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Aims: The subcutaneous implantable cardioverter-defibrillator (S-ICD) requires screening prior to implantation. Surface anatomical landmarks (SAL) guide the screening. The heart silhouette shows variations, therefore, these landmarks may differ. We aimed to determine the concordance between SAL and fluoroscopy guided screening, and analyze discordance predicting factors. Methods: We performed a conventional SAL guided screening (CS) in left and right parasternal electrode position (LPP/RPP) to candidates for S-ICD. Subsequently, we performed a fluoroscopy guided screening (FGS) according to cardiac silhouette. Screenings in which at least the result of one sensing vector did not coincide were considered “discordant”. A comparison was done between discordant vs. concordant cases. A simple binary logistic regression analysis was performed to assess the risk of being discordant individually for each of the variables. Results: The results of CS and FGS were compared in 110 patients (220 comparisons: 110 LPP and 110 RPP). 90 (40.91%) were discordant in at least one sensing vector (46 in LPP and 44 in RPP). In 3 patients (2.73%) the indication of which type of defibrillator was implanted changed according to the FGS. There were no significant differences between the discordant and concordant screening patients. Conclusion: There is a level of discordance between CS and FGS. There were no analyzed factors that were able to predict discordance between these two screening methods. It might be reasonable to perform FGS before implant.

This retrospective study evaluated 66 patients diagnosed with relapsed and/or refractory mantle cell lymphoma (R/R MCL) treated with ibrutinib in Spain in routine clinical practice. At diagnosis, patients had a median age of 64.5 years, 63.6% presented with intermediate/high sMIPI (simplified prognostic index for advanced-stage mantle cell lymphoma), 24.5% had the blastoid variant, and 55.6% had a Ki67 > 30%. Patients had received a median of 2 prior lines of therapy (range 1-2; min-max 1-7). Overall response rate was 63.5%, with 38.1% of patients achieving complete response (CR). With a median duration of ibrutinib exposure of 10.7 months (range 5.2-19.6; min-max 0.3-36), the median progression-free survival (PFS) and overall survival (OS) were 20 months [95% confidence interval (CI) 8.8-31.1] and 32 months (95% CI 22.6-41.3), respectively, and were not reached in patients achieving CR. No grade >= 3 cardiovascular toxicity or bleeding was reported. This study supports that treatment with ibrutinib leads to high response rates and favorable survival outcomes in patients with R/R MCL.

Technologies for control of indoor air quality are very important to ensure that health and comfort conditions are attained in closed environments. The indoor air quality market is fertile ground for adsorption technologies, both at larger industrial scale and for residential uses. The common strategy to design adsorption technologies considers constant inlet conditions, while for most indoor air control applications, the inlet conditions will change because of the partial removal of the contaminant. This work presents a generic modelling approach, where the adsorption technology is coupled with the indoor environment to be controlled. This approach enables a tailored and more accurate process design and additionally, it can also assist in the physical location of the removal unit and sensors to control its operation. Two different examples of application of this methodology are provided: control of CO2 in tightly closed environments and "peak shaving" of water vapor in bathrooms.

In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we use an ultra-deep sequencing approach with 2 · 10− 4 sensitivity (LiqBio-MRD) to track those mutations on 156 follow-up liquid biopsy samples from 55 treated patients. Positive LiqBio-MRD correlated with a higher risk of progression both at the interim evaluation (HR 13.0, 95% CI 2.70–63.4, p p p p

