Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro Detection of Occlusal Caries on Permanent Teeth by a Visual, Light-Induced Fluorescence and Photothermal Radiometry and Modulated Luminescence Methods

Background: The paradigm shift towards the nonsurgical management of dental caries relies on the early detection of the disease. Detection of caries at an early stage is of unequivocal importance for early preventive intervention. Objective: The aim of this in vitro study is to evaluate the performance of a visual examination using the International Caries Detection and Assessment System (ICDAS) criteria, two quantitative light-induced fluorescence (QLF) systems - Inspektor™ Pro and QLF-D Biluminator™ 2 (Inspektor Research Systems B.V., Amsterdam, The Netherlands) - and a photothermal radiometry and modulated luminescence, The Canary System® (Quantum Dental Technologies, Toronto, Ont., Canada) on the detection of primary occlusal caries on permanent teeth. Methods: A total of 60 teeth with occlusal surface sites ranging from sound to noncavitated lesions (ICDAS 0-4) were assessed with each detection method twice in a random order. Histological validation was used to compare methods for sensitivity, specificity, percent correct, and the area under the receiver operating characteristic curve (AUC), at standard and optimum sound thresholds. Interexaminer agreement and intraexaminer repeatability were measured using intraclass correlation coefficients. Results: Interexaminer agreement ranged between 0.48 (The Canary System®) and 0.96 (QLF-D Biluminator™ 2). Intraexaminer repeatability ranges were 0.33-0.63 (The Canary System®) and 0.96-0.99 (QLF-D Biluminator™ 2). The sensitivity range was 0.75-0.96 while that of specificity was 0.43-0.89. The AUC were 0.79 (The Canary System®), 0.87 (ICDAS), 0.90 (Inspektor™ Pro), and 0.94 (QLF-D Biluminator™ 2). Conclusion: ICDAS had the best combination of sensitivity and specificity followed by QLF-D Biluminator™ 2 at optimum threshold.
Evolutionary origin of the type 2 corticotropin‐releasing hormone receptor γ splice variant

Many G protein‐coupled receptors have splice variants, with potentially different pharmaceutical properties, expression patterns and roles. The human brain expresses three functional splice variants of the type 2 corticotropin‐releasing hormone: CRHR2α, –β and –γ. CRHR2γ has only been reported in humans, but its phylogenetic distribution, and how and when during mammalian evolution it arose, is unknown. Based on genomic sequence analyses, we predict that a functional CRHR2γ is present in all Old World monkeys and apes, and is unique to these species. CRHR2γ arose by exaptation of an intronic sequence—already present in the common ancestor of primates and rodents—after retrotransposition of a short interspersed nuclear element (SINE) and mutations that created a 5′ donor splice site and in‐frame start codon, 32–43 million years ago. The SINE is not part of the coding sequence, only of the 5′ untranslated region and may therefore play a role in translational regulation. Putative regulatory elements and an alternative transcriptional start site were added earlier to this genomic locus by a DNA transposon. The evolutionary history of CRHR2γ confirms some of the earlier reported principles behind the “birth” of alternative exons. The functional significance of CRHR2γ, particularly in the brain, remains to be showed.
Meta-analysis: Fact or fiction? How to interpret meta-analyses

Abstract Objectives. Widespread use of increasingly complex statistical methods makes it ever more challenging to adequately assess the results reported and conclusions drawn in meta-analytic research. This paper aims to identify potential fallacies by in-depth examination of recent publications on mood disorders. Methods. Three meta-analyses were selected based on availability of data and representativeness of methods employed. By means of detailed re-analysis, several widespread methodological problems were identified, and the example data were used to illustrate and discuss them. Results. General points addressed include clear formulation of the research question, choice of effect size measures, and general choice of model. Data quality problems like missing data and publication bias are discussed along with methods to deal with them. Furthermore, aspects of meta-analytic modelling like the use of fixed or random effects, data aggregation, as well as the use of subgroups are explained, and issues of excessive complexity and data dredging pointed out. Finally, the benefit of diagnostic tools like confidence bands and the importance of transparency regarding data and methodology for the interpretation of meta-analytic results are highlighted. Conclusions. Practically relevant quality criteria for readers to bear in mind when dealing with meta-analytic publications are summarized in a ten point checklist.
Therapeutic Targeting of CD146/MCAM Reduces Bone Metastasis in Prostate Cancer

