Miracle-dz/UniFAR-FTUs huggingface dataset:
Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study

BACKGROUND Standard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC. PATIENTS AND METHODS Eligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score ≥1. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), duration of response, progression-free survival and overall survival. RESULTS All 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9-31.4). Of the 13 patients with stable disease, 2 had stable disease lasting ≥24 weeks, for a disease control rate of 23.8% (95% CI 15.9-34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4 months (range 4.2 to 19.2+). Median progression-free survival was 2.1 months (95% CI 2.0-2.2), and median overall survival was 18.0 months (95% CI 12.9-23.0). CONCLUSIONS Pembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT02447003.
Novel Multi-Modal Tools to Enhance Disabled and Distance Learners’ Experience of Mathematics

This paper discusses ICT-related needs, with particular reference to studying mathematically-based disciplines, of several types of users – notably people with physical disabilities, online (distance) learners and people working or studying “on the move”, relying on mobile devices. We note the inadequacy of existing interfaces for mathematical input and output for these groups and investigate several options for addressing the problems. We present two tools that employ novel human computer interaction methods which allow users to create and edit mathematical content in electronic documents and address some of the above issues. We apply one of these in a user study in a classroom environment, aiming to investigate whether this system can assist students to learn mathematical concepts via creating mathematical e-content. We show that there is some evidence that, by using this tool, some students can improve their general understanding of mathematical concepts, comparing “deep” natural language descriptions with representations based on “shallow” application-specific interactions. DOI: http://dx.doi. org/10.4038/icter.v6i1. 6098 International Journal on Advances in ICT for Emerging Regions 2013 6(1)
Challenge of Developing a Herpes Simplex Virus Vaccine

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as human herpes virus 1 and 2 (HHV-1 and HHV-2), are two members of the herpes virus family, herpes viridae, which infect humans. Both HSV-1 (which produces most cold sores) and HSV-2 (which produces most genital herpes) are ubiquitous and contagious. They can be spread when an infected person is producing and shedding the virus. Herpes Simplex can be spread through contact with saliva, such as sharing drinks. HSV-2 is one of the most prevalent sexually transmitted infections worldwide. In addition to recurrent genital ulcers, HSV-2 causes neonatal herpes, and is associated with a 3-fold increased risk for HIV acquisition. Many HSV-2 vaccines have been studied in animal models, however, few have reached clinical trials, and those that have been tested in humans were not consistently effective. Here, I review HSV-2 pathogenesis, with a focus on novel understanding of mucosal immunobiology of HSV-2, and vaccine efforts to date, in an attempt to stimulate thinking about future directions for development of effective prophylactic and therapeutic HSV-2 vaccines.
EROSIVIDADE DA CHUVA: ANÁLISE DO FATOR DE EROSIVIDADE DA CHUVA E DISTRIBUIÇÃO DA PRECIPITAÇÃO PLUVIOMÉTRICA DE ALTAMIRA (PA)

In order to improve knowledge on rainfall erosivity in the municipality of Altamira (PA), the objective of this study was to calculate the erosivity index EI30 and to determine the erosivity factor (R), present in the Universal Soil Loss Equation USLE, through its original equation from rainfall data for the municipality, as well as to study the monthly distribution of EI30, the return period and the probability of occurrence of Altamira (PA) erosive rains. For this purpose, rainfall data obtained from the National Meteorology Institute (INMET) database were used in the period from 1987 to 2015, thus, the collected data were applied to the aforementioned calculations and expressions. The years of lowest and highest rainfall, respectively, were 1992 with 1,244.5 mm and 2006 with 2,740.1 mm. It was verified that the months of January, February, March and April were the most erosive ones, being recorded in 100% of the years analyzed for Altamira, being also the months where the highest pluviometric indexes occurred (64% of the precipitations), being that the month of March represents 18.75% of the rainfall, in contrast, the lowest observed indexes are centered in the months of July to October (8.7% of the precipitations). Annual rainfall erosivity in the study period ranged from 7,872.7 MJ mm ha-1 h-1 in 1990 to 14,237.4 MJ mm ha-1 h-1 in 2006. The R-factor value of the Soil Loss for the municipality of Altamira (PA), is 11,236.8 MJ mm ha-1 h-1ano-1, considered therefore with "Very Strong" erosivity class.
Relation between distance and pressure of acoustic signal

