway, considering patients of any age and gender with a diagnosis of tumor and a primary complaint of neck pain will be eligible for inclusion. Only studies conducted in primary care settings will be considered. Two authors will independently perform the study selection and data extraction phases. Results from the scoping review will be summarized descriptively through tables and diagrams. As a scoping review, we will highlight any gaps in the existing literature regarding our research questions.
Reporting standards for outbreak data: A systematic review
Authors: Grégoire Vanessa , Zhu Alex W , Haines Clint A. , Rivers Caitlin M 
Published: May 2024

AbstractThe current landscape of data reporting for outbreaks is ad hoc and inconsistent. Public health authorities have discretion to determine when, where, how, and what outbreak data to report. This uneven information flow hampers response efforts by decreasing the accountability and transparency needed to build public trust in the public health response. We performed a systematic literature review using the PubMed, EMBASE, MedLine Plus, and Google Scholar databases to identify existing guidelines that address timing, methodology and content of outbreak reporting. Our search strategy produced 46 manuscripts for initial screening to determine eligibility, after which we performed a full-text review of those selected for comprehensive evaluation. We identified four manuscripts that discuss minimum standards and expectations for outbreak reports. Included manuscripts highlight the absence of and the consequent need for minimum standards for what information should be reported to the public during outbreaks. Together, they suggest that the ideal outbreak report should contain information on disease severity, epidemic size and geographic extent, daily and total case count, demographics, transmissibility, signs and symptoms, probable disease transmission and exposure pathways, countermeasure status, and sources of uncertainty. This systematic review of existing guidelines is part of a larger effort to develop consensus guidelines for the public reporting of outbreak data.
COVID-19 vaccination atlas: an integrative systems vaccinology approach
Authors: Prates-Syed Wasim Aluísio , da Fonseca Dennyson Leandro Mathias , Pour Shahab Zaki , Schimke Lena F , Lira Aline , Cortes Nelson , Silva Jaqueline Dinis Queiroz , Carvalho Evelyn , Filgueiras Igor Salerno , Vinces Tania Geraldine Churascari , Chaves Lorena C. S. , Wunderlich Gerhard , Durães-Carvalho Ricardo , Câmara Niels O. S. , Dias Haroldo Dutra , Ochs Hans D. , Krieger José E. , Nakaya Helder I , Cabral-Marques Otávio , Cabral-Miranda Gustavo 
Published: May 2024

AbstractThe COVID-19 vaccinations have played a significant role in controlling the pandemic. To elucidate their impact on the immune system, a COVID-19 vaccination atlas was developed through an integrative systems vaccinology approach. The atlas includes both healthy individuals and those infected with or without prior vaccination, and covers the administration of five vaccines in different regimens: Covilo®, Zifivax®, Vaxzebria® or Covishield®, Spikevax®, and Comirnaty®. Critical markers were identified to discriminate the different types of vaccines and infection, in which infection was associated with GATA3, ZNF3, KMT2A, ASXL1, SP100, and GZMM, and vaccine types were marked by ITGAM, ACTG1, LGALS3, and STAT5B. Additionally, the immunological signatures of heterologous vaccination and infection were described, and it was also shown how a full vaccination regimen markedly limited the shift of immune responses during natural infection, thereby constraining disease progression. Finally, the common transcripts shared across COVID-19 vaccines and vaccines against other pathogens were described.
XplainScar: Explainable Artificial Intelligence to Identify and Localize Left Ventricular Scar in Hypertrophic Cardiomyopathy from 12-lead Electrocardiogram
Authors: Nezamabadi Kasra , Sivalokanathan Sanjay , Lee Ji Won , Tanriverdi Talha , Chen Meiling , Lu Daiyin , Abraham Jadyn , Sardaripour Neda , Li Pengyuan , Mousavi Parvin , Abraham M. Roselle 
Published: May 2024

AbstractLeft ventricular (LV) scar is a risk factor for sudden cardiac death and heart failure in hypertrophic cardiomyopathy (HCM). LV scar is frequent in HCM and evolves over time. Hence there is a need for LV scar detection and longitudinal monitoring. The current gold standard for LV scar detection is late gadolinium enhancement (LGE) on magnetic resonance imaging (MRI), which is limited by high cost and susceptibility to artifacts from implanted defibrillators. We introduceXplainScar, the first explainable machine learning method for LV scar detection and localization in HCM, using 12-lead electrocardiogram (ECG) data, which is not influenced by implanted devices. We use 500 patients from the JH-HCM Registry for model development, and 248 patients from the UCSF-HCM-Registry for validation.XplainScarcombines unsupervised and self-supervised ECG representation learning, resulting in high precision (90%), sensitivity (95%), specificity (80%) and F1-score (90%) for scar detection in the basal, mid, and apical LV myocardium, with a processing time of <1 minute per 10 patients. Basal LV scar prediction byXplainScaris dominated by QRS features, and mid/apical LV scar by T wave features.XplainScargeneralizes well to the held-out test UCSF data, with 88% precision, 90% sensitivity, 78% specificity, and F1-score of 89%. In summary,XplainScardemonstrates good performance for LV scar detection, and provides ECG signatures of basal, mid, and apical LV scar in HCM.XplainScaris publicly available athttps://github.com/KasraNezamabadi/XplainScar
Approximation of bone mineral density and subcutaneous adiposity using T1-weighted images of the human head
Authors: Kalc Polona , Hoffstaedter Felix , Luders Eileen , Gaser Christian , Dahnke Robert 
Published: May 2024

