A framework for user adaptation and profiling for social robotics in rehabilitation

Physical rehabilitation therapies for children present a challenge, and its success—the improvement of the patient’s condition—depends on many factors, such as the patient’s attitude and motivation, the correct execution of the exercises prescribed by the specialist or his progressive recovery during the therapy. With the aim to increase the benefits of these therapies, social humanoid robots with a friendly aspect represent a promising tool not only to boost the interaction with the pediatric patient, but also to assist physicians in their work. To achieve both goals, it is essential to monitor in detail the patient’s condition, trying to generate user profile models which enhance the feedback with both the system and the specialist. This paper describes how the project NAOTherapist—a robotic architecture for rehabilitation with social robots—has been upgraded in order to include a monitoring system able to generate user profile models through the interaction with the patient, performing user-adapted therapies. Furthermore, the system has been improved by integrating a machine learning algorithm which recognizes the pose adopted by the patient and by adding a clinical reports generation system based on the QUEST metricThis work is partially funded by grant RTI2018-099522-B-C43 of FEDER/Ministerio de Ciencia e Innovación - Ministerio de Universidades - Agencia Estatal de Investigació

Концепция создания гормонального контрацептивного средства с оптимальной фармакодинамикой

Приведены сведения о фундаментальных исследованиях стероидных соединений с гестагенной активностью, результатом которых стало создание дроспиренона. Представлены данные клинических исследований, доказывающие надежность контрацептивного эффекта нового препарата "Ярина(r)", содержащего дроспиренон и одновременно позволяющего получить ряд дополнительных преимуществ: повышение качества жизни, положительное влияние на общее самочувствие, хороший контроль цикла, уменьшение тяжести предменструальных симптомов, проявлений акне и себореи.The authors report about fundamental studies of steroid compounds with gestagenic activity, which stimulated Drospirenon production.The data of clinical investigations proving the reliability of contraceptive effect of a new drug Yarina(r) containing Drospirenon and allowing to obtain a number of additional advantages: improvement of the quality of life, positive influence on the general health, good control of the cycle, reduction of premenstrual signs severity, manifestations of acne and seborrhea are reported

Role of alkali-cyano group interaction in g-C3N4 based catalysts for hydrogen photo-production

Carbon nitride based materials incorporating K and Na alkali ions were used as support(s) to deposit platinum. The systems were tested in the photo-production of hydrogen using methanol as a sacrificial molecule. Tests under UV and sunlight-type illumination conditions showed an important promoting effect of the alkali ions irrespective of the illumination source characteristics. The measurement of the quantum efficiency was used to quantitatively assess the performance of the catalysts. Outstanding results were obtained, particularly under sunlight illumination. A complete characterization study of the materials was carried out to establish a structure-activity link. This link correlates catalytic activity with the capture of charge carrier species by surface cyano groups directly associated with the presence of alkali ions at the carbon nitride componen

Condicionantes pronósticos del ictus isquémico: utilidad de los biomarcadores sanguíneos en su predicción

