Miracle-dz/UniFAR-FTUs huggingface dataset:
Parameterizing the binding properties of dissolved organic matter with default values skews the prediction of copper solution speciation and ecotoxicity in soil

Parameterizing speciation models by setting the percentage of dissolved organic matter (DOM) that is reactive (% r‐DOM) toward metal cations at a single 65% default value is very common in predictive ecotoxicology. The authors tested this practice by comparing the free copper activity (pCu2+ = –log10[Cu2+]) measured in 55 soil sample solutions with pCu2+ predicted with the Windermere humic aqueous model (WHAM) parameterized by default. Predictions of Cu toxicity to soil organisms based on measured or predicted pCu2+ were also compared. Default WHAM parameterization substantially skewed the prediction of measured pCu2+ by up to 2.7 pCu2+ units (root mean square residual = 0.75–1.3) and subsequently the prediction of Cu toxicity for microbial functions, invertebrates, and plants by up to 36%, 45%, and 59% (root mean square residuals ≤9 %, 11%, and 17%), respectively. Reparametrizing WHAM by optimizing the 2 DOM binding properties (i.e., % r‐DOM and the Cu complexation constant) within a physically realistic value range much improved the prediction of measured pCu2+ (root mean square residual = 0.14–0.25). Accordingly, this WHAM parameterization successfully predicted Cu toxicity for microbial functions, invertebrates, and plants (root mean square residual ≤3.4%, 4.4%, and 5.8%, respectively). Thus, it is essential to account for the real heterogeneity in DOM binding properties for relatively accurate prediction of Cu speciation in soil solution and Cu toxic effects on soil organisms. Environ Toxicol Chem 2017;36:898–905. © 2016 SETAC
Dual antiplatelet therapy after coronary stenting

ABSTRACT Introduction: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the mainstay of pharmacotherapy in patients undergoing coronary stenting. Currently, three P2Y12 receptor inhibitors are approved for clinical use, including clopidogrel, prasugrel, and ticagrelor, with the latter two being preferred in patients presenting with an acute coronary syndrome. The introduction into clinical practice of newer-generation drug-eluting stent (DES) with safer profiles (i.e. less stent thrombosis) compared with earlier platforms have led recent guideline updates to re-evaluate the optimal duration of DAPT therapy, which are now based on evidence of a multitude of randomized clinical trials, registries, and meta-analysis and take into consideration the ischemic and bleeding risk profile of the patients. Areas covered: Most recent updates on DAPT duration from professional societies in the United States and Europe are discussed. Moreover, an assessment of clinical trials, registries, and meta-analysis leading to changes on practice guidelines analyzed. Expert opinion: The widespread introduction into clinical practice of newer-generation DES allows for shortening DAPT duration as also endorsed by practice guidelines. However, the optimal duration of DAPT therapy varies according to the individuals’ risk of ischemic and bleeding complications, with longer or shorter durations of treatment, respectively, that may be considered.
The acute toxicity of major ion salts to Ceriodaphnia dubia. II. Empirical relationships in binary salt mixtures

Many human activities increase concentrations of major geochemical ions (Na+1, K+1, Ca+2, Mg+2, Cl−1, SO4−2, and HCO3−1/CO3−2) in freshwater systems, and can thereby adversely affect aquatic life. Such effects involve several toxicants, multiple toxicity mechanisms, various ion interactions, and widely varying ion compositions across different water bodies. Previous studies of individual salt toxicities have defined some useful relationships; however, adding single salts to waters results in atypical compositions and does not fully address mixture toxicity. To better understand mechanisms and interactions for major ion toxicity, 29 binary mixture experiments, each consisting of 7 to 8 toxicity tests, were conducted on the acute toxicity of major ion salts and mannitol to Ceriodaphnia dubia. These tests showed multiple mechanisms of toxicity, including: 1) nonspecific ion toxicity, correlated with osmolarity and to which all ions contribute; and 2) cation‐dependent toxicities for potassium (K), magnesium (Mg), and calcium (Ca) best related to their chemical activities. These mechanisms primarily operate independently, except for additive toxicity of Mg‐dependent and Ca‐dependent toxicities. These mixture studies confirmed ameliorative effects of Ca on sodium (Na) and Mg salt toxicities and of Na on K salt toxicity, and further indicated lesser ameliorative effects of Ca on K salt toxicity and Mg on Na salt toxicity. These results provide a stronger basis for assessing risks from the complex mixtures of ions found in surface waters. Environ Toxicol Chem 2017;36:1525–1537. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Evaluation of a virtual anatomy course for clinical undergraduates.