Prostate Cancer is the most common cancer and the second leading cause of cancer-related death in males. When prostate cancer acquires castration resistance, incurable metastases, primarily in the bone, occur. The aim of this study is to test the applicability of targeting melanoma cell adhesion molecule (MCAM; CD146) with a mAb for the treatment of lytic prostate cancer bone metastasis. We evaluated the effect of targeting MCAM using in vivo preclinical bone metastasis models and an in vitro bone niche coculture system. We utilized FACS, cell proliferation assays, and gene expression profiling to study the phenotype and function of MCAM knockdown in vitro and in vivo. To demonstrate the impact of MCAM targeting and therapeutic applicability, we employed an anti-MCAM mAb in vivo. MCAM is elevated in prostate cancer metastases resistant to androgen ablation. Treatment with DHT showed MCAM upregulation upon castration. We investigated the function of MCAM in a direct coculture model of human prostate cancer cells with human osteoblasts and found that there is a reduced influence of human osteoblasts on human prostate cancer cells in which MCAM has been knocked down. Furthermore, we observed a strongly reduced formation of osteolytic lesions upon bone inoculation of MCAM-depleted human prostate cancer cells in animal model of prostate cancer bone metastasis. This phenotype is supported by RNA sequencing (RNA-seq) analysis. Importantly, in vivo administration of an anti-MCAM human mAb reduced the tumor growth and lytic lesions. These results highlight the functional role for MCAM in the development of lytic bone metastasis and suggest that MCAM is a potential therapeutic target in prostate cancer bone metastasis. Implications: This study highlights the functional application of an anti-MCAM mAb to target prostate cancer bone metastasis.
Is the Cool Kids programme working in outpatient psychiatric clinics? A Danish naturalistic effectiveness study

Abstract Background & aim: This study investigates the effectiveness of the Cool Kids programme in two outpatient psychiatric clinics for children with anxiety. Efficacy studies find that 60–80% of programme completers improve. It is unclear if the intervention is as effective in real-life clinical treatment, as only one previous Danish effectiveness study has ever been conducted. The goal of all evidence-based interventions is the successful transition from research environments to standard care clinical practice, but there can be substantial differences in the environment, therapists’ education and patient population in the two settings. Method: We have conducted a naturalistic effectiveness study of the Cool Kids programme using the Child Anxiety Life Interference Scale parent-report (N = 39) and child self-report (N = 40). Conclusion: The intervention significantly decreased the interference caused by anxiety symptoms in both the children’s and the parents’ lives from pre- to post-treatment and results were maintained during the 3-month follow up. Nevertheless, no additional significant reduction in interference was detected in the follow up contrary to the results from previous efficacy studies. Our results confirm that Cool Kids can be successfully implemented in clinical practice.
The Importance of Peripheral Nerves in Adipose Tissue for the Regulation of Energy Balance

Brown and white adipose tissues are essential for maintenance of proper energy balance and metabolic health. In order to function efficiently, these tissues require both endocrine and neural communication with the brain. Brown adipose tissue (BAT), as well as the inducible brown adipocytes that appear in white adipose tissue (WAT) after simulation, are thermogenic and energy expending. This uncoupling protein 1 (UCP1)-mediated process requires input from sympathetic nerves releasing norepinephrine. In addition to sympathetic noradrenergic signaling, adipose tissue contains sensory nerves that may be important for relaying fuel status to the brain. Chemical and surgical denervation studies of both WAT and BAT have clearly demonstrated the role of peripheral nerves in browning, thermogenesis, lipolysis, and adipogenesis. However, much is still unknown about which subtypes of nerves are present in BAT versus WAT, what nerve products are released from adipose nerves and how they act to mediate metabolic homeostasis, as well as which cell types in adipose are receiving synaptic input. Recent advances in whole-depot imaging and quantification of adipose nerve fibers, as well as other new research findings, have reinvigorated this field of research. This review summarizes the history of research into adipose innervation and brain–adipose communication, and also covers landmark and recent research on this topic to outline what we currently know and do not know about adipose tissue nerve supply and communication with the brain.
Convergence of surface energy calculations for various methods: (0 0 1) hematite as benchmark

