Miracle-dz/UniFAR-FTUs huggingface dataset:
Invited Speaker Abstracts

Because concomitant administration of two or more drugs is common practice for chronic diseases and complications, we have to consider it prudent to minimize the potential for drug-drug interactions (DDIs). Although several methods have been published describing the prediction of DDI on the basis of in vitro data, true inhibitor concentrations in the liver and intestine cannot be precisely predicted based on plasma concentrations or dosages alone. Therefore, a successful extrapolation of in vitro data to the in vivo situation in preclinical studies should promise a good prediction in human studies, and in vivo animal models as an additional tool could be employed. Many DDI studies have been reported in experimental animals, including mice, rats, rabbits, dogs, and monkeys. Among those animals, rats are widely used in preclinical studies and are considered to be the most convenient animal. However, it is well known that there are great species differences in the CYP enzymes responsible for drug metabolism between humans and rats. For example, several substrates exclusively metabolized by CYP3A in humans are also catalyzed by CYP2C enzymes in rats. In addition, the intestinal metabolism of CYP3A substrates in rats tends to be a lesser contribution, compared to that in humans, suggesting an underestimation of intestinal DDI. Recently, there has been increasing interest in the use of monkeys as an animal model to predict the clinical DDI potential of drug candidates in pharmaceutical companies because of the similarities in functional activities of drug-metabolizing enzymes between monkeys and humans. Because monkeys have higher metabolic activities in the intestine as well as in the liver, especially for CYP3A substrates, we can detect sensitively a DDI that might be caused by drug candidates in clinical studies. If data generated from these models could increase comfort that a drug would not be an inhibitor or inducer, we could confidently delay the DDI study until after proof of concept in the clinic. In this symposium, I would like to propose a practical decision tree for use of in vitro and in vivo data in preclinical species to predict human DDI.
More Maternal Vascular Malperfusion and Chorioamnionitis in Placentas After Expectant Management vs. Immediate Delivery in Fetal Growth Restriction at (Near) Term: A Further Analysis of the DIGITAT Trial

Objective: Management of late fetal growth restriction (FGR) is limited to adequate fetal monitoring and optimal timing of delivery. The Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT) trial compared induction of labor with expectant management in pregnancies at (near) term complicated by suspected FGR. Findings of the DIGITAT trial were that expectant monitoring prolonged pregnancy for 10 days and increased birth weight with only 130 grams. This resulted in more infants born below the 2.3rd percentile compared to induction of labor, respectively, 12.5% in induction of labor and 30.6% in expectant monitoring group. The main placental lesions associated with FGR are maternal vascular malperfusion, fetal vascular malperfusion, and villitis of unknown etiology. We investigated whether placentas of pregnancies complicated with FGR in the expectant monitoring group reveal more and more severe pathology due to pregnancy prolongation. Material and methods: The DIGITAT trial was a multicenter, randomized controlled trial with suspected FGR beyond 36 + 0 weeks. We now analyzed all available cases (n = 191) for placental pathology. The macroscopic details were collected and histological slides were recorded and classified by a single perinatal pathologist, blinded for pregnancy details and outcome. The different placental lesions were scored based on the latest international criteria for placental lesions as defined in the Amsterdam Placental Workshop Group Consensus Statement. Results: The presence of maternal vascular malperfusion and chorioamnionitis were higher in the expectant management group (p < 0.05 and p < 0.01, respectively). No differences in placental weight and maturation of the placenta between the induction of labor and the expectant management group were seen. Fetal vascular malperfusion, villitis of unknown etiology and nucleated red blood cell count did not differ between the groups. Conclusion: Expectant management of late FGR is associated with increased maternal vascular malperfusion and chorioamnionitis. This may have implications for fetal and neonatal outcome, such as programming in the developing child influencing health outcomes later in life.
Effects of zoledronic acid and dexamethasone on early phases of socket healing after tooth extraction in rats: A preliminary macroscopic and microscopic quantitative study