Introduction and Objectives Since different PET/CT (Positron Emission Tomography/Computed Tomography) scanners give different qualitative readings, a program for clinical trial qualification (CTQ) is mandatory to guarantee a reliable and reproducible use of PET/CT in prospective multi-centre clinical trials. Within this work we will show the results carried out in performing CTQ in Spain. Materials and Methods We set up, under the auspices of Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GELTAMO), a CTQ program consisting of the acquisition and analysis of 18 F uniformity and image quality phantoms for the reduction of inter-scanner variability (ISV). The ISV was estimated on background activity concentration (BAC) and sphere to background ratio (SBR) and defined as their 95% confidence level. Results Twenty-six out of 27 (96%) scanners fulfilled the CTQ requirements. The CTQ was fulfilled at the first round in 27% of the cases, while in 38%, 15% and 20%, two, three or more than three iterations, were required, respectively. The mean CTQ time was (1.8 ± 1.4) months (range: 0.3–4.6). The ISV in BAC and SBR were 20.3% and 67.7%. Conclusions The CTQ proven to be a reliable tool to reduce ISV. This enabled to set-up clinical trials in which PET/CT was used to evaluate different clinical endpoints.

espanolIntroduccion y objetivos Dado que los diferentes escaneres de PET/TC (tomografia por emision de positrones/tomografia computarizada) dan lecturas cualitativas diferentes, es obligatorio un programa de cualificacion de ensayos clinicos (CTQ) para garantizar un uso fiable y reproducible de la PET/TC en ensayos clinicos prospectivos multicentricos. Dentro de este trabajo mostraremos los resultados en la realizacion de CTQ en Espana. Materiales y metodos Hemos puesto en marcha, bajo los auspicios del Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GELTAMO), un programa de CTQ que consiste en la adquisicion y analisis de fantomas de uniformidad 18F y calidad de imagen para la reduccion de la variabilidad interescaner (ISV). La ISV se estimo sobre la concentracion de actividad de fondo (BAC) y la relacion esfera a fondo (SBR) y se definio como su intervalo de confianza (IC) del 95%. Resultados Veintiseis de los 27 escaneres (96%) cumplieron los requisitos de la CTQ. El CTQ se cumplio en la primera ronda en el 27% de los casos, mientras que en el 38%, 15% y 20% se requirieron dos, tres o mas de tres iteraciones, respectivamente. El tiempo medio de la CTQ fue de 1,8 ± 1,4 meses (rango: 0,3-4,6). El ISV en BAC y SBR fue 20,3 y 67,7%. Conclusiones El CTQ demostro ser una herramienta fiable para reducir la ISV. Esto permitio poner en marcha ensayos clinicos en los que se utilizo la PET/TC para evaluar diferentes criterios de valoracion clinica. EnglishIntroduction and objectives Since different PET/CT (Positron Emission Tomography/Computed Tomography) scanners give different qualitative readings, a program for clinical trial qualification (CTQ) is mandatory to guarantee a reliable and reproducible use of PET/CT in prospective multi-centre clinical trials. Within this work we will show the results carried out in performing CTQ in Spain. Materials and methods We set up, under the auspices of Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GELTAMO), a CTQ program consisting of the acquisition and analysis of 18F uniformity and image quality phantoms for the reduction of inter-scanner variability (ISV). The ISV was estimated on background activity concentration (BAC) and sphere to background ratio (SBR) and defined as their 95% confidence level. Results Twenty-six out of 27 (96%) scanners fulfilled the CTQ requirements. The CTQ was fulfilled at the first round in 27% of the cases, while in 38%, 15% and 20%, two, three or more than three iterations, were required, respectively. The mean CTQ time was (1.8 ± 1.4) months (range: 0.3-4.6). The ISV in BAC and SBR were 20.3% and 67.7%. Conclusions The CTQ proven to be a reliable tool to reduce ISV. This enabled to set-up clinical trials in which PET/CT was used to evaluate different clinical endpoints.

