Miracle-dz/UniFAR-FTUs huggingface dataset:
Venetoclax durable response in adult relapsed/refractory Philadelphia-negative acute lymphoblastic leukemia with JAK/STAT pathway alterations

High-risk relapsed/refractory adult Philadelphia-negative (Ph−) B-cell acute lymphoblastic leukemia (B-ALL) is a great challenge due to limited possibilities to achieve and maintain a complete response. This also applies to cases with extramedullary (EM) involvement that have poor outcomes and no accepted standard therapeutic approaches. The incidence of EM localization in relapsed/refractory B-ALL is poorly investigated: data on patients treated with blinatumomab reported a 40% rate. Some responses were reported in EM patients with relapsed/refractory B-ALL treated with inotuzumab ozogamicin or CAR-T. However, molecular mechanisms of response or refractoriness are usually investigated neither at the medullary nor at EM sites. In the complex scenario of pluri-relapsed/refractory B-ALL patients, new target therapies are needed. Our analysis started with the case of an adult pluri-relapsed Ph− B-ALL patient, poorly sensitive to inotuzumab ozogamicin, donor lymphocyte infusions, and blinatumomab in EM disease, who achieved a durable/complete response after treatment with the BCL2-inhibitor venetoclax. The molecular characterization of medullary and EM samples revealed a tyrosine kinase domain JAK1 mutation in the bone marrow and EM samples at relapse. By comparing the expression level of BCL2- and JAK/STAT pathway-related genes between the patient samples, 136 adult JAK1 wt B-ALL, and 15 healthy controls, we identified differentially expressed genes, including LIFR, MTOR, SOCS1/2, and BCL2/BCL2L1, that are variably modulated at diverse time points and might explain the prolonged response to venetoclax (particularly in the EM site, which was only partially affected by previous therapies). Our results suggest that the deep molecular characterization of both medullary and EM samples is fundamental to identifying effective and personalized targeted therapies.
Variation in CD8 T cell IFNγ differentiation to strains of Toxoplasma gondii is characterized by small effect QTLs with contribution from ROP16

Introduction Toxoplasma gondii induces a strong CD8 T cell response characterized by the secretion of IFNγ that promotes host survival during infection. The initiation of CD8 T cell IFNγ responses in vitro differs widely between clonal lineage strains of T. gondii, in which type I strains are low inducers, while types II and III strains are high inducers. We hypothesized this phenotype is due to a polymorphic “Regulator Of CD8 T cell Response” (ROCTR). Methods Therefore, we screened F1 progeny from genetic crosses between the clonal lineage strains to identify ROCTR. Naïve antigen-specific CD8 T cells (T57) isolated from transnuclear mice, which are specific for the endogenous and vacuolar TGD057 antigen, were measured for their ability to become activated, transcribe Ifng and produce IFNγ in response to T. gondii infected macrophages. Results Genetic mapping returned four non-interacting quantitative trait loci (QTL) with small effect on T. gondii chromosomes (chr) VIIb-VIII, X and XII. These loci encompass multiple gene candidates highlighted by ROP16 (chrVIIb-VIII), GRA35 (chrX), TgNSM (chrX), and a pair of uncharacterized NTPases (chrXII), whose locus we report to be significantly truncated in the type I RH background. Although none of the chromosome X and XII candidates bore evidence for regulating CD8 T cell IFNγ responses, type I variants of ROP16 lowered Ifng transcription early after T cell activation. During our search for ROCTR, we also noted the parasitophorous vacuole membrane (PVM) targeting factor for dense granules (GRAs), GRA43, repressed the response suggesting PVM-associated GRAs are important for CD8 T cell activation. Furthermore, RIPK3 expression in macrophages was an absolute requirement for CD8 T cell IFNγ differentiation implicating the necroptosis pathway in T cell immunity to T. gondii. Discussion Collectively, our data suggest that while CD8 T cell IFNγ production to T. gondii strains vary dramatically, it is not controlled by a single polymorphism with strong effect. However, early in the differentiation process, polymorphisms in ROP16 can regulate commitment of responding CD8 T cells to IFNγ production which may have bearing on immunity to T. gondii.
Assessing the scientific value and vulnerability of paleontological sites: a new analytic operational procedure

