Miracle-dz/UniFAR-FTUs huggingface dataset:
Familial Clustering of Mitral Valve Prolapse in the Community

Background— Knowledge of mitral valve prolapse (MVP) inheritance is based on pedigree observation and M-mode echocardiography. The extent of familial clustering of MVP among unselected individuals in the community using current, more specific echocardiographic criteria is unknown. In addition, the importance of nondiagnostic MVP morphologies (NDMs; first described in large pedigrees) has not been investigated in the general population. We hypothesized that parental MVP and NDMs increase the risk of offspring MVP. Methods and Results— Study participants were 3679 Generation 3 individuals with available parental data in the Offspring or the New Offspring Spouse cohorts. MVP and NDMs were distinguished by leaflet displacement >2 versus ⩽2 mm beyond the mitral annulus, respectively. We compared MVP prevalence in Generation 3 participants with at least 1 parent with MVP (n=186) with that in individuals without parental MVP (n=3493). Among 3679 participants (53% women; mean age, 40±9 years), 49 (1%) had MVP. Parental MVP was associated with a higher prevalence of MVP in Generation 3 participants (10 of 186, 5.4%) compared with no parental MVP (39 of 3493, 1.1%; adjusted odds ratio, 4.51; 95% confidence interval, 2.13–9.54; P<0.0001). When parental NDMs were examined alone, the prevalence of Generation 3 MVP remained higher (12 of 484, 2.5%) compared with those without parental MVP or NDMs (27 of 3009, 0.9%; adjusted odds ratio, 2.52; 95% confidence interval, 1.25–5.10; P=0.01). Conclusions— Parental MVP and NDMs are associated with increased prevalence of offspring MVP, highlighting the genetic substrate of MVP and the potential clinical significance of NDMs in the community.
Tissue‐specific mechanisms of alternative polyadenylation: Testis, brain, and beyond (2018 update)

Alternative polyadenylation (APA) is how genes choose different sites for 3′ end formation for mRNAs during transcription. APA often occurs in a tissue‐ or developmental stage‐specific manner that can significantly affect gene activity by changing the protein product generated, the stability of the transcript, its localization within the cell, or its translatability. Despite the important regulatory effects that APA has on tissue‐specific gene expression, only a few examples have been characterized mechanistically. In this 2018 update to our 2010 review, we examine mechanisms for the control of APA and update our understanding of the older mechanisms since 2010. We once postulated the existence of tissue‐specific factors in APA. However, while a few tissue‐specific polyadenylation factors are known, the emerging conclusion is that the majority of APA is accomplished by altering levels of core polyadenylation proteins. Examples of those core proteins include CSTF2, CPSF1, and subunits of mammalian cleavage factor I. But despite support for these mechanisms, no one has yet documented any of these proteins changing in either a tissue‐specific or developmental manner. Given the profound effect that APA can have on gene expression and human health, improved understanding of tissue‐specific APA could lead to numerous advances in gene activity control.
Enhanced Stability and CO/Formate Selectivity of Plasma-Treated SnOx/AgOx Catalysts during CO2 Electroreduction

CO2 electroreduction into useful chemicals and fuels is a promising technology that might be used to minimize the impact that the increasing industrial CO2 emissions are having on the environment. Although plasma-oxidized silver surfaces were found to display a considerably decreased overpotential for the production of CO, the hydrogen evolution reaction (HER), a competing reaction against CO2 reduction, was found to increase over time. More stable and C1-product-selective SnOx/AgOx catalysts were obtained by electrodepositing Sn on O2-plasma-pretreated Ag surfaces. In particular, a strong suppression of HER (below 5% Faradaic efficiency (FE) at −0.8 V vs the reversible hydrogen electrode, RHE) during 20 h was observed. Ex situ scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDS), quasi in situ X-ray photoelectron spectroscopy (XPS), and operando X-ray absorption near-edge structure spectroscopy (XANES) measurements showed that our synthesis led to a highly roughened surface containing stable Snδ+/Sn species that were found to be key in the enhanced activity and stable CO/formate (HCOO–) selectivity. Our study highlights the importance of roughness, composition, and chemical state effects in CO2 electrocatalysis.
Imaging Flow Cytometry to Assess Antigen‐Presenting‐Cell Function