Introduction:Recently there has been a renewal of therapeutic tools for the treatment of lymphoid neoplasms to increase the antitumor efficacy and reduce the toxicity generated by conventional chemotherapies, which adds to the intrinsic immunological dysfunction of the disease itself. To date, few data are published about infection risk of these new drugs, and the need for infectious prophylaxis is unknown. The aim of the study is to analyze the infectious complications in patients with LPD treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab and pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib) and PI3K inhibitors (idelalisib). Methods: Multicenter retrospective study in patients with LPD treated with targeted therapies (single agents or combination) in 18 Hematology centers in Spain, from the time of their commercial availability to March 2020. Patients in clinical trials were excluded as well as patients with active infections at the beginning of treatment. Results:During the study period, 380 patients were included.Baseline characteristics of the entire cohort are shown in Table 1.Median follow-up was 17.3 months (range 0-103), the longest follow-up corresponding to CLL patients (24 months, range 0-98) and the shortest to LBCL (5 months, range 0-25). Median exposure to target drugs was 8 months (range 0-72).Ibrutinib was administered to 219 patients(1 FL, 147 CLL, 27 MCL, 10 DLBCL, 1 TL and 32 WM, 1 HL),Brentuximab to 49(31 HL, 14 TL and 4 DLBCL) andIdelalisibto 35 patients (16 affected by chronic lymphocytic leukemia - CLL, 15 FL and 1 DLBCL, 1 WM, 1MCL, 1HL).Obinutuzumabcombinations were used in 10 (6 CLL, 3 FL, 1 MCL) and 5 HL patients (of which 4/5 underwent previous BMT) receivedNivolumab. A total number of 237 infectious events occurred in 148/380 patients (38.9%), 39% of which were grade 3 and 54/148 (36.4%) experienced 2 or more infective episodes: of those 54, 21 (38%) had underwent 3 or more lines of therapy and 28 (51%) had hypogammaglobulinemia. Hospitalization was required in 59.2% events. A bacterial cause of infection was reported in 40% of cases, and viral in 16%, including 11/237 (4,6%) SARS-CoV-2 infection. Invasive fungal infection (IFI) occurred in 3.3% (8/237). Noteworthy, no case of PJP was identified. Lung was the most frequent site of infection in 24% of cases (57/237) while the upper respiratory tract was involved in 17% of events (41/237). Urinary tract infections were diagnosed in 10% (24/237). Other sites involved were skin and soft tissue 7%, gastrointestinal tract 5,4%, bloodstream infections 3% and catheter related infections 2,5%. Considering drugs individually, 86 patients that receivedIbrutinib(39.2 %)experienced a total of 137 infectious episodes: 30% bacterial, 19% viral, 5% fungal and 45% clinical and image-based infections; the 17(34.6%of those who received Brentuximab, experienced a total of 16 infectious episodes: 56% bacterial, 37.5% viral infections and one catheter-related sepsis. Of those who receivedIdelalisib,18 (51.4%)experienced a total of 28 episodes: 42% bacterial, 14% viral and 7% fungal. Four patients treated withObinutuzumabcombinations (40%) experienced one infection during treatment (25% bacterial and 75% viral). Only one patient treated withNivolumabexperienced more than three infections, he was also under corticosteroid treatment. Focusing on IFI (Table 2): 7/8 infections were identified in CLL patients, 6 out 7 being on ibrutinib treatment and 1/7 on Idelalisib.Aspergilluswas the fungus most frequently isolated. The targeted drug was discontinued temporarily in 4 patients and indefinitely in 3. Twenty three (6%) patients died due to infection in our series. Conclusions: 1. We identified 38.7% infections in our LPD patients treated with targeted drugs, with a median drug-exposure time of 8 months (range 0-72), with a non-negligible incidence of bacterial infections. 2. The highest rates of infection were found in patients treated with with Idelalisib and Ibrutinib (51.4% and 39.2% respectively). 3. IFI (3.3%) occurred with low frequency, mostly in CLL patients during ibrutinib treatment, leading to its temporal discontinuation in most of the cases. 4. No case of PJP was identified in our cohort. 5. An analysis to determine risk factors for infection and the optimal monitoring and prophylaxis for these patients is ongoing. Disclosures Hernandez-Rivas: Janssen:Membership on an entity's Board of Directors or advisory committees;Abbvie:Membership on an entity's Board of Directors or advisory committees;Roche:Membership on an entity's Board of Directors or advisory committees;AstraZeneca:Membership on an entity's Board of Directors or advisory committees;Gilead:Membership on an entity's Board of Directors or advisory committees;Celgene/BMS:Membership on an entity's Board of Directors or advisory committees;Rovi:Membership on an entity's Board of Directors or advisory committees.Lopez-Guillermo:novartis:Consultancy;celgene:Consultancy, Research Funding;roche:Consultancy, Research Funding;gilead:Consultancy, Research Funding.