AbstractBones and brain are intricately connected and scientific interest in their interaction is growing. This has become particularly evident in the framework of clinical applications for various medical conditions, such as obesity and osteoporosis. The adverse effects of obesity on brain health have long been recognised, but few brain imaging studies provide sophisticated body composition measures. Here we propose to extract the following bone- and adiposity-related measures from T1-weighted MR images of the head: an approximation of skull bone mineral density (BMD), skull bone thickness, and two approximations of subcutaneous fat (i.e., the intensity and thickness of soft non-brain head tissue). The measures pertaining to skull BMD, skull bone thickness, and intensi-ty-based adiposity proxy proved to be reliable (r=.93/.83/.74,p<.001) and valid, with high correlations to DXA-de-rived head BMD values (rho=.70,p<.001) and MRI-derived abdominal subcutaneous adipose volume (rho=.62,p<.001). Thickness-based adiposity proxy had only a low retest reliability (r=.58,p<.001).The outcomes of this study constitute an important step towards extracting relevant non-brain features from available brain scans.
Associating EEG Functional Networks and the Effect of Sleep Deprivation as Measured Using Psychomotor Vigilance Tests
Authors: Mason Sophie L. , Junges Leandro , Woldman Wessel , Ftouni Suzanne , Anderson Clare , Terry John R. , Bagshaw Andrew P. 
Published: May 2024

ABSTRACTPeople are routinely forced to undertake cognitive challenges under the effect of sleep deprivation, due to professional and social obligations forcing them to ignore their circadian clock. However, low intra-individual and high inter-individual differences in behavioural outcomes are known to occur when people are sleep deprived, leading to the conclusion that trait-like differences to sleep deprivation could explain the differing levels of resilience. Within this study we consider if trait-like resilience to sleep deprivation, measured using psychomotor vigilance tests over a 40h constant routine protocol, could be associated with graph metrics (mean node strength, clustering coefficient, characteristic path length and stability) calculated from EEG functional networks acquired when participants are well rested (baseline). Furthermore, we investigated how stability (the consistency of a participant’s functional network over time measured using 2-D correlation) changed over the constant routine. We showed evidence of strong significant correlations between high mean node strength, low characteristic path length and high stability at baseline with a general resilience to extended sleep deprivation, although the same features lead to vulnerability during the period of natural sleep onset, highlighting non-uniform correlations over time. We also show significant differences in the levels of stability between resilient and vulnerable groups.
A single-cell eQTL atlas of the human cerebellum reveals vulnerability of oligodendrocytes in essential tremor
Authors: Castonguay Charles-Etienne , Aboasali Farah , Medeiros Miranda , Becret Théodore , Schmilovich Zoe , Khayachi Anouar , Rajput Alex , Dion Patrick A. , Rouleau Guy A 
Published: May 2024

AbstractEssential tremor (ET) is a movement disorder characterized by an upper-limb postural and action tremor. It is one of the most common neurological disorders, affecting 1% of the worldwide population. Despite strong evidence for genetic factors driving the aetiology of ET, the underlying pathophysiology remains poorly understood. To understand the effects of genetic risk factors in ET on the cerebellum, the brain region thought to be affected by the disease, we built a population-scale single-cell atlas of the human cerebellar cortex comprised of over 1 million cells from 109 individuals. Using single-cell expression quantitative trait loci and mendelian randomization, we found evidence of ET-associated variants in theBACE2locus causally linked to its downregulation in cerebellar oligodendrocytes. We highlight a genetically vulnerable population ofBACE2-expressing immature oligodendrocytes, suggestive of demyelination. We also find dysfunctional processes affecting interactions between Golgi cells, Purkinje layer interneurons, and oligodendrocytes in ET. Our study suggests a crucial role for cerebellar oligodendrocytes in the pathogenesis of ET.
Exploring the dynamics and interactions of the N-myc transactivation domain through solution NMR
Authors: Rejnowicz Ewa , Batchelor Matthew , Leen Eoin , Ahangar Mohd Syed , Richards Mark W. , Kalverda Arnout P. , Bayliss Richard 
Published: May 2024

ABSTRACTThe myc family of proteins (c-, N- and L-myc) are transcription factors (TFs) responsible for maintaining the proliferative program in cells. They consist of a C-terminal domain that mediates heterodimerisation with Max and DNA binding, and an N-terminal disordered region culminating in the transactivation domain (TAD). The TAD participates in many protein–protein interactions, notably with kinases that promote stability (Aurora-A) or degradation (ERK1, GSK3) via the ubiquitin-proteasome system. Structural characterization of the TAD of N-myc, is very limited, with the exception of a crystal structure of Aurora-A bound to a helical region of N-myc. We probed the structure, dynamics and interactions of N-myc TAD using nuclear magnetic resonance (NMR) spectroscopy following its complete backbone assignment enabled by a truncation approach. Chemical shift analysis revealed that N-myc has two regions with clear helical propensity: one region within Trp77–Glu86 and the second between Ala122–Glu132. These regions also have more restricted ps–ns motions than the rest of the TAD, and, along with another known interaction site (myc box I), have comparatively high transverse (R2)15N relaxation rates, indicative of slower timescale dynamics and/or chemical exchange. Collectively these features suggest differential propensities for structure and interaction, either internal or with binding partners, across the TAD. Solution studies on the interaction between N-myc and Aurora-A revealed a previously uncharacterised binding site. The specificity and kinetics of sequential phosphorylation of N-myc by ERK1 and GSK3 were characterised using NMR and showed no significant structural changes through the rest of the TAD. When doubly phosphorylated on residues Ser62 and Thr58, N-myc formed a robust interaction with the Fbxw7–Skp1 complex. Our study provides foundational insights into N-myc TAD dynamics and a backbone assignment that will underpin future work on the structure, dynamics, interactions and regulatory post-translational modifications of this key oncoprotein.