Miracle-dz/UniFAR-FTUs huggingface dataset:
Deconstructing the failure: Analyzing the unanswered questions within educational Q&A

Community Question and Answering (CQA) is a well‐known platform for knowledge sharing and social learning. CQA services have expanded into the education sector, where school students are the main users. Here, CQA functions as a non‐traditional learning environment in which students use their own knowledge to construct the knowledge base. However, there have been cases where some questions are not answered within such a Q&A system. This failure may occur if a question is unclear, complex, inappropriate, or unrelated to the subject in which it is contextualized. While experts do not answer posted questions, co‐users moderate responses and help maintain answer quality. However, due to the presence of users from diverse cultural and linguistic backgrounds, many questions remain unanswered. The current study analyzes and explores the failed questions collected from Brainly, a social learning Q&A platform for school students. The quality of 1,000 questions extracted from this service is analyzed based on human‐based ratings and extracted textual features. The findings show that a relationship can be drawn between the non‐textual assessment results and the objective textually extracted features. This further encourages the study of why a question might be of poor quality. The findings also show which subjects contain the highest number of unanswered questions. These results will further help us to understand how questions should be restructured to obtain answers from their askers' peers.
Current Landscape of Targeted Therapies for Hormone-Receptor Positive, HER2 Negative Metastatic Breast Cancer

The majority of deaths from MBC are in patients with hormone receptor (HR) positive, HER2 negative disease. Endocrine therapy (ET) remains the backbone of treatment in these cases, improving survival and quality of life. However, treatment can lose effectiveness due to primary or acquired endocrine resistance. Analysis of mechanisms of ET resistance has led to the development of a new generation of targeted therapies for advanced breast cancer. In addition to anti-estrogen therapy with selective estrogen receptor modulators, aromatase inhibitors, and/or selective estrogen receptor degraders, combinations with cyclin dependent kinase (CDK) 4/6 inhibitors have led to substantial progression free survival (PFS) improvements in the first and second line settings. While the PI3K/AKT/mTOR pathway is known to be an important growth pathway in HR positive breast cancer, PI3K inhibitors have been disappointing due to modest effect sizes and significant toxicity. The mTOR inhibitor everolimus significantly improves progression free survival when added to ET, and recent studies have improved supportive care allowing less toxicity. While these combination targeted therapies improve outcomes and often delay initiation of chemotherapy, long term overall survival data are lacking and data for the ideal strategy for sequencing these agents remains unclear. Ongoing research evaluating potential biomarkers and mechanisms of resistance is anticipated to continue to improve outcomes for patients with HR positive metastatic breast cancer. In this review, we will discuss management and ongoing challenges in the treatment of advanced HR positive, HER2 negative breast cancer, highlighting single agent and combination endocrine therapies, targeted therapies including palbociclib, ribociclib, abemaciclib, and everolimus, and sequencing of therapies in the clinic.
An Event Calculus Formalization of Timed Automata

Both the Event Calculus and Timed Automata are two very well known Knowledge Representation and Model Checking techniques. Specifically, the Event Calculus is a logic framework that allows the concept of time to explicitly appear inside formulas, while at the same time avoiding to step outside First Order Logic. It provides the machinery to perform what is known as Commonsense Reasoning, and an ontology to express Domain Knowledge with three main elements: fluents (time-dependent properties), events and timepoints. This ontology is particularly suited to intuitively model intelligent agents’ knowledge, thanks also to the powerful reasoning capabilities of the formalism. On the other hand, Timed Automata are a special kind of Finite State Machines, in which state transitions can be also governed by time contraints. One of their main applications is to formally verify and validate Real-Time systems, expressed as Timed Automata networks. This kind of validation has been already successfully used to demonstrate the soundness of several algorithms, via the help of Model Checkers such as UPPAAL. This work proposes a common point among these techniques, or more precisely, a methodology to translate the graph representations of (Discrete) Timed Automata into Event Calculus logic predicates. Additionally, a performance evaluation of a Prolog implementation of this technique is shown, looking for possible relationships between Model Checking and the various Event Calculus reasoning types.
3D Strokes on Visible Structures in Direct Volume Rendering