Background The exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is still unknown. The aim of this paper was to investigate the effects of zoledronic acid and dexamethasone on the early phases of socket healing in rats subjected to tooth extractions. Material and Methods Thirty male Sprague-Dawley rats were divided into 2 groups: pharmacologically treated group (T, n=20) and non-pharmacologically treated group (C, n=10). T group rats received 0.1 mg/Kg of zoledronic acid (ZOL) and 1 mg/Kg of dexamethasone (DEX) three times a week for 10 consecutive weeks. C group rats were infused with vehicle. After 9 weeks from the first infusion, first maxillary molars were extracted in each of the rats. Quantitative macroscopic and microscopic analysis was performed to evaluate socket healing 8 days after extraction. Results Pharmacologically treated rats showed significant inhibition of bone remodeling. Connective tissue/alveolar bone ratio, osteoclast number and woven bone deposition were significantly reduced in group T compared to group C. Conversely, the proportion of necrotic bone was higher in group T compared to group C (0.8% and 0.3%, respectively. P=0.031). ZOL plus DEX do not cause gross effects on socket healing at a macroscopic level. Conclusions Our findings confirmed that exposure to ZOL plus DEX impairs alveolar wound repair. Inhibition of osteoclastic resorption of socket walls after tooth extraction and the inability to dispose of the necrotic bone may be considered the initial steps of MRONJ onset. Key words:Medication-related osteonecrosis of the jaw, zoledronic acid, dexamethasone, tooth extraction, rat.
Refinement of the Child Amblyopia Treatment Questionnaire (CAT-QoL) using Rasch analysis

ABSTRACT Aims or Purpose: The Child Amblyopia Treatment Questionnaire (CAT-QoL) was developed using a “bottom-up” methodological approach. Interviews with children with amblyopia identified items (questions) and response levels to be tested in a draft questionnaire consisting of 11 items (sad, feeling on face, hurt, doing schoolwork, cross, how other children treat you, doing things, worried, upset with family, playing with friends, happy). This study describes the refinement of the descriptive system for the CAT-QoL instrument using the application of Rasch analysis. Methods: A multi-centre pilot study was conducted, and data collected from 342 participants. Participants were asked to self-complete the appropriate treatment version of the CAT-QoL questionnaire socio-demographic and clinical data were collected by the clinician using a standardised proforma. A “measure” of child’s health was obtained from the parent by asking how they would rate their child’s health over the previous week. Rasch analysis techniques were applied to refine the questionnaire. Rasch was used to examine response categories and collapse item response levels, identify poorly performing items, and explore local dependency of items. Results: A total of 331 subjects were included in the study sample, however only 315 were accepted into the RUMM program as a number of subjects had missing questions responses on the CAT-QoL. RUMM also excluded a further 41 subjects as these demonstrated extreme responses. Disordered response categories were found for each item, requiring adjacent response levels to be combined. This was applied to all items, and the model fit was re-examined. Two items were found to have poor fit (cross and happy) and were removed from the measure and the model fit was re-examined. No statistically significant differential item functioning (DIF) was found for any item, using person factors of age, sex or general health. Two items showed some dependency (worried and upset with family), and the poorer fitting item was subsequently removed (upset with family). This resulted in a refined CAT-QoL instrument that consists of 8-items, each with three-level response scales. Conclusion: The refined CAT-QoL instrument includes the following items: sad, feeling on face, hurt, doing work at school, how other children treat you, doing things, worried and playing with friends. The CAT-QoL can be Rasch scored, with a range of 0–16 where a greater value indicates a worse quality of life (or greater impact of treatment on the individual). The CAT-QoL may be useful in determining how amblyopia treatment affects children, and offers an alternative to generic patient reported outcome measures.
The Structure of Protection and Growth in the Late 19th Century

Many papers have explored the relationship between average tariff rates and economic growth, when theory suggests that the structure of protection is what should matter. We therefore explore the relationship between economic growth and agricultural tariffs, industrial tariffs, and revenue tariffs, for a sample of relatively well-developed countries between 1875 and 1913. Industrial tariffs were positively correlated with growth. Agricultural tariffs were negatively correlated with growth, although the relationship was often statistically insignificant at conventional levels. There was no relationship between revenue tariffs and growth.
Impacts of Surgery on Symptom Burden and Quality of Life in Pituitary Tumor Patients in the Subacute Post-operative Period

Background: Pituitary tumors are rare but are associated with significant symptoms that impact patients' quality of life (QOL). Surgery remains one of the most effective treatment options for long term disease control and symptom benefit, but symptom, and quality of life recovery in the subacute period has not been previously reported. This study aimed to better understand the impact of surgery on patients' symptom burden and QOL in the subacute post-surgical period. Methods: Twenty-three adult patients with pituitary tumors undergoing surgical resection at University of North Carolina Cancer Hospital were enrolled in this study. M.D. Anderson Symptom Inventory Brain Tumor Module, European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires were collected pre- and 1-month post- surgical resection and differences were analyzed for individual and groups of symptoms and QOL using Wilcoxon signed-rank tests. Results: Twenty adult patients had both pre-operation and post-operation follow-up visits; 60% had functional pituitary adenomas. Seven symptoms including fatigue, memory, vision, numbness, speaking, appearance, and weakness were significantly improved at the 1-month post-operation visit while one symptom, sleep, worsened. Global Health Status/QOL measurements was improved minimally from 63 (SD 25) at pre-operation to 67 (SD 22) at 1-month post-operation without statistical significance. Conclusions: This study demonstrated a rapid improvement of many symptoms in the subacute post-operative period in pituitary tumor patients. Disturbed sleep was identified as the only symptom to worsen post-operatively, encouraging potential prospective interventions to improve sleep, and subsequently improve the QOL in pituitary tumor patients following surgical intervention.
Association Between Periodontitis and Cognitive Impairment in Adults: A Systematic Review