espanolEl procesamiento de frutas y verduras genera alrededor de 1,3 billones de toneladas por ano de residuos a lo largo de toda la cadena de produccion. Con el proposito de agregar valor a los residuos de mora provenientes de una despulpadora de un mercado local, se determino la capacidad antioxidante y antibacteriana con tres cepas de bacterias. Los residuos presentaron una alta cantidad de la antocianina cianidina-3-rutinosido (2520 mg/kg de muestra) mediante el analisis del sistema de cromatografia liquida de ultra alta resolucion (UHPLC), una acidez titulable de 1,28 %, un pH acido 3,23 y un contenido de cenizas de 0,45 %. El extracto hidrometanolico 80:20 % (v/v) presento la mayor capacidad antioxidante por el metodo DPPH (40,53 µmol equivalente trolox, TE), mientras que el extracto liofilizado mostro la mayor capacidad antioxidante por el metodo del acido 2,2´-azino-bis (3-etilbenzotiazolina-6-sulfonico) (ABTS) (60,31 µmol equivalente trolox, TE). La actividad antibacteriana dependio de la cantidad del extracto hidrometanolico y del tipo de cepa (las Gram positivas fueron mas sensibles), siendo S. aureus la bacteria mas sensible (15,3 mm a 8 mg/mL de extracto). S. aureus y E. coli presentaron una sensibilidad alta respecto a la concentracion minima inhibitoria (MCI) (3 mg/mL y 4 mg/mL, respectivamente). EnglishFruit and vegetable production generate around 1.3 billion tons per year of waste throughout the entire production chain. To add value to blackberry residues, the antioxidant and antibacterial capacity was determined with three strains of bacteria. The residues showed a high amount of the anthocyanin cyanidin-3-rutinoside (2520 mg/kg of the sample) by UHPLC analysis, titratable acidity of 1.28 %, an acidic pH 3.23, and a content of ashes of 0.45 %. The 80:20 % (v/v) hydromethanolic extract presented the highest antioxidant capacity by the DPPH method (40.53 µmol Trolox equivalents, TE), while the lyophilized extract presented a superior antioxidant capacity by the ABTS method (60.31 µmol Trolox equivalents, TE). Antibacterial activity was dependent on the concentration of the hydromethanolic extract and the type of strain (Gram-positive were most sensitive than Gram-negative), with Staphylococcus aureus being the most sensitive bacteria (15.3 mm at 8 mg/mL of extract). S. aureus and Escherichia coli presented a high sensitivity concerning the MCI (3 mg/mL and 4mg/mL, respectively).

