Miracle-dz/UniFAR-FTUs huggingface dataset:
Incentives in the insurance industry

Positieve invloed provisieverbod op advieskwaliteit twijfelachtig Vanwege zorgen over de prikkelwerking van provisies is in Nederland een provisieverbod ingesteld voor complexe financiele producten (zoals hypotheken, levensverzekeringen en arbeidsongeschiktheidsverzekeringen). Bij dergelijke producten moet de klant voortaan direct afrekenen voor advies. Het doel van het provisieverbod is om de advieskwaliteit te verbeteren. Janko Gorter toont in zijn proefschrift echter aan dat de positieve invloed op de advieskwaliteit twijfelachtig is. Verzekeraars kunnen de tussenpersoon namelijk ook omzeilen door direct advies te geven aan klanten; dergelijke gedrag van verkopers ligt zelfs voor de hand bij consumenten die zich onvoldoende bewust zijn van de financiele prikkels achter financieel advies. Met behulp van een micro-economisch model laat Gorter zien dat een provisieverbod het aantrekkelijk maakt voor verzekeraars om gelijktijdig twee advieskanalen te bestieren: een intermediair kanaal en een direct kanaal. Het intermediaire kanaal is aantrekkelijk voor alerte klanten die de prikkels achter advies volledig doorgronden. Omdat deze klanten de intermediair rechtstreeks belonen voor advies, is de advieskwaliteit optimaal. Klanten met minder oog voor adviesprikkels geven echter de voorkeur aan direct advies. Gorter pleit voor extra toezicht op direct advies door financiele instellingen in landen met een provisieverbod, zoals Nederland en het Verenigd Koninkrijk. De hiervoor benodigde capaciteit kan mogelijk (deels) worden uitgespaard bij het gedragstoezicht op tussenpersonen.
Recommended Practices and Benchmark Activity for Hydrogen and Oxygen Electrocatalysis in Water Splitting and Fuel Cells

Electrochemical energy storage by making H2 an energy carrier from water splitting relies on four elementary reactions, i.e., the hydrogen evolution reaction (HER), hydrogen oxidation reaction (HOR), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR). Herein, the central objective is to recommend systematic protocols for activity measurements of these four reactions and benchmark activities for comparison, which is critical to facilitate the research and development of catalysts with high activity and stability. Details for the electrochemical cell setup, measurements, and data analysis used to quantify the kinetics of the HER, HOR, OER, and ORR in acidic and basic solutions are provided, and examples of state‐of‐the‐art specific and mass activity of catalysts to date are given. First, the experimental setup is discussed to provide common guidelines for these reactions, including the cell design, reference electrode selection, counter electrode concerns, and working electrode preparation. Second, experimental protocols, including data collection and processing such as ohmic‐ and background‐correction and catalyst surface area estimation, and practice for testing and comparing different classes of catalysts are recommended. Lastly, the specific and mass activity activities of some state‐of‐the‐art catalysts are benchmarked to facilitate the comparison of catalyst activity for these four reactions across different laboratories.
A Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension (RADIOSOUND-HTN)

Background: Both radiofrequency and ultrasound endovascular renal sympathetic denervation (RDN) have proven clinical efficacy for the treatment of hypertension. We performed a head-to-head comparison of these technologies. Methods: Patients with resistant hypertension were randomly assigned in a 1:1:1 manner to receive either treatment with (1) radiofrequency RDN of the main renal arteries; (2) radiofrequency RDN of the main renal arteries, side branches, and accessories; or (3) an endovascular ultrasound–based RDN of the main renal artery. The primary end point was change in systolic daytime ambulatory blood pressure at 3 months. Results: Between June 2015 and June 2018, 120 patients were enrolled (mean age, 64±9 years±SD; mean daytime blood pressure, 153/86±12/13 mm Hg). Of these, 39 were randomly assigned to radiofrequency main renal artery ablation, 39 to combined radiofrequency ablation of the main artery and branches, and 42 to ultrasound-based treatment. Baseline daytime blood pressure, clinical characteristics, and treatment were well balanced between the groups. At 3 months, systolic daytime ambulatory blood pressure decreased by 9.5±12.3 mm Hg (P<0.001) in the whole cohort. Although blood pressure was significantly more reduced in the ultrasound ablation group than in the radiofrequency ablation group of the main renal artery (–13.2±13.7 versus –6.5±10.3 mm Hg; mean difference, –6.7 mm Hg; global P=0.038 by ANOVA, adjusted P=0.043), no significant difference was found between the radiofrequency ablation groups (–8.3±11.7 mm Hg for additional side branch ablation; mean difference, –1.8 mm Hg; adjusted P>0.99). Similarly, the blood pressure reduction was not found to be significantly different between the ultrasound and the side branch ablation groups. Frequencies of blood pressure response ≥5 mm Hg were not significantly different (global P=0.77). Conclusions: In patients with resistant hypertension, endovascular ultrasound–based RDN was found to be superior to radiofrequency ablation of the main renal arteries only, whereas a combined approach of radiofrequency ablation of the main arteries, accessories, and side branches was not. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT02920034.
The effect of leukocyte-platelet-rich fibrin on bone morphogenetic protein-2 and insulin-like growth factor-1 levels in patients with chronic periodontitis: a randomized split mouth clinical trail

