Miracle-dz/UniFAR-FTUs huggingface dataset:
Enamel staining with e-cigarettes, tobacco heating products and modern oral nicotine products compared with cigarettes and snus: An in vitro study.

PURPOSE To evaluate the effect of cigarette smoke, smokeless tobacco (e.g. snus), tobacco heating products (THP), electronic cigarettes (EC), and modern oral nicotine products on tooth staining. METHODS In this in vitro study, staining was assessed for 86 days following exposure of bovine enamel samples to a scientific reference cigarette (1R6F), a THP (glo), an EC (ePen 3), a reference snus product (CRP1.1), and a modern oral product (LYFT). Red wine and coffee were used as positive controls and DMSO and complete artificial saliva as negative controls. Whether brushing could reduce staining levels was also assessed. Changes in staining levels were assessed using the Commission Internationale de L'éclairage L*a*b* method. RESULTS Enamel staining increased with incubation time, and cigarette smoke, snus, coffee and wine induced statistically higher staining levels. THP, EC and modern oral exposure induced minimal staining levels that were also comparable to negative control samples. At day 86, ΔE mean and SD values were 28.50 ± 3.14, 19.76 ± 1.26, 17.35 ± 3.44, 16.22 ± 2.07, 18.30 ± 3.82, 4.10 ± 1.99, 11.30 ± 2.60, 49.56 ± 2.44 for cigarette, glo, EC with blended tobacco, EC with rich tobacco, reference snus product, modern oral product, coffee or wine. The control ΔE mean and SD values at day 86 were 18.68 ± 3.89 for DMSO and 2.17± 0.78 for complete artificial saliva. The ΔE values for all DMSO extracted samples and control increased from day 1 to 86, which suggests that the DMSO used to extract the samples contributes to the enamel sample staining levels. Staining levels were reduced by brushing. CLINICAL SIGNIFICANCE Cigarette smoke, red wine, snus and coffee stained enamel. Exposure to THP, EC or modern oral product extracts for 86 days resulted in minimal enamel staining. Further studies are required to assess the long-term impact on staining and the oral cavity following consumer exclusive use of EC, THP or modern oral products.
What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

Among the main challenges in further advancing therapeutic strategies for Huntington’s disease (HD) is the development of biomarkers which must be applied to assess the efficiency of the treatment. HD is a dreadful neurodegenerative disorder which has its source of pathogenesis in the central nervous system (CNS) but is reflected by symptoms in the periphery. Visible symptoms include motor deficits and slight changes in peripheral tissues, which can be used as hallmarks for prognosis of the course of HD, e.g., the onset of the disease symptoms. Knowing how the pathology develops in the context of whole organisms is crucial for the development of therapy which would be the most beneficial for patients, as well as for proposing appropriate biomarkers to monitor disease progression and/or efficiency of treatment. We focus here on molecular peripheral biomarkers which could be used as a measurable outcome of potential therapy. We present and discuss a list of wet biomarkers which have been proposed in recent years to measure pre- and postsymptomatic HD. Interestingly, investigation of peripheral biomarkers in HD can unravel new aspects of the disease pathogenesis. This especially refers to inflammatory proteins or specific immune cells which attract scientific attention in neurodegenerative disorders.
Nanomaterial-based Optical and Electrochemical Biosensors for Amyloid beta and Tau: Potential for early diagnosis of Alzheimer’s Disease