El objetivo del estudio fue conocer el porcentaje medio de accesibilidad física de un conjunto de instalaciones deportivas convencionales en Extremadura, así como determinar el porcentaje de accesibilidad de cada de una de las zonas que formaban parte de dichas instalaciones deportivas. Específicamente, 38 pistas polideportivas cubiertas fueron analizadas (19 de la provincia de Cáceres y 19 de la provincia de Badajoz), cumplimentando un total de 1673 ítems con el cuestionario de accesibilidad propuesto por el Consejo Superior de Deportes y el Instituto Biomecánico de Valencia (CSD/IBV, 2009). Los resultados mostraron que el porcentaje medio de accesibilidad fue del 50.6%. Las zonas con mayor puntuación de accesibilidad fue el de salas y despachos (72%), y ascensores (88%). En cambio, las zonas con menor accesibilidad fueron la recepción (13%) y el comedor/restaurante/bar (33%). Estos resultados revelan que la accesibilidad física no fue completa y que, por tanto, colectivos de personas con movilidad reducida podrían disminuir su participación en los programas deportivos ofertados al encontrar diferentes barreras de entrada en los espacios deportivos analizados. Se recomienda mejorar la accesibilidad física de los espacios deportivos ya que ayudaría a mejorar la integración y normalización de personas con discapacidad física en las actividades cotidianas de la sociedad. Abstract. The purpose of this study was to find out the mean percentage of physical accessibility of a group of conventional sports facilities in Extremadura, and also to determinate the percentage of accessibility of each different zone that constitutes these sports facilities. Specifically, 38 indoor courts from pavilions were analyzed (19 from the province of Caceres and 19 from the province of Badajoz), filling out 1673 items with the accessibility questionnaire proposed by the Spanish Sports Council and the Biomechanical Institute of Valencia (CSD/IBV, 2009). The results showed that the average percentage of accessibility was 50.6%. The zones with the highest accessibility score were the rooms and offices (72%), and elevators (88%). On the contrary, the areas with the lowest accessibility rate were the reception (13%), and the dining hall/restaurant/bar (33%). These results revealed that physical accessibility is not complete, and therefore, the participation of groups of persons with reduced mobility in sport programmes offered by the local governments could decrease due to the existence of different accessibility barriers. It is recommended to improve the physical accessibility in sports facilities since it would increase the participation of people with reduced mobility in sports activities, and therefore, their integration and normalization in the daily activities of society.

Anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) have shown promise in follicular lymphoma (FL) as post-induction therapy, by enhancing antibody-dependent cellular cytotoxicity (ADCC). However, cytotoxic cells are reduced after this treatment. We hypothesised that ex vivo expanded lymphokine-activated killer (LAK) cells administered to FL-remission patients are safe and improve anti-CD20 efficacy. This open, prospective, phase II, single-arm study assessed safety and efficacy of ex vivo expanded LAK cells in 20 FL-remission patients following rituximab maintenance. Mononuclear cells were obtained in odd rituximab cycles and stimulated with interleukin 2 (IL-2) for 8 weeks, after which >5 × 108 LAK cells were injected. Patients were followed-up for 5 years. At the end of maintenance, peripheral blood cells phenotype had not changed markedly. Natural killer, LAK and ADCC activities of mononuclear cells increased significantly after recombinant human IL-2 (rhIL-2) stimulation in all cycles. Rituximab significantly enhanced cytotoxic activity. No patients discontinued treatment. There were no treatment-related serious adverse events. Three patients had progressed by the end of follow-up. After a median (interquartile range) follow-up of 59.4 (43.8-70.9) months, 85% of patients remained progression free. No deaths occurred. Quality-of-life improved throughout the study. Post-induction LAK cells with rituximab seem safe in the long term. Larger studies are warranted to confirm efficacy.

Lymphomas are a large, heterogeneous group of neoplasms with well-defined characteristics, and this heterogeneity highlights the importance of epidemiological data. Knowledge of local epidemiology is essential to optimise resources, design clinical trials, and identify minority entities. Given there are few published epidemiological data on lymphoma in Spain, the Spanish Lymphoma and Autologous Bone Marrow Transplant Group created the RELINF project. The aim of this project is to determine the frequencies and distribution of lymphoid neoplasms in Spain and to analyse survival. We developed an online platform for the prospective collection of data on newly diagnosed cases of lymphoma in Spain between January 2014 and July 2018; 11,400 patients were registered. Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) were the most frequent lymphomas in our series. Marginal B cell lymphoma frequency was higher than that reported in other studies, representing more than 11% of mature B cell lymphomas. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) was the most common subtype of T cell lymphoma, and NK/T cell lymphomas were more frequent than expected (5.4% of total). Hodgkin's lymphoma accounted for 12% of lymphoproliferative syndromes. Overall survival was greater than 90% at 2 years for indolent B cell lymphomas, and approximately 60% for DLBCL, somewhat lower than that previously reported. Survival was poor for PTCL-NOS and angioimmunoblastic T cell lymphoma, as expected; however, it was somewhat better than that in other studies for anaplastic large cell anaplastic lymphoma kinase lymphomas. This is the first prospective registry to report the frequencies, distribution, and survival of lymphomas in Spain. The frequencies and survival data we report here are globally consistent with that reported in other Western countries. These updated frequencies and survival statistics are necessary for developing appropriate management strategies for neoplasias in the Spanish population.

