Miracle-dz/UniFAR-FTUs huggingface dataset:
Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease

OBJECTIVE Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome. RESEARCH DESIGN AND METHODS In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4–12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A1c and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A1c ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L (fasting) or ≥11.1 mmol/L (random). RESULTS At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68–0.88; P < 0.001), and a need to treat 40 patients for 3 years to prevent 1 incident case of diabetes. Considering only those with prediabetes at baseline, the number needed to treat for 3 years to prevent 1 incident case of diabetes was 25. Dalcetrapib also decreased the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes. CONCLUSIONS In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.
Mapping and characterising areas with high levels of HIV transmission in sub-Saharan Africa: A geospatial analysis of national survey data

Background In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15–29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. Methods and findings We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008–2009 and 2015–2016), which included about 113,000 adults—of which there were about 53,000 young adults (27,000 women, 28,000 men)—from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys. Conclusions We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,—such as sex workers and migrant populations—could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA.
Five-year follow-up of fundus autofluorescence and retinal sensitivity in the fellow eye in exudative age-related macular degeneration in Japan

Purpose To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). Methods Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. “Close” was defined as the portion within 1 degree from the border of any abnormal FAF, and “Distant” was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects. Results We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF (“Distant”: p<0.001, time2 from baseline: p<0.001, angle: p<0.001). The mean retinal sensitivity of the “Close” tended to deteriorate after the third year and eventually showed the similar sensitivity as the portion within the abnormal FAF. Conclusion FAF patterns can change about half during the 5 years and the retinal sensitivity near abnormal FAF tends to deteriorate after the third year.
The Pharmacology Education Partnership: Improving High School Biology and Chemistry

The Pharmacology Education Partnership (PEP) is a curriculum we developed for high school biology and chemistry teachers, providing them with tools to teach biology and chemistry principles using pharmacology topics (e.g., drugs of abuse). This partnership between Duke University Medical Center and the North Carolina School of Science and Math (NCSSM) was funded by a Science Education Drug Abuse Partnership Award from the National Institute on Drug Abuse. The major premise of our project was that high school students might learn basic concepts in biology and chemistry better if the material was presented in the context of something interesting and relevant to their own lives. Forty-seven teachers across the US were trained to use the curriculum in their classrooms (a second project is ongoing with ~220 teachers being trained across the US). The PEP project includes several components such as curriculum design, science content, and professional development. The PEP project has been tested in 3500 students nationally and has demonstrated significant achievement in high school biology and chemistry in those classrooms using the PEP modules. The results of the study were published in the Journal of Research in Science Teaching (Schwartz-Bloom and Halpin, 2003). Below, several of the features and our findings are summarized.
Calculation of the Isobaric Heat Capacities of the Liquid and Solid Phase of Organic Compounds at 298.15K by Means of the Group-Additivity Method

The calculation of the isobaric heat capacities of the liquid and solid phase of molecules at 298.15 K is presented, applying a universal computer algorithm based on the atom-groups additivity method, using refined atom groups. The atom groups are defined as the molecules’ constituting atoms and their immediate neighbourhood. In addition, the hydroxy group of alcohols are further subdivided to take account of the different intermolecular interactions of primary, secondary, and tertiary alcohols. The evaluation of the groups’ contributions has been carried out by solving a matrix of simultaneous linear equations by means of the iterative Gauss–Seidel balancing calculus using experimental data from literature. Plausibility has been tested immediately after each fitting calculation using a 10-fold cross-validation procedure. For the heat capacity of liquids, the respective goodness of fit of the direct (r2) and the cross-validation calculations (q2) of 0.998 and 0.9975, and the respective standard deviations of 8.24 and 9.19 J/mol/K, together with a mean absolute percentage deviation (MAPD) of 2.66%, based on the experimental data of 1111 compounds, proves the excellent predictive applicability of the present method. The statistical values for the heat capacity of solids are only slightly inferior: for r2 and q2, the respective values are 0.9915 and 0.9874, the respective standard deviations are 12.21 and 14.23 J/mol/K, and the MAPD is 4.74%, based on 734 solids. The predicted heat capacities for a series of liquid and solid compounds have been directly compared to those received by a complementary method based on the "true" molecular volume and their deviations have been elucidated.
Social representations of the prevention of heterosexual transmission of HIV among young Africans from five countries, 1997-2014

