Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypical Characterization of Spleen Remodeling in Murine Experimental Visceral Leishmaniasis

Background: Visceral leishmaniasis (VL) is caused by Leishmania infantum or L. donovani infection. One of the main problems related to this disease is the emergence of severe clinical forms with a lethality of 5–20%, even while under specific treatment. In humans and other species susceptible to fatal VL, such as dogs and hamsters, the disruption of splenic white pulp (WP) is accompanied by disease progression. Control of VL progression is seen in BALB/c mice, as evidenced by a mild clinical presentation and controlled parasite replication in the liver and spleen. In this study, we investigated the features involved in the morphological remodeling of splenic compartments associated with the control of VL progression to death. Methods: We evaluated cohorts of BALB/c mice after 30, 60, and 90 days of infection by L. infantum. Spleen morphology, cell population subsets and cytokine production were studied in the spleen using flow- and histo-cytometry. Results: Intraperitoneal infection with 108 promastigotes of L. infantum led to progressive increases in spleen size at 60 and 90 days after infection. Splenomegaly was the only clinical sign of disease observed. At 30 days after infection, hyperplasia in the WP and decreased numbers of plasmacytoid dendritic cells were observed. The WP hyperplasia subsided at 60 days post-infection. However, the splenomegaly remained in association with increased numbers of macrophages, B and T lymphocytes and plasma cells. An increased number of lymphoid tissue inducer (LTi) cells was observed; these were distributed around the periarteriolar lymphoid sheath in control mice and scattered throughout the red pulp in the Leishmania-infected mice. After 90 days of infection, increased IL-6 and IFN-γ production was seen in the spleen, as well as higher frequencies of follicular and plasmacytoid dendritic cells. Conclusion: The data presented herein emphasizes the potential role of spleen remodeling in the control of severe forms of VL and highlights features potentially involved in this process.
Toxicity and Pharmacogenomic Biomarkers in Breast Cancer Chemotherapy

Breast cancer (BC) is one of the most prevalent types of cancer worldwide with high morbidity and mortality rates. Treatment modalities include systemic therapy, in which chemotherapy is a major component in many cases. Several chemotherapeutic agents are used in combinations or as single agents with many adverse events occurring in variable frequencies. These events can be a significant barrier in completing the treatment regimens. Germline genomic variants are thought of as potential determinants in chemotherapy response and the development of side effects. Some pharmacogenomic studies were designed to explore germline variants that can be used as biomarkers for predicting developing toxicity or adverse events during chemotherapy in BC. In this review, we reassess and summarize the major findings of pharmacogenomic studies of chemotherapy toxicity during BC management. In addition, deficiencies hampering utilizing these findings and the potential targets of future research are emphasized. Main insufficiencies in toxicity pharmacogenomics studies originate from study design, sample limitations, heterogeneity of selected genes, variants, and toxicity definitions. With the advent of high throughput genotyping techniques, researchers are expected to explore the identified as well as the potential genetic biomarkers of toxicity and efficacy to improve BC management. However, to achieve this, the limitations of previous work should be evaluated and avoided to reach more conclusive and translatable evidence for personalizing BC chemotherapy.
Plastome Evolution in Dolomiaea (Asteraceae, Cardueae) Using Phylogenomic and Comparative Analyses

