Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of Oral Health Impact Profile-14 and its association with Hypossialia in a Sjögren Syndrome Portuguese Population.

AIMS The objective of this study was to perform the Portuguese transcultural adaptation of the original Brazilian version of the Oral Health Impact Profile-14 (OHIP-14) while evaluating the association between hyposalivation and quality of life in a Sjögren´s Syndrome population. METHODS The original Brazilian version of the Oral Health Impact Profile-14 was culturally adapted following the guidelines for cross-cultural adaptation of health-related quality of life measures. The questionnaires were administered by trained and calibrated dental doctors to 86 patients with Sjögren´s Syndrome. Oral Health Impact Profile-14 properties were examined including reliability, internal consistency and test-retest reliability, using Cronbach's alpha, total and inter-item correlation, and intra-class correlation coefficients, respectively. Whole saliva secretion rates and hyposalivation-related variables were collected and statistically analyzed. Spearman´s rho correlations were obtained between salivary flows and OHIP -14 domains and total score. Alpha was set at 0.05. Informed consents and local ethical committee clearance were obtained. RESULTS Each question of the questionnaire performed adequately. Cronbach alpha values for the 14 questions were 0.89 for both test administrations and were lower if item removed. Scores for both questionnaire administration and ICC results presented good to excellent reliability with ICC ranging from 84% to 92%. Mean salivary flow rate was 0.05 (SD: 0.03) ml/min and mean stimulated salivary flow was 0.57 (SD: 0.44) ml/min, which are within expected values in a population with hyposalivation. The results describe a negative and significant correlation between total OHIP-14-PT score, physical pain, physical disability domain and stimulated and differential salivary flows. There was a negative and significant correlation between unstimulated salivary flow with physical pain. CONCLUSION Within the limitations of this study, the OHIP-14-PT seems to be a valid and reliable instrument for measuring oral health related quality of life in patients with Sjögren´s Syndrome. Both differential and stimulated salivary flows seem to correlate negatively with age and the quality of life is significantly diminished by lower stimulated salivary flow rates.
Cerebrospinal fluid GAP-43 in early multiple sclerosis

Background/Objective Novel biomarkers identifying and predicting disease activity in multiple sclerosis (MS) would be valuable for primary diagnosis and as outcome measures for monitoring therapeutic effects in clinical trials. Axonal loss is present from the earliest stages of MS and correlates with disability measures. Growth-associated protein 43 (GAP-43) is a presynaptic protein with induced expression during axonal growth. We hypothesized this protein could serve as a biomarker of axonal regeneration capacity in MS. Methods We developed a novel GAP-43 enzyme-linked immunosorbent assay for quantification in cerebrospinal fluid (CSF) and measured GAP-43 levels in 71 patients with clinically isolated syndrome, 139 MS patients and 51 controls. Results GAP-43 concentrations were similar in patients and controls. Nevertheless, GAP-43 levels were higher in patients with >10 T2-magnetic resonance imaging (MRI) lesions (p = 0.005). CSF GAP-43 concentrations correlated with CSF mononuclear cell counts (p = 0.031) and were inversely correlated with patient age (p = 0.038) with a trend for higher CSF GAP-43 concentrations in patients with gadolinium-enhancing MRI lesions and positive CSF oligoclonal immunoglobulin G status. Conclusion Our results suggest that axonal regeneration capacity is relatively preserved in early MS. CSF GAP-43 concentration is positively associated with markers of inflammation, suggesting possible inflammatory-driven expression of this growth-associated protein in early MS.
Exogenous lipoid pneumonia: an important cause of interstitial lung disease in infants