In this paper, we investigated if the distance can be judged by mutually comparing sound from a source with that from another. We further intended to correlate this sound comparison with the relative distance. It was made clear from the result that the sound loudness exhibited good correlation with the distance. In other words, the distance can be estimated by comparing the sound heard with the standard sound. As for the relation between the distance and the sound heard by the examinee, the consistency index was good and the correlation was consistent. The sound loudness sharply fell with distance, down to about 1 m, and slowly decreased beyond this distance. <<ETX>>
Projecto de implementação de módulos de qualidade na Procter & Gamble

New market imperatives guides organizations to conduct their business strategies, efficiently, reducing losses and waste. The quality modules implementation project consists in the implementation of a set of methodologies and tools for quality control, applied to a packing line, of consumer goods products. The goal was to establish ideal equipment and processes conditions, promoting the state of zero defects and zero losses, by reducing the process variability, define and validate parameters of the equipment, and daily manage critical factors. The methodology called Quality Maintenance is characterized by two distinct phases. The first covers the troubleshooting of line through Pareto analysis, priority defects, calculated from the Risk Prediction Number, and related equipment in the Product Defect Matrix. The causes of those defects are analyzed using the Ishikawa diagrams. Confirming the cause-effect relationship is defined a plan that includes measures to improve by removing these defects. Reducing process variability, promote a free loss and defects state. In the second phase the Quality Maintenance, focuses again on the equipment, identifying the critical variables and parameters, that being out of control, will cause defects. These are integrated into the PCS line. The Process Control Strategy is a system of quality control which includes systems for monitoring and managing daily bind parameters, and Daily Management Systems, and integrates the Statistical Process Control, methodologically, that allows to identify and reduce causes remarkable variability. With this development, according to the phases of the Quality Maintenance has been further reduced in the first instance, the number of defects (calculated in parts per million: ppm's) between 10 to 30%. Maintaining these conditions is provided by PCS, where he expects an improvement in performance of the process (Process Reliability) in 1.04% and the overall increase in MTBF (Mean Time Between Failures). Projecto de Implementação de Módulos de Qualidade
Embalagem plástica para flocão de milho biofortificado.

Devido a carencia de micronutrientes que sao essenciais para a saude, vem sendo desenvolvido no Brasil produtos biofortificados. O objetivo desse estudo foi levantar informacoes sobre os efeitos de quatro tipos de embalagem e do tipo de acondicionamento (com e sem vacuo), na perda de qualidade de flocao de milho biofortificado. Os resultados mostraram que em todas as embalagens avaliadas houve preservacao dos carotenoides, tendo um destaque para o PETmet/PEBD com vacuo que teve uma maior retencao do teor de carotenoides pro-vitamina A e maior preservacao da cor.
Retrieval of remotely sensed imagery using spectral information content

The retrieval of images in professional remote sensing databases is based on world-oriented information like for example the location of the scene, the utilised scanner, and the date of acquisition. However, these descriptions are not meaningful for many users who have a limited knowledge about remote sensing but nevertheless have to work with satellite imagery. Therefore the retrieval of an appropriate scene is often almost impossible since adequate techniques are not provided by the database systems. This paper proposes the content-based retrieval for satellite imagery using the query-by-example approach. The main contribution is the reliable and scanner independent technique for the feature extraction and representation. The entire approach is unsupervised to stay abreast of the daily increasing huge data volume.
Bistatic radar scattering experiments of parallel wire grids

The continued interest in bistatic polarimetric radar, particularly for SAR applications, has resulted in the requirement for additional simple, well characterized targets for external calibration. These targets must enable both bistatic and polarimetric radar modes to be calibrated, often to a precision of less than 1 dB. Previous research has shown that the use of wire grid structures could be a suitable bistatic calibration reference. In this paper we investigate the far-field bistatic scattering from a grid of parallel thin wires of different grid spacings. Experiments are conducted using the European Microwave Signature Laboratory (EMSL) over a frequency range of between 5 to 15 GHz for bistatic angles from 5 degrees to 150 degrees. The data was calibrated and compared to a Method of Moments (MOM) theoretical solution.
Parallel Matrix Condensation for Calculating Log-Determinant of Large Matrix