Dolomiaea is a medicinally important genus of Asteraceae endemic to alpine habitats of the Qinghai-Tibet Plateau (QTP) and adjacent areas. Despite significant medicinal value, genomic resources of Dolomiaea are still lacking, impeding our understanding of its evolutionary history. Here, we sequenced and annotated plastomes of four Dolomiaea species. All analyzed plastomes share the gene content and structure of most Asteraceae plastomes, indicating the conservation of plastome evolutionary history of Dolomiaea. Eight highly divergent regions (rps16-trnQ, trnC-petN, trnE-rpoB, trnT-trnL-trnF, psbE-petL, ndhF-rpl32-trnL, rps15-ycf1, and ycf1), along with a total of 51–61 simple sequence repeats (SSRs) were identified as valuable molecular markers for further species delimitation and population genetic studies. Phylogenetic analyses confirmed the evolutionary position of Dolomiaea as a clade within the subtribe Saussureinae, while revealing the discordance between the molecular phylogeny and morphological treatment. Our analysis also revealed that the plastid genes, rpoC2 and ycf1, which are rarely used in Asteraceae phylogenetic inference, exhibit great phylogenetic informativeness and promise in further phylogenetic studies of tribe Cardueae. Analysis for signatures of selection identified four genes that contain sites undergoing positive selection (atpA, ndhF, rbcL, and ycf4). These genes may play important roles in the adaptation of Dolomiaea to alpine environments. Our study constitutes the first investigation on the sequence and structural variation, phylogenetic utility and positive selection of plastomes of Dolomiaea, which will facilitate further studies of its taxonomy, evolution and conservation.
Estivation in the Apple Snail Pomacea maculata: Mobilization of Calcium Granules in the Lung

ABSTRACT The effect of long-term estivation on the abundance of calcium granules in the lung tissue of the apple snail Pomacea maculata Perry was studied. Electron-dispersive spectrophotometric analysis of the shell and the granular inclusions in the lung show that both structures are composed of calcium carbonate. The layers forming the shell are similar to those found in the shells of other gastropods. Calcium granules are extremely abundant in the tissues of the lung of P. maculata. The spherical granules consist of concentric layers of material inside calcium cells. There are three distinct populations of hemocytes in P. maculata hemolymph, two cell types with granulocytic morphology and one agranular type. Selective staining shows that hemocytes contain large amounts of calcium, implicating these cells in the transport of calcium carbonate from storage sites to other tissues. The pCO2 of the hemolymph increases in estivating gastropods, and it has been suggested that stores of solid calcium carbonate are mobilized to buffer the resulting acidity. Results of this study show that a large decrease in the abundance of calcium carbonate granules in the lung tissue occurs during estivation. In addition, there is evidence that a calcium binding protein is present in the hemocytes.
Processing False Beliefs in Preschool Children and Adults: Developing a Set of Custom Tasks to Test the Theory of Mind in Neuroimaging and Behavioral Research

The theory of mind (ToM) is the ability to attribute mental states to others and is extremely important for social functioning. It has been widely examined in both behavioral and neuroimaging research, usually with the use of the many versions of the false-belief (FB) task. However, there is still not enough evidence from studies on the neurodevelopmental mechanisms of ToM mostly because of methodological limitations: lack of selectivity, mismatch of experimental and control tasks, and focusing on participants older than 6 years old. In the current study, we attempted to develop a computerized tool for ToM assessment suitable for both behavioral and neuriomaging testing in preschoolers. We designed a version of the classic change-of-location task with custom visuals and three fine-tuned conditions: FB, true-belief, and no-belief (NB). The usability of the task for further application in neurodevelopmental research was tested with three methods: first, behaviorally, with the use of a touch screen on a group of 75 children, followed by a functional MRI (fMRI) study on 13 adults, and a functional near-infrared spectroscopy (fNIRS) study on 19 preschool children. In line with our expectations, on the behavioral level, our task elicited the all-or-none performance in preschoolers. There was also a progression of performance with age in the FB condition. On the neural level, we observed the activation of structures involved in the ToM brain network in response to our task in both adults and children. The results therefore suggest that our task can be a useful tool for studying ToM development and its neural underpinnings.
Severe Adenovirus Pneumonia Requiring Extracorporeal Membrane Oxygenation Support in Immunocompetent Children