HIV prevention has evolved dramatically since the 1990s. The ABC trilogy (abstinence, be faithful, use a condom) has expanded to incorporate a range of biomedical prevention strategies, including voluntary medical male circumcision, pre- and post-exposure prophylaxis, and treatment-as-prevention, and to accommodate structural and combination prevention approaches. This study examines how young Africans from five epidemiologically and socio-culturally diverse countries (Swaziland, Kenya, Nigeria, Burkina Faso and Senegal) made sense of the evolving prevention of sexual transmission of HIV between 1997 and 2014. It uses a distinctive data source: 1,343 creative narratives submitted to HIV-themed scriptwriting competitions by young people aged 10–24. The study triangulates between analysis of quantifiable characteristics of the narratives, thematic qualitative analysis, and narrative-based approaches. Over time, HIV prevention themes become less prominent. Condoms are represented less often from 2008, though representations become more favourable. Biomedical prevention is all but absent through 2014. While prevention strategies may be described as effective in narratorial commentary, they are rarely depicted as preventing HIV, but are evoked instead in moralistic cautionary tales or represented as ineffective. Over time, an increasing proportion of protagonists are female. One in five narratives acknowledge structural drivers of HIV, but these are generally either disempowering or condemn characters for failing to prevent HIV in the face of often overwhelming structural challenges. In the context of combination prevention, there is a need to disseminate an empowering cultural narrative that models successful use of HIV prevention strategies despite structural constraints and avoids blaming and stigma.
Dental Implications of Eating Disorders

Eating disorders are nowadays a grave and, unfortunately, growing social problem. Their etiology is multifactorial with complex psychological, biological, familial and socio-cultural mechanisms playing a role. Socio-cultural factors are becoming more and more relevant, including the impact of mass media which provides socially accepted standards of attractiveness. They set the socially valued norms of appearance and show the impact of complying or failing to comply to these norms. Eating disorders lead to numerous anomalies in the oral cavity. They affect both the teeth and soft tissues. Although dry mouth, oral mucosa injuries, diseases of periodontium, dental decay are observed in patients, still the most common findings are non-carious lesions. Dental treatment is multipronged, mainly conservative and prosthetic. However, a crucial element of problem management is the prevention of further formation of erosive lesions. For such treatment to be effective, simultaneous implementation of psychological therapy is needed. Therefore, it is necessary to provide comprehensive health care to patients suffering from eating disorders (Dent. Med. Probl. 2016, 53, 4, 524–528).
Investigating Student Perceptions of the Chemistry Laboratory and Their Approaches to Learning in the Laboratory

This dissertation explores student perceptions of the instructional chemistry laboratory and the approaches students take when learning in the laboratory environment. To measure student perceptions of the chemistry laboratory, a survey instrument was developed. 413 students responded to the survey during the Fall 2011 semester. Students’ perception of the usefulness of the laboratory in helping them learn chemistry in high school was related to several factors regarding their experiences in high school chemistry. Students’ perception of the usefulness of the laboratory in helping them learn chemistry in college was also measured. Reasons students provided for the usefulness of the laboratory were categorized.To characterize approaches to learning in the laboratory, students were interviewed midway through semester (N=18). The interviews were used to create a framework describing learning approaches that students use in the laboratory environment. Students were categorized into three levels: students who view the laboratory as a requirement, students who believe that the laboratory augments their understanding, and students who view the laboratory as an important part of science. These categories describe the types of strategies students used when conducting experiments.To further explore the relationship between students’ perception of the laboratory and their approaches to learning, two case studies are described. These case studies involve interviews in the beginning and end of the semester. In the interviews, students reflect on what they have learned in the laboratory and describe their perceptions of the laboratory environment.In order to encourage students to adopt higher-level approaches to learning in the laboratory, a metacognitive intervention was created. The intervention involved supplementary questions that students would answer while completing laboratory experiments. The questions were designed to encourage students to think critically about the laboratory procedures. In order to test the effects of the intervention, an experimental group (N=87) completed these supplementary questions during two laboratory experiments while a control group (N=84) performed the same experiments without these additional questions. The effects of the intervention on laboratory exam performance were measured. Students in the experimental group had a higher average on the laboratory exam than students in the control group.
Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain

Significance This work provides evidence that soluble and oligomeric amyloid protein stokes neuronal inflammation during the earliest stages of Alzheimer’s disease. Identifying neuron-derived factors that engage the brain’s immune system will provide insight into how vulnerable neurons might interact with other immune cells to propagate cytotoxic signaling cascades and cellular dysfunction during disease development. Chronic inflammation during Alzheimer’s disease (AD) is most often attributed to sustained microglial activation in response to amyloid-β (Aβ) plaque deposits and cell death. However, cytokine release and microgliosis are consistently observed in AD transgenic animal models devoid of such pathologies, bringing into question the underlying processes that may be at play during the earliest AD-related immune response. We propose that this plaque-independent inflammatory reaction originates from neurons burdened with increasing levels of soluble and oligomeric Aβ, which are known to be the most toxic amyloid species within the brain. Laser microdissected neurons extracted from preplaque amyloid precursor protein (APP) transgenic rats were found to produce a variety of potent immune factors, both at the transcript and protein levels. Neuron-derived cytokines correlated with the extent of microglial activation and mobilization, even in the absence of extracellular plaques and cell death. Importantly, we identified an inflammatory profile unique to Aβ-burdened neurons, since neighboring glial cells did not express similar molecules. Moreover, we demonstrate within disease-vulnerable regions of the human brain that a neuron-specific inflammatory response may precede insoluble Aβ plaque and tau tangle formation. Thus, we reveal the Aβ-burdened neuron as a primary proinflammatory agent, implicating the intraneuronal accumulation of Aβ as a significant immunological component in the AD pathogenesis.
Human papillomavirus prevalence in oral potentially malignant disorders: systematic review and meta-analysis.