ABSTRACT Introduction Alzheimer’s disease (AD), a heterogeneous pathological process representing the most common causes of dementia worldwide, has required early and accurate diagnostic tools. Neuropathological hallmarks of AD involve the aberrant accumulation of Amyloid beta (Aβ) into Amyloid plaques and hyperphosphorylated Tau into neurofibrillary tangles, occurring long before the onset of brain dysfunction. Areas covered:Considering the significance of Aβ and Tau in AD pathogenesis, these proteins have been adopted as core biomarkers of AD, and their quantification has provided precise diagnostic information to develop next-generation AD therapeutic approaches. However, conventional diagnostic methods may not suffice to achieve clinical criteria that are acceptable for proper diagnosis and treatment. The advantages of nanomaterial-based biosensors including facile miniaturization, mass fabrication, ultra-sensitivity, make them useful to be promising tools to measure Aβ and Tau simultaneously for accurate validation of low-abundance yet potentially informative biomarkers of AD. Expert opinion The study has identified the potential application of advanced biosensors as standardized clinical diagnostic tools for AD, evolving the way for new and efficient AD control with minimum economic and social burden. After clinical trial, nanobiosensors for measuring Aβ and Tau simultaneously possess innovative diagnosis of AD to provide significant contributions to primary Alzheimer’s care intervention.
Clinical variables of severe Chronic Spontaneous Urticaria from total IgE standpoint: a retrospective study.

Summary Background. Baseline total IgE levels have recently emerged as a prognostic factor for the clinical response to omalizumab in patients with severe chronic spontaneous urticaria (CSU). Objective. To investigate the main clinical features of patients with severe CSU from the standpoint of baseline total IgE. Methods. 153 patients (M/F 52/101; mean age 49,7 years) with severe CSU were studied. Based on IgE levels patients were divided into 5 subgroups and a ROC curve was built to define a threshold level omalizumab response. Atopic status, thyroid autoimmunity, activation of the coagulation cascade, and response to omalizumab were studied as well. Results. The subgroups did not differ in terms of age and gender. Atopy prevailed in the subgroup showing elevated IgE. Thyroid autoimmunity and elevated D-dimer levels were similarly distributed in the five subgroups. 94 patients showed a prompt response to omalizumab. The likelihood of a prompt response was higher in males (p less than 0.01). In the subgroup showing the lowest IgE levels only 10% responded promptly to the drug; these proportions were 60%, 65%, 81% and 83% in the remaining groups. 66% of those in group A did not respond at all to omalizumab. A threshold IgE level of 18 IU/ml was detected for omalizumab response. Conclusions. Baseline total IgE show a high high prognostic value for omalizumab response with a threshold level of 18 IU/ml. Males seem more responsive to omalizumab. Most patients show a mixed clinical picture where signs of atopic status co-exist with signs of an autoimmune disease.
Sexual segregation in the foraging behaviour of a slightly dimorphic seabird: influence of the environment and fishery activity.

Sexual segregation in foraging strategies has been little studied in marine species with slight Sexual Size Dimorphism (SSD), particularly regarding the role of environmental conditions and fishery activities. Sexual differences in fishery attendance are of particular concern because uneven mortality associated with bycatch may exacerbate impacts in wildlife populations. Using a seabird species with slight SSD, the Scopoli's shearwater (Calonectris diomedea), we assessed sexual differences in foraging strategies and evaluated whether annual environmental conditions and fishery activity shaped such differences. We used a four-year dataset combining bird GPS tracking, stable isotope analysis, the North Atlantic Oscillation index (NAO, as main proxy of the annual environmental conditions), and fishing vessel positioning data (Vessel Monitoring System, VMS) from the North Western Mediterranean, a region under intense fishery pressure. From 2012 to 2015, we tracked 635 foraging trips from 78 individuals. Females showed a greater foraging effort, a lower fishery attendance, a lower trophic level, and a narrower isotopic niche width than males. Moreover, in years with unfavourable environmental conditions, both sexes showed a lower fishery attendance and increased foraging effort compared to the year with most favourable conditions. Our results revealed that environmental conditions influence space use, feeding resources, and fishery attendance differently in males and females, overall suggesting competitive exclusion of females by males from main foraging areas and feeding resources, particularly in unfavourable environmental conditions. We highlight the importance of evaluating sexual segregation under disparate environmental conditions, particularly in species with slight SSD, since segregation may pass otherwise unnoticed if only years with similar environmental conditions are considered. The higher fishery attendance of males likely explains the male-biased bycatch ratio for this species. Thus, inter-sexual differences in foraging strategies can lead to an unbalanced exposure to relevant threats and have implications for the conservation of long-lived species.
From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