Objective: To highlight severe adenovirus pneumonia in immunocompetent patients by analysis of severe adenovirus pneumonia associated with acute respiratory distress syndrome in whom extracorporeal membrane oxygenation (ECMO) support is required. Methods:Pediatric patients with adenovirus pneumonia and ECMO supports in our hospital from February 2018 to May 2019 were retrospectively analyzed, and having 100 common adenovirus pneumonia children as a control. Results:A total of 8 patients, including 4 boys (50.0%), were enrolled. They were previously immunocompetent with a median age of 31 months. They were admitted as persistent fever and cough for more than one week. Median time prior to development of respiratory failure requiring intubation and invasive mechanical ventilation was 5 days. Venoarterial ECMO support as rescue ventilation was instituted after a median time of 24.5 h of conventional mechanical ventilator support. The median duration on ECMO support was 9 days and mechanical ventilation was 14 days, respectively. Six patients (75%) were recovered and 2 (25%) died. Median length of stay in ICU and hospital were 27.5 days and 47.5 days, respectively. Conclusion:The promising outcomes of our cases suggested that ECMO support for rescue ventilation may be considered when symptoms deteriorated in adenovirus pneumonia patients, and may improve outcome. However, sequelae of adenovirus pneumonia and ECMO-related complications should also be taken into account.
Impact of Paranasal Sinus Invasion on Oncologic and Dosimetric Outcomes in Nasopharyngeal Carcinoma Following Intensity-Modulated Radiation Therapy—Implications for Risk Stratification and Planning Optimization

Purpose: This study aims to investigate the prognostic value and dosimetric impact of paranasal sinus invasion (PSI) in patients with nasopharyngeal carcinoma (NPC), and further to explore the feasibility of an integrative prognostic model based on anatomic, volumetric, and dosimetric features. Methods: Two hundred six patients with T3 NPC receiving intensity-modulated radiation therapy (IMRT) were retrospectively analyzed. Dosimetric parameters were calculated from dose–volume histograms. Primary gross tumor volume (GTV-P) and dosimetric parameters were categorized using optimal cutpoints determined by R. Local recurrence-free survival (LRFS) was estimated using Kaplan–Meier method. Independent risk factors for LRFS were identified through univariable and multivariable analyses by Cox proportional hazards models. Results: The incidence of PSI was 10.7% (22/206). Patients with PSI had significantly inferior 5-year LRFS (77.3 vs. 93.8%, P = 0.006). IMRT plans for patients with PSI had larger dose heterogeneity, higher frequency of underdosing, and higher maximum dose to optic structures. When categorized by optimal cutpoints, GTV-P > 38.67 cm3 (5-year LRFS, 84.8 vs. 97.4%, P = 0.008), and V66.88 < 89.87% (5-year LRFS, 67.1 vs. 94.5%, P < 0.001) were associated with significantly worse local outcome. Multivariable analyses showed that PSI, GTV-P > 38.67 cm3, and V66.88 < 89.87% were independent risk factors for local relapse, either in patients with or without concurrent chemotherapy. An integrative prognostic model was then established upon the cumulative score of risk factors. Subgroups with score of 0, 1–2, and 3 had distinctive local outcomes; the 5-year LRFS was 96.6, 84.7, and 58.3%, respectively (P < 0.001). Conclusions: Paranasal sinus invasion jeopardized local control in T3 NPC patients due to large tumor burden and inadequate radiation dose in GTV-P. The presence of PSI, GTV-P, and radiation underdosing combined are critical for the risk stratification of local failure.
Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis

