Análisis aerobiológico del polen de Cupressaceae en Granada (sureste P. Ibérica): su repercusión en la población atópica

XV lnternational A.P.L.E. Symposium of Palynolog

EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting

[EN] Introduction: Durvalumab is the new standard of care for unresectable locally advanced NSCLC, with PD-L1 _1% and who did not have progression after CRT treatment in the European Union. Our study compares the effectiveness and the frequency of radiation pneumonitis in patients treated with concurrent CRT with or without durvalumab consolidation during the same period in real clinical practice. Methods: A single-center retrospective study. 71 treated patients with unresectable stage III NSCLC were included between March 2018 and December 2021, 37 with CRT followed by durvalumab and 34 with CRT alone. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated since the date of the end CRT. Propensity score matching (PSM) 1:1 was used to account for differences in baseline characteristics. Results: Median age was 67 years (range 46-82). 25.4% of the patients were _75 years old. 78.9% were men and 53.5% former smokers. 54.9% had squamous histology and 28%, 51% and 21% stage IIIA, IIIB and IIIC disease, respectively. The most used scheme was carboplatinpaclitaxel (43.7%), receiving induction chemotherapy in up to 54.9% of patients. 73.2% received between 60-66 Gy doses of radiotherapy. Median time from end of CRT to onset durvalumab was 44 days (range 13-120) with a median of 14 infusions (range 6-27). Of the 34 patients without durvalumab treatment, the expression PD-L1 <1% (58.8%) was the most frequent cause for rejecting consolidation therapy. After PSM analysis, patients distributions were well balanced. With a median follow-up of 19.7 months (range 1.4-36.6); median rw-PFS was 9.3 months (95% CI, 5-13.5) without durvalumab and 17 months (95% CI, 11-22.9) with durvalumab (p¼0.013). Median rw-OS was 19.3 months (95% CI, 3.8-34.8) without durvalumab and 29.9 months (95% CI, 23.3-36.6) with durvalumab (p¼0.241) with a rw-OS% at 6, 18 and 24 months of 90%, 62% and 49% vs 100%, 86% and 74%, respectively. The rate of radiation pneumonitis was more frequent with durvalumab consolidation (56.8% against 44.1%), (p¼0.346), especially within 3 months after CRT. G3 pneumonitis was only observed in the consolidation therapy. Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation after CRT in real-world patients with unresectable stage III NSCLC. Further sample and longer follow-up are required to obtain more accurate results. Active surveillance and appropriate management for radiation pneumonitis are needed, in especially in candidates for consolidation treatmentS

EP05.02-002 Who Benefits More of Durvalumab after Chemoradiotherapy (CRT) in Real-World Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)?

[EN] Introduction: Durvalumab received EMA approval as consolidation therapy (CT) for unresectable stage III NSCLC with PD-L1 _1% and who did not have progression after CRT. Our objective was to analyze in real clinical practice the effectiveness of durvalumab and explore the clinical factors that may be associated with the benefit from CT. Methods: Retrospective study was made at Hospital of Leon (Spain), including 37 patients with locally advanced NSCLC treated with durvalumab after CRT treatment between March 2018 and october 2021 (40.5% patients were included in the durvalumab early access program). The neutrophil-to-lymphocyte ratio (NLR) could identified after CRT as a factor that may be benefit from durvalumab. Results: Median age was 67 years (range 46-82 years). 40.5% of patients were _70 years old. 78.4% were male and 51.4% smokers. 54% had non-squamous histology. PD-L1 expression was <1% in 5% and not available in 8% patients. 2.7% ROS1 rearrangements, 5.4% KRAS mutations and not available in 43.2% patients. Stage IIIA, IIIB, IIIC disease were 24.3%, 54.1% and 21.6%, respectively. Median time from end of CRT to onset durvalumab was 44 days (range 13-120 days). Overall median CT duration was 214.8 days (range 69-399 days) with a median of 14 infusions (range 6-27 infusions). With a median follow up of 19.7 months (range 1.4-34.9 months); 67.6% had stopped CT: 37.8% due to completing treatment, 16.2% disease progression, 10.8% adverse event and 2.7% due to COVID19 infection. Median real-world progressionfree survival (rwPFS) was 17 months (95% CI, 11-23). Median realworld overall survival (rwOS) was 29.9 months (95% CI, 23.3-36.6). % rwOS at 6, 18 and 24 months were 100%, 86.9% and 74.5%, respectively. For patients with post-CRT NLR not exceeding the cohort median value of 6, receipt of durvalumab was associated with an improvement in rwOS (median not reached vs 25.7 months; p¼0.025). 56.8% patients had any grade of radiation pneumonitis (median time from CRT start: 119 days [range 36-241 days]). Of these, 19% patients developed worsening of radiation pneumonitis with durvalumab. 54,1% developed immune-mediated toxicity, mostly G1-2 (85.1%). Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation in this patients population in a real-life setting. We identified low NLR after CRT as a potentially predictive factor for the benefit of CT in locally advanced NSCLC.S