Abstract The present study evaluates the effects of leukocyte-platelet-rich fibrin (L-PRF) combined with open flap debridement (OFD) on clinical parameters and growth factors levels (GFL) in chronic periodontitis (CP) patients. This trial was registered at clinicaltrials.gov as NCT02594605. 16 patients (32 sites) with chronic periodontitis who had at least two areas of horizontal bone loss, were treated with OFD alone or L-PRF with OFD (OFD + L-PRF). GFL in gingival crevicular fluid (GCF) were analyzed at baseline, 1 week, 2 weeks and 4 weeks after operation. Probing depth (PD) and clinical attachment level (CAL) were measured at baseline and 6 months postoperatively. PD reduction and CAL gain were significantly higher in the OFD + L-PRF sites than in OFD sites. OFD + L-PRF group showed significantly increased bone morphogenetic protein-2 and insulin-like growth factor-1 at 2 weeks compared with baseline. L-PRF combined with OFD significantly increases GFL and thus, it enhances the periodontal healing on CP patients.
Numerical Investigation of the Fracture Properties of Pre-Cracked Monocrystalline/Polycrystalline Graphene Sheets

The fracture properties of pre-cracked monocrystalline/polycrystalline graphene were investigated via a finite element method based on molecular structure mechanics, and the mode I critical stress intensity factor (SIF) was calculated by the Griffith criterion in classical fracture mechanics. For monocrystalline graphene, the size effects of mode I fracture toughness and the influence of crack width on the mode I fracture toughness were investigated. Moreover, it was found that the ratio of crack length to graphene width has a significant influence on the mode I fracture toughness. For polycrystalline graphene, the strain energy per unit area at different positions was calculated, and the initial fracture site (near grain boundary) was deduced from the variation tendency of the strain energy per unit area. In addition, the effects of misorientation angle of the grain boundary (GB) and the distance between the crack tip and GB on mode I fracture toughness were also analyzed. It was found that the mode I fracture toughness increases with increasing misorientation angle. As the distance between the crack tip and GB increases, the mode I fracture toughness first decreases and then tends to stabilize.
The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis

Amino acid catabolism is frequently executed in mitochondria; however, it is largely unknown how aberrant amino acid metabolism affects mitochondria. Here we report the requirement for mitochondrial saccharopine degradation in mitochondrial homeostasis and animal development. In Caenorhbditis elegans, mutations in the saccharopine dehydrogenase (SDH) domain of the bi-functional enzyme &agr;-aminoadipic semialdehyde synthase AASS-1 greatly elevate the lysine catabolic intermediate saccharopine, which causes mitochondrial damage by disrupting mitochondrial dynamics, leading to reduced adult animal growth. In mice, failure of mitochondrial saccharopine oxidation causes lethal mitochondrial damage in the liver, leading to postnatal developmental retardation and death. Importantly, genetic inactivation of genes that raise the mitochondrial saccharopine precursors lysine and &agr;-ketoglutarate strongly suppresses SDH mutation-induced saccharopine accumulation and mitochondrial abnormalities in C. elegans. Thus, adequate saccharopine catabolism is essential for mitochondrial homeostasis. Our study provides mechanistic and therapeutic insights for understanding and treating hyperlysinemia II (saccharopinuria), an aminoacidopathy with severe developmental defects.
Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice

Background Tetrahydrobiopterin is a cofactor of endothelial NO synthase (eNOS), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan), an orally active synthetic form of tetrahydrobiopterin on eNOS uncoupling and congenital heart defects (CHDs) induced by pregestational diabetes mellitus in mice. Methods and Results Adult female mice were induced to pregestational diabetes mellitus by streptozotocin and bred with normal male mice to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHDs were identified by histological analysis. Cell proliferation, eNOS dimerization, and reactive oxygen species production were assessed in the fetal heart. Pregestational diabetes mellitus results in a spectrum of CHDs in their offspring. Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHDs from 59% to 27%, and major abnormalities, such as atrioventricular septal defect and double‐outlet right ventricle, were absent in the sapropterin‐treated group. Lineage tracing reveals that pregestational diabetes mellitus results in decreased commitment of second heart field progenitors to the outflow tract, endocardial cushions, and ventricular myocardium of the fetal heart. Notably, decreased cell proliferation and cardiac transcription factor expression induced by maternal diabetes mellitus were normalized with sapropterin treatment. Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered reactive oxygen species levels in the fetal heart. Conclusions Sapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation, and prevents the development of CHDs in the offspring. Thus, sapropterin may have therapeutic potential in preventing CHDs in pregestational diabetes mellitus.
Blockade of microglial adenosine A2A receptor suppresses elevated pressure‐induced inflammation, oxidative stress, and cell death in retinal cells

