Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management.

Mucopolysaccharidosis type IVA (MPS IVA, or Morquio syndrome type A) is an inherited metabolic lysosomal disease caused by the deficiency of the N-acetylglucosamine-6-sulfate sulfatase enzyme. The deficiency of this enzyme accumulates the specific glycosaminoglycans (GAG), keratan sulfate, and chondroitin-6-sulfate mainly in bone, cartilage, and its extracellular matrix. GAG accumulation in these lesions leads to unique skeletal dysplasia in MPS IVA patients. Clinical, radiographic, and biochemical tests are needed to complete the diagnosis of MPS IVA since some clinical characteristics in MPS IVA are overlapped with other disorders. Early and accurate diagnosis is vital to optimizing patient management, which provides a better quality of life and prolonged life-time in MPS IVA patients. Currently, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available for patients with MPS IVA. However, ERT and HSCT do not have enough impact on bone and cartilage lesions in patients with MPS IVA. Penetrating the deficient enzyme into an avascular lesion remains an unmet challenge, and several innovative therapies are under development in a preclinical study. In this review article, we comprehensively describe the current diagnosis, treatment, and management for MPS IVA. We also illustrate developing future therapies focused on the improvement of skeletal dysplasia in MPS IVA

Multiscale, multimodal analysis of tumor heterogeneity in IDH1 mutant vs wild-type diffuse gliomas.

Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated data from protein, genomic and MR imaging from 20 treatment-naïve glioma cases and 16 recurrent GBM cases. Multiplexed immunofluorescence (MxIF) was used to generate single cell data for 43 protein markers representing all cancer hallmarks, Genomic sequencing (exome and RNA (normal and tumor) and magnetic resonance imaging (MRI) quantitative features (protocols were T1-post, FLAIR and ADC) from whole tumor, peritumoral edema and enhancing core vs equivalent normal region were also collected from patients. Based on MxIF analysis, 85,767 cells (glioma cases) and 56,304 cells (GBM cases) were used to generate cell-level data for 24 biomarkers. K-means clustering was used to generate 7 distinct groups of cells with divergent biomarker profiles and deconvolution was used to assign RNA data into three classes. Spatial and molecular heterogeneity metrics were generated for the cell data. All features were compared between IDH mt and IDHwt patients and were finally combined to provide a holistic/integrated comparison. Protein expression by hallmark was generally lower in the IDHmt vs wt patients. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion also differed between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. A coherent picture of enhanced angiogenesis in IDHwt tumors was derived from multiple platforms (genomic, proteomic and imaging) and scales from individual proteins to cell clusters and heterogeneity, as well as bulk tumor RNA and imaging features. Longer overall survival for IDH1mt glioma patients may reflect mutation-driven alterations in cellular, molecular, and spatial heterogeneity which manifest in discernable radiological manifestations

L'efecte de la pràctica del record en l'aprenentatge: Una proposta per millorar l'aprenentatge i el rendiment dels alumnes

La pràctica del record pot ser una eina fonamental per a l'aprenentatge i la consolidació dels coneixements. No obstant, les estratègies d'ensenyament tradicionals sovint no promouen de forma adequada aquesta pràctica. Per això, és important explorar noves metodologies pedagògiques que incorporin la pràctica del record com a eina per a la consolidació dels coneixements. D'aquesta manera, els alumnes podran desenvolupar la seva capacitat de recordar i aplicar els coneixements adquirits a llarg termini. La pràctica del record no ha de ser vista com una simple memorització mecànica de continguts, sinó com una oportunitat per aprofundir en el coneixement. Mitjançant la pràctica del record, els alumnes poden adquirir les capacitats necessàries per afrontar les exigències del món actual i futur, i desenvolupar competències com la capacitat de relacionar, comparar, sintetitzar, analitzar i aplicar el coneixement adquirit a altres situacions. Això també implica l'ús de preguntes i activitats que promoguin la comprensió del contingut i la seva relació amb altres conceptes. En aquest treball s'ha realitzat una introducció teòrica del tema escollit seguit d'un treball experimental per avaluar l'impacte de la pràctica del record en l'aprenentatge de les matemàtiques. Les proves s'han realitzat en un conjunt anomenat "Matelliga" durant el segon trimestre del curs 2022-23. S'han realitzat en un total de vuit proves utilitzant diverses plataformes com ara Quizizz, Kahoot! i Socrative pe