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018El ictus es una de las principales causas de mortalidad y discapacidad en nuestro medio. El pronóstico del ictus depende en gran parte de factores basales no modificables como la edad o la gravedad inicial del mismo, pero también de circunstancias que ocurren durante la historia natural del mismo y conllevan un mal desenlace. En la presente tesis doctoral nos focalizamos en éstas últimas, las complicaciones del ictus. Así, nuestros objetivos en el presente trabajo son, en primer lugar, establecer cuáles de las complicaciones del ictus presentan un mayor impacto sobre el pronóstico del mismo en nuestro medio. En segundo lugar, evaluar en qué indicaciones el uso de biomarcadores sanguíneos constituye una necesidad asistencial. En tercer lugar, evaluar la asociación de los biomarcadores sanguíneos al pronóstico del ictus y las complicaciones del mismo en la literatura y, finalmente testar el valor predictivo de biomarcadores candidatos para las indicaciones identificadas en los puntos anteriores. Para esto hemos realizado un análisis del registro de ictus de la Sociedad Española de Neurología (RENISEN), en el que identificamos que el edema cerebral con hipertensión intracraneal y las infecciones respiratorias son las complicaciones con un mayor impacto sobre la mortalidad del ictus, encontrándose en un segundo escalón las complicaciones cardiológicas. Un interesante hallazgo de este análisis es que el impacto de esas complicaciones depende de la gravedad del ictus. Por otra parte, hemos realizado una encuesta a neurólogos vasculares europeos en los que vemos que la indicación más demandada para el uso de biomarcadores en el ictus es el manejo de las terapias de reperfusión. A través de revisiones sistemáticas y metaanálisis, hemos detectado que el uso de biomarcadores para el manejo de las complicaciones del ictus ha sido poco estudiado. De entre los marcadores metaanalizados, la proteína C-reactiva constituye un candidato para el manejo de las infecciones asociadas al ictus. Respecto a los estudios experimentales, hemos identificado dos candidatos nuevos para guiar las terapias de reperfusión, la proteasa activadora del factor VII (FSAP) y la proteasa de clivaje del factor de Von Willebrand (ADAMTS13), relacionadas con la recanalización arterial, y hemos descrito la utilidad de la medición de troponina I ultrasensible en la fase aguda del ictus, identificando a los pacientes con mayor riesgo de desarrollar complicaciones cardiológicas. Si nuestros resultados se confirmasen en estudios prospectivos, podríamos llegar a implementar el uso de biomarcadores sanguíneos en pacientes con ictus isquémico para el manejo de las complicaciones del mismo.Stroke represents one of the main causes of mortality and disability. Stroke outcome depends mainly on baseline, non-modifiable factors, such as age or stroke severity, but also on several conditions that may occur across the natural history of stroke and leads to a poor outcome. In the present doctoral thesis we focus on these conditions, namely post-stroke complications. Therefore, our objectives in the present project are: first, to assess which post-stroke complications have the highest impact on stroke prognosis; second, to evaluate in which indications the use of blood biomarkers is more demanded by physicians; third, to evaluate across the literature whether the association between blood biomarkers and stroke outcome and complications has been assessed; and fourth, to test the predictive value of some candidates for the previously identified indications. To assess these objectives, we performed a comprehensive analysis of the stroke registry of the Spanish Neurological Society (RENISEN), finding that brain edema with increased intracranial pressure and respiratory tract infections were the complications with the highest impact on in-hospital mortality, followed by cardiologic complications in a second step. An interesting finding of the analysis is that the impact of these complications depends on stroke severity. Moreover, we performed a survey across European stroke neurologists, finding that the indication in which the use of biomarkers is more requested is the management of reperfusion therapies. By applying systematic reviews and meta-analysis, we have found that the use of biomarkers for the management of post-stroke complications has been poorly studied. From the meta-analyzed biomarkers, C-reactive protein appears as a surrogate biomarker for the management of post-stroke infections. Regarding experimental studies, factor seven activating protease (FSAP) and ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13), both associated with arterial recanalization, have emerged as candidates to guide reperfusion therapies. Moreover, we have described a role for high-sensitive troponin-I determination in acute stroke, in identifying those patients at the highest risk of suffering cardiologic complications. If our results are confirmed in future prospective studies evaluating the prognostic implications of the use of these biomarkers, such biomarkers could be translated into clinical practice for the management of post-stroke complications

Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients

BackgroundCART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations.MethodEleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death.ResultsAfter a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression.ConclusionThis is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results

Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study

Grupo Español de Trasplante Hematopoyético (GETH) and Grupo Español de Linfoma y Trasplante Autólogo (GELTAMO).We performed a retrospective multicenter study including 140 patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) from March 1995 to November 2018. Our objective was to analyze long term outcomes. Seventy-four percent had received a previous auto-SCT (ASCT) and the median number of lines pre-allo-SCT was 3 (range 1–9). Three year-event free survival (EFS) and overall survival (OS) were 38% and 44%, respectively. Non-relapse mortality (NRM) at day 100 was 19%. Cumulative incidence of grade III–IV acute graft versus host disease (GVHD) at day 100 was 16% and moderate/severe chronic GVHD at 3 years 34%. Active disease at allo-SCT (HR 1.95, p = 0.039) (HR 2.19, p = 0.019), HCT-CI ≥ 2 (2.45, p = 0.002) (HR 2.33, p = 0.006) and donor age >37 years (HR 2.75, p = 0.014) (HR 1.98, p = 0.043) were the only independent variables both for PFS and OS, respectively. NRM was significantly modified by HCT-CI ≥ 2 (HR 4.8, p = 0.008), previous ASCT (HR 4.4, p = 0.048) and grade III–IV acute GVHD on day 100 (HR 6.13, p = 0.016). Our data confirmed that allo-SCT is a curative option for patients with R/R DLBCL, displaying adequate results for fit patients with chemosensitive disease receiving an allo-SCT from a young donor

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Altres ajuts: acords transformatius de la UABWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13311-023-01385-1

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E-4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E-4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease