Miracle-dz/UniFAR-FTUs huggingface dataset:
Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma

The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Their current application in multiple myeloma (MM) is rather uncertain, as discordant results have been reported by distinct research groups concerning especially the expression of PD-1/PD-L1 molecules on malignant plasma cells or on the responsible immune effector cell populations, respectively. In MM it seems that an approach based on combination treatment might be appropriate as unsatisfactory results have been yielded by monotherapy with PD-1/PD-L1 inhibitors. Immunomodulatory drugs, which are the current cornerstone of MM treatment, are the most logical partners as they possess many possibly synergistic effects. Nevertheless, the initially optimistic results have become disappointing due to the excessive and unpredictable toxicity of the combination of pembrolizumab with lenalidomide or pomalidomide. The FDA has suspended or put on hold several phase 3 trials in relapsed as well as in newly diagnosed myeloma patients. There are also other potentially synergistic and promising combinations, such as the anti-CD38 monoclonal antibody daratumumab, irradiation, etc. Not only the effective partner but also the correct timing of the initiation of the PD-1/PD-L1 inhibitors treatment seems to be of utmost importance. These strategies are currently being examined in various stages of myeloma such as during consolidation post autologous stem cell transplantation, targeting minimal residual disease or even in high risk smoldering myeloma.
Análisis sectoriales del ebook científico-técnico en España: En busca de algunas claves de su desarrollo

El objetivo general de la tesis doctoral es estudiar el ebook cientifico-tecnico en Espana en diferentes ambitos del conocimiento y desde la perspectiva de cuatro agentes relevantes en el sector editorial. Mas concretamente, se plantean dos estudios de caso a nivel macro en los que se aborda el tratamiento del ebook por parte de las agencias de suscripciones Swets y Ebsco, y por parte de una muestra de las editoriales academicas espanolas especializadas en Humanidades y Ciencias Sociales. De forma complementaria, se abordan dos estudios de caso micro: el de los bibliotecarios y usuarios de la Biblioteca del Instituto de Quimica-Fisica “Rocasolano” (Biqfr) del Consejo Superior de Investigaciones Cientificas (CSIC). Las metodologias empleadas en estos estudios han sido basicamente las entrevistas en profundidad y las encuestas. Los aspectos analizados varian en funcion del agente analizado pero van desde la actitud hacia el ebook, hacia las estrategias de marketing, las formulas de compra, las modificaciones en la politica editorial, la gestion bibliotecaria o la aceptacion por parte de los usuarios. Estos estudios has permitido identificar no solo como se ha producido la evolucion del ebook cientifico desde su aparicion sino, sobre todo, los cambios que ha producido y esta produciendo en el sector de la informacion cientifica. Tambien ha permitido observar las fortalezas y debilidades de cada agente con respecto al ebook y, por tanto, los problemas que quedan por afrontar. El analisis de distintos sectores ayuda a interrelacionar la actividad de los distintos agentes del sector editorial y detectar las demandas de unos hacia otros o, lo que es lo mismo, la repercusion de las acciones de unos en los otros. Ademas esta tesis doctoral pretende dejar constancia de una etapa del ebook en Espana, sabiendo que su realidad es efimera puesto que es un recurso en cambio permanente.
Woulda, Coulda, Shoulda: Counterfactually-Guided Policy Search

Learning policies on data synthesized by models can in principle quench the thirst of reinforcement learning algorithms for large amounts of real experience, which is often costly to acquire. However, simulating plausible experience de novo is a hard problem for many complex environments, often resulting in biases for model-based policy evaluation and search. Instead of de novo synthesis of data, here we assume logged, real experience and model alternative outcomes of this experience under counterfactual actions, actions that were not actually taken. Based on this, we propose the Counterfactually-Guided Policy Search (CF-GPS) algorithm for learning policies in POMDPs from off-policy experience. It leverages structural causal models for counterfactual evaluation of arbitrary policies on individual off-policy episodes. CF-GPS can improve on vanilla model-based RL algorithms by making use of available logged data to de-bias model predictions. In contrast to off-policy algorithms based on Importance Sampling which re-weight data, CF-GPS leverages a model to explicitly consider alternative outcomes, allowing the algorithm to make better use of experience data. We find empirically that these advantages translate into improved policy evaluation and search results on a non-trivial grid-world task. Finally, we show that CF-GPS generalizes the previously proposed Guided Policy Search and that reparameterization-based algorithms such Stochastic Value Gradient can be interpreted as counterfactual methods.
Phenolic Profiles, Antioxidant Capacities, and Inhibitory Effects on Digestive Enzymes of Different Kiwifruits