Periodontitis is an oral inflammatory disease and may contribute to low-grade systemic inflammation. Based on the contribution of periodontitis to systemic inflammation and the potential role of systemic inflammation in neuroinflammation, many epidemiological studies have investigated a possible association between periodontitis and mild cognitive impairment or dementia. The purpose of this study was to evaluate the clinical/epidemiological evidence regarding the association between periodontitis and cognitive decline in adult patients. A search conducted between September and October 2018 was performed in the electronic databases PubMed, Scopus, Web of Science, The Cochrane Library, LILACS, OpenGrey, and Google Scholar, with no publication date or language restrictions. Analytical observational studies in adults (P—Participants), with (E—Exposure) and without periodontitis (C—Comparison) were included in order to determine the association between periodontitis and cognitive decline (O—Outcome). The search identified 509 references, of which eight observational studies were accorded with the eligibility criteria and evaluated. The results should, however, be interpreted cautiously due to the limited number of studies. This systematic review points to the need for further well-designed studies, such as longitudinal observational studies with control of modifiable variables, as diagnostic criteria and time since diagnosis of periodontitis and cognitive impairment, to confirm the proposed association.
Off-Label Use of Bumetanide for Brain Disorders: An Overview

Bumetanide (BTN or BUM) is a FDA-approved potent loop diuretic (LD) that acts by antagonizing sodium-potassium-chloride (Na-K-Cl) cotransporters, NKCC1 (SLc12a2) and NKCC2. While NKCC1 is expressed both in the CNS and in systemic organs, NKCC2 is kidney-specific. The off-label use of BTN to modulate neuronal transmembrane Cl− gradients by blocking NKCC1 in the CNS has now been tested as an anti-seizure agent and as an intervention for neurological disorders in pre-clinical studies with varying results. BTN safety and efficacy for its off-label use has also been tested in several clinical trials for neonates, children, adolescents, and adults. It failed to meet efficacy criteria for hypoxic-ischemic encephalopathy (HIE) neonatal seizures. In contrast, positive outcomes in temporal lobe epilepsy (TLE), autism, and schizophrenia trials have been attributed to BTN in studies evaluating its off-label use. NKCC1 is an electroneutral neuronal Cl− importer and the dominance of NKCC1 function has been proposed as the common pathology for HIE seizures, TLE, autism, and schizophrenia. Therefore, the use of BTN to antagonize neuronal NKCC1 with the goal to lower internal Cl− levels and promote GABAergic mediated hyperpolarization has been proposed. In this review, we summarize the data and results for pre-clinical and clinical studies that have tested off-label BTN interventions and report variable outcomes. We also compare the data underlying the developmental expression profile of NKCC1 and KCC2, highlight the limitations of BTN’s brain-availability and consider its actions on non-neuronal cells.
Comparative Study of Phenolic Profiles, Antioxidant and Antiproliferative Activities in Different Vegetative Parts of Ramie (Boehmeria nivea L.)

Ramie (Boehmeria nivea L.) is usually cultivated as a fiber crop, but it is also well known for its potential use in animal feeding with viable commercial applications. In this study, the phenolics profile as well as cellular antioxidant and antiproliferative activities were investigated in free and bound fractions of six different vegetative parts from Boehmeria nivea L. The highest total phenolic content was observed in bud (4585 ± 320 mg GAE/100 g DW), whereas root and petiole had the lowest total phenolic contents, 442.8 ± 9.8 and 630.9 ± 27.0 mg GAE/100 g DW, respectively. Likewise, phloem had the most abundant total flavonoids (2755 ± 184 mg CE/100 g DW), whereas the lowest flavonoid contents was found in root and petiole, 636.9 ± 44.2 and 797.4 ± 87.6 mg CE/100 g DW, respectively. Xylem and bud depicted remarkable antioxidant and antiproliferative activities, which could be explained by their diverse phenolic composition, especially chlorogenic acid and epicatechin. The Boehmeria nivea L. plant might be a valuable resource for high value-added phenolic compounds used in food and non-food industries.
Effects of Killing Methods on Lipid Oxidation, Colour and Microbial Load of Black Soldier Fly (Hermetia illucens) Larvae

