Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV-1 Molecular Epidemiology, Transmission Clusters and Transmitted Drug Resistance Mutations in Central Brazil

We aimed to characterize HIV-1 molecular epidemiology and transmission clusters among heterosexual (HET) and men who have sex with men (MSM) individuals, as well as transmitted drug resistance mutations (TDRM) in Central-Western Brazil. This cross-sectional survey was conducted among 190 antiretroviral naïve HIV-1 infected individuals. Proviral DNA was extracted, and nested PCR amplified partial polymerase gene (PR/RT). After sequencing, subtypes were assigned, and the sequences were analyzed for the occurrence of possible transmission networks. Calibrated Population Resistance (CPR) tool from Stanford HIV Database was used to investigate the presence of TDRM. Among 150 individuals whose samples were successfully sequenced, the most prevalent HIV-1 subtype was B, followed by recombinant forms. The occurrence of twenty transmission clusters composed by at least two sequences was verified, suggesting the existence of transmission clusters among individuals from the same or distinct sexual orientations. Intermediate level of TDRM (12%) was found in the study population, and almost half of the subjects with TDRM had more than one resistance mutation. No correlations between sexual orientation and the presence of TDRM, HIV-1 subtypes/recombinants forms were verified. Taken together, the necessity of the continuous monitoring of the TDRM to verify the importance of pre-genotyping and to delineate future strategies in primary antiretroviral therapy. Likewise, the knowledge of the HIV-1 transmission networks in Brazil would allow the implementation of effective HIV-1 prevention strategies in local settings.
SERS Probing of Proteins in Gold Nanoparticle Agglomerates

The collection of surface-enhanced Raman scattering (SERS) spectra of proteins and other biomolecules in complex biological samples such as animal cells has been achieved with gold nanoparticles that are introduced to the sample. As a model for such a situation, SERS spectra were measured in protein solutions using gold nanoparticles in the absence of aggregating agents, allowing for the free formation of a protein corona. The SERS spectra indicate a varied interaction of the protein molecule with the gold nanoparticles, depending on protein concentration. The concentration-dependent optical properties of the formed agglomerates result in strong variation in SERS enhancement. At protein concentrations that correspond to those inside cells, SERS signals are found to be very low. The results suggest that in living cells the successful collection of SERS spectra must be due to the positioning of the aggregates rather than the crowded biomolecular environment inside the cells. Experiments with DNA suggest the suitability of the applied sample preparation approach for an improved understanding of SERS nanoprobes and nanoparticle-biomolecule interactions in general.
Seventy Years of Chlamydia Vaccine Research – Limitations of the Past and Directions for the Future

Chlamydia is a major bacterial pathogen that infects humans, as well as a wide range of animals, including marsupials, birds, cats, pigs, cattle, and sheep. Antibiotics are the only treatment currently available, however, with high rates of re-infection, there is mounting pressure to develop Chlamydia vaccines. In this review, we analyzed how Chlamydia vaccine trials have developed over the past 70 years and identified where future trials need to be focused. There has been a strong bias toward studies targeting C. muridarum and C. trachomatis within mice and a lack of studies matching chlamydial species to their end target host. Even though a large number of specific antigenic targets have been studied, the results from whole-cell vaccine targets show slightly more promising results overall. There has also been a strong bias toward systemic vaccine delivery systems, despite the finding that mucosal delivery systems have shown more promising outcomes. However, the only successful vaccines with matched chlamydial species/infecting host are based on systemic vaccine delivery methods. We highlight the extensive work done with mouse model trials and indicate that whole cell antigenic targets are capable of inducing an effective response, protecting from disease and reducing shedding rates. However, replication of these results using antigen preparations more conducive to commercial vaccine production has proven difficult. To date, the Major Outer Membrane Protein (MOMP) has emerged as the most suitable substitute for whole cell targets and its delivery as a combined systemic and mucosal vaccine is most effective. Finally, although mouse model trials are useful, differences between hosts and infecting chlamydial strains are preventing vaccine formulations from mouse models to be translated into larger animals or intended hosts.
Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis

Hemophagocytic lymphohistocytosis (HLH) is characterized by fulminant cytokine storm leading to multiple organ dysfunction and high mortality. HLH is classified into familial (fHLH) and into secondary (sHLH). fHLH is rare and it is due to mutations of genes encoding for perforin or excretory granules of natural killer (NK) cells of CD8-lymphocytes. sHLH is also known as macrophage activation syndrome (MAS). Macrophage activation syndrome (MAS) in adults is poorly studied. Main features are fever, hepatosplenomegaly, hepatobiliary dysfunction (HBD), coagulopathy, cytopenia of two to three cell lineages, increased triglycerides and hemophagocytosis in the bone marrow. sHLH/MAS complicates hematologic malignancies, autoimmune disorders and infections mainly of viral origin. Pathogenesis is poorly understood and it is associated with increased activation of macrophages and NK cells. An autocrine loop of interleukin (IL)-1β over-secretion leads to cytokine storm of IL-6, IL-18, ferritin, and interferon-gamma; soluble CD163 is highly increased from macrophages. The true incidence of sHLH/MAS among patients with sepsis has only been studied in the cohort of the Hellenic Sepsis Study Group. Patients meeting the Sepsis-3 criteria and who had positive HSscore or co-presence of HBD and disseminated intravascular coagulation (DIC) were classified as patients with macrophage activation-like syndrome (MALS). The frequency of MALS ranged between 3 and 4% and it was an independent entity associated with early mortality after 10 days. Ferritin was proposed as a diagnostic and surrogate biomarker. Concentrations >4,420 ng/ml were associated with diagnosis of MALS with 97.1% specificity and 98% negative predictive value. Increased ferritin was also associated with increased IL-6, IL-18, IFNγ, and sCD163 and by decreased IL-10/TNFα ratio. A drop of ferritin by 15% the first 48 h was a surrogate finding of favorable outcome. There are 10 on-going trials in adults with sHLH; two for the development of biomarkers and eight for management. Only one of them is focusing in sepsis. The acronym of the trial is PROVIDE (ClinicalTrials.gov NCT03332225) and it is a double-blind randomized clinical trial aiming to deliver to patients with septic shock treatment targeting their precise immune state. Patients diagnosed with MALS are receiving randomized treatment with placebo or the IL-1β blocker anakinra.
CD11c+ Cells Are Gatekeepers for Lymphocyte Trafficking to Infiltrated Islets During Type 1 Diabetes

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that affects more than 19 million people with incidence increasing rapidly worldwide. For T cells to effectively drive T1D, they must first traffic to the islets and extravasate through the islet vasculature. Understanding the cues that lead to T cell entry into inflamed islets is important because diagnosed T1D patients already have established immune infiltration of their islets. Here we show that CD11c+ cells are a key mediator of T cell trafficking to infiltrated islets in non-obese diabetic (NOD) mice. Using intravital 2-photon islet imaging we show that T cell extravasation into the islets is an extended process, with T cells arresting in the islet vasculature in close proximity to perivascular CD11c+ cells. Antigen is not required for T cell trafficking to infiltrated islets, but T cell chemokine receptor signaling is necessary. Using RNAseq, we show that islet CD11c+ cells express over 20 different chemokines that bind chemokine receptors expressed on islet T cells. One highly expressed chemokine-receptor pair is CXCL16-CXCR6. However, NOD. CXCR6−/− mice progressed normally to T1D and CXCR6 deficient T cells trafficked normally to the islets. Even with CXCR3 and CXCR6 dual deficiency, T cells trafficked to infiltrated islets. These data reinforce that chemokine receptor signaling is highly redundant for T cell trafficking to inflamed islets. Importantly, depletion of CD11c+ cells strongly inhibited T cell trafficking to infiltrated islets of NOD mice. We suggest that targeted depletion of CD11c+ cells associated with the islet vasculature may yield a therapeutic target to inhibit T cell trafficking to inflamed islets to prevent progression of T1D.
Resilience Mediates the Relationship Between Social Support and Quality of Life in Patients With Primary Glaucoma