Different methods for calculating the surface energy from ab initio simulations are applied to the relaxed (0 0 1) surface of the metal oxide hematite (-Fe2O3). The simulations are carried out with a rather moderate k-point grid with shrinking factors of (6 6 6) for all bulk and (6 6) for all slab simulations. Very good convergence is obtained if a linear fit of the slab energies with respect to the number of layers in the slab is performed. In comparison to the other methods employed, this procedure is ultimately the most accurate and reliable method for extracting convergent surface energies from (0 0 1) hematite slabs. Additionally, we propose a way to determine the least possible starting point for calculating the surface energy by the linear-fit method. Furthermore, we find the Boettger method to perform nearly equally well, if the bulk energy is extracted from the energy difference per layer between the slabs with 12 and 18 layers thickness. Both methods give a surface energy of 2.43 J m−2 with a deviation of less than 0.005 J m−2. The standard approach, which uses a separate bulk simulation, instead shows a significant linear divergence with increasing number of layers in the slab. We also carried out bulk simulations with a surface-oriented bulk unit cell, but found it in our case not to improve the convergence of the standard approach.
Clinical and radiographic peri-implant health status around narrow diameter implant-supported single and splinted crowns.

BACKGROUND Studies assessing and comparing clinical and radiographic peri-implant status around narrow diameter implant-supported single crowns (NDISCs) and splinted crowns (NDISPs) are scarce. OBJECTIVE The aim of this retrospective study was to estimate and compare complication rates, patient satisfaction, peri-implant status and peri-implant bone loss (PBL) of NDISCs and NDISPs. MATERIALS AND METHODS Patients receiving narrow diameter implants (NDIs) in the posterior mandible were assessed. Technical complication and patient satisfaction were recorded. Clinical peri-implant plaque index (PI), bleeding on probing (BoP), probing depth (PD) and PBL were assessed. Technical complications and patient satisfaction were recorded. Log-rank test was computed to evaluate the influence of prostheses type and NDIs location on technical complications. P-value less than 0.05 was regarded as significant. RESULTS Seventy-eight patients (43 male and 35 females) agreed to follow up. The mean follow-up duration of the patients was 3.6 years. A total of 102 (43 NDISCs and 59 NDISPs) NDIs with moderately rough surfaces were included. No significant differences in PI, BoP, or PD were observed between NDISCs and NDISPs. The average PBL score was 1.17 (range: 0.03-4.15) at implant level and 1.14 (range: 0.03-4.14) at patient level. Seven implants and three patients showed peri-implantitis. The rates of technical complication of single crowns were significantly higher than those of splinted crowns (P = 0.036). PBL was significantly higher in molar sites than those in premolar sites (P = 0.041). A total of 67 patients (85.9%) were satisfied with the esthetics of the crowns, while a total of 59 patients (75.6%) were satisfied with the function of the crowns. CONCLUSION NDISCs and NDISPs offer high patient satisfaction and tolerable complication rates. Peri-implant conditions and peri-implant bone levels were comparable around NDISCs and NDISPs. However, bone loss of implants was higher in molar sites than those implants in premolar sites.
Lysozyme Aptamer-Functionalized Magnetic Nanoparticles for the Purification of Lysozyme from Chicken Egg White

Lysozyme is in high demand due to its many favorable characteristics such as being naturally occurring, non-toxic, and easy to digest and absorb. Recently, superparamagnetic nanoparticles with strong magnetic responsiveness have attracted significant interest for enzyme purification. The aptamer of the enzyme can be chemically synthesized rapidly at a large scale using simple and low-cost preparation methods. Therefore, Fe3O4 nanoparticles (Fe3O4 NPs) were prepared by chemical co-precipitation and were then functionalized with amino groups to produce NH2-Fe3O4 NPs. The specific reaction of aldehyde and amino groups was used to attach lysozyme aptamers with specific sequences to NH2-Fe3O4 NPs to produce Apt-NH2-Fe3O4 NPs. The synthesized materials were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), hysteresis loop analysis, and thermogravimetric analysis (TGA). The optimal experimental conditions for adsorption of lysozyme were investigated. The effects of initial lysozyme concentration, adsorption time, pH, reaction temperature, and ionic strength were determined. The maximum adsorption capacity and relevant activity of Apt-NH2-Fe3O4 NPs was 460 mg·g−1 and 16,412 ± 55 U·mg−1 in an aqueous lysozyme solution. In addition, as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis analysis, lysozyme could be separated from crude fresh egg white using Apt-NH2-Fe3O4 NPs with an amount up to 113 ± 4.2 mg·g−1 and an activity up to 16,370 ± 46 U·mg−1.
Endovascular Treatment of Unruptured MCA Bifurcation Aneurysms Regardless of Aneurysm Morphology: Short- and Long-Term Follow-Up