Glaucoma is a retinal degenerative disease characterized by the loss of retinal ganglion cells and damage of the optic nerve. Recently, we demonstrated that antagonists of adenosine A2A receptor (A2AR) control retinal inflammation and afford protection to rat retinal cells in glaucoma models. However, the precise contribution of microglia to retinal injury was not addressed, as well as the effect of A2AR blockade directly in microglia. Here we show that blocking microglial A2AR prevents microglial cell response to elevated pressure and it is sufficient to protect retinal cells from elevated pressure‐induced death. The A2AR antagonist SCH 58261 or the knockdown of A2AR expression with siRNA in microglial cells prevented the increase in microglia response to elevated hydrostatic pressure. Furthermore, in retinal neural cell cultures, the A2AR antagonist decreased microglia proliferation, as well as the expression and release of pro‐inflammatory mediators. Microglia ablation prevented neural cell death triggered by elevated pressure. The A2AR blockade recapitulated the effects of microglia depletion, suggesting that blocking A2AR in microglia is able to control neurodegeneration in glaucoma‐like conditions. Importantly, in human organotypic retinal cultures, A2AR blockade prevented the increase in reactive oxygen species and the morphological alterations in microglia triggered by elevated pressure. These findings place microglia as the main contributors for retinal cell death during elevated pressure and identify microglial A2AR as a therapeutic target to control retinal neuroinflammation and prevent neural apoptosis elicited by elevated pressure.
Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis.

CONTEXT Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts. OBJECTIVE Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy. SETTING Two university-based, public hospitals and a private gynecology practice in Australia. DESIGN AND PARTICIPANTS Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119). RESULTS Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively. CONCLUSION Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups' findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.
Protein model discrimination attempts using mutational sensitivity, predicted secondary structure, and model quality information

Structure prediction methods often generate a large number of models for a target sequence. Even if the correct fold for the target sequence is sampled in this dataset, it is difficult to distinguish it from other decoy structures. An attempt to solve this problem using experimental mutational sensitivity data for the CcdB protein was described previously by exploiting the correlation of residue depth with mutational sensitivity (r ~ 0.6). We now show that such a correlation extends to four other proteins with localized active sites, and for which saturation mutagenesis datasets exist. We also examine whether incorporation of predicted secondary structure information and the DOPE model quality assessment score, in addition to mutational sensitivity, improves the accuracy of model discrimination using a decoy dataset of 163 targets from CASP. Although most CASP models would have been subjected to model quality assessment prior to submission, we find that the DOPE score makes a substantial contribution to the observed improvement. We therefore also applied the approach to CcdB and four other proteins for which reliable experimental mutational data exist and observe that inclusion of experimental mutational data results in a small qualitative improvement in model discrimination relative to that seen with just the DOPE score. This is largely because of our limited ability to quantitatively predict effects of point mutations on in vivo protein activity. Further improvements in the methodology are required to facilitate improved utilization of single mutant data.
Regulation of water‐soluble glucan synthesis by the Streptococcus mutans dexA gene effects biofilm aggregation and cariogenic pathogenicity

The cariogenic pathogen Streptococcus mutans effectively utilizes dietary sucrose for the synthesis of exopolysaccharides (EPS), which act as a scaffold for its biofilm and thus contribute to its cariogenic pathogenicity. Dextranase (Dex), which is a type of glucanase, participates in the degradation of water-soluble glucan (WSG); however, the structural features of the EPS regulated by the dexAgene have received limited attention. Our recent studies reported novel protocols to fractionate and analyzed the structural characteristics of glucans from S mutans biofilms. In this study, we identify the role of the S mutans dexAgene in dextran-dependent aggregation in biofilm formation. Our results show that deletion of dexA (SmudexA) results in increased transcription of EPS synthesis-related genes, including gtfB, gtfD, and ftf. Interestingly, we reveal that inactivating the dexA gene may lead to elevated WSG synthesis in S mutans , which results in dysregulated cariogenicity in vivo. Furthermore, structural analysis provides new insights regarding the lack of mannose monosaccharides, especially in the WSG synthesis of the SmudexA mutants. The biofilm phenotypes that are associated with the reduced glucose monosaccharide composition in both WSG and water-insoluble glucan shift the dental biofilm to reduce the cariogenic incidence of the SmudexA mutants. Taken together, these data reveal that EPS synthesis fine-tuning by the dexA gene results in a densely packed EPS matrix that may impede the glucose metabolism of WSG, thereby leading to the lack of an energy source for the bacteria. These results highlight dexA targeting as a potentially effective tool in dental caries management.
The Development of Chronic Critical Illness Determines Physical Function, Quality of Life, and Long-Term Survival Among Early Survivors of Sepsis in Surgical ICUs*