In order to obtain high-quality kiwifruits with health-promoting characteristics, physicochemical properties, phenolic profiles, antioxidant capacities, and inhibitory effects on digestive enzymes (pancreatic lipase and α-glucosidase), of fourteen different types of kiwifruit obtained from China were systematically investigated and compared. Noticeable variations in the fruits’ physicochemical properties and phenolic profiles were observed among them. The total phenolic content of Actinidia chinensis cv. Hongshi, A. chinensis cv. Jinshi, and A. chinensis cv. Jinlong were 16.52 ± 0.26 mg GAE/g DW (dry weight), 13.38 ± 0.20 mg GAE/g DW, and 11.02 ± 0.05 mg GAE/g DW, respectively, which were much higher than those of the other tested kiwifruits. According to high performance liquid chromatography (HPLC) analysis, phenolic compounds, including procyanidin B1, procyanidin B2, (−)-epicatechin, chlorogenic acid, gallic acid, and quercetin-3-rhamnoside, were found to be the major compounds in kiwifruits, while procyanidin B1, procyanidin B2, and chlorogenic acid were the most abundant phenolic compounds. Furthermore, all the tested kiwifruits exerted remarkable antioxidant capacities and inhibitory effects on pancreatic lipase and α-glucosidase. Indeed, A. chinensis cv. Hongshi, Actinidia chinensis cv. Jinshi, and Actinidia chinensis cv. Jinlong exhibited much better antioxidant capacities and inhibitory effects on digestive enzymes than those of the other tested kiwifruits. Particularly, A. polygama showed the highest inhibitory activity on α-glucosidase. Therefore, Actinidia chinensis cv. Hongshi, Actinidia chinensis cv. Jinshi, and Actinidia chinensis cv. Jinlong, as well as A. polygama could be important dietary sources of natural antioxidants and natural inhibitors against pancreatic lipase and α-glucosidase, which is helpful for meeting the growing demand for high-quality kiwifruits with health-promoting characteristics in China.
Distributed Ledger Technology for Smart Cities, the Sharing Economy, and Social Compliance

This paper describes how distributed ledger technologies (DLTs) can be used to enforce social contracts and to orchestrate the behavior of agents trying to access a shared resource. The first part of this paper analyzes the advantages and disadvantages of using DLTs architectures to implement certain control systems in an Internet of Things (IoT) setting and then focuses on a specific type of DLT based on a directed acyclic graph. In this setting, we propose a set of delay differential equations to describe the dynamical behavior of the Tangle, an IoT-inspired directed acyclic graph designed for the cryptocurrency IOTA. The second part proposes an application of DLTs as a mechanism for dynamic deposit pricing, wherein the deposit of digital currency is used to orchestrate access to a network of shared resources. The pricing signal is used as a mechanism to enforce the desired level of compliance according to a predetermined set of rules. After presenting an illustrative example, we analyze the control system and provide sufficient conditions for the stability of the network.
Development of Flipped Classroom model to improve the students' performance

The use of flipped-classroom methodology has increased recently in higher education. However, there is a lack of quantitative data on students' performance, especially in engineering courses. A flipped-classroom methodology has been developed in two different engineering degrees with 167 students. In both degrees also a control group with 156 students has been taught using the classical methodology. Through the data collected it is possible to measure the impact of learning (through the usual exams), to reduce the class absenteeism and to increase the exams attendance. Also, the students' implication with the new methodology can be checked by the use of YouTube analytics. The results show that the flipped-classroom model improves the results, at least in partial examinations. Furthermore, as the marks dispersion are lower, can be state that diversity has been treated in a better way.
Negotiating Corners With Teleoperated Mobile Robots With Time Delay