This unit describes methods for quantifying phagocytosis and imaging the immunological synapse between T cells and antigen‐presenting cells (APCs), with both techniques delivering valuable information about APC function. These aspects of APC biology have traditionally been challenging to quantify, and imaging flow cytometry, which harnesses the high‐throughput nature of flow cytometry combined with the capacity of microscopy to deliver spatial localization, facilitates analysis of these APC functions in a fashion that was previously not possible. Imaging flow cytometry allows large numbers of events to be captured and large amounts of fluorescence data to be quantified at the physical location of markers of interest, both on the cell surface and in intracellular compartments, combining key features of traditional flow cytometry and fluorescence microscopy. © 2019 by John Wiley & Sons, Inc.
Impact of Different Acoustic Components on EEG-based Auditory Attention Decoding in Noisy and Reverberant Conditions

Recently, a least-squares-based method has been proposed to decode auditory attention from single-trial EEG recordings for an acoustic scenario with two competing speakers. This method aims at reconstructing the attended speech envelope from the EEG recordings using a trained spatio-temporal filter. While the performance of this method has been mainly studied for noiseless and anechoic acoustic conditions, it is important to fully understand its performance in realistic noisy and reverberant acoustic conditions. In this paper, we investigate auditory attention decoding (AAD) using EEG recordings for different acoustic conditions (anechoic, reverberant, noisy, and reverberant-noisy). In particular, we investigate the impact of different acoustic conditions for AAD filter training and for decoding. In addition, we investigate the influence on the decoding performance of the different acoustic components (i.e. reverberation, background noise and interfering speaker) in the reference signals used for decoding and the training signals used for computing the filters. First, we found that for all considered acoustic conditions it is possible to decode auditory attention with a decoding performance larger than 90%, even when the acoustic conditions for AAD filter training and for decoding are different. Second, when using reference signals affected by reverberation and/or background noise, a comparable decoding performance as when using clean reference signals can be obtained. In contrast, when using reference signals affected by the interfering speaker, the decoding performance significantly decreases. Third, the experimental results indicate that it is even feasible to use training signals affected by reverberation, background noise and/or the interfering speaker for computing the filters.
Pathophysiology of Migraine

Our understanding of migraine pathophysiology is a work in progress. As more is learned about migraine, it seems that the probability of identifying a single unifying explanation for this common disorder becomes less and less. Although the neuroanatomy and elements of pain physiology underlying migraine attacks are probably shared pathophysiologic elements, the emerging complexity of migraine genetics suggests that the acute attack may be the final common expression of more than one type of initiating abnormality. After a brief summary of the neuroanatomic structures involved in the generation of migraine attacks and the traditional theories of migraine, the author focuses on the current understanding of migraine genetics and reviews recent data from the neuroimaging and the neurophysiology of migraine.
Computational Complexity as an Ultimate Constraint on Evolution

Experiments show that evolutionary fitness landscapes can have a rich combinatorial structure due to epistasis. For some landscapes, this structure can produce a computational constraint that prevents evolution from finding local fitness optima—thus overturning the traditional assumption that local fitness peaks can always be reached quickly if no other evolutionary forces challenge natural selection. Here, I introduce a distinction between easy landscapes of traditional theory where local fitness peaks can be found in a moderate number of steps, and hard landscapes where finding local optima requires an infeasible amount of time. Hard examples exist even among landscapes with no reciprocal sign epistasis; on these semismooth fitness landscapes, strong selection weak mutation dynamics cannot find the unique peak in polynomial time. More generally, on hard rugged fitness landscapes that include reciprocal sign epistasis, no evolutionary dynamics—even ones that do not follow adaptive paths—can find a local fitness optimum quickly. Moreover, on hard landscapes, the fitness advantage of nearby mutants cannot drop off exponentially fast but has to follow a power-law that long-term evolution experiments have associated with unbounded growth in fitness. Thus, the constraint of computational complexity enables open-ended evolution on finite landscapes. Knowing this constraint allows us to use the tools of theoretical computer science and combinatorial optimization to characterize the fitness landscapes that we expect to see in nature. I present candidates for hard landscapes at scales from single genes, to microbes, to complex organisms with costly learning (Baldwin effect) or maintained cooperation (Hankshaw effect). Just how ubiquitous hard landscapes (and the corresponding ultimate constraint on evolution) are in nature becomes an open empirical question.
Global biochemical and structural analysis of the type IV pilus from the Gram-positive bacterium Streptococcus sanguinis