OBJECTIVES We aimed to provide pooled estimates of human papillomavirus (HPV) prevalence in oral potentially malignant disorders (OPMD) and evaluate the impact of presence of epithelial dysplasia. METHODS We searched Pubmed, Embase and Cochrane Library databases for studies that examined the prevalence of HPV DNA in OPMD tested by polymerase chain reaction (PCR). RESULTS Across 52 eligible studies (2677 cases) we found an overall pooled HPV prevalence of 22.5% (95% confidence interval [CI] 16.6-29.0). Between-study heterogeneity was 93%. When stratified by subgroup, the pooled HPV prevalence in leukoplakia (1232 cases) was 20.2% (95% CI 11.2-31.1), lichen planus (767 cases) 23.0% (95% CI 15.0-32.2), oral submucous fibrosis (238 cases) 28.6% (95% CI 23.0-34.5), proliferative verrucous leukoplakia (60 cases) 24.7% (95% CI 1.8-62.0), and OPMD unspecified (377 cases) was 25.4% (95% CI 16.2-35.8). Information on presence of epithelial dysplasia was available in 19 studies and the results did not vary substantially between non-dysplastic and dysplastic samples. HPV16 was the predominant genotype among HPV positive OPMD cases (48.2%, 95% CI 31.4-65.2). CONCLUSION We found a pooled HPV DNA prevalence of 22.5 % in OPMD cases with great between-study heterogeneity. The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia.
Putting the Pieces Together: Completing the Mechanism of Action Jigsaw for Sipuleucel-T

Abstract Sipuleucel-T is an autologous cellular immunotherapy that induces an immune response targeted against prostatic acid phosphatase (PAP) to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. In the phase III IMPACT study, sipuleucel-T was associated with a statistically significantly increased overall survival (OS) (median = 4.1 months) vs placebo. Patients with baseline prostate-specific antigen levels in the lowest quartile (≤22.1 ng/mL) exhibited a 13-month improvement in OS with sipuleucel-T. Together, this led sipuleucel-T to be approved and recommended as first-line therapy in various guidelines for treatment of metastatic castration-resistant prostate cancer. This review discusses the varied findings about the mechanisms of action of sipuleucel-T, bringing them together to form a more coherent picture. These pieces include inducing a statistically significant increase in antigen-presenting cell activation; inducing a peripheral immune response specific to the target (PAP) and/or immunizing (PA2024) antigens; stimulating systemic cytotoxic T-lymphocyte activity; and mediating antigen spread (ie, increased antibody responses to secondary proteins in addition to PAP and PA2024). Each of these pieces individually correlates with OS. Sipuleucel-T also traffics T cells to the prostate and is associated with long-term immune memory such that a second course of treatment induces an anamnestic immune response. Prostate cancer does not have a strongly inflamed microenvironment, thus its response to immune checkpoint inhibitors is limited. Because sipuleucel-T is able to traffic T cells to the tumor, it may be an ideal combination partner with immunotherapies including immune checkpoint inhibitors or with radiation therapy.
Long INterspersed element‐1 mobility as a sensor of environmental stresses

Long INterspersed element (LINE‐1, L1) retrotransposons are the most abundant transposable elements in the human genome, constituting approximately 17%. They move by a “copy‐paste” mechanism, involving reverse transcription of an RNA intermediate and insertion of its cDNA copy at a new site in the genome. L1 retrotransposition (L1‐RTP) can cause insertional mutations, alter gene expression, transduce exons, and induce epigenetic dysregulation. L1‐RTP is generally repressed; however, a number of observations collected over about 15 years revealed that it can occur in response to environmental stresses. Moreover, emerging evidence indicates that L1‐RTP can play a role in the onset of several neurological and oncological diseases in humans. In recent years, great attention has been paid to the exposome paradigm, which proposes that health effects of an environmental factor should be evaluated considering both cumulative environmental exposures and the endogenous processes resulting from the biological response. L1‐RTP could be an endogenous process considered for this application. Here, we summarize the current understanding of environmental factors that can affect the retrotransposition of human L1 elements. Evidence indicates that L1‐RTP alteration is triggered by numerous and various environmental stressors, such as chemical agents (heavy metals, carcinogens, oxidants, and drugs), physical agents (ionizing and non‐ionizing radiations), and experiential factors (voluntary exercise, social isolation, maternal care, and environmental light/dark cycles). These data come from in vitro studies on cell lines and in vivo studies on transgenic animals: future investigations should be focused on physiologically relevant models to gain a better understanding of this topic.