In this paper, we present the summary of results from a teleoperation study to assess the application of a mobile robot cornering law with the inclusion of a time delay on the returned video stream. The intent is to demonstrate this application to an analogous scenario like teleoperating from Earth a rover at the south Lunar pole. The first experiment compared course completion times for outdoor driving circuits in ideal lighting without time delay, ideal lighting with time delay, and in darkness with time delay and a low-angled spotlight. The second experiment studied cornering times for various time delays and lighting conditions in an indoor setting. The results show that teleoperating a mobile robot with the presence of time delay still complies with the previously developed cornering law. The combined results from the cornering study and the outdoor driving course are interpreted to show that the total time to complete a driving course with a time-delayed video can be predicted based on a known number of turns.
Loss of complement regulatory proteins on uninfected erythrocytes in vivax and falciparum malaria anemia

Anemia is a major complication of malaria, driven largely by loss of uninfected RBCs during infection. RBC clearance through loss of complement regulatory proteins (CRPs) is a significant contributor to anemia in Plasmodium falciparum infection, but its role in Plasmodium vivax infection is unknown. CRP loss increases RBC susceptibility to macrophage clearance, a process that is also regulated by CD47. We compared CRPs and CD47 expression on infected and uninfected RBCs in adult patients with vivax and falciparum malaria and different anemia severities from Papua, Indonesia. Complement activation and parasite-specific complement-fixing antibodies were measured by ELISA. Levels of CR1 and CD55 were reduced in severe anemia in both falciparum and vivax malaria. Loss of CRPs and CD47 was restricted to uninfected RBCs, with infected RBCs having higher expression. There was no association among complement-fixing antibodies, complement activation, and CRP loss. Our findings demonstrate that CRP loss is a pan-species, age-independent mechanism of malarial anemia. Higher levels of CRP and CD47 expression on infected RBCs suggest that parasites are protected from complement-mediated destruction and macrophage clearance. Lack of associations between protective antibodies and CRP loss highlight that complement pathogenic and protective pathways are distinct mechanisms during infection.
Comparison of Oxidative Stress Effects on Senescence Patterning of Human Adult and Perinatal Tissue-Derived Stem Cells in Short and Long-term Cultures

Human Mesenchymal Stem Cells (hMSCs) undergo senescence in lifespan. In most clinical trials, hMSCs experience long-term expansion ex vivo to increase cell number prior to transplantation, which unfortunately leads to cell senescence, hampering post-transplant outcomes. Hydrogen peroxide (H2O2) in vitro represents a rapid, time and cost-effective tool, commonly used as oxidative stress tantalizing the stem cell ability to cope with a hostile environment, recapitulating the onset and progression of cellular senescence. Here, H2O2 at different concentrations (ranging from 50 to 400 μM) and time exposures (1 or 2 hours - h), was used for the first time to compare the behavior of human Adipose tissue-derived Stem Cells (hASCs) and human Wharton's Jelly-derived MSCs (hWJ-MSCs), as representative of adult and perinatal tissue-derived stem cells, respectively. We showed timely different responses of hASCs and hWJ-MSCs at low and high subculture passages, concerning the cell proliferation, the cell senescence-associated β-Galactosidase activity, the capability of these cells to undergo passages, the morphological changes and the gene expression of tumor protein p53 (TP53, alias p53) and cyclin dependent kinase inhibitor 1A (CDKN1A, alias p21) post H2O2 treatments. The comparison between the hASC and hWJ-MSC response to oxidative stress induced by H2O2 is a useful tool to assess the biological mechanisms at the basis of hMSC senescence, but it could also provide two models amenable to test in vitro putative anti-senescence modulators and develop anti-senescence strategies.
Common atrium and the associated malformations