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

Transiciones, conflictos y democracia : estudios de coyuntura

México ha vivido un largo proceso de transición que ha desencadenado dinamismos económicos, culturales y políticos. En la actual coyuntura, estos dinamismos muestran toda su complejidad, su inevitable articulación y la tensión entre las fuerzas que intentan sostener un viejo modelo de gobernar y decidir el rumbo del país, y aquellas que buscan abrirse a un espectro mucho más amplio y diversificado de actores. En ellos se conjuntan las aspiraciones más legítimas de los mexicanos por avanzar en el reconocimiento y respeto de la pluralidad étnica, de género y entre generaciones, y por impulsar una dinámica en la que —en medio de los procesos de mundialización— los distintos grupos e intereses de los mexicanos puedan ser incluidos. La transición mexicana tiende a centrarse en la dimensión política. La intensidad que cobran los procesos políticos y el énfasis que importantes analistas ponen en dichos procesos, contribuyen a que esta asociación vaya cobrandoíuerza. En este sentido, es necesario advertir que en las transiciones la tendencia privatizadora, la reducción del gasto social, así como la necesidad de pactos sociales que sean respetados, la participación creciente de la sociedad civil, etc. son factores importantes que, en medio de contradicciones, van generando nuevos esquemas de relación entre gobierno y sociedad.ITESO, A.C

Indirect DNA Readout by an H-NS Related Protein: Structure of the DNA Complex of the C-Terminal Domain of Ler

Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family

The labor market effects of technology shocks

We analyze the effects of neutral and investment-specific technology shocks on hours worked and unemployment. We characterize the response of unemployment in terms of job separation and job finding rates. We find that job separation rates mainly account for the impact response of unemployment while job finding rates for movements along its adjustment path. Neutral shocks increase unemployment and explain a substantial portion of unemployment and output volatilityinvestment-specific shocks expand employment and hours worked and mostly contribute to hours worked volatility. We show that this evidence is consistent with the view that neutral technological progress prompts Schumpeterian creative destruction, while investment specific technological progress has standard neoclassical feature

HAWC Study of Very-High-Energy γ\gamma-ray Spectrum of HAWC J1844-034

Recently, the region surrounding eHWC J1842-035 has been studied extensively by gamma-ray observatories due to its extended emission reaching up to a few hundred TeV and potential as a hadronic accelerator. In this work, we use 1,910 days of cumulative data from the High Altitude Water Cherenkov (HAWC) observatory to carry out a dedicated systematic source search of the eHWC J1842-035 region. During the search we have found three sources in the region, namely, HAWC J1844-034, HAWC J1843-032, and HAWC J1846-025. We have identified HAWC J1844-034 as the extended source that emits photons with energies up to 175 TeV. We compute the spectrum for HAWC J1844-034 and by comparing with the observational results from other experiments, we have identified HESS J1843-033, LHAASO J1843-0338, and TASG J1844-038 as very-high-energy gamma-ray sources with a matching origin. Also, we present and use the multi-wavelength data to fit the hadronic and leptonic particle spectra. We have identified four pulsar candidates in the nearby region from which PSR J1844-0346 is found to be the most likely candidate due to its proximity to HAWC J1844-034 and the computed energy budget. We have also found SNR G28.6-0.1 as a potential counterpart source of HAWC J1844-034 for which both leptonic and hadronic scenarios are feasible.Comment: 13 pages, 9 figures, published in Ap

Gamma/Hadron Separation with the HAWC Observatory

The High Altitude Water Cherenkov (HAWC) gamma-ray observatory observesatmospheric showers produced by incident gamma rays and cosmic rays with energyfrom 300 GeV to more than 100 TeV. A crucial phase in analyzing gamma-raysources using ground-based gamma-ray detectors like HAWC is to identify theshowers produced by gamma rays or hadrons. The HAWC observatory records roughly25,000 events per second, with hadrons representing the vast majority($>99.9\%$) of these events. The standard gamma/hadron separation technique inHAWC uses a simple rectangular cut involving only two parameters. This workdescribes the implementation of more sophisticated gamma/hadron separationtechniques, via machine learning methods (boosted decision trees and neuralnetworks), and summarizes the resulting improvements in gamma/hadron separationobtained in HAWC.<br