0000000000497093
AUTHOR
David Gomez-cabrero
Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma
AbstractThe historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time …
Adhérence au régime méditerranéen, indice de masse corporelle et risque de diabète de type 2 : résultats de l’étude UK Biobank
Discipline Epidemiologie. Introduction et but de l’etude Au cours des dernieres decennies, l’incidence du diabete de type II (DT2) a augmente de maniere significative a travers le monde, entrainant une augmentation de la morbidite et de la mortalite associees. En termes de prevention, les preuves s’accumulent quant a l’association entre l’adherence a un regime de type Mediterraneen et un moindre risque de DT2. Dans cette etude, nous nous sommes interesses a l’effet potentiellement mediateur de l’indice de masse corporelle (IMC) en tant que mecanisme sous-jacent a cette relation. Materiel et methodes Les participants de la UK Biobank ayant des donnees cliniques sur le statut diabetique et ay…
Prevalence and distribution of human papillomavirus findings in swab specimens from gynaecology clinics of the east coast of Spain.
The objective of this study was to determine the prevalence of human papillomavirus (HPV) among females in the east coast of Spain. A total of 1956 women visiting gynaecology clinics for routine check-ups were included in the study. Swabs were analyzed for HPV DNA by consensus polymerase chain reaction followed by direct sequencing. The overall HPV prevalence was 12.99%. HPV vaccine types 6, 11, 16 and 18 were detected in 6.13% of female participants.
The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
Abstract:We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain -…
The role of overweight in the association between the Mediterranean diet and the risk of type 2 diabetes mellitus: a mediation analysis among 21 585 UK biobank participants
Abstract Background There is growing evidence that the Mediterranean (Medi) diet may lower the risk of type 2 diabetes mellitus (T2DM). Whether this association is due to the Medi diet by itself or is mediated by a diet-associated lower rate of overweight is uncertain. Our aim was to disentangle these relationships among UK adults. Methods Based on 21 585 participants from the UK Biobank cohort, the adherence to the Medi diet (high fruits, vegetables, legumes, cereals, fish, olive oil; low meat, dairy products; and intermediate alcohol intakes) was assessed (range 0–18). Data on diabetes were self-reported, and overweight was defined as a body mass index (BMI) ≥ 25 kg/m². A mediation analys…
Distribution of human papillomavirus types in women from Valencia, Spain, with abnormal cytology.
Objective To determine human papillomavirus (HPV) types among cervical smears using polymerase chain reaction (PCR) and to contribute to the knowledge of human papillomavirus genotype distribution and prevalence of oncogenic types in cervical lesions in Spain. Study Design Consensus PCR and direct sequencing of PCR products (DNA HPV typing) were used in a retrospective study to determinate the type or types of HPV on 974 cytology smears of women with abnormal cytology results. Results Of 974 smears, 79.8% were high-risk (H-R) HPVs, 19.7% low-risk (L-R) HPVs, 4.6% indeterminate-risk (I-R) HPVs, considering both single and multiple infections. Multiple infections were detected in 4.7% of the …