Exogenous lipoid pneumonia (ELP), an important cause of interstitial lung disease, often goes unrecognized. We conducted a retrospective study of children with histologically confirmed ELP at Red Cross Children’s Hospital, South Africa. Twelve children of Zimbabwean heritage aged 2.1–10.8 months were identified between 2012 and 2017. Repeated oral administration of plant‐based oil for cultural reasons was reported by 10 of 11 caregivers. Cough (12/12), tachypnoea (11/12), hypoxia (9/12), and diffuse alveolar infiltrates on chest radiography (12/12) were common at presentation. Chest computed tomography revealed ground‐glass opacification with lower zone predominance (9/9) and interlobular septal thickening (8/9). Bronchoalveolar lavage specimens appeared cloudy/milky, with abundant lipid‐laden macrophages and extracellular lipid on Oil‐Red‐O staining (12/12), with polymicrobial (6/12) and Mycobacterium abscessus (2/12) co‐infection. Antibiotics, systemic corticosteroids, and therapeutic lavage were interventions in all eight and five patients, respectively. Clinicians should consider ELP in children with non‐resolving pneumonia in settings with similar practices.
Efficiently Manifesting Asynchronous Programming Errors in Android Apps

Android, the #1 mobile app framework, enforces the single-GUI-thread model, in which a single UI thread manages GUI rendering and event dispatching. Due to this model, it is vital to avoid blocking the UI thread for responsiveness. One common practice is to offload long-running tasks into async threads. To achieve this, Android provides various async programming constructs, and leaves developers themselves to obey the rules implied by the model. However, as our study reveals, more than 25% apps violate these rules and introduce hard-to-detect, fail-stop errors, which we term as aysnc programming errors (APEs). To this end, this paper introduces APEChecker, a technique to automatically and efficiently manifest APEs. The key idea is to characterize APEs as specific fault patterns, and synergistically combine static analysis and dynamic UI exploration to detect and verify such errors. Among the 40 real-world Android apps, APEChecker unveils and processes 61 APEs, of which 51 are confirmed (83.6% hit rate). Specifically, APEChecker detects 3X more APEs than the state-of-art testing tools (Monkey, Sapienz and Stoat), and reduces testing time from half an hour to a few minutes. On a specific type of APEs, APEChecker confirms 5X more errors than the data race detection tool, EventRacer, with very few false alarms.
Arithmetic Word Problem Solver using Frame Identification

Automatic Word problem solving has always posed a great challenge for the NLP community. Usually a word problem is a narrative comprising of a few sentences and a question is asked about a quantity referred in the sentences. Solving word problem involves reasoning across sentences, identification of operations, their order, relevant quantities and discarding irrelevant quantities. In this paper, we present a novel approach for automatic arithmetic word problem solving. Our approach starts with frame identification. Each frame can either be classified as a state or an action frame. The frame identification is dependent on the verb in a sentence. Every frame is unique and is identified by its slots. The slots are filled using dependency parsed output of a sentence. The slots are entity holder, entity, quantity of the entity, recipient, additional information like place, time. The slots and frames helps to identify the type of question asked and the entity referred. Action frames act on state frame(s) which causes a change in quantities of the state frames. The frames are then used to build a graph where any change in quantities can be propagated to the neighboring nodes. Most of the current solvers can only answer questions related to the quantity, while our system can answer different kinds of questions like `who', `what' other than the quantity related questions `how many'. There are three major contributions of this paper. 1. Frame Annotated Corpus (with a frame annotation tool) 2. Frame Identification Module 3. A new easily understandable Framework for word problem solving
The Risk of Offspring Psychiatric Disorders in the Setting of Maternal Obesity and Diabetes

