Development of a prediction model for short-term remission of patients with Crohn’s disease treated with anti-TNF drugs

Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn’s disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR

Oxaliplatin in combination with liver-specific expression of interleukin 12 reduces the immunosuppressive microenvironment of tumours and eradicates metastatic colorectal cancer in mice

BACKGROUND AND AIMS: New options are needed for the management and prevention of colorectal cancer liver metastases. Interleukin 12 (IL-12) is an immunostimulatory cytokine with proven antitumour effect in animal models. Despite evidence indicating its biological effect in humans, neither the recombinant protein nor gene therapy vectors expressing IL-12 have shown a relevant benefit in patients with cancer. OBJECTIVE: To develop a new approach to overcome the difficulties in obtaining a suitable expression pattern and the immunosuppressive milieu in the tumours which contribute to this poor performance. METHODS: A high-capacity ('gutless') adenoviral vector carrying a liver-specific, mifepristone (Mif)-inducible system for the expression of IL-12 (HC-Ad/RUmIL-12) was used in combination with chemotherapy. Tumours were established in the liver of C57BL/6 mice by inoculation of MC38 colon cancer cells. RESULTS: Intrahepatic injection of HC-Ad/RUmIL-12 and tailored induction regimens allowed the maintenance of safe and efficient levels of IL-12 in vivo. An individualised, stepwise increase in the dose of Mif (125-4000 μg/kg) was needed to compensate for the progressive but transient downregulation of the inducible system. Repeated cycles of Mif induction (every 24 h for 10 days) were needed for optimal tumour eradication. However, complete protection against tumour rechallenge was seen in < 25% of the animals. The administration of oxaliplatin (5 mg/kg intraperitoneally) 3 days before starting the induction regimen achieved efficient elimination of liver metastases with a single cycle of IL-12 induction, and improved protection against tumour rechallenge. This was associated with a shift in the tumour microenvironment towards a more pro-immunogenic phenotype, with an increase in the CD8+/T regulatory cell ratio and a reduction in myeloid-derived suppressor cells. These effects were not seen with 5-fluorouracil, irinotecan or gemcitabine

Reto de las mipymes para incursionar en el marketing digital en tiempos de COVID-19

This article describes the crisis that micro, small and medium enterprises have experienced throughout the country during the health emergency (COVID-19), due to low production and reduced sales. It aims to examine the effects of incorporating digital business marketing that becomes a mechanism to deal with this problem and to fill the digital gap of these companies. This issue is addressed considering the socioeconomic difference between those communities that have access to information and communication technologies and those that do not.  In order to collect information, an exploratory comparative descriptive analysis was carried out of the main research studies on the relationship between business digital marketing and the outcomes in business development, employee commitment, positioning, consumer satisfaction and financial performance. Additionally, the authors propose criteria to help bridge this digital gap. The findings show that, despite the existence of great divergences, the companies that today, in face of the current crisis, attempt to leverage their digital technology and connectivity capacity are going to be benefited by an increase in sales and market sustainability with international exposure.Este artículo describe la crisis que las micro, pequeñas y medianas empresas han experimentado en todo el país durante la emergencia sanitaria (COVID-19), a raíz de la baja producción y la reducción en las ventas. Se busca observar los efectos de la incorporación del marketing digital empresarial que se convierte en un mecanismo para solucionar la problemática y para romper la brecha digital en estas empresas, entendida desde la diferencia socioeconómica entre aquellas comunidades que tienen accesibilidad a las tecnologías de la información y la comunicación y aquellas que no. Para la compilación de información se emplea un análisis exploratorio, comparativo y descriptivo de las principales investigaciones sobre la relación entre marketing digital empresarial y el rendimiento obtenido en el desarrollo empresarial, compromiso de los trabajadores, posicionamiento, satisfacción del consumidor y rendimiento financiero; además los autores de este estudio plasman sus criterios para contribuir a eliminar esta brecha digital. Los resultados demuestran que, a pesar de la existencia de grandes divergencias, las empresas que hoy debido a la crisis están tratando de mostrar su capacidad tecnológica digital y de conectividad van a ser beneficiadas con un aumento en sus ventas y su sostenibilidad en el mercado con una prospectiva internacional

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum