218 research outputs found
Data processing for direct marketing through Big Data
Traditional marketing performs promotion through various channels such as news in newspapers, radio, etc., but those promotions are aimed at all people, whether or not interested in the product or service being promoted. This method usually leads to high expenses and a low response rate by potential customers. That is why, nowadays, because there is a very competitive market, mass marketing is not safe, hence specialists are focusing efforts on direct marketing. This method studies the characteristics, needs and also selects a group of customers as a target for the promotion. Direct marketing uses predictive modeling from customer data, with the aim of selecting the most likely to respond to promotions. This research proposes a platform for the processing of data flows for target customer selection processes and the construction of required predictive response models
A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin
Signatura genètica; Biomarcadors predictius; TrabectedinaFirma genĂ©tica; Biomarcadores predictivos; TrabectedinaGene signature; Predictive biomarkers; TrabectedinPredictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.This study was funded by the Spanish Group for Research on Sarcoma (GEIS) and partially by PharmaMar. The authors would like to thank the GEIS data center for data management. The authors also thank the donors and the Hospital Universitario Virgen del RocĂo—Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041) for part of the human specimens used in this study. David S. Moura is recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155)
Epidemiological characterization of ischemic heart disease at different altitudes: a nationwide population-based analysis from 2011 to 2021 in Ecuador
Background Cardiovascular diseases, including ischemic heart disease, are the leading cause of prema- ture death and disability worldwide. While traditional risk factors such as smoking, obesity, and diabetes have been thoroughly investigated, non-traditional risk factors like high-alti- tude exposure remain underexplored. This study aims to examine the incidence and mortal- ity rates of ischemic heart disease over the past decade in Ecuador, a country with a diverse altitude profile spanning from 0 to 4,300 meters. Methods We conducted a geographic distribution analysis of ischemic heart disease in Ecuador, uti- lizing hospital discharge and mortality data from the National Institute of Census and Statis- tics for the years 2011–2021. Altitude exposure was categorized according to two distinct classifications: the traditional division into low ( 2,500 m) altitudes, as well as the classification proposed by the International Society of Mountain Medicine, which delineates low (2500 m. Men had more pronounced rates across altitudes, exhibiting 138.7% and 150.0% higher incidence at low and high altitudes respectively, and mortality rates increased by 48.3% at low altitudes and 23.2% at high altitudes relative to women. Conclusion Ecuador bears a significant burden of ischemic heart disease (IHD), with men being more affected than women in terms of incidence. However, women have a higher percentage of mortality post-hospital admission. Regarding elevation, our analysis, using two different alti- tude cutoff points, reveals higher mortality rates in low-altitude regions compared to high- altitude areas, suggesting a potential protective effect of high elevation on IHD risk. Never- theless, a definitive dose-response relationship between high altitude and reduced IHD risk could not be conclusively established
Ancient DNA evidence for the ecological globalization of cod fishing in medieval and post-medieval Europe
Understanding the historical emergence and growth of long-range fisheries can provide fundamental insights into the timing of ecological impacts and the development of coastal communities during the last millennium. Whole-genome sequencing approaches can improve such understanding by determining the origin of archaeological fish specimens that may have been obtained from historic trade or distant water. Here, we used genome-wide data to individually infer the biological source of 37 ancient Atlantic cod specimens (ca 1050-1950 CE) from England and Spain. Our findings provide novel genetic evidence that eleventh- to twelfth-century specimens from London were predominantly obtained from nearby populations, while thirteenth- to fourteenth-century specimens were derived from distant sources. Our results further suggest that Icelandic cod was indeed exported to London earlier than previously reported. Our observations confirm the chronology and geography of the trans-Atlantic cod trade from Newfoundland to Spain starting by the early sixteenth century. Our findings demonstrate the utility of whole-genome sequencing and ancient DNA approaches to describe the globalization of marine fisheries and increase our understanding regarding the extent of the North Atlantic fish trade and long-range fisheries in medieval and early modern time
Nanoemulsion stability: experimental evaluation of the flocculation rate from turbidity measurements
The coalescence of liquid drops induces a higher level of complexity compared
to the classical studies about the aggregation of solid spheres. Yet, it is
commonly believed that most findings on solid dispersions are directly
applicable to liquid mixtures. Here, the state of the art in the evaluation of
the flocculation rate of these two systems is reviewed. Special emphasis is
made on the differences between suspensions and emulsions. In the case of
suspensions, the stability ratio is commonly evaluated from the initial slope
of the absorbance as a function of time under diffusive and reactive
conditions. Puertas and de las Nieves (1997) developed a theoretical approach
that allows the determination of the flocculation rate from the variation of
the turbidity of a sample as a function of time. Here, suitable modifications
of the experimental procedure and the referred theoretical approach are
implemented in order to calculate the values of the stability ratio and the