Between May 2008 and July 2017, endovascular treatment of 1184 aneurysms in 827 patients was performed in a single institution. Twenty-four percent of these aneurysms were located at the MCA, and 150 unruptured MCA bifurcation aneurysms treated with coiling, stent-assistedcoiling, or endovascular flow diverter (WEB device) were identified for this retrospective data analysis. The procedure-associated good clinical outcome was 89.9%, and the mortality rate was 2.7%. Short-term follow-up good clinical outcome/mortality rates were 91.3%/0.7%. At discharge, 137 patients had an mRS of 0–2 (91.3%) and 13 had an mRS of 3–6 (8.7%). The authors conclude that regardless of the architecture of MCA bifurcation aneurysms, endovascular treatment can be performed with low morbidity/mortality rates. BACKGROUND AND PURPOSE: The optimal treatment of unruptured middle cerebral aneurysms is still under debate. Although today almost any aneurysm can be treated endovascularly, there is a lack of data comparing endovascular and microsurgical repair of MCA aneurysms. The aim of our analysis is to provide data on the efficacy, clinical outcome, complications and re-treatment rates of endovascular treatment of this subtype of aneurysms. MATERIALS AND METHODS: Between May 2008 and July 2017, endovascular treatment of 1184 aneurysms in 827 patients was performed in our department. Twenty-four percent of these aneurysms were located at the MCA, and 150 unruptured MCA bifurcation aneurysms treated with coiling, stent-assisted-coiling, or endovascular flow diverter (WEB device) were identified for this retrospective data analysis. Ninety-six percent of all aneurysms, ruptured and unruptured, were treated by an endovascular approach, which yields a low selection bias for aneurysms suitable for endovascular treatment. Follow-up examinations were performed after 12 and 36 months and then every 1–3 years after embolization. Procedures were analyzed for periprocedural complications, outcome, and retreatment rate of the WEB (n = 38) and coiling with (n = 45) or without stent assistance (n = 67). RESULTS: The procedure-associated good clinical outcome (mRS ≦ 2) was 89.9%, and the mortality rate was 2.7%. Short-term follow-up good clinical outcome/mortality rates were 91.3%/0.7%. At discharge, 137 patients had an mRS of 0–2 (91.3%) and 13 had an mRS of 3–6 (8.7%). The retreatment rate was significantly higher in the WEB group (21.1%) compared with the coiling group with (5.9%) or without (2.2%) stent placement (P < .05). CONCLUSIONS: Regardless of the architecture of MCA bifurcation aneurysms, the endovascular treatment can be performed with low morbidity/mortality rates. The higher retreatment rate in the WEB group correlates with the learning curve in choosing the right device size.
Switching medication products during the treatment of psychiatric illness

Abstract Background. The common practice of switching between branded (reference) medications and their corresponding generic products, between generic products, or even from a generic product to a branded medication during the treatment of central nervous system (CNS) disorders may compromise efficacy and/or tolerability. Methods. We assessed the published literature from March 1, 2010 through June 30, 2017 via PubMed using the MeSH term ‘generics, drugs’ alone and in combination with class-specific terms (e.g., ‘anticonvulsants’, ‘mood stabilisers’), for studies detailing outcomes following product switches. Results. Although some studies comparing the initiation of reference versus generic drugs suggest equivalence between products, several studies detailing a switch between reference and generic products describe reductions in efficacy, reduced medication adherence and persistence, and increased overall health care resource utilization and costs associated with generic substitution. Conclusion. When product switches are considered, they should only proceed with the full knowledge of both patient and provider.
Detection and Control of Unannounced Exercise in the Artificial Pancreas Without Additional Physiological Signals