Introduction: Paleontological heritage rarely receives the same legislative attention as archeological heritage. Part of the problem seems to be, at least in some contexts (e.g., Italy), the difficulty of acknowledging fossils as distinct assets from other cultural heritage objects and the lack of expertise among the administrative functionaries. This study aims to describe and test an objective analytic operational procedure that could allow for the assessment of the relevance of any fossiliferous site and its potential vulnerability in its present state. Methods: The estimations were obtained using several quantitative and qualitative parameters that could describe the probability of fossil recovery for each site (Pr) and the scientific and cultural interest of the locality (In). Each parameter has subcategories for better defining. The product of probability and interest results in the scientific value (S), generally expressed as a percentage (S*). The vulnerability index (V) of productive and active sites considers the use of the land (U) and the natural erosion (E). The parameters were thought to apply to any type of fossil locality. We tested the indexes on 22 localities (7 of which were with paleoichnological records and 15 with direct body-fossil evidence), all different from one another. Results: The results show that the proposed indexes well describe and characterize each locality. Most of the sites are moderately vulnerable (V between 1 and 3) except for large quarry sites (e.g., Pirro Nord, Italy and Solnhofen, Germany) whose vulnerability indexes fell in the maximum degree of risk. Discussion: The operational procedure presented here is a simple, objective, and remotely applicable method allowing paleontologists and non-expert personnel to categorize localities and, therefore, act as a base to plan actions in paleontological heritage management relative to territorial development and land use.
Targeting NETs using dual-active DNase1 variants

Background Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA (dsDNA) and chromatin, respectively. Methods Here, we engineered a dual-active DNase with combined DNase1 and DNase1L3 activities and characterized the enzyme for its NET degrading potential in vitro. Furthermore, we produced a mouse model with transgenic expression of the dual-active DNase and analyzed body fluids of these animals for DNase1 and DNase 1L3 activities. We systematically substituted 20 amino acid stretches in DNase1 that were not conserved among DNase1 and DNase1L3 with homologous DNase1L3 sequences. Results We found that the ability of DNase1L3 to degrade chromatin is embedded into three discrete areas of the enzyme's core body, not the C-terminal domain as suggested by the state-of-the-art. Further, combined transfer of the aforementioned areas of DNase1L3 to DNase1 generated a dual-active DNase1 enzyme with additional chromatin degrading activity. The dual-active DNase1 mutant was superior to native DNase1 and DNase1L3 in degrading dsDNA and chromatin, respectively. Transgenic expression of the dual-active DNase1 mutant in hepatocytes of mice lacking endogenous DNases revealed that the engineered enzyme was stable in the circulation, released into serum and filtered to the bile but not into the urine. Conclusion Therefore, the dual-active DNase1 mutant is a promising tool for neutralization of DNA and NETs with potential therapeutic applications for interference with thromboinflammatory disease states.
Morphologic and genic effects of waste pollution on the reproductive physiology of Paracentrotus lividus lmk: a mesocosm experiment

A considerable amount of coastal contamination is caused by wastes deriving from household and the degradation and the metabolism of plants and animals, even if our attention is commonly focused on industrial pollutants and contaminants. Waste pollutants are mainly represented by highly diluted soluble compounds and particles deriving from dead organisms. This complex combination, consisting of suspended particles and dissolved nutrients, has a significant impact on coastal planktonic and benthic organisms, also playing an active role in the global cycles of carbon. In addition, production practices are nowadays shifting towards recirculated aquaculture systems (RAS) and the genic responses of target organisms to the pollution deriving from animal metabolism are still scarcely addressed by scientific investigations. The reservoir of organic matter dissolved in the seawater is by far the least understood if compared to that on land, cause only a few compounds have been identified and their impacts on animals and plants are poorly understood. The tendency of these compounds to concentrate at interfaces facilitates the absorption of dissolved organic compound (DOC) onto suspended particles. Some DOC components are chemically combined with dissolved metals and form complexes, affecting the chemical properties of the seawater and the life of the coastal biota. In this research, we compared the reproductive performances of the common sea urchin Paracentrotus lividus cultured in open-cycle tanks to those cultured in a recirculating aquaculture system (RAS), where pollution progressively increased during the experiment due to animal escretions. Sea urchins were cultured for 7 months under these two conditions and their gametes were collected. Embryos resulting by in vitro fertilization were analyzed by Real Time qPCR to identify possible effects of pollution-induced stress. The fertility of sea urchins was evaluated, as well as the gonadosomatic indices and the histological features of gonads. Our results indicate that pollution due to excess of nutrients, event at sub-lethal concentrations, may hardly impact the reproductive potential of this key species and that chronic effects of stress are revealed by the analyses of survival rates and gene expression.
IMAGE GENERATION TECHNIQUES USING GENERATIVE ADVERSARIAL NETWORKS