flocculation rate corresponding to a dodecane-in-water nanoemulsion stabilized
with sodium dodecyl sulfate. Four analytical expressions of the turbidity are
tested, basically differing in the optical cross section of the aggregates
formed. The first two models consider the processes of: a) aggregation (as
described by Smoluchowski) and b) the instantaneous coalescence upon
flocculation. The other two models account for the simultaneous occurrence of
flocculation and coalescence. The latter reproduce the temporal variation of
the turbidity in all cases studied (380 \leq [NaCl] \leq 600 mM), providing a
method of appraisal of the flocculation rate in nanoemulsions
Engineering of III-Nitride Semiconductors on Low Temperature Co-fired Ceramics
This work presents results in the feld of advanced substrate solutions in order to achieve high
crystalline quality group-III nitrides based heterostructures for high frequency and power devices or for
sensor applications. With that objective, Low Temperature Co-fred Ceramics has been used, as a noncrystalline
substrate. Structures like these have never been developed before, and for economic reasons
will represent a groundbreaking material in these felds of Electronic. In this sense, the report presents
the characterization through various techniques of three series of specimens where GaN was deposited
on this ceramic composite, using diferent bufer layers, and a singular metal-organic chemical vapor
deposition related technique for low temperature deposition. Other single crystalline ceramic-based
templates were also utilized as substrate materials, for comparison purposes
Mycobacterium phlei cell wall complex directly induces apoptosis in human bladder cancer cells
Intact mycobacteria and mycobacterial cell wall extracts have been shown to inhibit the growth of human and murine bladder cancer. Their mechanism of action is, however, poorly understood. Mycobacterium phlei mycobacterial cell complex (MCC) is a cell wall preparation that has mycobacterial DNA in the form of short oligonucleotides complexed on the cell wall surface. In this study, we have investigated the possibility that MCC has anti-cancer activity that is mediated by two different mechanisms – a direct effect on cancer cell proliferation and viability and an indirect effect mediated by the production of interleukin 12 (IL-12), a cytokine known to possess anti-cancer activity. We have found that, although MCC is a potent inducer of IL-12 and IL-6 synthesis in monocytes and macrophages either in vitro or in vivo, it is unable to induce the synthesis of either IL-12, IL-6 or granulocyte–macrophage colony-stimulating factor (GM-CSF) by the human transitional bladder cancer cell lines HT-1197 and HT-1376. MCC is not directly cytotoxic towards these cancer cells, but induces apoptosis as determined by nuclear DNA fragmentation and by the release of nuclear mitotic apparatus protein. Mycobacterium phlei DNA associated with MCC is responsible for the induction of apoptosis. Our results indicate that MCC directly effects bladder cancer cells by inhibiting cellular proliferation through the induction of apoptosis, and has the potential for an indirect anti-cancer activity by stimulating cancer-infiltrating monocytes/macrophages to synthesize IL-12. © 1999 Cancer Research Campaig
HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade
Background: Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. Methods: A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated. Results: A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P <. 001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P =. 01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P <. 001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P =. 02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P =. 01). Conclusions: Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer
Pulmonary Arterial Hypertension Affects the Rat Gut Microbiome
We have analysed whether pulmonary arterial hypertension (PAH) alters the rat faecal microbiota.
Wistar rats were injected with the VEGF receptor antagonist SU5416 (20 mg/kg s.c.) and followed
for 2 weeks kept in hypoxia (10% O2, PAH) or injected with vehicle and kept in normoxia (controls).
Faecal samples were obtained and microbiome composition was determined by 16S rRNA gene
sequencing and bioinformatic analysis. No effect of PAH on the global microbiome was found (α- or
β-diversity). However, PAH-exposed rats showed gut dysbiosis as indicated by a taxonomy-based
analysis. Specifically, PAH rats had a three-fold increase in Firmicutes-to-Bacteroidetes ratio. Within
the Firmicutes phylum, there were no large changes in the relative abundance of the bacterial families
in PAH. Among Bacteroidetes, all families were less abundant in PAH. A clear separation was observed
between the control and PAH clusters based on short chain fatty acid producing bacterial genera.
Moreover, acetate was reduced in the serum of PAH rats. In conclusion, faecal microbiota composition is
altered as a result of PAH. This misbalanced bacterial ecosystem might in turn play a pathophysiological
role in PAH by altering the immunologic, hormonal and metabolic homeostasis.This study is supported by grants from Mineco (SAF2014-55399-R, SAF2014-55523-R,
SAF2016-77222 and SAF2017-84494-C2-1R), Instituto de Salud Carlos III (PI15/01100), with funds from the
European Union (Fondo Europeo de Desarrollo Regional FEDER). M.C., G.M-P. and S.E-R. are funded by
Universidad Complutense, Fondo de GarantĂa Juvenil (Comunidad de Madrid) and Ciberes grant with funds
from FundaciĂłn Contra la HipertensiĂłn Pulmonar, a FPU grant from Ministerio de EducaciĂłn, respectively.
J.L.I.G is a CNIC IPP COFUND Fellow and has received funding from the People Programme (Marie Curie
Actions) of the FP7/2007-2013 under REA grant agreement n° 600396. The CNIC is supported by MEIC-AEI and
the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505)
MEsenchymal StEm cells for Multiple Sclerosis (MESEMS):a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis
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