AIM To implement and evaluate a series of interactive clinically applied anatomy tutorials for final year dental undergraduate students. METHODS A 6-week voluntary virtual program of tutorials for final year dental undergraduates, with pre- and post-tutorial testing, was evaluated using a priority sequence model (QualQuan). A purposive sample (n = 15) was taken of the year group (n = 69) and the initial qualitative phase in depth interviews were carried out until data saturation (n = 13). The emergent recurrent themes from the qualitative data were then phrased into a variety of non-leading questions. These questions were issued in the form of an anonymous electronic questionnaire to the whole student body. RESULTS There was a good uptake of the tutorials with 84% of the students accessing at least one tutorial before sitting their final examinations. A response rate of 70% was achieved for the quantitative evaluative questionnaire phase of the study. Overall perceptions of the course were favourable although a number of modifications were suggested. These included a more concise presentation of the mainstream tutorial text with hyper links to more detailed content. Students also indicated a desire for more line diagrams. These changes, it was suggested, would help with the on-line readability of the tutorials. The primary focus for the students' learning appeared to be provided by the pre- and post-tutorial tests even though explicit learning outcomes were provided for each tutorial. CONCLUSION This study demonstrates that a well-designed virtual course can help to vertically integrate, and make clinically relevant, one of the basic sciences underpinning dental surgery. It has shown that formative assessment acts as a powerful tool to focus student attention and direct student learning. This leads to the conclusion that formative assessments have to be designed with as much care and attention as summative assessments.
SGLT2 inhibitors in the pipeline for the treatment of diabetes mellitus in Japan

ABSTRACT Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors have been available for the treatment of type 2 diabetes (T2DM) in Japan since April 2014. The prescription rate in Japan is low in comparison to Western countries. We summarize the results obtained from the phase 3 clinical trials and clinical studies involving Japanese T2DM patients. We also discuss the current situation and the future prospects of SGLT2 inhibitors in Japan. Areas covered: Unexpected adverse events, such as cerebral infarction and diabetic ketoacidosis have been reported from clinics shortly after the initiation of SGLT2 inhibitor treatment. However, the reductions in blood glucose levels and body weight have been demonstrated in phase 3 trials using 6 types of SGLT2 inhibitors, while observational studies of Japanese T2DM patients, which were performed in the clinical setting, showed that the incidence of adverse drug reactions, such as severe hypoglycemia, was low. Expert opinion: SGLT2 inhibitors are also considered to be effective for treating Japanese patients with T2DM. When prescribing SGLT2 inhibitors, it is necessary to ensure that they are used appropriately because the Japanese T2DM patient population has a high proportion of elderly individuals and a high incidence of cerebrovascular disease.
Advances in chemical pharmacotherapy for managing acute decompensated heart failure

ABSTRACT Introduction: Acute decompensated heart failure (ADHF) contributes largely to the burden of heart failure and is associated with a poorer prognosis. Although numerous clinical trials evaluated the benefit of newer medications for ADHF, most of them were not successful. Areas covered: This review focusses on the updates on recent developments in chemical pharmacotherapy for the management of ADHF. A MEDLINE search for relevant review articles and original investigations on newer drugs for ADHF provided us with necessary literature. Expert opinion: Currently, popular therapies like diuretics, vasodilators, and inotropes offer symptomatic relief but do not provide survival benefit. Although multiple medications targeting novel pathways in ADHF were studied extensively, they failed to show either symptomatic or mortality benefit in available randomized trials. Improving our understanding of the complex pathophysiology of ADHF along with designing studies which include patients who are more representative of the real-world heart failure population, standardizing methods for endpoint assessment, and evaluating the role on novel biomarkers of organ dysfunction is important to improve ADHF research. Enhancing preventive strategies like improving baseline therapy in chronic heart failure patients and developing strategies for early identification of ADHF are important as our quest for innovative ADHF pharmacotherapy continues.
Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer

ABSTRACT Introduction: Tubulin inhibitors including taxanes and vinca alkaloids are important components of chemotherapy regimens used in advanced non-small cell lung cancer (NSCLC). Despite a treatment paradigm shift due to molecularly-targeted therapies and immunotherapy, a majority of patients will receive chemotherapy during their treatment course. Either used alone or in combination, tubulin inhibitors have demonstrated clinical benefits in different settings of lung cancer management. Areas covered: This review first discusses FDA-approved tubulin inhibitors for NSCLC, such as paclitaxel, docetaxel, vinorelbine, and nab-paclitaxel. The article then provides a summary of novel tubulin inhibitors, including cabazitaxel, eribulin, ixabepilone, patupilone, plinabulin, new colchicine analogues and others. It also discusses new tubulin inhibitor combinations with immunotherapy (PD-1/PD-L1 inhibitors) and molecularly-targeted therapies (e.g. anti-angiogenic agents, mTOR inhibitors, heat shock protein 90 inhibitors, MEK inhibitors, and anti-HER3 agents). Lastly, emerging data on potential resistance mechanisms and predictive biomarkers for tubulin inhibitors are explored. Expert opinion: Tubulin inhibitors will likely continue to play important roles in NSCLC management due to the advent of novel agents and combinations. Through further understanding of tumor biology, investigation of drug resistance, and development of predictive biomarkers, we will be better positioned to incorporate microtubule inhibition into patient specific treatment strategies.
Evaluation of a blended learning course for teaching oral radiology to undergraduate dental students.