Therapeutic drug monitoring (TDM) and model‐informed precision dosing (MIPD) have evolved as important tools to inform rational dosing of antibiotics in individual patients with infections. In particular, critically ill patients display altered, highly variable pharmacokinetics and often suffer from infections caused by less susceptible bacteria. Consequently, TDM has been used to individualize dosing in this patient group for many years. More recently, there has been increasing research on the use of MIPD software to streamline the TDM process, which can increase the flexibility and precision of dose individualization but also requires adequate model validation and re‐evaluation of existing workflows. In parallel, new minimally invasive and noninvasive technologies such as microneedle‐based sensors are being developed, which—together with MIPD software—have the potential to revolutionize how patients are dosed with antibiotics. Nonetheless, carefully designed clinical trials to evaluate the benefit of TDM and MIPD approaches are still sparse, but are critically needed to justify the implementation of TDM and MIPD in clinical practice. The present review summarizes the clinical pharmacology of antibiotics, conventional TDM and MIPD approaches, and evidence of the value of TDM/MIPD for aminoglycosides, beta‐lactams, glycopeptides, and linezolid, for which precision dosing approaches have been recommended.
Identification of Novel Biomarkers Associated With the Prognosis and Potential Pathogenesis of Breast Cancer via Integrated Bioinformatics Analysis

Background: Breast cancer is the most commonly diagnosed malignancy and a major cause of cancer-related deaths in women globally. Identification of novel prognostic and pathogenesis biomarkers play a pivotal role in the management of the disease. Methods: Three data sets from the GEO database were used to identify differentially expressed genes (DEGs) in breast cancer. Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway analyses were performed to elucidate the functional roles of the DEGs. Besides, we investigated the translational and protein expression levels and survival data of the DEGs in patients with breast cancer from the Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, Human Protein Atlas, and Kaplan Meier plotter tool databases. The corresponding change in the expression level of microRNAs in the DEGs was also predicted using miRWalk and TargetScan, and the expression profiles were analyzed using OncomiR. Finally, the expression of novel DEGs were validated in Chinese breast cancer tissues by RT-qPCR. Results: A total of 46 DEGs were identified, and GO analysis revealed that these genes were mainly associated with biological processes involved in fatty acid, lipid localization, and regulation of lipid metabolism. Two novel biomarkers, ADH1A and IGSF10, and 4 other genes (APOD, KIT, RBP4, and SFRP1) that were implicated in the prognosis and pathogenesis of breast cancer, exhibited low expression levels in breast cancer tissues. Besides, 14/25 microRNAs targeting 6 genes were first predicted to be associated with breast cancer prognosis. RT-qPCR results of ADH1A and IGSF10 expression in Chinese breast cancer tissues were consistent with the database analysis and showed significant down-regulation. Conclusion: ADH1A, IGSF10, and the 14 microRNAs were found to be potential novel biomarkers for the diagnosis, treatment, and prognosis of breast cancer.
Dolutegravir pharmacokinetics during co-administration with either artemether/lumefantrine or artesunate/amodiaquine.