Polyacrylonitrile (PAN) nanofibers were prepared by electrospinning and coated with zeolitic imidazolate framework-8 (ZIF-8) by a phase conversion growth method and investigated for CO2 capture. The PAN nanofibers were pre-treated with NaOH, and further coated with zinc hydroxide, which was subsequently converted into ZIF-8 by the addition of 2-methyl imidazolate. In the resulting flexible ZIF-8/PAN composite nanofibers, ZIF-8 loadings of up to 57 wt% were achieved. Scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS) showed the formation of evenly distributed submicron-sized ZIF-8 crystals on the surface of the PAN nanofibers with sizes between 20 and 75 nm. X-ray photoelectron spectroscopy (XPS) and carbon-13 nuclear magnetic resonance (13C NMR) investigations indicated electrostatic interactions and hydrogen bonds between the ZIF-8 structure and the PAN nanofiber. The ZIF-8/composite nanofibers showed a high BET surface area of 887 m2 g−1. CO2 adsorption isotherms of the ZIF-8/PAN composites revealed gravimetric CO2 uptake capacities of 130 mg g−1 (at 298 K and 40 bar) of the ZIF-8/PAN nanofiber and stable cyclic adsorption performance.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Objective/Background: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era—that is, in patients treated in induction and rescued only with chemotherapy. Methods: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). Results: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of

Background: Freezing rate of second-generation cryoballoon (CB) is a biophysical parameter that could assist pulmonary vein isolation. The aim of this study is to assess freezing rate (time to reach –30°C ([TT-30C]) as an early predictor of acute pulmonary vein isolation using the CB. Methods: Biophysical data from CB freeze applications within a multicenter, nation-wide CB ablation registry were gathered. Successful application (SA), was defined as achieving durable intraprocedural vein isolation with time to isolation in under 60 s (SA-TTI

In the finance sector, time series forecasting has been widely used in situations such as stock prices forecasting and equity market forecasting. In recent years, techniques of computer vision include become increasingly popular in the monetary assumption of periodicity. A hot subject is how to mark information from macroeconomic variables to assess the accuracy rate of computer vision techniques and, as a result, final investment returns. Existing information from macroeconomic variables labelling methods primarily mark data and comparing current data to data from a limited period in the future. Information from a macroeconomic variable, on the other hand, are often quasi, with apparent unpredictability in the brief period. As a result, such tagging methods struggled to identify the time series analysis information’s persistent trend functionality, resulting in a misalignment among their pigeonhole results and actual market inclination. A new pigeonhole approach called “continuous trend labeling” is proposed in this paper to fix the issue. This article presents a novel feature preprocessing tack that avoids taking a gander distortion that plagues continuous data consistency and preprocessing approaches. The principle of constant trend marking and an advanced tagging framework for removing consistent trend characteristics from time-series data were then presented, along with a detailed logical explanation. Experiments on the ensembled model yielded a scoring accuracy of 52 percent, which was close to the Cagliari teams. The results were determined by combining all of the networks' ratings. Even though it appears to be a low percentage, being right on a trade position more than 50% of the time is considered good, particularly when looking at the data in isolation. Our labelling system is significantly superior to classifiers and other identification evaluation measures; province tagging approaches are used. According to the observations of the study, word embeddings like LSTM and GRU are suitable to finance related time series data prediction.