AIMS The purpose of this study was to develop and implement a blended course (a combined face-to-face and online instruction) on undergraduate oral radiology and evaluate it by comparing its educational effectiveness (derived from students' performance and answers to questionnaires) to a conventional course's. Students' attitudes concerning the blended methodology were also registered. METHODOLOGY An original course was developed and implemented, and its electronic version was uploaded to an e-learning educational platform. The course was attended by two groups of final-year students, who were taught by either the conventional face-to-face methodology or the blended learning methodology. Students answered a series of questionnaires, before and after following the course, regarding their perceptions, attitudes and evaluation of the course. Additionally, they completed knowledge assessment tests and their grades (before and after the course) were compared. Educational effectiveness of the course was determined by analysing the results of the questionnaires and the tests. RESULTS Students in the blended group performed significantly better than their colleagues of the conventional group in the post-course knowledge test, and female students of the blended group performed better than male students. Students evaluated high the course content, organisation, educational material, and the blended group students additionally appreciated the course design and clarity of instructions. Students' attitudes towards elements of blended learning (effectiveness, motivation and active engagement) were very positive. Most of the blended group students, who attended the face-to-face meeting (approx. 91%), evaluated it as helpful for summarising the subject and clarifying difficult issues. CONCLUSIONS Blended learning is effective and well evaluated by dental students and can be implemented in undergraduate curriculum for teaching oral radiology.
A comparison of computer- and hand-generated clinical dental notes with statutory regulations in record keeping.

INTRODUCTION Dental patient records should be of high quality, contain information to allow for good continuity of care and clinical defence (should the need ever arise) and, ideally, facilitate clinical audit. Handwritten dental records have been assessed for their compliance to statutory regulations, but the same cannot be levelled at computer-generated notes. This study aimed to compare and analyse the compliance of both methods of data recording with statutory regulations. METHOD Fifty consecutive sets of handwritten notes and 50 sets of computer-generated notes were audited for compliance with a number of legal requirements and desirable characteristics for dental records and the results compared. The standard set for compliance with all characteristics was 100%. RESULTS The computer-generated notes satisfied the set standard for 8 of the 11 legal requirements and three of six desirable characteristics. The handwritten notes satisfied the set standard for 1 of 11 legal requirements and none of the desirable characteristics. A statistical difference (using a 95% confidence interval) between the two methods was observed in 5 of 11 legal characteristics and three of six desirable characteristics, all of which were in favour of computer-generated notes. CONCLUSIONS Within the limitations of this study, computer-generated notes achieved a much higher compliance rate with the set parameters, making defence in cases of litigation, continuity of care and clinical audit easier and more efficient.
Anticonvulsant drugs for generalized tonic-clonic epilepsy

ABSTRACT Introduction: Primary generalized tonic clonic seizures (pGTCS) are still linked to major concerns for the clinic and hazards for patients suffering from idiopathic generalized epilepsy (IGE), so a quick search of the most effective and appropriate therapy is needed to control them. The key criteria for proper treatment are syndromic diagnosis and distinction between newly diagnosed and refractory patients. Other criteria include age, gender and comorbidities. Areas covered: Treatment for pGTCS has expanded in the last two years, with new antiepileptic drugs like perampanel joining valproic acid, lamotrigine, levetiracetam, topiramate, while further evidence-based data are required for zonisamide and lacosamide. Expert opinion: Currently, valproic acid can be considered as a first choice in male or menopausal women, and in the absence of weight issue, both in adults and in children, and in the absence of side effects such as insomnia and headache. Today, valproic acid is not recommended in child-bearing age and in relation to possible cognitive problems, especially in children. Lamotrigine and levetiracetam can be a viable alternative as a first choice. Topiramate is also effective as a first choice, but concerns may arise from its potential cognitive and memory adverse side effects. Additionally, perampanel and lacosamide are promising treatments.
Localization of parathyroid disease with ‘sequential multiphase and dual-tracer’ technique and comparison with neck ultrasound