Abstract Common atrium (CA) is a rare complex congenital heart disease. The studies of CA are mostly case reports, while few have been done regarding its morphological characteristics. We aimed to determine CA characteristics and diagnostic accuracy in assessing associated malformations in these patients with low-dose dual-source computed tomography (DSCT). Twenty-one pediatric and adolescent CA patients underwent low-dose DSCT. Different ventricular types and associated malformations were assessed. The diagnostic accuracy of DSCT and transthoracic echocardiography (TTE) in evaluating associated malformations were assessed. The effective doses of DSCT were calculated. Patients (n = 21) were divided into CA with biventricular physiology (n = 7) and CA with single ventricle (SV) (n = 14). There were 3 types of SV morphology: single left ventricle (n = 5), single right ventricle (n = 6), and undifferentiated ventricle (n = 3). In all, 22 associated malformations were seen in CA and 56 in CA with SV. DSCT was superior to TTE for detecting intracardiac anomalies (sensitivity: DSCT, 92.31% vs TTE, 76.92%), great vessels anomalies (sensitivity: DSCT, 100.00% vs TTE, 77.50%), and of collateral vessels (sensitivity: DSCT, 100% vs TTE, 20.00%). The estimated mean effective dose was 0.95 ± 0.44 mSv (<1 mSv). This study indicated that low-dose DSCT is an ideal alternative for pediatric and adolescent patients with CA, providing morphological details of CA and associated malformations with high accuracy.
Percutaneous endoscopic ventral facetectomy: An innovative substitute of open decompression surgery for lateral recess stenosis surgical treatment?

Background: Percutaneous transforaminal endoscopic surgery (PTES) constitutes an innovative method principally recruited for the treatment of lumbar disc herniation. Indication spectrum of PTES is constantly widened in current years. Hence, PTES has been proposed to represent a satisfactory alternative for the treatment of lateral recess stenosis (LRS), being defined as percutaneous endoscopic ventral facetectomy (PEVF) in these cases. The aim of this original study is to determine, for the first time in the literature, the outcomes of PEVF, especially in otherwise healthy nonelderly patients with LRS, alongside with special focus in health-related quality of life (HRQoL) assessment. Materials and Methods: Eighty-five otherwise healthy individuals from 58 to 64 years were diagnosed with LRS, being subjected to successful PEVF. Patients were prospectively evaluated in 6 weeks, in 3, 6, and 12 months, and in 2 years postoperatively. Visual analog scales (VASs) were separately utilized for leg and low back pain evaluation (VAS-LP and VAS-BP, respectively), whereas Short Form-36 (SF-36) questionnaire was sequentially implemented for HRQoL assessment. Results: All indexes of SF-36 as well as VAS-LP featured maximal amelioration in 6 weeks postoperatively, with subsequent further enhancement until 3 months and successor stabilization until 2 years. In contrast, VAS-BP presented minimal quantitative amelioration in 6 weeks, featuring no additional alterations. Values of all indexes in all follow-up intervals were demonstrated to be statistically significant in comparison with preoperative values (P < 0.05). No remarkable differentiation was observed between distinct parameters of SF-36. Conclusions: PEVF implementation in nonelderly patients with LRS was displayed to be safe and effective, providing alongside considerable improvement in HRQoL 2 years postoperatively.
Crystal structures of VIM‐1 complexes explain active site heterogeneity in VIM‐class metallo‐β‐lactamases

Metallo‐β‐Lactamases (MBLs) protect bacteria from almost all β‐lactam antibiotics. Verona integron‐encoded MBL (VIM) enzymes are among the most clinically important MBLs, with VIM‐1 increasing in carbapenem‐resistant Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae) that are among the hardest bacterial pathogens to treat. VIM enzymes display sequence variation at residues (224 and 228) that in related MBLs are conserved and participate in substrate binding. How they accommodate this variability, while retaining catalytic efficiency against a broad substrate range, has remained unclear. Here, we present crystal structures of VIM‐1 and its complexes with a substrate‐mimicking thioenolate inhibitor, ML302F, that restores meropenem activity against a range of VIM‐1 producing clinical strains, and the hydrolysed product of the carbapenem meropenem. Comparison of these two structures identifies a water‐mediated hydrogen bond, between the carboxylate group of substrate/inhibitor and the backbone carbonyl of the active site zinc ligand Cys221, that is common to both complexes. Structural comparisons show that the responsible Cys221‐bound water is observed in all known VIM structures, participates in carboxylate binding with other inhibitor classes, and thus effectively replicates the role of the conserved Lys224 in analogous complexes with other MBLs. These results provide a mechanism for substrate binding that permits the variation at positions 224 and 228 that is a hallmark of VIM MBLs.
Prejudices and Discrimination as Goal Activated and Threat Driven: The Affordance Management Approach Applied to Sexual Prejudice