Objectives: This study sought to examine mortality, health-related quality of life, and physical function among sepsis survivors who developed chronic critical illness. Design: Single-institution, prospective, longitudinal, observational cohort study assessing 12-month outcomes. Setting: Two surgical/trauma ICUs at an academic tertiary medical and level 1 trauma center. Patients: Adult critically ill patients that survived 14 days or longer after sepsis onset. Interventions: None. Measurements and Main Results: Baseline patient characteristics and function, sepsis severity, and clinical outcomes of the index hospitalization were collected. Follow-up physical function (short physical performance battery; Zubrod; hand grip strength) and health-related quality of life (EuroQol-5D-3L, Short Form-36) were measured at 3, 6, and 12 months. Hospital-free days and mortality were determined at 12 months. We compared differences in long-term outcomes between subjects who developed chronic critical illness (≥ 14 ICU days with persistent organ dysfunction) versus those with rapid recovery. The cohort consisted of 173 sepsis patients; 63 (36%) developed chronic critical illness and 110 (64%) exhibited rapid recovery. Baseline physical function and health-related quality of life did not differ between groups. Those who developed chronic critical illness had significantly fewer hospital-free days (196 ± 148 vs 321 ± 65; p < 0.0001) and reduced survival at 12-months compared with rapid recovery subjects (54% vs 92%; p < 0.0001). At 3- and 6-month follow-up, chronic critical illness patients had significantly lower physical function (3 mo: short physical performance battery, Zubrod, and hand grip; 6 mo: short physical performance battery, Zubrod) and health-related quality of life (3- and 6-mo: EuroQol-5D-3L) compared with patients who rapidly recovered. By 12-month follow-up, chronic critical illness patients had significantly lower physical function and health-related quality of life on all measures. Conclusions: Surgical patients who develop chronic critical illness after sepsis exhibit high healthcare resource utilization and ultimately suffer dismal long-term clinical, functional, and health-related quality of life outcomes. Further understanding of the mechanisms driving the development and persistence of chronic critical illness will be necessary to improve long-term outcomes after sepsis.
Raw versus Processed EEG: Which One is Better?

Automated Long-Term EEG Review: Fast and Precise Analysis in Critical Care Patients. Koren JP, Herta J, Fürbass F, Pirker S, Reiner-Deitemyer V, Fiederer F, Flechsenhar J, Hartmann M, Kluge T, Baumgartner C Front Neurol 2018;9:454. Background Ongoing or recurrent seizure activity without prominent motor features is a common burden in neurological critical care patients and people with epilepsy during ICU stays. Continuous EEG (CEEG) is the gold standard for detecting ongoing ictal EEG patterns and monitoring functional brain activity. However CEEG review is very demanding and time consuming. The purpose of the present multirater, EEG expert reviewer study, is to test and assess the clinical feasibility of an automatic EEG pattern detection method (Neurotrend). Methods Four board certified EEG reviewers used Neurotrend to annotate 76 CEEG datasets à 6 h (in total 456 h of EEG) for rhythmic and periodic EEG patterns (RPP), unequivocal ictal EEG patterns and burst suppression. All reviewers had a predefined time limit of 5 min (± 2 min) per CEEG dataset and were compared to a predefined gold standard (conventional EEG review with unlimited time). Subanalysis of specific features of RPP was conducted as well. We used Gwet's AC1 and AC2coefficients to calculate interrater agreement (IRA) and multirater agreement (MRA). Also, we determined individual performance measures for unequivocal ictal EEG patterns and burst suppression. Bonferroni-Holmes correction for multiple testing was applied to all statistical tests. Results Mean review time was 3.3 min (± 1.9 min) per CEEG dataset. We found substantial IRA for unequivocal ictal EEG patterns (0.61–0.79; mean sensitivity 86.8%; mean specificity 82.2%, p < 0.001) and burst suppression (0.68–0.71; mean sensitivity 96.7%; mean specificity 76.9% p < 0.001). Two reviewers showed substantial IRA for RPP (0.68–0.72), whereas the other two showed moderate agreement (0.45–0.54), compared to the gold standard (p < 0.001). MRA showed almost perfect agreement for burst suppression (0.86) and moderate agreement for RPP (0.54) and unequivocal ictal EEG patterns (0.57). Conclusions We demonstrated the clinical feasibility of an automatic critical care EEG pattern detection method on two levels: (1) reasonable high agreement compared to the gold standard, (2) reasonable short review times compared to previously reported EEG review times with conventional EEG analysis.