The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America

Classical homocystinuria is due to cystathionine beta-synthase (CBS) deficiency. More than 130 mutations, which differ in prevalence and severity, have been described at the CBS gene. Mutation p.I278T is very prevalent, has been found in all European countries where it has been looked for with the exception of the Iberian peninsula, and is known to respond to vitamin B-6. On the other hand, mutation p.T191M is prevalent in Spain and Portugal and does not respond to B-6. We analysed 30 pedigrees from Spain, Portugal, Colombia and Argentina, segregating for homocystinuria. the p.T191M mutation was detected in patients from all four countries and was particularly prevalent in Colombia. the number of p.T191M alleles described in this Study, together with those previously published, is 71. the prevalence of p.T191M among CBS mutant alleles in the different countries was: 0.75 in Colombia, 0.52 in Spain, 0.33 in Portugal, 0.25 in Venezuela, 0.20 in Argentina and 0.14 in Brazil. Haplotype analyses suggested a double origin for this mutation. No genotype-phenotype correlation other than the B-6-nonresponsiveness Could be established for the p.T191M mutation. Additionally,. three new mutations, p.M173V, p.I429del and c.69_70+8de110, were found. the p.M173V was associated with a mild, B-6-responsive, phenotype.Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, SpainUniv Nacl Cordoba, Ctr Estud Metab Congenitas, Hosp Ninos, Cordoba, ArgentinaPontificia Univ Javeriana, Inst Genet Humana, Bogota, ColombiaUniv Antioquia, Fac Med, Depto Fisiol & Bioquim, Medellin, ColombiaFundac Estud Enfermedades Neurometab, Buenos Aires, DF, ArgentinaInst Genet Med Jacinto Magalhaes, Oporto, PortugalUniversidade Federal de São Paulo, UNIFESP, EPM, Dept Pediat, São Paulo, BrazilHosp Ramon y Cajal, Serv Pediat, Unidad Enfermedades Metab, Madrid, SpainHosp Univ Materno Infantil, Unidad Gastroenterol & Nutr, Las Palmas Gran Canaria, SpainHosp Infantil Le Fe, Unidad Nutr & Metab, Valencia, SpainHosp Clin Univ Santiago, Dept Pediat, Santiago de Compostela, SpainCorp Sanitaria Clin, Inst Bioquim Clin, Barcelona, SpainHosp St Joan Deu, Serv Bioquim, Barcelona, SpainUniversidade Federal de São Paulo, UNIFESP, EPM, Dept Pediat, São Paulo, BrazilWeb of Scienc

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Effects of Dairy Product Consumption on Height and BoneMineral Content in Children: A Systematic Review of Controlled Trials

There is a physiological basis for the roles of selected nutrients, especially proteins, calcium, and vitamin D, in growth and development, which are at a maximum during the pediatric period. Milk and dairy products are particularly rich in this group of nutrients. The present systematic review summarizes the available evidence relating dairy product intake with linear growth and bone mineral content in childhood and adolescence. A search was conducted in the MEDLINE (via PubMed) and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines and included intervention-controlled clinical trials with dairy products in children from 1 January, 1926 to 30 June, 2018. The risk of bias for each study was assessed using the Cochrane methodology. The number of study participants, the type of study and doses, the major outcomes, and the key results of the 13 articles included in the review are reported. The present systematic review shows that supplementing the usual diet with dairy products significantly increases bone mineral content during childhood. However, the results regarding a possible relation between dairy product consumption and linear growth are inconclusive.This study was partially funded by the University of Granada Plan Propio de Investigación 2016, Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Plan Propio de Investigación 2018, Programa Contratos-Puente, the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, and European Regional Development Funds (ref. SOMM17/6107/UGR)

The Consensus Definition of Bronchopulmonary Dysplasia Is an Adequate Predictor of Lung Function at Preschool Age

Bronchopulmonary dysplasia; Lung function; Preschool ageDisplasia broncopulmonar; Función pulmonar; Edad preescolarDisplàsia broncopulmonar; Funció pulmonar; Edat preescolarBackground: Recent attempts to refine the definition bronchopulmonary dysplasia (BPD) have based its predictive capacity on respiratory outcome in the first 2 years of life, eliminating the pre-existing requirement of 28 days of oxygen therapy prior to 36 weeks postmenstrual age (PMA). The objective of this study was to assess the utility of the 2001 consensus definition in predicting impaired lung function at preschool age. Methods: This cohort study included children aged 4–6 years old who were born at gestational age (GA) <32 weeks or bodyweight <1500 g. Univariate and multivariate analyses were performed to assess differences in antenatal and neonatal variables between BPD and non-BPD children. All participants underwent incentive spirometry. Lung function parameters were contrasted with the Global Lung Function Initiative (GLI-2012) reference equations and, together with antenatal and neonatal variables, compared among the different subgroups (no BPD, mild BPD, and moderate-to-severe BPD). A multivariate model was generated to identify independent risk factors for impaired lung function. Results: GA, hemodynamically significant patent ductus arteriosus, and late sepsis were independent risk factors for the development of BPD. A total of 119 children underwent incentive spirometry. All lung function parameters were significantly altered relative to reference values. Greater impairment of lung function was observed in the mild BPD vs. the no BPD group (forced expiratory volume in the first 0.75 seconds [FEV0.75]: −1.18 ± 0.80 vs. −0.55 ± 1.13; p = 0.010), but no difference in forced vital capacity (FVC) was observed (−0.32 ± 0.90 vs. −0.18 ± 1; p = 0.534). The moderate-to-severe BPD group exhibited the most severe FEV0.75 reduction (FEV0.75: −2.63 ± 1.18 vs. −0.72 ± 1.08; p = 0.000) and was the only condition with FVC impairment (FVC: −1.82 ± 1.12 vs. −0.22 ± 0.87; p = 0.000). The multivariate analysis identified a diagnosis of moderate-to-severe BPD as an independent risk factor for lung function impairment. Conclusion: The 2001 consensus definition of BPD has adequate predictive capacity for lung function measured by spirometry at 4–6 years of age. Moderate-to-severe BPD was the best predictor of respiratory impairment. Children with mild BPD showed greater alteration of FEV0.75 than those without BPD.This study was partially financed with funds from the IDIS research group C012 (Santiago de Compostela) and Miguel Servet Biomedical Foundation (Zaragoza)