In this paper we describe VisiTrace, a novel technique to draw 3D lines in 3D volume rendered images. It allows to draw strokes in the 2D space of the screen to produce 3D lines that run on top or in the center of structures actually visible in the volume rendering. It can handle structures that only shortly occlude the structure that has been visible at the starting point of the stroke and is able to ignore such structures. For this purpose a shortest path algorithm finding the optimal curve in a specially designed graph data structure is employed. We demonstrate the usefulness of the technique by applying it to MRI data from medicine and engineering, and show how the method can be used to mark or analyze structures in the example data sets, and to automatically obtain good views toward the selected structures.
Parent Observations of the Health Status of Infants With Clefts of the Lip: Results From Qualitative Interviews

Objective: To explore, using semistructured qualitative interviews, parent observations of their infant’s health as they relate to having a cleft lip or cleft lip and cleft palate (CL±P) and/or associated treatments. Design: Cross-sectional, qualitative study across 3 sites. Setting: Parents were recruited from 3 academic craniofacial centers. Most interviews were conducted over the telephone, audio-recorded, and transcribed. Participants: Forty-one parents (31 English-, 10 Spanish-speaking) were interviewed. Parents had a child ages 1 to 35 months diagnosed with CL±P. Main Outcome Measure(s): Twelve domains reflecting infant health and well-being, likely affected by a CL±P and/or associated treatments, were identified from clinical experience and literature review. Study investigators conducted semistructured interviews based on 12 identified domains. After transcripts of the interviews were reviewed, our multidisciplinary team selected illustrative quotes from each domain that reflected consistent observations made by parents. Results: Parents’ responses covered all 12 domains. Specifically, parents discussed the domain of feeding most frequently, followed by observations about sleep, development, comfort, breathing, and vocalization. Conclusions: We found that parents of infants with clefts provided caregiver-centered language useful in describing their daily observations. No additional domains of infant health were noted by parents. We will use these observations and language to develop and validate a parent-reported observation diary that can augment assessments of the impacts of interventions on infants who are receiving care for CL±P.
Evaluation of ADA HbA1c criteria in the diagnosis of pre-diabetes and diabetes in a population of Chinese adolescents and young adults at high risk for diabetes: a cross-sectional study

Objective We aimed to assess haemoglobin A1c (HbA1c) for the diagnosis of pre-diabetes and diabetes in a population of Chinese youths at risk of metabolic syndrome. Setting Beijing, China. Participants A total of 581 subjects aged 14–28 years underwent evaluation including an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell function and a number of cardiovascular disease risk factors were evaluated. Receiver operating characteristic (ROC) curves were used to assess the screening efficacy of HbA1c. Results Using OGTT data as a standard, the majority (70.0%, 7/10) of subjects with diabetes would have been diagnosed with HbA1c ≥6.5%. In contrast, only 28.1% (16/57) of subjects with pre-diabetes possessed elevated HbA1cs, while the majority (68.4%) had normal HbA1cs. On the contrary, a total of 8.1% (39/479) of youths in the normal HbA1c category (<5.7%) and 21.3% in the pre-diabetes category had pre-diabetes. In the ROC analysis, the area under the curve (AUC) for HbA1c identifying pre-diabetes was 0.680(95% CI 0.640 to 0.719); the optimal threshold was 5.5%, with a sensitivity of 61.4% and specificity of 68.5%. For type 2 diabetes mellitus, the AUC for HbA1c was 0.970 (0.952 to 0.982), and the optimal threshold was 6.1%, with a sensitivity of 90.0% and a specificity of 98.7%. Applying these new cut-offs, pre-diabetic participants (HbA1c 5.5%–6.1%) had lower disposition index and higher risk of dyslipidaemia (OR=1.61,95% CI 1.10 to 2.37) and metabolic syndrome (OR=2.09, 1.27 to 3.45) than those with normal HbA1c (<5.5%). Conclusion The American Diabetes Association’s established HbA1c criteria for pre-diabetes and diabetes (5.7% and 6.5%) may not be appropriately applied to adolescents and young adults in China. Our findings suggest that those with HbA1c of 5.5%–6.1% already exhibit impaired β-cell function and increased cardiometabolic risk factors which may warrant intervention. Trial registration number NCT03421444.
Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β