Polyacrylonitrile (PAN) nanofibers were prepared by electrospinning and coated with zeolitic imidazolate framework-8 (ZIF-8) by a phase conversion growth method and investigated for CO

Follicular lymphoma (FL) is considered an indolent disorder with a relatively favourable course. With modern day treatments, long remissions are often achieved both in front-line and relapsed settings. However, a subset of patients has a more aggressive course and a poorer outcome. Both, PET-CT and minimal residual disease (MRD) evaluation by PCR defines groups of patients with different prognoses. MRD measurement by NGS is being studied to predict relapse prior to diagnostic imaging in large B cell lymphoma; however, it has never been used in FL. The aim of the present study is to validate a sensitive and standardizable approach to measure liquid Biopsy MRD (LiqBio-MRD) by NGS with >90% applicability and 2E-4 resolution, and to analyse its prognostic impact in FL patients. Firstly, the best source to identify genetic MRD markers was determined. Genomic DNA from paraffin embedded (FFPE) lymph node biopsies and/or cell free DNA (cfDNA) from peripheral blood (PB) was obtained from 29 FL cases at diagnosis and sequenced with a short length Ampliseq Custom Panel (Thermo-Fisher). This panel was designed to cover all coding regions of 56 lymphoma specific genes in FFPE and cfDNA samples. By applying this panel with an average depth of 700X, a total of 122 somatic mutations were detected in 37 baseline samples. 15 of these lymph node samples presented 65 mutations (average of 4 mutations per patient, rank 1-9), with a mean Variant Read Frequency (VRF) of 0.33 (0.06-0.77). On the other hand, the 21 cfDNA samples presented 71 mutations (average of 3 mutations per patient, rank 0-8), with a mean VRF of 0.21 (0.02-1.0). Notably, in 3 cases the mutations were only detected in the lymph node. Paired samples were available for 13 cases. Of the 72 somatic mutations identified in these cases, only 14 were present in both samples (Figure 1A, left). Besides the higher number of mutations in the lymph nodes, a mean decrease of 0.14 VRF was observed in cfDNA (0.21; 0.03-0.53) compared to lymph nodes (0.35; 0.09-0.76) (Figure 1A, Right). From the initial 29 FL cases, 16 had PB sequential samples available. Three patients were put under observation and the rest received an anthracycline based regimen plus R-maintenance. In treated patients, PET-CT was carried out at diagnosis and after 4 and 6 cycles of treatment. During follow-up, cfDNA was available after 4 (n=10) and 6 cycles of treatment (n=10). Median follow up was 18 months. To quantify LiqBio-MRD in the 31 follow-up samples, we defined an approach involving the sequencing of 12 NGS data points per mutation identified at diagnosis. Three of these data points were tumour sample replicates. The other 9 points were obtained from healthy control donor DNA. All LiqBio-MRD samples were sequenced with at least 100.000x and analysed applying the NGS-MRD algorithm described elsewhere (Onecha, E et al. Hematologica 2019). The mean mutation rate (noise) in controls for the studied mutations was 1.4E-5 (0 - 8E-5) below the targeted sensibility of 2E-4. The LOD was defined for every follow-up sample based on the initial amount of cfDNA used in the test. On average 39.6ng (13-66 ng) were used for cfDNA MRD monitoring. All somatic mutations were considered potential MRD markers (Figure 1B), however the degree of MRD in each follow-up sample was defined by the somatic mutation with higher VRF. MRD values were significantly lower in complete response (CR) cases compared to those with active disease (p=0.001, Figure 1C, left). Notably, MRD positivity in the interim or at the end of treatment resulted in significantly inferior PFS (median 12 months vs not reached, P = 0.09, Figure 1C, right). An extension of the cohort and clinical impact of LiqBio-MRD test will be presented at the meeting. Our results demonstrate for the first time that NGS based MRD quantification is feasible in Liquid Biopsies from FL. Despite the marked spatial genetic heterogeneity of FL, which is better identified in cfDNA, the dilution of the signal in these samples suggests the use of both; lymph node biopsies and cfDNA at diagnosis to identify all potential MRD markers. The lower degree of MRD in CR evaluations (according to the 2014 Lugano response assessment) and the existence of patients in CR with positive and negative MRD suggest the potential of our LiqBio-MRD test to prospectively identify patients with different outcome. Nevertheless, more patients and a longer follow-up are necessary to draw meaningful conclusions. Figure 1 Disclosures Heredia: Altum sequencing: Current Employment. Rufian:Altum sequencing: Current Employment. Carrillo:Altum sequencing: Current Employment. Wang:Hosea Precision Medical Technology Co., Ltd: Current Employment. Canales:Janssen: Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Takeda: Speakers Bureau; Sandoz: Honoraria; Janssen: Speakers Bureau; Novartis: Honoraria; Sandoz: Speakers Bureau; Janssen: Speakers Bureau; Takeda: Speakers Bureau; Roche: Honoraria; iQone: Honoraria; Janssen: Honoraria; Sandoz: Honoraria; Novartis: Honoraria; Roche: Honoraria; Roche: Speakers Bureau; Karyopharm: Honoraria; Gilead: Honoraria; Sandoz: Speakers Bureau; Roche: Speakers Bureau. Martinez-López:Janssen, BMS, Sanofi, Novartis, Incyte, F. Hoffmann-La Roche and Amgen: Honoraria, Other: Advisory boards; Janssen, Novartis, BMS, Incyte: Consultancy; Hosea and Altum: Membership on an entity's Board of Directors or advisory committees.