BACKGROUND In sub-Saharan Africa, artemisinin-containing therapies for malaria treatment are regularly co-administered with ART. Currently, dolutegravir-based regimens are recommended as first-line therapy for HIV across most of Africa. OBJECTIVES To investigate the population pharmacokinetics of dolutegravir during co-administration with artemether/lumefantrine or artesunate/amodiaquine, two commonly used antimalarial therapies. METHODS We developed a population pharmacokinetic model of dolutegravir with data from 26 healthy volunteers in two Phase 2 studies with a total of 403 dolutegravir plasma concentrations at steady state. Volunteers received 50 mg of dolutegravir once daily alone or in combination with standard treatment doses of artemether/lumefantrine (80/480 mg) or artesunate/amodiaquine (200/540 mg). RESULTS A two-compartment model with first-order elimination and transit compartment absorption best described the concentration-time data of dolutegravir. Typical population estimates for clearance, absorption rate constant, central volume, peripheral volume and mean absorption transit time were 0.713 L/h, 1.68 h-1, 13.2 L, 5.73 L and 1.18 h, respectively. Co-administration of artemether/lumefantrine or artesunate/amodiaquine increased dolutegravir clearance by 10.6% (95% CI 4.09%-34.5%) and 26.4% (95% CI 14.3%-51.4%), respectively. Simulations showed that simulated trough concentrations of dolutegravir alone or in combination with artemether/lumefantrine or artesunate/amodiaquine are maintained above the dolutegravir protein-adjusted IC90 of 0.064 mg/L for more than 99% of the individuals. CONCLUSIONS Dolutegravir dose adjustments are not necessary for patients who are taking standard 3 day treatment doses of artemether/lumefantrine or artesunate/amodiaquine.
Use of artificial intelligence on Electroencephalogram (EEG) waveforms to predict failure in early school grades in children from a rural cohort in Pakistan

Universal primary education is critical for individual academic growth and overall adult productivity of nations. Estimates indicate that 25% of 59 million primary age out of school children drop out and early grade failure is one of the factors. An objective and feasible screening measure to identify at-risk children in the early grades can help to design appropriate interventions. The objective of this study was to use a Machine Learning algorithm to evaluate the power of Electroencephalogram (EEG) data collected at age 4 in predicting academic achievement at age 8 among rural children in Pakistan. Demographic and EEG data from 96 children of a cohort along with their academic achievement in grade 1–2 measured using an academic achievement test of Math and language at the age of 7–8 years was used to develop the machine learning algorithm. K- Nearest Neighbor (KNN) classifier was used on different model combinations of EEG, sociodemographic and home environment variables. KNN model was evaluated using 5 Stratified Folds based on the sensitivity and specificity. In the current dataset, 55% and 74% failed in the mathematics and language test respectively. On testing data across each fold, the mean sensitivity and specificity was calculated. Sensitivity was similar when EEG variables were combined with sociodemographic, and home environment (Math = 58.7%, Language = 66.3%) variables but specificity improved (Math = 43.4% to 50.6% and Language = 32% to 60%). The model requires further validation for EEG to be used as a screening measure with adequate sensitivity and specificity to identify children in their preschool age who may be at high risk of failure in early grades.
Clinical Significance of Velamentous Cord Insertion Prenatally Diagnosed in Twin Pregnancy

Background: The purpose of this study was to evaluate the prevalence of velamentous cord insertion (VCI) and the actual association between pathologically confirmed VCI and perinatal outcomes in twins based on the chorionicity. Methods: All twin pregnancies that received prenatal care at a specialty clinic for multiple pregnancies, from less than 12 weeks of gestation until delivery in a single institution between 2015 and 2018 were included in this retrospective cohort study. Results: A total of 941 twins were included in the study. The prevalence of VCI in dichorionic (DC) twins and monochorionic diamniotic (MCDA) twins was 5.8% and 7.8%, respectively (p = 0.251). In all study population, the prevalence of vasa previa and placenta accreta spectrum was higher in VCI group than that of non-VCI group (p = 0.008 and 0.022). In MCDA twins with VCI, birth weight, 1 and 5-min Apgar score were lower than DC twins with VCI (p = 0.010, 0.002 and 0.000). There was no significant association between VCI and selective fetal growth restriction (p = 0.486), twin-to-twin transfusion syndrome (p = 0.400), and birth-weight discordance (>20% and >25%) (p = 0.378 and 0.161) in MCDA twins. Conclusion: There was no difference in the incidence of VCI in twins based on the chorionicity. Moreover, VCI was not a risk factor for adverse perinatal outcomes excepting vasa previa and placenta accreta spectrum, which had a high incidence in twins with VCI.
Role of intracellular complement activation in kidney fibrosis