ObjectiveThe aim of the study was to evaluate the accuracy of the sequential multiphase and dual-tracer (SMADT) technique utilizing technetium-99m pertechnetate (99mTcO4) and dynamic technetium-99m-2-methoxyisobutylisonitrile (99mTc-MIBI) with single-photon emission computed tomography/computed tomography (SPECT/CT) for localization of hyperfunctioning parathyroid tissue and compare the results with ultrasound (US). Materials and methodsSixty-four patients with hyperparathyroidism were scanned over 4 years. For the SMADT technique, 80 MBq 99mTcO4 was injected with dynamic thyroid image acquisition started at 20 min, followed by 900 MBq 99mTc-MIBI injection at 30 min; the dynamic imaging continued for 50 min. SPECT was acquired at 60 min, with SPECT/CT of the neck at 3 h. Subsequent subtraction and statistical difference analyses were performed. Neck US was carried out within 3 months. Findings for each parathyroid gland and thyroid were classified as positive or negative. The patients underwent surgical resection of parathyroid tissue on the basis of imaging results. SMADT and US findings were correlated with histology as the gold standard. ResultsEighty-six histological samples were resected. The sensitivity of SMADT for localization to individual glands was 70.6% [95% confidence interval (CI)=58.1–80.7%] and that for neck US was 60.3% (95% CI=47.7–71.8%, P=0.26). Specificity was 94.4% (95% CI=70.6–99.7%) for SMADT and 72.2% (95% CI=46.4–89.2%) for neck US (P=0.13). Sensitivities in multigland disease were 63.6% (95% CI=31.6–87.6%) for SMADT and 36.4% (95% CI=12.4–68.4%) for US (P=0.37) and in nodular thyroid disease were 83.8% (95% CI=67.3–93.2%) and 66.7% (95% CI=48.9–80.9%), respectively (P=0.07). ConclusionSMADT results in better localization of varying parathyroid pathologies and complements the role of US in patients with multigland disease and nodular thyroid.
The comet assay in Folsomia candida: A suitable approach to assess genotoxicity in collembolans

The present study shows the comet assay technique being successfully applied for the first time to one of the most widely used soil organisms in standardized ecotoxicological tests, Folsomia candida, providing a step forward in assessing the genotoxicity induced by xenobiotics. Because collembolans have a high content of chitin, a new methodology was developed in which the heads of the collembolans were separated from the rest of the body, allowing the hemolymph to leak out. This procedure allows the cells to be released, and after lysis the genetic material is available for the comet assay. Among other key procedures, the use of 30 organisms (20‐ to 22‐d‐old adults) per replicate and the correct amount of cells with genetic material (translated as 10 μL of suspension) applied on the agarose gel were determinants for the success of the results obtained. The methodology was validated by exposing F. candida to a representative metallic element (cadmium) and a representative of organophosphates, the insecticide dimethoate, for a shorter time period of 10 d, compared with the 28 d for the International Organization for Standardization 11267 method. Within this method, the relatively low percentage of DNA damage (30%) observed in controls and the significant increase in terms of percentage of DNA damage for almost all the concentrations of dimethoate and Cd (reaching 52% and 56% of damage in the highest concentrations, respectively) confirmed the genotoxic effect of both compounds and validated this technique. The comet assay proved to be a sensitive technique to detect DNA strand breaks in collembolans’ cells. Environ Toxicol Chem 2017;36:2514–2520. © 2017 SETAC
Educational needs in the field of detection of domestic violence and neglect: the opinion of a population of French dentists.

OBJECTIVES The attitude of French dentists concerning domestic abuse has hardly ever been documented upon so far. The purpose of this study is to investigate the attitudes, knowledge and practices of a population of French general dental practitioners towards the prevention and detection of signs of neglect and abuse in order to determine the educational needs both during undergraduate curriculum and continuing education sessions. METHODS A total of 418 general dental practitioners all practising in the French area of Puy de Dôme were invited to participate in the study. The survey was conducted with questionnaires including multiple-choice or open questions and VAS scales. RESULTS The response rate was 54% (228/418). Only 5.7% of the practitioners systematically look for signs of neglect or abuse when treating their patients. 36% declare having already come across one or several cases of abuse and 48% having suspected at least one. The patients concerned were mainly women (54%). Only 28% would adopt an attitude in compliance with the French legislation if confronted with a case of abuse or domestic violence. 75.9% of the practitioners would like more training and assistance in the detection and care of abused patients and particularly as regards signs of abuse and the legal framework. CONCLUSIONS More information and training concerning abuse and domestic violence is required in the French undergraduate dental curriculum in order to help practitioners deal with such patients.
Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period

ABSTRACT Objective: To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). Research design and methods: In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. Results: The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was −0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Conclusion: Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. Clinical trial registration: NCT02081599