Second-generation antipsychotics (SGA) are a pharmacological class widely used in psychiatry thanks to their efficacy and good tolerability profile. One of the most used SGA is aripiprazole (ARI) because of its several formulations and safe metabolic and cardiac profile. As reported in a recent review, there are growing numbers of reports about ARI-induced gambling disorder (ARI-induced GD) which should encourage clinicians to use ARI more cautiously. Given the common genetic susceptibility of both GD and ARI's clinical response to a genetic polymorphism on the D2 receptor (DRD2/ANKK1 Taq1A; rs1800497), the hypothesis regarding the origin of this phenomenon could be found in the altered sensitization of dopamine's receptors that certain individuals carry genetically. The identification of a possible genetic susceptibility (detectable by genetic tests) could provide clinicians with an explanation for the ARI-induced GD and the possibility of using genetic screening tools for those cases of suspected predisposition; this would allow the clinician to prescribe ARI with less apprehension. The confirmation of this hypothesis through future pharmacogenetic studies may be useful for clinicians to have a correct understanding of the phenomenon.
Metabolic Hydrogen Flows in Rumen Fermentation: Principles and Possibilities of Interventions

Rumen fermentation affects ruminants productivity and the environmental impact of ruminant production. The release to the atmosphere of methane produced in the rumen is a loss of energy and a cause of climate change, and the profile of volatile fatty acids produced in the rumen affects the post-absorptive metabolism of the host animal. Rumen fermentation is shaped by intracellular and intercellular flows of metabolic hydrogen centered on the production, interspecies transfer, and incorporation of dihydrogen into competing pathways. Factors that affect the growth of methanogens and the rate of feed fermentation impact dihydrogen concentration in the rumen, which in turn controls the balance between pathways that produce and incorporate metabolic hydrogen, determining methane production and the profile of volatile fatty acids. A basic kinetic model of competition for dihydrogen is presented, and possibilities for intervention to redirect metabolic hydrogen from methanogenesis toward alternative useful electron sinks are discussed. The flows of metabolic hydrogen toward nutritionally beneficial sinks could be enhanced by adding to the rumen fermentation electron acceptors or direct fed microbials. It is proposed to screen hydrogenotrophs for dihydrogen thresholds and affinities, as well as identifying and studying microorganisms that produce and utilize intercellular electron carriers other than dihydrogen. These approaches can allow identifying potential microbial additives to compete with methanogens for metabolic hydrogen. The combination of adequate microbial additives or electron acceptors with inhibitors of methanogenesis can be effective approaches to decrease methane production and simultaneously redirect metabolic hydrogen toward end products of fermentation with a nutritional value for the host animal. The design of strategies to redirect metabolic hydrogen from methane to other sinks should be based on knowledge of the physicochemical control of rumen fermentation pathways. The application of new –omics techniques together with classical biochemistry methods and mechanistic modeling can lead to exciting developments in the understanding and manipulation of the flows of metabolic hydrogen in rumen fermentation.
Robust functional mapping of layer-selective responses in human lateral geniculate nucleus with high-resolution 7T fMRI

The lateral geniculate nucleus (LGN) of the thalamus is the major subcortical relay of retinal input to the visual cortex. It plays important roles in visual perception and cognition and is closely related with several eye diseases and brain disorders. Primate LGNs mainly consist of six layers of monocular neurons with distinct cell types and functions. The non-invasive measure of layer-selective activities of the human LGN would have broad scientific and clinical implications. Using high-resolution functional magnetic resonance imaging (fMRI) at 7 Tesla (T) and carefully designed visual stimuli, we achieved robust functional mapping of eye-specific and also magnocellular/parvocellular-specific laminar patterns of the human LGN. These laminar patterns were highly reproducible with different pulse sequences scanned on separate days, between different subjects, and were in remarkable consistency with the simulation from high-resolution histology of the human LGNs. These findings clearly demonstrate that 7T fMRI can robustly resolve layer-specific responses of the human LGN. This paves the way for future investigation of the critical roles of the LGN in human visual perception and cognition, as well as the neural mechanisms of many developmental and neurodegenerative diseases.
Carbohydrate Conjugates in Vaccine Developments