Calculating the log-determinant of a matrix is useful for statistical computations used in machine learning, such as generative learning which uses the log-determinant of the covariance matrix to calculate the log-likelihood of model mixtures. The log-determinant calculation becomes challenging as the number of variables becomes large. Therefore, finding a practical speedup for this computation can be useful. In this study, we present a parallel matrix condensation algorithm for calculating the log-determinant of a large matrix. We demonstrate that in a distributed environment, Parallel Matrix Condensation has several advantages over the well-known Parallel Gaussian Elimination. The advantages include high data distribution efficiency and less data communication operations. We test our Parallel Matrix Condensation against self-implemented Parallel Gaussian Elimination as well as ScaLAPACK (Scalable Linear Algebra Package) on 1000 x1000 to 8000x8000 for 1,2,4,8,16,32,64 and 128 processors. The results show that Matrix Condensation yields the best speed-up among all other tested algorithms. The code is available on this https URL
Promises and Pitfalls in the Use of PD-1/PD-L1 Inhibitors in Multiple Myeloma

In the biology of multiple myeloma (MM), immune dysregulation has emerged as a critical component for novel therapeutic strategies. This dysfunction is due to a reduced antigen presentation, a reduced effector cell ability and a loss of reactive T cells against myeloma, together with a bone marrow microenvironment that favors immune escape. The Programmed Death-1 (PD-1) pathway is associated with the regulation of T cell activation and with the apoptotic pathways of effector memory T cells. Specifically, the binding with PD-1 ligand (PD-L1) on the surface of tumor plasma cells down-regulates T cell-proliferation, thus contributing to the immune escape of tumor cells. In relapsed and/or refractory MM (RRMM) patients, PD-1/PD-L1 blockade was analyzed by using nivolumab, pembrolizumab, and durvalumab. Outcomes with single agents were unsatisfactory, whereas combination strategies with backbone immunomodulatory drugs (IMiDs) suggested a synergistic action in such a complex immunological landscape, even in patients previously refractory to these drugs. Nevertheless, these combinations were also associated with an increased incidence of adverse events. This review aims to analyze the available preclinical and clinical data on the role of PD-1/PD-L1 inhibitors in MM therapy, focusing on available preliminary efficacy and safety data and offering insights for future investigation.
Follow-Up Study of a Chronic Pain Patients : A Clinical and Health Psychology Approach

Our research was focused on effect of resilience on quality of life and mood outcomes in chronic pain patients using longitudinal data. We also wanted to compare effect of resilience to other illness and demographic variables as well as other adjustment factors (e.g. life events). ATINER CONFERENCE PAPER SERIES No: PSY2013-0521 7 The sample consisted of 300 patients with chronic pain. At entry into the cohort, patients had been diagnosed with chronic pain within the last 5 years. Baseline measures were administered between 1996 and 2000. Methods: A psychosocial test battery was administered to all patients treated at National Center for Spinal Disorders. Psychosocial parameters such as demographic (objective) variables of adjustment (work and family status), quality of life, depression, anxiety, resilience, spiritual orientation were measured. Results: No significant differences were found between either depression or anxiety scores at baseline and follow-up. Trait anxiety, depression and quality of life scores differed significantly from standard data available for the general population, deteriorated with time but were unrelated to age or gender. Resilience scores of the patients did not differ significantly from the Hungarian preliminary standards. Four variables explained 57,1% of variance in quality of life outcomes, resilience being the most powerful predictor of all. Anxiety and depression were also strongly predicted by resilience (r square = 0,59 for anxiety and r square = 64% for depression). Further predictors were pain symptoms and some spirituality variables. No life event or other health/illness variable effects emerged. Conclusions: Illness and life event effects are buffered by resilience, a very powerful predictor of adaptive outcomes. Though there is deterioration in quality of life and mood through the course of illness, outcomes are remarkably better in resilient patients. The impact of this variable may result from through successful emotional regulation and more effective recovery from stress events.
The Interleukin-10 Family of Cytokines and Their Role in the CNS

Resident cells of the central nervous system (CNS) play an important role in detecting insults and initiating protective or sometimes detrimental host immunity. At peripheral sites, immune responses follow a biphasic course with the rapid, but transient, production of inflammatory mediators giving way to the delayed release of factors that promote resolution and repair. Within the CNS, it is well known that glial cells contribute to the onset and progression of neuroinflammation, but it is only now becoming apparent that microglia and astrocytes also play an important role in producing and responding to immunosuppressive factors that serve to limit the detrimental effects of such responses. Interleukin-10 (IL-10) is generally considered to be the quintessential immunosuppressive cytokine, and its ability to resolve inflammation and promote wound repair at peripheral sites is well documented. In the present review article, we discuss the evidence for the production of IL-10 by glia, and describe the ability of CNS cells, including microglia and astrocytes, to respond to this suppressive factor. Furthermore, we review the literature for the expression of other members of the IL-10 cytokine family, IL-19, IL-20, IL-22 and IL-24, within the brain, and discuss the evidence of a role for these poorly understood cytokines in the regulation of infectious and sterile neuroinflammation. In concert, the available data indicate that glia can produce IL-10 and the related cytokines IL-19 and IL-24 in a delayed manner, and these cytokines can limit glial inflammatory responses and/or provide protection against CNS insult. However, the roles of other IL-10 family members within the CNS remain unclear, with IL-20 appearing to act as a pro-inflammatory factor, while IL-22 may play a protective role in some instances and a detrimental role in others, perhaps reflecting the pleiotropic nature of this cytokine family. What is clear is that our current understanding of the role of IL-10 and related cytokines within the CNS is limited at best, and further research is required to define the actions of this understudied family in inflammatory brain disorders.
Enhancing the Activation and Releasing the Brakes: A Double Hit Strategy to Improve NK Cell Cytotoxicity Against Multiple Myeloma

Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients, we were able to isolate autologous tumor cells, and we could demonstrate that IL-2/15 stimulated autologous NK cells were able to significantly improve their killing capacity of autologous tumor cells. With the aim to further improve the NK cell killing capacity against MM cells, we investigated the potential use of NK specific check point inhibitors with focus on NKG2A because this inhibitory NK cell receptor was upregulated following ex vivo cytokine stimulation and MM cells showed HLA-E expression that could even be increased by exposure to IFN-γ. Importantly, blocking of NKG2A resulted in a significant increase in the NK cell-mediated lysis of different MM target cells. Finally, these results let suggest that combining cytokine induced NK cell activation and the specific check point inhibition of the NKG2A-mediated pathways can be an effective strategy to optimize NK cell therapeutic approaches for treatment of multiple myeloma.
Social support has both positive and negative effects on the relationship of work stress and alcohol consumption

Previous studies imply that certain combinations of work stressors, social support (SS), and other conditions could lead to both increased and decreased alcohol consumption. Thus, we evaluated both positive and negative influences of social support on the work stress–alcohol consumption relationship in a general population. The study design was a cross-sectional survey. Of a probability sample of persons 25 years of age or older and living in the United States (n = 3617), subjects who drank and who were without missing values with respect to study variables were analysed (n = 967 or 94). Since previous studies have suggested the necessity of adopting the sensitivity hypothesis (i.e. different stressors require different social supports), hierarchical regression analyses were carried out to test the effects of interactions between two types of social support (e.g. family social support or out-of-family social support) and two types of work stressors (e.g. job psychological demand, job decision latitude) on alcohol consumption. Our analysis verified that (1) social support had both positive and negative effects on the work stress–alcohol relationship. Specifically, (2) interactions between physical activity and decision latitude, and between child support and psychological job demand were related to decreased alcohol consumption. However, (3) interactions between spouse support and decision latitude, and between informal social integration and psychological job demand, were related to increased alcohol consumption. It has been suggested that social support is not of universal benefit in reducing excessive drinking and may sometimes be a reinforcing factor. Since the external validity of these findings might be limited because of the small sample size in some analyses, further study is necessary. Copyright © 2003 John Wiley & Sons, Ltd.
The effect of transferrin-targeted, resveratrol-loaded liposomes on neurosphere cultures of glioblastoma: implications for targeting tumour-initiating cells

Abstract Glioblastomas (GBMs) are known to harbour subsets of cells known as tumour-initiating cells (TICs), which are responsible for the maintenance, invasiveness and recurrence of GBMs. Conventional chemotherapeutics act on rapidly dividing cells, sparing the TICs and result in tumour relapse. Resveratrol (RES) has shown chemopreventive effects in all the major stages of cancer including initiation, promotion and progression, but poor physicochemical and pharmacokinetic properties limit its use as a free drug. Hence we developed a liposomal formulation of RES (RES-L) to eradicate both the bulk tumour cells and TICs in GBMs. Since both these subpopulations of cells are known to over-express transferrin receptors, we developed transferrin-targeted RES-L (Tf-RES-L) to enhance tumour-specific delivery. We studied the effects of RES on neurospheres (NS) used as an in vitro model to study TICs derived from GBM cell lines. Free RES and RES formulations inhibited the anchorage-independent growth of GBM neurospheres. The NS-derived cells expressed TfRs and the Tf-targeted liposomes showed a significantly higher association with NS versus the non-targeted liposomes. Finally an increased activation of caspases 3/7 was seen when NS were treated with RES formulations. Together, these studies advocate for further investigations with RES-L and the use Tf to target the TIC populations.