Objective: Glaucoma is a serious disease causing blindness, which seriously affects the quality of life of patients. Previous studies have reported that both resilience and social support play important roles in enhancing the quality of life of patients with some diseases. The purpose of this study is to investigate if resilience mediates the relationship between social support and quality of life in patients with primary glaucoma. Methods: We conducted a cross-sectional study with 120 patients with primary glaucoma in China. The Connor-Davidson Resilience Scale was used to measure resilience, and social support was measured by the Perceived Social Support Scale. The Glaucoma Quality of Life-15 questionnaire was used to measure quality of life. Results: There were significant positive correlations between all dimensions and total scores on the resilience, social support, and quality of life scales (p < 0.01). Both resilience and social support could predict these patients' quality of life. A bootstrap test showed that resilience had a partial mediating effect on the relationship between social support and quality of life (p < 0.05). Conclusion: Resilience mediates the relationship between social support and quality of life in primary glaucoma patients. This finding suggests that increasing resilience and social support can improve the quality of life of primary glaucoma patients in clinical practice.
Does Male Circumcision Reduce Women's Risk of Sexually Transmitted Infections, Cervical Cancer, and Associated Conditions?

Background: Male circumcision (MC) is proven to substantially reduce men's risk of a number of sexually transmitted infections (STIs). We conducted a detailed systematic review of the scientific literature to determine the relationship between MC and risk of STIs and associated conditions in women. Methods: Database searches by “circumcision women” and “circumcision female” identified 68 relevant articles for inclusion. Examination of bibliographies of these yielded 14 further publications. Each was rated for quality using a conventional rating system. Results: Evaluation of the data from the studies retrieved showed that MC is associated with a reduced risk in women of being infected by oncogenic human papillomavirus (HPV) genotypes and of contracting cervical cancer. Data from randomized controlled trials and other studies has confirmed that partner MC reduces women's risk not only of oncogenic HPV, but as well Trichomonas vaginalis, bacterial vaginosis and possibly genital ulcer disease. For herpes simplex virus type 2, Chlamydia trachomatis, Treponema pallidum, human immunodeficiency virus and candidiasis, the evidence is mixed. Male partner MC did not reduce risk of gonorrhea, Mycoplasma genitalium, dysuria or vaginal discharge in women. Conclusion: MC reduces risk of oncogenic HPV genotypes, cervical cancer, T. vaginalis, bacterial vaginosis and possibly genital ulcer disease in women. The reduction in risk of these STIs and cervical cancer adds to the data supporting global efforts to deploy MC as a health-promoting and life-saving public health measure and supplements other STI prevention strategies.
Atrial Fibrillation and Risk of Dementia: Epidemiology, Mechanisms, and Effect of Anticoagulation

Atrial fibrillation (AF) is one of the cardiovascular risk factors for dementia. Several longitudinal studies have reported an association between AF and dementia independently of stroke history. Although the mechanisms underlying this association are not fully understood, proposed mechanisms include cerebral hypoperfusion, inflammation, genetic factors, cerebral microbleeds, and recurrent silent cerebral ischemia. Oral anticoagulation can be used to minimize risk of cognitive decline and dementia, given that brain insults can be caused by chronic microemboli or microbleeds. However, controversy on the effects of warfarin and direct oral anticoagulants on this risk exists. This article will address these aspects, with data on the studies already published and a critical view on this subject.
Papulopustular Dermatitis in X-Linked Chronic Granulomatous Disease