: GANs were first described in a year 2014, which is quite recently for algorithms. Although, during its time of existence, lots of various modifications and areas of possible usage were found. One of such area is image generation sphere, in which this algorithm is able to achieve results that, in some cases, do not differ from pictures drawn by a person or photographs of certain objects.
Exploring Data-Driven Approaches to Support Depression Therapy

Depression is a prevalent problem in today’s society and one of the world’s most common mental health illnesses. We envision that data-driven approaches can support patients and therapists. There is a huge potential for generating a high-level understanding of the user’s state of mind by continuously tracking the user via mobile sensing. While this can accelerate the therapy, constant user tracking raises a number of ethical and privacy concerns. Thus, consolidating the benefits and risk is important to ensure that the benefits of user tracking will outweigh the risks for patients
Gamma-Ray Bursts at High Redshift

Gamma-Ray Bursts (GRBs) are very energetic explosions. Probably they are the most energetic events in our universe following the Big Bang. A GRB is characterized by an intense flash of ∞-radiation, in which » 10 51 i 10 53 ergs is released in a few seconds, followed by an afterglow in all parts of the electromagnetic spectrum. Although not observed yet, theory suggests that the first generation of stars is a likely candidate for providing the progenitors of GRBs. In this article we will derive the GRB-rate for a dark matter halo at a redshift z. By using the Press-Schechter formalism we ask ourselves the question what the probability is that such a halo existed at that particular redshift. We will also derive a luminosity function for the afterglow following the actual GRB. The latter luminosity function will be compared with the sensitivities of the near infrared (NIR) camera on the upcoming James Webb Space Telescope (JWST). Finally we will try to infer whether we expect to find a GRB afterglow in a random field of the latter telescope. In 1963, during the cold war, a Nuclear Test Ban Treaty (NTBT) was signed by the governments of the USSR, the USA and the UK. This treaty prohibited the testing of nuclear devices in the atmosphere as well as in space. The USA wanted to make sure that the other countries involved did not violate the treaty and therefore they launched the Vela-satellites. These were satellites equipped with ∞, X-ray and neutron detectors. In this way nuclear activities in the atmosphere or in space would certainly be detected. However, the fourth version of the satellites detected a serie of ∞-flashes that did not have the characteristics of nuclear activities on earth. It was only later on, when the satellites were able to determine directions for the events, that these ∞-flashes turned out to have a cosmic origin. The discovery of GRBs in the late sixties was declassified in the beginning of the seventies. This lead to a burst of publications by astronomers wondering what was causing these ∞flashes. For a long time astronomers could not agree whether these flashes had a cosmological or a galactic origin. In 1990 the Compton Gamma-Ray Observatory was launched. This satellite was equipped with the Burst And Transient Source Experiment (BATSE), an instrument that was able to monitor almost the entire sky for ∞-flashes. It turned out that GRBs were randomly distributed across the sky, strongly favoring the theory of a cosmological origin. However, a lot of astronomers still believed that GRBs had their origin in the galactic halo because there
DIAGNOSTIC ACCURACY OF Β-HCG AND NITRAZINE PAPER TEST IN VAGINAL WASHINGS TAKING AMNIOTIC FLUID POOLING AS GOLD STANDARD OF DIAGNOSING PREMATURE RUPTURE OF MEMBRANES