Using a Finnish nationwide cohort, we investigate the combined effects of maternal diabetes and obesity on the risk of offspring psychiatric and mild neurodevelopmental disorders. BACKGROUND: Prenatal exposure to metabolic disturbances is associated with increased risk of offspring neurodevelopmental impairment and autism spectrum disorder, while little is known about the joint effect of maternal obesity and diabetes. With this study, we aim to assess the joint effect of maternal obesity and diabetes on the risk for offspring psychiatric and mild neurodevelopmental disorders. METHODS: Nationwide registries were used to link data of all live births in Finland between 2004 and 2014 (n = 649 043). Cox proportional hazards modeling adjusting for potential confounders was applied to estimate the effect of maternal obesity, pregestational diabetes mellitus (PGDM), and gestational diabetes mellitus, as well as their joint effects, on the outcomes of offspring psychiatric and mild neurodevelopmental diagnoses and offspring prescription of psychotropic drugs. RESULTS: Among mothers without diabetes, severely obese mothers had 67% to 88% increased risk of having a child with mild neurodevelopmental disorders (hazard risk ratio [HR] = 1.69; 95% confidence interval [CI] = 1.54–1.86), attention-deficit/hyperactivity disorder or conduct disorder (HR = 1.88; 95% CI = 1.58–2.23), and psychotic, mood, and stress-related disorders (HR = 1.67; 95% CI = 1.31–2.13) compared with mothers with a normal BMI. PGDM implied a further risk increase for all groups of psychiatric diagnoses with onset in childhood or adolescence in mothers with severe obesity. Marked effects were found particularly for autism spectrum disorder (HR = 6.49; 95% CI = 3.08–13.69), attention-deficit/hyperactivity disorder and conduct disorder (HR = 6.03; 95% CI = 3.23–11.24), and mixed disorders of conduct and emotions (HR = 4.29; 95% CI = 2.14–8.60). Gestational diabetes mellitus did not increase the risk highly for these offspring disorders. CONCLUSIONS: Maternal PGDM combined with severe maternal obesity markedly increases the risk of several children’s psychiatric and mild neurodevelopmental disorders.
Lysosome biogenesis in health and disease

This review focuses on the pathways that regulate lysosome biogenesis and that are implicated in numerous degenerative storage diseases, including lysosomal storage disorders and late‐onset neurodegenerative diseases. Lysosomal proteins are synthesized in the endoplasmic reticulum and trafficked to the endolysosomal system through the secretory route. Several receptors have been characterized that execute post‐Golgi trafficking of lysosomal proteins. Some of them recognize their cargo proteins based on specific amino acid signatures, others based on a particular glycan modification that is exclusively found on lysosomal proteins. Nearly all receptors serving lysosome biogenesis are under the transcriptional control of transcription factor EB (TFEB), a master regulator of the lysosomal system. TFEB coordinates the expression of lysosomal hydrolases, lysosomal membrane proteins, and autophagy proteins in response to pathways sensing lysosomal stress and the nutritional conditions of the cell among other stimuli. TFEB is primed for activation in lysosomal storage disorders but surprisingly its function is impaired in some late‐onset neurodegenerative storage diseases like Alzheimer's and Parkinson's, because of specific detrimental interactions that limit TFEB expression or activation. Thus, disrupted TFEB function presumably plays a role in the pathogenesis of these diseases. Multiple studies in animal models of degenerative storage diseases have shown that exogenous expression of TFEB and pharmacological activation of endogenous TFEB attenuate disease phenotypes. These results highlight TFEB‐mediated enhancement of lysosomal biogenesis and function as a candidate strategy to counteract the progression of these diseases.
A transient cortical state with sleep-like sensory responses precedes emergence from general anesthesia in humans

During awake consciousness, the brain intrinsically maintains a dynamical state in which it can coordinate complex responses to sensory input. How the brain reaches this state spontaneously is not known. General anesthesia provides a unique opportunity to examine how the human brain recovers its functional capabilities after profound unconsciousness. We used intracranial electrocorticography and scalp EEG in humans to track neural dynamics during emergence from propofol general anesthesia. We identify a distinct transient brain state that occurs immediately prior to recovery of behavioral responsiveness. This state is characterized by large, spatially distributed, slow sensory-evoked potentials that resemble the K-complexes that are hallmarks of stage two sleep. However, the ongoing spontaneous dynamics in this transitional state differ from sleep. These results identify an asymmetry in the neurophysiology of induction and emergence, as the emerging brain can enter a state with a sleep-like sensory blockade before regaining responsivity to arousing stimuli.
Progress on norovirus vaccine research: public health considerations and future directions