Environmental enrichment (EE) is a rodent behavioral paradigm that can model the cognitive benefits to humans associated with intellectual activity and exercise. We recently discovered EE's anti‐inflammatory protection of brain microglia against soluble oligomers of human amyloid β‐protein (oAβ). Mechanistically, we report that the key factor in microglial protection by EE is chronically enhanced β‐adrenergic signaling. Quantifying microglial morphology and inflammatory RNA profiles revealed that mice in standard housing (SH) fed the β‐adrenergic agonist isoproterenol experienced similar protection of microglia against oAβ‐induced inflammation as did mice in EE. Conversely, mice in EE fed the β‐adrenergic antagonist propranolol lost microglial protection against oAβ. Mice lacking β1/β2‐adrenergic receptors showed no protection of microglia by EE. In SH mice, quantification of norepinephrine in hippocampus and interstitial fluid showed that oAβ disrupted norepinephrine homeostasis, and microglial‐specific analysis of β2‐adrenergic receptors indicated a decreased receptor level. Both features were rescued by EE. Thus, enhanced β‐adrenergic signaling at the ligand and receptor levels mediates potent benefits of EE on microglial inflammation induced by human Aβ oligomers in vivo.
Extrapulmonary Nontuberculous Mycobacterial Disease Surveillance — Oregon, 2014–2016

Nontuberculous mycobacteria (NTM), ubiquitous in soil and water, usually infect immunocompromised persons. However, even healthy persons are susceptible to infection through percutaneous inoculation. Although 77% of NTM diseases manifest as primarily pulmonary illnesses (1), NTM also infect skin, bones, joints, the lymphatic system, and soft tissue. NTM infections can have incubation periods that exceed 5 years (2), often require prolonged treatment, and can lead to sepsis and death. Extrapulmonary NTM outbreaks have been reported in association with contaminated surgical gentian violet (3), nail salon pedicures (4), and tattoos received at tattoo parlors (5), although few surveillance data have been available for estimating the public health burden of NTM. * On January 1, 2014, the Oregon Health Authority designated extrapulmonary NTM disease a reportable condition. To characterize extrapulmonary NTM infection, estimate resources required for surveillance, and assess the usefulness of surveillance in outbreak detection and investigation, 2014–2016 extrapulmonary NTM surveillance data were reviewed, and interviews with stakeholders were conducted. During 2014–2016, 134 extrapulmonary NTM cases (11 per 1 million persons per year) were reported in Oregon. The age distribution was bimodal, with highest incidence among persons aged <10 years (20 per 1 million persons per year) and persons aged 60–69 years (18 per 1 million persons per year). The most frequently reported predisposing factors (occurring within 14–70 days of symptom onset) were soil exposure (41/98; 42%), immunocompromised condition (42/124; 34%), and surgery (32/120; 27%). Overall, 43 (33%) patients were hospitalized, 18 (15%) developed sepsis, and one (0.7%) died. Surveillance detected or helped to control two outbreaks at low cost. Jurisdictions interested in implementing extrapulmonary NTM surveillance can use the Council of State and Territorial Epidemiologists (CSTE) standardized case definition (6) for extrapulmonary NTM reporting or investigative guidelines maintained by the Oregon Health Authority (7).
Ultra-Violet Radiation Has a Limited Impact on Seasonal Differences in the Acropora Muricata Holobiont

Environmental conditions are known to influence corals and their associated communities of microorganisms. However, our insights into the impacts of seasonal changes in ultraviolet radiation (UVR) on both coral physiology and microbiome remain very limited. To address this challenge, we maintained the coral Acropora muricata shaded from UVR or under ambient UVR levels during two contrasting seasons, i.e. summer and winter, and assessed the impact of UVR on the coral holobiont at each season. To this end, we analysed the physiology (e.g. calcification, protein content, photosynthesis-related parameters) and coral microbiota composition, as well as the abundance and composition of the microbial communities and organic matter contents of the surrounding seawater. Our results show major seasonal effects on coral phenotype: (1) a lower host biomass and photosynthesizing, but fast calcifying phenotype in summer, and (2) a higher host biomass and photosynthesizing, but slow calcifying phenotype in winter. UVR had only a significant impact on Symbiodinium functioning. Specifically, high UVR levels reduced photosynthesis efficiency in summer, but an increase in chlorophyll a content may have compensated for this effect. The coral microbiota, which was variable but generally dominated by Endozoicomonas, was not affected by UVR, but its composition differed between seasons. In contrast, UVR had a major, but differential impact on the seawater microbial communities at both seasons. Particularly in summer, bacteria from the Alteromonadaceae were significantly more abundant (15-fold; up to 75%) in seawater under ambient UVR levels. Overall, our study suggests that UVR has only a limited impact on coral holobiont composition and functioning, despite major fluctuations in the surrounding seawater microbiome; seasonal changes in the holobiont are thus mostly driven by other environmental factors.
Incorporation of silica nanoparticles to PLGA electrospun fibers for osteogenic differentiation of human osteoblast-like cells