Here we describe two term male infants diagnosed with X-linked CGD who present, in addition to frequent infection, with a unique papulopustular skin rash. CGD is caused by a number of genetic defects that impair phagocyte function. This disease results in recurrent infections and granuloma formation. Rarely do patients develop cutaneous symptoms, unless associated with autoimmune disorders such as systemic erythematous lupus (1). Each male infant mentioned here was diagnosed with CGD based on abnormal DHR testing and confirmatory genetic testing. The presenting papulopustular dermatitis was initially characterized as non-classic appearing eczema and subsequently found to be refractory to usual eczema treatment and antibiotics. After obtaining written informed consent from both families, we have documented photographs of the development of a characteristic rash in two newly diagnosed infants with CGD. One infant underwent cutaneous biopsy with histologic evaluation and negative cultures. The dermatitis for both infants was refractory to topical and systemic therapies, and resolved after bone marrow transplantation. Our objective was to characterize cutaneous findings in X-linked CGD and emphasize the importance of considering further immune workup in patients who present with unusual cutaneous findings that do not fit with common infant rashes in conjunction with concerning features for primary immunodeficiency.
QuaSE: Accurate Text Style Transfer under Quantifiable Guidance

We propose the task of Quantifiable Sequence Editing (QuaSE): editing an input sequence to generate an output sequence that satisfies a given numerical outcome value measuring a certain property of the sequence, with the requirement of keeping the main content of the input sequence. For example, an input sequence could be a word sequence, such as review sentence and advertisement text. For a review sentence, the outcome could be the review rating; for an advertisement, the outcome could be the click-through rate. The major challenge in performing QuaSE is how to perceive the outcome-related wordings, and only edit them to change the outcome. In this paper, the proposed framework contains two latent factors, namely, outcome factor and content factor, disentangled from the input sentence to allow convenient editing to change the outcome and keep the content. Our framework explores the pseudo-parallel sentences by modeling their content similarity and outcome differences to enable a better disentanglement of the latent factors, which allows generating an output to better satisfy the desired outcome and keep the content. The dual reconstruction structure further enhances the capability of generating expected output by exploiting the couplings of latent factors of pseudo-parallel sentences. For evaluation, we prepared a dataset of Yelp review sentences with the ratings as outcome. Extensive experimental results are reported and discussed to elaborate the peculiarities of our framework.
Why Pacing Frequency Affects the Production of Early Afterdepolarizations in Cardiomyocytes: An Explanation Revealed by Slow/Fast Analysis of a Minimal Model

Early afterdepolarizations (EADs) are pathological voltage oscillations in cardiomyocytes that have been observed in response to a number of pharmacological agents and disease conditions. Phase-2 EADs consist of small voltage fluctuations that occur during the plateau of an action potential, typically under conditions in which the action potential is elongated. Although a single-cell behavior, EADs can lead to tissue-level arrhythmias, including ventricular tachycardia. Much is currently known about the biophysical mechanisms (i.e., the roles of ion channels and intracellular Ca2+ stores) for the various forms of EADs, due partially to the development and analysis of mathematical models. This includes the application of slow/fast analysis, which takes advantage of timescale separation inherent in the system to simplify its analysis. We take this further, using a minimal 3D model to demonstrate that the phase-2 EADs are canards that are formed in the neighborhood of a folded node singularity. This knowledge allows us to determine the number of EADs that can be produced for a given parameter set without performing computer simulations, and provides guidance on parameter changes that can facilitate or inhibit EAD production. With this approach, we demonstrate why periodic stimulation, as would occur in an intact heart, preferentially facilitates EAD production when applied at low frequencies,. We also explain the origin of complex alternan dynamics that can occur with intermediate-frequency stimulation, in which varying numbers of EADs are produced with each stimulation. These revelations fall out naturally from an understanding of folded node singularities, but are hard or impossible to glean from a knowledge of the biophysical mechanism for EADs alone. Therefore, an understanding of the canard mechanism is a useful complement to an understanding of the biophysical mechanism that has been developed over years of experimental and computational investigations.
Evaluation of Appearance-Based Methods and Implications for Gaze-Based Applications