ABSTRACT Introduction: Noroviruses are the leading cause of foodborne illness worldwide, account for approximately one-fifth of acute gastroenteritis (AGE) cases globally, and cause a substantial economic burden. Candidate norovirus vaccines are in development, but there is currently no licensed vaccine. Areas covered: Noroviruses cause approximately 684 million cases and 212,000 deaths per year across all age groups, though burden estimates vary by study and region. Challenges to vaccine research include substantial and rapidly evolving genetic diversity, short-term and homotypic immunity to infection, and the absence of a single, well-established correlate of protection. Nonetheless, several norovirus vaccine candidates are currently in development, utilizing virus-like particles (VLPs), P particles, and recombinant adenoviruses. Of these, a bivalent GI.1/GII.4 VLP-based intramuscular vaccine (Phase IIb) and GI.1 oral vaccine (Phase I) are in clinical trials. Expert Commentary: A norovirus vaccine should target high-risk populations, including the young and the elderly, and protect them against the most common circulating norovirus strains. A norovirus vaccine would be a powerful tool in the prevention and control of norovirus while lessening the burden of AGE worldwide. However, more robust burden and cost estimates are needed to justify investments in and guide norovirus vaccine development.
Bounds for the Diameter of the Weight Polytope

A weighted game or a threshold function in general admits different weighted representations even if the sum of non-negative weights is fixed to one. Here we study bounds for the diameter of the corresponding weight polytope. It turns out that the diameter can be upper bounded in terms of the maximum weight and the quota or threshold. We apply those results to approximation results between power distributions, given by power indices, and weights.
Library of congress subject heading (LCSH) browsing and natural language searching

Controlled topical vocabularies (CVs) are built into information systems to aid browsing and retrieval of items that may be unfamiliar, but it is unclear how this feature should be integrated with standard keyword searching. Few systems or scholarly prototypes have attempted this, and none have used the most widely used CV, the Library of Congress Subject Headings (LCSH), which organizes monograph collections in academic libraries throughout the world. This paper describes a working prototype of a Web application that concurrently allows topic exploration using an outline tree view of the LCSH hierarchy and natural language keyword searching of a real‐world Science and Engineering bibliographic collection. Pilot testing shows the system is functional, and work to fit the complex LCSH structure into a usable hierarchy is ongoing. This study contributes to knowledge of the practical design decisions required when developing linked interactions between topical hierarchy browsing and natural language searching, which promise to facilitate information discovery and exploration.
Combining Concept Annotation and Pattern Structures for Guiding Ontology Mapping

Formal Concept Analysis (FCA) is a mathematical framework classifying in formal concepts a set of objects w.r. t. their common attributes. To this aim, FCA relies on a binary incidence relationship indicating whether an object has an attribute. On one hand, in order to consider more complex descriptions for objects (e.g., intervals, graphs), FCA has been extended with Pattern Structures. On the other hand, in a previous work, we introduced the notion of Concept Annotation, adding a third dimension to formal concepts, computed over the extent, without modifying the original classification. In this paper, we combine Concept Annotation with the formalism of Pattern Structures and we consider multiple annotation possibilities, i.e., multiple annotations for one concept and computing the annotation over the intent. We illustrate our approach and its interest with two use cases: (i) suggesting mappings between ontology classes and (ii) finding specific classes frequently associated as domain and range of a predicate.
Fibroblast Growth Factor-23 May Follow Cardiovascular Disease Rather than Causing It in Chronic Kidney Disease.

We read the article “Fibroblast growth factor-23 and risks of cardiovascular and noncardiovascular diseases: A meta-analysis” by Marthi et al. [1][1] with great interest. The study provided an important demonstration that serum higher fibroblast growth factor-23 (FGF-23) level was positively
Nonparametric Gaussian mixture models for the multi-armed contextual bandit