Vaccines are powerful tools that can activate the immune system for protection against various diseases. As carbohydrates can play important roles in immune recognition, they have been widely applied in vaccine development. Carbohydrate antigens have been investigated in vaccines against various pathogenic microbes and cancer. Polysaccharides such as dextran and β-glucan can serve as smart vaccine carriers for efficient antigen delivery to immune cells. Some glycolipids, such as galactosylceramide and monophosphoryl lipid A, are strong immune stimulators, which have been studied as vaccine adjuvants. In this review, we focus on the current advances in applying carbohydrates as vaccine delivery carriers and adjuvants. We will discuss the examples that involve chemical modifications of the carbohydrates for effective antigen delivery, as well as covalent antigen-carbohydrate conjugates for enhanced immune responses.
Host Fingerprinting for Web Servers Authentication

: Fingerprinting is a biometric technique for computing a unique profile associated to a physical person for authentication purpose. It has been successfully applied also to software entities by using hash functions for integrity checking after downloading. In the paper, we propose a fingerprinting algorithm to identify a machine during a client-server authentication process. In detail, this host identifier can be used for connecting to a database server without using an account storing a plain-text password. After the presentation of experimental results, we show some real scenarios where this solution can be applied.
Stable Feature Selection for Gene Expression using Enhanced Binary Particle Swarm Optimization

: Feature subset selection (FSS) is an intractable optimization problem in high-dimensional gene expression datasets, leading to an explosion of local minima. While binary variants of particle swarm optimization (BPSO) have been applied to solve the FSS problem, increasing dimensionality of the feature space pose additional challenges to these techniques imparing their ability to select most relevant feature subsets in the massive presence of uninformative features. Most FSS optimization techniques focus on maximizing classi-ﬁcation performance while minimizing subset size but usually fail to account for solution stability or feature relevance in their optimization process. In particular, stability in FSS is interpreted differently compared to PSO. Although a large volume of published studies on each stability issue separately exists, wrapper models that tackle both stability problems at the same time are still missing. Speciﬁcally, we introduce a novel ap-praoch COMBPSO (COMBinatorial PSO) that features a novel ﬁtness function, integrating feature relevance and solution stability measures with classiﬁcation performance and subset size as well as PSO adaptations to enhance the algorithm’s convergence abilities. Applying our approach to real disease-speciﬁc gene expression data, we found that COMBPSO has similar classiﬁcation performance compared to BPSO, but provides reliable classiﬁcation with considerably smaller and more stable gene subsets.
Perceiving the Focal Point of a Painting with AI: Case Studies on Works of Luc Tuymans

: We report the ﬁrst steps in investigating how we can use AI to study contemporary painting practices and viewer experiences, focusing in particular on the work of Luc Tuymans. We review ﬁrst various possible aspects of painting that could be studied and point to some relevant AI techniques to do so. Then we zoom in on one speciﬁc topic: How is a viewer guided to the focal point of the painting. This is not purely a matter of visual perception but also of interpretation and meaning making. Painters deliberately create focal points based on sophisticated knowledge of human perception and interpretation. Inspired by their insights and practices we can use AI research to unpack the process and thus provide a more insightful characterization of how paintings are perceived and made, compared to statistically derived embeddings. We argue that profound challenges must still be overcome before AI systems handle the identiﬁcation of focal points, let alone arrive at the rich interpretations human viewers construct of paintings or other types of art works.
High-performance Algorithms using Deep Learning in Turn-based Strategy Games

: The development of AlphaGo has increased the interest of researchers in applying deep learning and reinforcement learning to games. However, using the AlphaZero algorithm on games with complex data structures and vast search space, such as turn-based strategy games, has some technical challenges. The problem involves performing complex data representations with neural networks, which results in a very long learning time. This study discusses methods that can accelerate the learning of neural networks by solving the problem of the data representation of neural networks using a search tree. The proposed algorithm performs better than existing methods such as the Monte Carlo Tree Search (MCTS). The automatic generation of learning data by self-play does not require a big learning database beforehand. Moreover, the algorithm also shows excellent match results with a win rate of more than 85% against the conventional algorithms in the new map which is not used for learning.