Increased expression of complement C1r, C1s and C3 in kidney cells plays an important role in the pathogenesis of kidney fibrosis. Our studies suggest that activation of complement in kidney cells with increased generation of C3 and its fragments occurs by activation of classical and alternative pathways. Single nuclei RNA sequencing studies in kidney tissue from unilateral ureteral obstruction mice show that increased synthesis of complement C3 and C5 occurs primarily in renal tubular epithelial cells (proximal and distal), while increased expression of complement receptors C3ar1 and C5ar1 occurs in interstitial cells including immune cells like monocytes/macrophages suggesting compartmentalization of complement components during kidney injury. Although global deletion of C3 and macrophage ablation prevent inflammation and reduced kidney tissue scarring, the development of mice with cell‐specific deletion of complement components and their regulators could bring further insights into the mechanisms by which intracellular complement activation leads to fibrosis and progressive kidney disease.
Molecular Design and Polymer Structure Control Based on Polymer Crystal Engineering. Topochemical Polymerization of 1,3-Diene Mono- and Dicarboxylic Acid Derivatives Bearing a Naphthylmethylammonium Group as the Countercation

The topochemical polymerization of the alkylammonium salts of (Z,Z)-, (E,Z)-, and (E,E)-1,3-diene mono- or dicarboxylic acids, i.e., of the muconic and sorbic acid derivatives, is described from the viewpoint of polymer crystal engineering. Not only the (Z,Z)- but also the (E,E)-derivatives polymerize to give a high molecular weight polymer in the crystalline state under UV irradiation when a naphthylmethylammonium moiety is introduced to these monomers as the countercation. NMR spectroscopy confirms the formation of the stereoregular meso- or erythro-diisotactic-trans-2,5-polymer during the polymerization, irrespective of the configuration of the monomers and the structure of the substituents. The single-crystal structure analysis of the naphthylmethylammonium salt of sorbic acid reveals the stacking of the diene moieties in the columns formed in the crystals, favorable for the topochemical polymerization. The photopolymerization reactivity and the stereochemistry of the resulting polymers are determined.
‘Lines in the sand’: an Australian qualitative study of patient group practices to promote independence from pharmaceutical industry funders

Objectives To study how patient groups that accept pharmaceutical industry money perceive and manage the risk of undue influence from their sponsors. Design Empirical ethics approach using a qualitative interview study. Setting The Australian patient group sector. Participants 27 participants from 23 patient groups, purposively recruited for diversity of group characteristics (degree of pharmaceutical industry funding, health focus, location) and participant role (staff, board members). Analysis Interview data were transcribed and read repeatedly to identify concepts and patterns in the data. These were grouped into conceptual categories that described and explained the findings. We used an inductive analytical approach to identify important themes and concepts in the data. Results Participants in this study described how the patient group sector receives pressure from pharmaceutical company funders to act in ways that prioritise company interests. Groups worked to try and protect their credibility and ability to act in ways of their own choosing using practical rules or ‘lines in the sand’ about industry funding activities. They were grouped around the dominant topics of: sponsor exclusivity, brand marketing, agenda setting, advocacy and content of group activities. Lines in the sand were largely experience-driven and ethically informed; they varied between groups. There was also variable transparency among groups about financial interactions with pharmaceutical companies. Conclusions It is important to know about patient group practices around pharmaceutical industry funders as this allows public scrutiny about the adequacy of such practices. Inadequate strategies may mean that funders can influence patient groups activities in ways that do not necessarily prioritise the interests of members. We found that groups differed in their approach, with little independent external guidance to inform responses to commonly encountered types of influence. Inadequate transparency limits the ability of the public to make informed assessments about the risk of bias over the activities of groups that accept industry funding.