Stereotypes, prejudices, and discriminatory behaviors directed toward people based on their sexual orientation vary broadly. Existing perspectives on sexual prejudice argue for different underlying causes, sometimes provide disparate or conflicting evidence for its roots, and typically fail to account for variances observed across studies. We propose an affordance management approach to understanding sexual prejudice, which weds the fundamental motives theory with the sociofunctional threat-based approach to prejudice to provide a broader explanation for the causes and outcomes of sexual prejudice and to explain inter- and intragroup prejudices more broadly. Prejudices arise as specific emotions designed to engage functional behavioral responses to perceived threats and opportunities (i.e., affordances) posed by different sexual orientation groups, and interact with the perceiver’s chronic or temporarily activated fundamental motives (e.g., parenting, mating), which determine the relevance of certain target affordances. Our perspective predicts what stereotype content is likely to direct specific affective and behavioral reactions (i.e., the stereotypes that relay threat- and opportunity-relevant information) and when the affordance-emotion-behavior link is likely to engage (i.e., when those threats and opportunities are directly relevant to the perceiver’s current fundamental goal). This article synthesizes the extant sexual prejudice literature from an affordance management approach to demonstrate how fundamental goals interact with preexisting perceptions to drive perceptual, affective, and behavioral responses toward sexual orientation groups, and provides a degree of explanatory power heretofore missing from the prejudice literature.
Glucose Sensing Using Slot Waveguide-Based SOI Ring Resonator

An optical ring resonator based sensor is proposed for bio-sensing applications. It is applied to glucose level monitoring in blood samples in the range 10 to 200 mg/dl using minimal invasive technique. Two configurations of ring resonator are proposed that are based on ridge and slot waveguide. The average sensitivity of slot ring resonator is observed to be 360 nm/RIU, which is six times higher (60 nm/RIU) than that of ridge ring resonator. Both the sensor configurations are adept to respond to slight variation in glucose concentration, which affects the refractive index and ultimately the spectral shift of the resonator.
Specific Members of the Gut Microbiota are Reliable Biomarkers of Irradiation Intensity and Lethality in Large Animal Models of Human Health

The development of effective biomarkers for detecting the magnitude of radiation exposure and resiliency of host response is crucial to identifying appropriate treatment strategies after radiation exposure. We hypothesized that the gastrointestinal resident bacteria would demonstrate predictable, dose-dependent changes after radiation exposure across two large animal models of acute radiation syndrome. Here, Göttingen minipigs (GMP) (n = 50) and rhesus macaques (n = 48) were exposed to five dose levels (resulting in mortality rates of 33–100% and 25–68.7%, respectively). Fecal samples taken prior to and after irradiation (day 0 for GMP; day 0, 3 and 14 for macaques) were used for 16S rRNA gene sequence amplicon high-throughput sequencing. Baseline gut microbiota profiles were dissimilar between GMP and macaques, however, radiation appeared to have similar effect at the phylum level, resulting in Bacteroidetes decrease and Firmicutes increase in both models. The abundance of the main Bacteroidetes genus (Bacteroides for GMP, Prevotella for macaques) was profoundly decreased by irradiation. Intracellular symbionts [Elusimicrobia in GMP, Treponema (Spirochaetes) in macaques] consistently increased after irradiation, suggesting their use as potential biomarkers of intestinal injury, and potential negative effect on health. Prevotella, Lactobacillus, Clostridium XIVa, Oscillibacter and Elusimicrobium/Treponema abundances were found to be very significantly correlated with radiation intensity. Furthermore, Prevotella, Enterorhabdus and Ruminococcus and Enterorhabdus maintenance was strongly associated with survival in GMP, while Prevotella, Oscillibacter and Treponema were strongly associated with survival and Streptococcus with death in macaques. Overall, we found that a wide range of gut bacterial genera known to be abundant in the human gut microbiota are excellent biomarkers of radiation intensity and resilience in animal models, and that detrimental effects can be monitored, and potentially prevented, by targeting selected genera.