Abstract The development of bone tissue engineering scaffolds still remains a challenging field, although various biomaterials have been developed for this purpose. Electrospinning is a promising approach to fabricate nanofibers with an interconnected porous structure, which can support cell adhesion, guide cell proliferation and regulate cell differentiation. The aim of this study is to fabricate composite fibers composed of poly(lactic-co-glycolic acid) (PLGA) and silica nanoparticles (NPs) via electrospinning and investigate the effect of PLGA/SiO2 composite fibers on the cellular response of osteoblast-like cells (SaOS-2 cells). SEM and EDX analysis showed that silica NPs were homogenously dispersed in the composite fibers. The mechanical behavior of the fibers showed that silica NPs acted as reinforcements at concentrations of 2.5 and 5 mg/ml. The incorporation of silica NPs led to enhancement of cell attachment and spreading on PLGA/SiO2 composite fibers. SaOS-2 cells cultured on PLGA/SiO2 composite fibers exhibited increased alkaline phosphatase activity, collagen secretion and bone nodules formation. The bone nodules formation of SaOS-2 cells increased along with the amount of incorporated silica NPs. The present findings indicate that PLGA/SiO2 composite fibers can stimulate osteogenic differentiation of SaOS-2 cells and may be a promising candidate scaffold for bone tissue engineering.
Retrospective study to identify risk factors for chronic kidney disease in children with congenital solitary functioning kidney detected by neonatal renal ultrasound screening

Abstract To evaluate the prognostic significance of factors frequently associated with a reduction in renal mass, such as prematurity, low birth weight, and congenital anomalies of kidney and urinary tract (CAKUT), in patients with solitary functioning kidney (SFK) and investigate signs of early renal injury due to glomerular hyperfiltration damage or dysplasia in the remaining kidney. Retrospective observational study of congenital SFK diagnosed and followed at a tertiary care hospital over a period of 10 years in which 32,900 newborns underwent routine neonatal abdominal ultrasound screening. We analyzed age at diagnosis, sex, gestational age, anthropometric measurements at birth and prenatal and neonatal ultrasound findings, in addition to follow-up data corresponding to imaging findings (ultrasound, micturating cystourethrography, dimercaptosuccinic acid renal, and scintigraphy), ipsilateral CAKUT, compensatory hypertrophy, and renal injury in the form of albuminuria, blood pressure, and estimated glomerular filtration rate (eGFR). In total, 128 congenital SFK cases were detected (1 per 257 live births). Of these, 117 (91.4%) were diagnosed by neonatal ultrasound screening and 44.5% of these had been previously identified by prenatal ultrasound. Neonatal ultrasound had a specificity of 100% and a sensitivity of 92.1%. Forty-five patients (35.2%) had ipsilateral CAKUT and the most common type was urinary collecting system anomalies (75.5%). Over a median follow-up of 6.3 years (1–10 years), compensatory renal hypertrophy was observed in 81 patients (63.7%), most of whom had ipsilateral CAKUT (76.1% vs 56.6% of patients without ipsilateral CAKUT). Albuminuria and hypertension were observed in 3.12% and 5% of patients, respectively, and both were associated with ipsilateral CAKUT (P < .05). In addition, 75% of albuminuria cases (P = .031), 83.3% of hypertension cases (P = .004), and 100% of decreased eGFRcases (P = .031) were significantly associated with CAKUT (renal parenchymal anomaly category), being the strongest predictor of GFR the presence or absence of CAKUT. Neonatal ultrasound screening is useful for the early diagnosis of SFK. The presence of ipsilateral CAKUT should be evaluated in all patients with SFK as congenital anomalies of the renal parenchyma are associated with a poorer prognosis. Because morbidity from CAKUTs may not develop until adulthood, patients should be closely followed throughout life.
On the Convergence of A Class of Adam-Type Algorithms for Non-Convex Optimization