Simple Summary The projected global population growth by 2050 will require an increase in the production of high-quality food. Insects represent a promising alternative ingredient for feed with a lower environmental impact than conventional livestock such as poultry, swine and bovine species. In a context of commercial-scale production and considering the great diversity of insects, it is crucial to optimize the processing steps, including those used to kill insects. In addition to being able to maximize the nutritional and microbiological quality of the final product, insect killing methods should be rapid and effective. This project aims to optimize killing methods, i.e., blanching, desiccation, freezing (−20 °C; −40 °C; liquid nitrogen), high hydrostatic pressure, grinding and asphyxiation (CO2; N2; vacuum conditioning), and to evaluate their impact on the composition, lipid oxidation, colour and microbiological quality on the black soldier fly larvae. Blanching appears to be the most appropriate strategy since it is a rapid and effective killing method reducing larval moisture while minimizing lipid oxidation, microbial contamination and colour alteration. Ultimately, this work will help to establish a standardized protocol that meets the Canadian regulatory quality requirements for feed. Abstract Black soldier fly (BSF) larvae represent a promising alternative ingredient for animal feed. Post-production processing can, however, affect their quality. This project aimed to optimize larval killing by comparing the effects on the nutritional and microbiological quality of 10 methods, i.e., blanching (B = 40 s), desiccation (D = 60 °C, 30 min), freezing (F20 = −20 °C, 1 h; F40 = −40 °C, 1 h; N = liquid nitrogen, 40 s), high hydrostatic pressure (HHP = 3 min, 600 MPa), grinding (G = 2 min) and asphyxiation (CO2 = 120 h; N2 = 144 h; vacuum conditioning, V = 120 h). Some methods affected the pH (B, asphyxiation), total moisture (B, asphyxiation and D) and ash contents (B, p < 0.001). The lipid content (asphyxiation) and their oxidation levels (B, asphyxiation and D) were also affected (p < 0.001). Killing methods altered the larvae colour during freeze-drying and in the final product. Blanching appears to be the most appropriate strategy since it minimizes lipid oxidation (primary = 4.6 ± 0.7 mg cumen hydroperoxide (CHP) equivalents/kg; secondary = 1.0 ± 0.1 mg malondialdehyde/kg), reduces microbial contamination and initiates dehydration (water content = 78.1 ± 1.0%). We propose herein, an optimized protocol to kill BSF that meet the Canadian regulatory requirements of the insect production and processing industry.
Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.
Decolonising knowledge: Enacting the civic role of the university in a community-based project

The need to work in partnership with communities in a meaningful and impactful way has become a core part of university planning, in many countries around the world. In the Global South, the potential for the Eurocentric knowledges and power structures to dominate such partnerships is pervasive. This article reports on findings of a participatory action research project conducted with community members in a socio-economically disadvantaged community in South Africa who had identified a need to improve school-community cooperation in educating local children. Analysis of our findings, framed against broader cultural and historical contexts, suggests that when the role of university-based ‘experts’ is one of facilitation rather than ‘delivery,’ then not only is participation more effective, but, also, the process and products of knowledge democratisation can be realised more effectively. We thus provide unique insight into the way relationships between the university and the community can be reconceptualised, from a position of knowledge and epistemic hierarchy to one of epistemic democracy. We discuss the (civic) role of the university in enabling this co-construction of knowledge, and in developing the shared meanings and understandings that promote decolonisation and enable social change.
Learning to calibrate: Providing standards to improve calibration accuracy for different performance levels

textabstractThis experimental study explores whether feedback in the form of standards helps students in giving more accurate performance estimates not only on current tasks but also on new, similar tasks and whether performance level influences the effect of standards. We provided 122 first‐year psychology students with seven texts that contained key terms. After reading each text, participants recalled the correct definitions of the key terms and estimated the quality of their recall. Half of the participants subsequently received standards and again estimated their own performance. Results showed that providing standards led to better calibration accuracy, both on current tasks and on new, similar tasks, when standards were not available yet. Furthermore, with or without standards, high performers calibrated better than low performers. However, results showed that especially low performers' calibration accuracy benefitted from receiving standards.
Rotten Apples: An Investigation of the Prevalence and Predictors of Teacher Cheating

We develop an algorithm for detecting teacher cheating that combines information on unexpected test score fluctuations and suspicious patterns of answers for students in a classroom. Using data from the Chicago Public Schools, we estimate that serious cases of teacher or administrator cheating on standardized tests occur in a minimum of 4-5 percent of elementary school classrooms annually. Moreover, the observed frequency of cheating appears to respond strongly to relatively minor changes in incentives. Our results highlight the fact that incentive systems, especially those with bright line rules, often induce behavioral distortions such as cheating. Statistical analysis, however, may provide a means of detecting illicit acts, despite the best attempts of perpetrators to keep them clandestine.