The purpose of this study was to develop an algorithm that detects aerobic exercise and triggers disturbance rejection actions to prevent exercise-induced hypoglycemia. This approach can provide a solution to poor glycemic control during and after aerobic exercise, a major hindrance in the participation of exercise by patients with type 1 diabetes. This novel exercise-induced hypoglycemia reduction algorithm (EHRA) detects exercise using a threshold on a disturbance term, a parameter estimated from an augmented minimal model using an unscented Kalman filter. After detection, the EHRA triggers the following three actions: First, a carbohydrate suggestion, second, a reduction in basal insulin and the insulin-on-board maximum limit, and finally, a 30% reduction of the next insulin meal bolus. The EHRA was tested in silico using a 15-day scenario with 8 exercise sessions of 50 min at <inline-formula><tex-math notation="LaTeX">$60\%\text{VO}_{2\text{max}}$</tex-math></inline-formula> on alternating days. The EHRA was able to obtain improved results when compared to strategies with and without exercise announcement. The unannounced, announced, and EHRA strategies all obtained an overall percentage of time in range (70–180 mg/dl) of 94% and a percentage of time <inline-formula><tex-math notation="LaTeX">$< $</tex-math></inline-formula>70 mg/dl of 2%, 0%, and 0%, respectively. The EHRA was tested for robustness during exercise sessions of +25% and <inline-formula><tex-math notation="LaTeX">$-$</tex-math></inline-formula>25% intensity and results suggest that the EHRA is able to account for variability in exercise intensity, duration, and patient dynamics such as glucose uptake rate and insulin sensitivity.
M/EEG-Based Bio-Markers to Predict the MCI and Alzheimer's Disease: A Review From the ML Perspective

This paper reviews the state-of-the-art neuromarkers development for the prognosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The first part of this paper is devoted to reviewing the recently emerged machine learning (ML) algorithms based on electroencephalography (EEG) and magnetoencephalography (MEG) modalities. In particular, the methods are categorized by different types of neuromarkers. The second part of the review is dedicated to a series of investigations that further highlight the differences between these two modalities. First, several source reconstruction methods are reviewed and their source-level performances explored, followed by an objective comparison between EEG and MEG from multiple perspectives. Finally, a number of the most recent reports on classification of MCI/AD during resting state using EEG/MEG are documented to show the up-to-date performance for this well-recognized data collecting scenario. It is noticed that the MEG modality may be particularly effective in distinguishing between subjects with MCI and healthy controls, a high classification accuracy of more than 98% was reported recently; whereas the EEG seems to be performing well in classifying AD and healthy subjects, which also reached around 98% of the accuracy. A number of influential factors have also been raised and suggested for careful considerations while evaluating the ML-based diagnosis systems in the real-world scenarios.
Knowledge about the predictive value of reward conditioned stimuli modulates their interference with cognitive processes

Stimuli conditioned with a substance can generate drug-approach behaviors due to their acquired motivational properties. According to implicit theories of addiction, these stimuli can decrease cognitive control automatically. The present study (n = 49) examined whether reward-associated stimuli can interfere with cognitive processes in the absence of knowledge about stimulus–outcome contingencies. Conditioned stimuli (CS) were paired with high-reward (HR) or low-reward (LR) probabilities of monetary reward using a Pavlovian learning task. Participants were categorized as Aware or Unaware of contingencies using a Bayesian analysis. CS were then used as task-irrelevant distractors in modified flanker and N-back tasks. Results show HR CS can generate increased interference in the flanker task for participants Unaware of contingencies, contributing further evidence for the existence of implicit Pavlovian conditioning. For the N-back task, working memory performance was affected by HR CS, albeit only for Aware participants. These results suggest that CS can interfere implicitly with cognitive processes in a similar way to drug-related stimuli. Such an effect could occur in a stimulus-driven fashion, devoid of top-down goal-directedness. These findings have implications for the conceptualization and study of implicit processes in addiction and highlights the necessity to reconsider the measurement of such phenomena.