TPS7586 Background: EO2463 is a therapeutic vaccine designed to activate existing commensal bacteria-specific memory T cells that cross-react with B cell markers in order to drive anti-tumor immune activity against B-cell malignancies. The four microbial-derived, synthetically produced peptides contained in EO2463 (OMP72, OMP64, OMP65, and OMP66), correspond to cytotoxic CD8 T cell HLA-A2 restricted epitopes, and exhibit molecular mimicry with the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor), respectively. In pre-clinical models, these peptides can generate strong immune responses and specifically stimulate cross-reactive cytotoxic CD8 T cells to recognize the chosen B cell targets. EO2463 also contains a CD4 helper peptide referred to as universal cancer peptide 2, derived from the human telomerase reverse transcriptase catalytic subunit. The present study is a first-in-human clinical trial of this microbiome-derived peptide therapeutic cancer vaccine approach in patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL). Methods: This four-cohort phase 1/2 trial will investigate EO2463 monotherapy, and combinations of EO2463/lenalidomide (EL), EO2463/rituximab (ER), and EO2463/lenalidomide/rituximab (ER2), for treatment of patients with FL and MZL. Cohort 1 is a safety lead-in dose-finding in patients with relapsed/refractory (RR) disease, with a 3-by-3 design to establish the recommended phase 2 dose (RP2D) for EO2463 monotherapy and to confirm the safety of the RP2D for combination schedules of EL, and ER2. After the recommended EO2463 monotherapy dose is established, cohorts 2, 3, and 4 will open to accrual. Cohort 2 will investigate EO2463 monotherapy in patients with newly diagnosed FL/MZL who are not in need of treatment; cohort 3 will investigate EO2463 monotherapy, followed by ER in patients with limited tumor burden who need treatment, and cohort 4 will further investigate EL, followed by ER2 in the RR setting. EO2463 will be administered SC 4 times at 2-week intervals, followed by continued booster administrations every 4 weeks for 9 (Cohorts 2 and 3) or 12 (Cohorts 1 and 4) months. Inclusion/exclusion criteria, and the design and schedule of the intense immune and safety monitoring will be presented. The safety lead-in dose-finding is currently ongoing, and no safety concerns have been observed thus far. Clinical trial information: NCT04669171.

Background Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). Methods Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real‐life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. Results Severe infections incidence was 23% during 17‐month median follow‐up; cumulative incidence was higher in the first 3–6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3–1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1–4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05–3.3). Infection‐related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. Conclusion A high proportion of patients presented severe infections during follow‐up, with non‐negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered., Our data describe the infection risk associated with the use of targeted drugs in the treatment of lymphoproliferative diseases in real‐life setting and suggest some infection risk factors that could identify the need for antimicrobial prophylaxis in a selected group of patients.