Appearance-based gaze estimation methods that only require an off-the-shelf camera have significantly improved but they are still not yet widely used in the human-computer interaction (HCI) community. This is partly because it remains unclear how they perform compared to model-based approaches as well as dominant, special-purpose eye tracking equipment. To address this limitation, we evaluate the performance of state-of-the-art appearance-based gaze estimation for interaction scenarios with and without personal calibration, indoors and outdoors, for different sensing distances, as well as for users with and without glasses. We discuss the obtained findings and their implications for the most important gaze-based applications, namely explicit eye input, attentive user interfaces, gaze-based user modelling, and passive eye monitoring. To democratise the use of appearance-based gaze estimation and interaction in HCI, we finally present OpenGaze (www.opengaze.org), the first software toolkit for appearance-based gaze estimation and interaction.
Additive Margin SincNet for Speaker Recognition

Speaker Recognition is a challenging task with essential applications such as authentication, automation, and security. The SincNet is a new deep learning based model which has produced promising results to tackle the mentioned task. To train deep learning systems, the loss function is essential to the network performance. The Softmax loss function is a widely used function in deep learning methods, but it is not the best choice for all kind of problems. For distance-based problems, one new Softmax based loss function called Additive Margin Softmax (AM-Softmax) is proving to be a better choice than the traditional Softmax. The AM-Softmax introduces a margin of separation between the classes that forces the samples from the same class to be closer to each other and also maximizes the distance between classes. In this paper, we propose a new approach for speaker recognition systems called AM-SincNet, which is based on the SincNet but uses an improved AM-Softmax layer. The proposed method is evaluated in the TIMIT dataset and obtained an improvement of approximately 40% in the Frame Error Rate when compared to SincNet.
Learning Choice Functions

We study the problem of learning choice functions, which play an important role in various domains of application, most notably in the field of economics. Formally, a choice function is a mapping from sets to sets: Given a set of choice alternatives as input, a choice function identifies a subset of most preferred elements. Learning choice functions from suitable training data comes with a number of challenges. For example, the sets provided as input and the subsets produced as output can be of any size. Moreover, since the order in which alternatives are presented is irrelevant, a choice function should be symmetric. Perhaps most importantly, choice functions are naturally context-dependent, in the sense that the preference in favor of an alternative may depend on what other options are available. We formalize the problem of learning choice functions and present two general approaches based on two representations of context-dependent utility functions. Both approaches are instantiated by means of appropriate neural network architectures, and their performance is demonstrated on suitable benchmark tasks.
Effects of Moderation and Opinion Heterogeneity on Attitude towards the Online Deliberation Experience

Online deliberation offers a way for citizens to collectively discuss an issue and provide input for policymakers. The overall experience of online deliberation can be affected by multiple factors. We decided to investigate the effects of moderation and opinion heterogeneity on the perceived deliberation experience, by running the first online deliberation experiment in Singapore. Our study took place in three months with three phases. In phase 1, our 2,006 participants answered a survey, that we used to create groups of different opinion heterogeneity. During the second phase, 510 participants discussed about the population issue on the online platform we developed. We gathered data on their online deliberation experience during phase 3. We found out that higher levels of moderation negatively impact the experience of deliberation on perceived procedural fairness, validity claim and policy legitimacy; and that high opinion heterogeneity is important in order to get a fair assessment of the deliberation experience.
On Possibility and Impossibility of Multiclass Classification with Rejection

We investigate the problem of multiclass classification with rejection, where a classifier can choose not to make a prediction to avoid critical misclassification. We consider two approaches for this problem: a traditional one based on confidence scores and a more recent one based on simultaneous training of a classifier and a rejector. An existing method in the former approach focuses on a specific class of losses and its empirical performance is not very convincing. In this paper, we propose confidence-based rejection criteria for multiclass classification, which can handle more general losses and guarantee calibration to the Bayes-optimal solution. The latter approach is relatively new and has been available only for the binary case, to the best of our knowledge. Our second contribution is to prove that calibration to the Bayes-optimal solution is almost impossible by this approach in the multiclass case. Finally, we conduct experiments to validate the relevance of our theoretical findings.