Background: Premature Rupture of Membranes (PROM) is common in obstetrics and management of such patients depends on whether the rupture has occurred or not. With membranes ruptured the fetus is deprived of protection provided within the amniotic cavity. Beta-Human chorionic gonadotrophin (β-HCG) is a hormone and is present in high concentration in amniotic fluid as well as in the blood and urine of the mother and is studied as possible predictor of preterm labour and as marker of PROM. Objectives: To compare the diagnostic accuracy of Β-hCG & nitrazine paper test in vaginal washings taking amniotic fluid pooling as gold standard for diagnosing premature rupture of membranes. Methods: It was a comparative cross-sectional study conducted at Unit Department, of Obstetrics & Gynecology, Lahore General Hospital, Lahore. After that vaginal washings were taken for β-hCG testing. A pregnancy test kit (Accu Check) was used for detection of β-hCG in vaginal fluid washings. According to amount of µ-hCG in the washings the result has been positive as early as 40 Seconds but for labelling the result negative 5 minutes complete reaction time has been observed. On Nitrazine kit, the positive test is indicated by distinct colour band on both; control and test side. Results: Mean age of women was 27.17+4.55 years. Mean age of gestation was 36.16 + 3.30 weeks. Sensitivity & specificity of Nitrazine Paper Test were 92.17% & 66.67%. However, the PPV & NPV for Nitrazine Paper Test was 98.15% & 30.77% respectively. Sensitivity & specificity of β-hCG Test was 94.35% & 75%. However, the PPV & NPV for β-hCG test was 98.64% & 40.91% respectively. Conclusion: Results of this stud y showed that B-subunit of hCG measured by over-the-counter available pregnancy test kit is a dependable quick and easy test for detection of premature rupture of membranes. This test can be performed on the bed side of the patient without Lab involvement. This test can be promoted as an additional help for the diagnosis of doubtful and ambiguous cases of premature rupture of membranes.
On the predictive performance of the almost unbiased Liu estimator

ABSTRACT Regression models are usually used in forecasting (predicting) unknown values of the response variable y. This article considers the predictive performance of the almost unbiased Liu estimator compared to the ordinary least-squares estimator, principal component regression estimator, and Liu estimator. Finally, we present a numerical example to explain the theoretical results and we obtain a region where the almost unbiased Liu estimator is uniformly superior to the ordinary least-squares estimator, principal component regression estimator, and Liu estimator.
The dual danger of

Background. Pyometra, a collection of purulent material within the endometrial cavity, is a relatively uncommon gynaecological condition. Spontaneous perforation of the uterus is an infrequent complication of pyometra, most often the result of malignant conditions in the uterus. Case presentation. We report the case of an elderly woman who had acute abdominal pain due to a ruptured uterus secondary to pyometra resulting from an infected endometrial mass diagnosed on computed tomography. She underwent an urgent exploratory laparotomy and a total hysterectomy and bilateral salpingo-oophorectomy were performed. Her CA-125 level was raised (102.3 U/ml) and the histopathological examination (HPE) of the endometrial mass confirmed an endometrial carcinoma. The rest of the HPE
Bolus of ropivacaine 0.1% versus 0.2% in obstetric epidural analgesia: a comparative prospective study