We here adopt Bayesian nonparametric mixture models to extend multi-armed bandits in general, and Thompson sampling in particular, to complex scenarios where there is reward model uncertainty. The multi-armed bandit is a sequential allocation task where an agent must learn a policy that maximizes long term payoff, where only the reward of the played arm is observed at each interaction with the world. In the stochastic bandit setting, at each interaction, the reward for the selected action is generated from an unknown distribution. Thompson sampling is a generative and interpretable multi-armed bandit algorithm that has been shown both to perform well in practice, and to enjoy optimality properties for certain reward functions. Nevertheless, Thompson sampling requires knowledge of the true reward model, for calculation of expected rewards and sampling from its parameter posterior. In this work, we extend Thompson sampling to complex scenarios where there is model uncertainty, by adopting a very flexible set of reward distributions: nonparametric Gaussian mixture models. The generative process of Bayesian nonparametric mixtures naturally aligns with the Bayesian modeling of multi-armed bandits: the nonparametric model autonomously determines its complexity in an online fashion, as new rewards are observed for the played arms. By characterizing each arm's reward distribution with independent Dirichlet process mixtures and per-mixture parameters, the proposed method sequentially learns the model that best approximates the true underlying reward distribution, achieving successful performance in synthetic and real datasets. Our contribution is valuable for practical scenarios, as it avoids stringent case-by-case model specifications, and yet attains reduced regret in diverse bandit settings.
New Insights in Cardiac β-Adrenergic Signaling During Heart Failure and Aging

Heart failure (HF) has become increasingly common within the elderly population, decreasing their survival and overall quality of life. In fact, despite the improvements in treatment, many elderly people suffer from cardiac dysfunction (HF, valvular diseases, arrhythmias or hypertension-induced cardiac hypertrophy) that are much more common in an older fragile heart. Since β-adrenergic receptor (β-AR) signaling is abnormal in failing as well as aged hearts, this pathway is an effective diagnostic and therapeutic target. Both HF and aging are characterized by activation/hyperactivity of various neurohormonal pathways, the most important of which is the sympathetic nervous system (SNS). SNS hyperactivity is initially a compensatory mechanism to stimulate contractility and maintain cardiac output. Unfortunately, this chronic stimulation becomes detrimental and causes decreased cardiac function as well as reduced inotropic reserve due to a decrease in cardiac β-ARs responsiveness. Therapies which (e.g., β-blockers and physical activity) restore β-ARs responsiveness can ameliorate cardiac performance and outcomes during HF, particularly in older patients. In this review, we will discuss physiological β-adrenergic signaling and its alterations in both HF and aging as well as the potential clinical application of targeting β-adrenergic signaling in these disease processes.
Xenopus: An Undervalued Model Organism to Study and Model Human Genetic Disease

The function of normal and defective candidate genes for human genetic diseases, which are rapidly being identified in large numbers by human geneticists and the biomedical community at large, will be best studied in relevant and predictive model organisms that allow high-speed verification, analysis of underlying developmental, cellular and molecular mechanisms, and establishment of disease models to test therapeutic options. We describe and discuss the pros and cons of the frog Xenopus, which has been extensively used to uncover developmental mechanisms in the past, but which is being underutilized as a biomedical model. We argue that Xenopus complements the more commonly used mouse and zebrafish as a time- and cost-efficient animal model to study human disease alleles and mechanisms.
A novel CRX frameshift mutation causing cone-rod dystrophy in a Chinese family

Background: Cone-rod dystrophy (CORD) is an inherited, progressive retinal disorder with genetic and phenotypic heterogeneity. Here, we aimed to identify the pathogenic mutation in affected individuals in a Chinese family with autosomal dominant cone-rod dystrophy (adCORD). Methods: Genomic DNA and clinical examination results were collected from a Chinese family presenting with adCORD. The candidate disease-causing mutations were screened with whole-exome sequencing (WES) and bioinformatics analyses. Sanger sequencing was used for validation and cosegregation analysis. Results: A novel frameshift mutation (NM_000554.4; c.538dupG:p.Val180fs) in exon 4 of the CRX gene was identified in all affected individuals in the Chinese family with adCORD. Cosegregation analysis confirmed that this mutation was cosegregated with the disease. This variant, which results in premature termination of the protein, was absent from all public variant databases or internal exome databases. Conclusions: We used whole-exome sequencing to identify a novel CRX mutation causing adCORD in a Chinese family. This study broadens the known pathogenic mutation spectrum of the CRX gene and shows the potential of WES in identifying the pathogenic mutations of CORD disease.