This paper studies a class of adaptive gradient based momentum algorithms that update the search directions and learning rates simultaneously using past gradients. This class, which we refer to as the "Adam-type", includes the popular algorithms such as the Adam, AMSGrad and AdaGrad. Despite their popularity in training deep neural networks, the convergence of these algorithms for solving nonconvex problems remains an open question. This paper provides a set of mild sufficient conditions that guarantee the convergence for the Adam-type methods. We prove that under our derived conditions, these methods can achieve the convergence rate of order $O(\log{T}/\sqrt{T})$ for nonconvex stochastic optimization. We show the conditions are essential in the sense that violating them may make the algorithm diverge. Moreover, we propose and analyze a class of (deterministic) incremental adaptive gradient algorithms, which has the same $O(\log{T}/\sqrt{T})$ convergence rate. Our study could also be extended to a broader class of adaptive gradient methods in machine learning and optimization.
Global metabolomic responses in urine from atm deficient mice in response to LD50/30 gamma irradiation doses

Exposures to ionizing radiation (IR) may either be accidental or intentional, for medical purposes or even through terrorist actions. As certain populations emerge to be more radiosensitive than others, it is imperative to assess those individuals and treat them accordingly. To demonstrate the feasibility of rapid identification of such cases, we utilized the highly radiosensitive mouse model Atm–/– in the C57BL/6 background, and evaluated the urinary responses in 8–10 week old male mice at early time points (4, 24, and 72 h) after exposure to their respective LD50/30 doses [4 Gy for Atm–/–, and 8 Gy for wild type (WT)]. Urinary profiles from heterozygous animals exhibited remarkably similar responses to WT before and after radiation exposure. However, genotypic differences (WT or Atm–/–) were the primary driver to responses to radiation. Putative metabolites were validated through tandem mass spectrometry and included riboflavin, uric acid, d‐ribose, d‐glucose, pantothenic acid, taurine, kynurenic acid, xanthurenic acid, 2‐oxoadipic acid, glutaric acid, 5′‐deoxy‐5′‐methylthioadenosine, and hippuric acid. These metabolites mapped to several interconnected metabolic pathways which suggest that radiosensitive mouse models have underlying differences significantly impacting overall metabolism. This was further amplified by ionizing radiation at different time points. This study further emphasizes that genetically based radiosensitivity is reflected in the metabolic processes, and can be directly observed in urine. These differences in turn can potentially be used to identify individuals that may require altered medical treatment in an emergency radiological situation or modification of a regimen during a radiotherapy session. Environ. Mol. Mutagen. 59:576–585, 2018. © 2018 Wiley Periodicals, Inc.
Current and future therapies for targeting HER2 mutations in gastrointestinal cancer

ABSTRACT Introduction: Gastrointestinal (GI) cancers altogether represent the most common cancer type. HER2 is found to be present in nearly all histologic types of GI cancers in variable degrees of expression. Over the last decade, substantial advances have been made in targeting HER2-positive cancers. Areas covered: The present review summarizes the current progress and future directions for HER2 targeted therapies in GI cancers, including esophagogastric, pancreaticobiliary, and colon cancers. To date trastuzumab is the only anti-HER2 therapy approved for metastatic esophagogastric adenocarcinoma. Efforts are ongoing to expand the therapeutic role of HER2 to other GI cancers and overcome mechanisms of drug resistance. Novel agents and combinations are being tested in most HER2 positive GI cancers including early stage disease. These are of recent interest in colorectal cancer with studies indicating that HER2 overexpression might increase resistance to anti-EGFR therapy and may be potentially targeted. Expert commentary: With the current ability to sequence tumors and detect genetic alterations, emphasis should be put on genomically-selected pan-tumor targeted therapies. HER2 is a perfect example of a promising drug target in GI cancers.