Objective. Aim of this study is to compare the effect of the initial bolus: 10 ml of ropivacaine 0.2% (small volume, high concentration) and 20 ml of ropivacaine 0.1% (high volume, low concentration) during obstetric labor on the motor block, hemodynamic consequences, analgesia and parturient satisfaction. Patients and Methods. 56 parturients were included in this prospective, randomized, double-blind study. The parturients were randomized into two groups: group 1 receiving an initial bolus of 10ml of ropivacaine at 0.2% + 5 gamma of sufentanil and group 2 receiving an initial bolus of 20ml of ropivacaine at 0.2% + 5 gamma of sufentanil. The main endpoint was the evaluation of motor block. The secondary judgment criteria were: haemodynamic consequences, evaluation of obstetric analgesia by visual analogical scale, evaluation of the sensory level and satisfaction of the parturient. Results. The haemodynamic consequences were comparable for the 2 groups (p>0.05). The means of the VAS were similar (p>0.05). Motor block was similar in the 2 groups (14.81% for group 1 versus 6.89% for group 2 with p=0.57). A statistically significant difference was noted according to the sensory level which was higher in group 2 (p<0.05). The mean satisfaction was without significant difference (p=0.64). The adverse effects were similar in the two groups (p>0.05). Conclusions . Our study does not show a benefit of the use of a high volume low concentration compared to the use of small volume high concentration during the induction of the epidural.
GROUP 8 - IMAGE INPAINTING WITH GENERATIVE ADVERSARIAL NETWORK

For the challenge of inpainting missing parts in an image, recent deep learning-based techniques have demonstrated promising results. In this paper, we designed a deep neural network to deal with the task of image inpainting. The goal of this task is for the model to gain whole image understanding and generate plausible results for missing parts in an image. Our model has a GAN structure with a generator and a discriminator. For the generator part, we designed architectures similar to the UNet and ResNet. For the discriminator, we used simple convolutional neural networks in combination with feed-forward neural nets. We trained our network with loss functions that incorporate pixel-wise reconstruction loss and adversarial loss. The model is trained on the COCO dataset provided by Microsoft. Results demonstrate that the models are capable of generating missing patches and provide useful applications.
LOW-RESOURCE TEXT CLASSIFICATION USING CROSS-LINGUAL MODELS FOR BULLYING DETECTION IN THE UKRAINIAN LANGUAGE

Annotation: This paper aims on building bullying detection model for Ukrainian language. Considering absence of labeled datasets for bullying detection and classification in Ukrainian, small Ukrainian dataset (4k samples) was gathered and used for testing models in this research. Taking into account very small number of Ukrainian datasets in general this dataset is publicly available for testing and benchmarking other text classification models. Modern approaches to text class classification in low-resource languages are studied in the paper. We apply zero-shot technique and evaluate performance of modern multilingual, cross-lingual state-of-the-art models and embeddings for text classification in Ukrainian language, including mBERT, XLM-R, LASER and MUSE. Experimental results shows that zero-shot approaches for classification task allow to achieve F1 score of 67-69% for multilingual models trained on English dataset only, having 88-91% test accuracy on English data. We also show that machine translation of English data can be used for estimating model performance in other languages, i.e. only 0-2% difference in test accuracy compared to natural data was received for best models XLM-R and LASER. Zero-shot approach for binary detection task showed even better results 81% compared to 91,59% on original English data. We then enhance the best XLM-R model by training it on our natural Ukrainian data-set and confirm benefits of augmenting low-resource language dataset with machine translations from resource-rich English data. Finally, the model for bullying detection in the Ukrainian language is built achieving F1 score of 91,59% with only 12k samples dataset in different languages.
A Self-Attention Based Hybrid CNN-LSTM for Speaker-Independent Speech Emotion Recognition

Emotion recognition through speech signals has grown a lot as it facilitates humanmachine interaction. In this manuscript, we propose a new self-attention-based convolution bidirectional long short term memory (Bi LSTM) with a gender embedding method. It beats the attention-based convolution BiLSTM method by 3.43%. Emotional characteristics are vulnerable to non-emotional influences such as the speaker, speech modes, and atmosphere. We have presumed that computing delta-deltas and deltas for individualized characteristics not retains only useful emotional intimation but also reduces the influence of irrelevant emotional variables, resulting in fewer miss classifications [1]. We have also presumed that the gender of the speaker also plays a significant role when we are dealing with speech signals. Therefore, we have done gender embedding and fed it as an input to our self-attention-based convolution BiLSTM along with extracted features. The self-attention system has shown exceptional abilities in learning taskspecific feature representations. We have carried out the analysis of the interactive emotional dyadic motion capture (IEMOCAP) dataset that confirms the efficiency of the introduced method. We have achieved confirmed outcomes in terms of unweighted average recall (UAR).