Type IV pili (Tfp) are functionally versatile filaments, widespread in prokaryotes, that belong to a large class of filamentous nanomachines known as type IV filaments (Tff). Although Tfp have been extensively studied in several Gram-negative pathogens where they function as key virulence factors, many aspects of their biology remain poorly understood. Here, we performed a global biochemical and structural analysis of Tfp in a recently emerged Gram-positive model, Streptococcus sanguinis. In particular, we focused on the five pilins and pilin-like proteins involved in Tfp biology in S. sanguinis. We found that the two major pilins, PilE1 and PilE2, (i) follow widely conserved principles for processing by the prepilin peptidase PilD and for assembly into filaments; (ii) display only one of the post-translational modifications frequently found in pilins, i.e. a methylated N terminus; (iii) are found in the same heteropolymeric filaments; and (iv) are not functionally equivalent. The 3D structure of PilE1, solved by NMR, revealed a classical pilin-fold with a highly unusual flexible C terminus. Intriguingly, PilE1 more closely resembles pseudopilins forming shorter Tff than bona fide Tfp-forming major pilins, underlining the evolutionary relatedness among different Tff. Finally, we show that S. sanguinis Tfp contain a low abundance of three additional proteins processed by PilD, the minor pilins PilA, PilB, and PilC. These findings provide the first global biochemical and structural picture of a Gram-positive Tfp and have fundamental implications for our understanding of a widespread class of filamentous nanomachines.
Telemedicine in the ICU: clinical outcomes, economic aspects, and trainee education.

PURPOSE OF REVIEW The evidence base for telemedicine in the ICU (tele-ICU) is rapidly expanding. The last 2 years have seen important additions to our understanding of when, where, and how telemedicine in the ICU adds value. RECENT FINDINGS Recent publications and a recent meta-analysis confirm that tele-ICU improves core clinical outcomes for ICU patients. Recent evidence further demonstrates that comprehensive tele-ICU programs have the potential to quickly recuperate their implementation and operational costs and significantly increase case volumes and direct contribution margins particularly if additional logistics and care standardization functions are embedded to optimize ICU bed utilization and reduce complications. Even though the adoption of tele-ICU is increasing and the vast majority of today's medical graduates will regularly use some form of telemedicine and/or tele-ICU, telemedicine modules have not consistently found their way into educational curricula yet. Tele-ICU can be used very effectively to standardize supervision of medical trainees in bedside procedures or point-of-care ultrasound exams, especially during off-hours. Lastly, tele-ICUs routinely generate rich operational data, as well as risk-adjusted acuity and outcome data across the spectrum of critically ill patients, which can be utilized to support important clinical research and quality improvement projects. SUMMARY The value of tele-ICU to improve patient outcomes, optimize ICU bed utilization, increase financial performance and enhance educational opportunities for the next generation of providers has become more evident and differentiated in the last 2 years.
Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

The aim of this study was to evaluate the efficacy and safety of pemafibrate in people with type 2 diabetes and hypertriglyceridaemia over a 52‐week period. Participants were randomly assigned to receive treatment with placebo or pemafibrate at a dose of 0.2 or 0.4 mg/d for 24 weeks (treatment period 1). The main results from treatment period 1 have been reported previously. The assigned treatment was continued up to week 52, except that the placebo was changed to pemafibrate 0.2 mg/d after week 24 (treatment period 2). The percentage changes in fasting serum triglyceride (TG) levels at week 52 (last observation carried forward) were −48.2%, −42.3%, and −46.4% in the placebo/pemafibrate 0.2 mg/d (n = 57), pemafibrate 0.2 mg/d (n = 54), and pemafibrate 0.4 mg/d (n = 55) groups, respectively. Levels of TG, non‐HDL cholesterol and total cholesterol stably decreased, whereas levels of HDL cholesterol increased with pemafibrate treatments over 52 weeks. Pemafibrate was well tolerated throughout the study period. The present study is the first to show that pemafibrate treatment substantially ameliorated lipid abnormalities and was well tolerated for 52 weeks in people with type 2 diabetes and hypertriglyceridaemia.
Learning Discriminant Direction Binary Palmprint Descriptor

Palmprint directions have been proved to be one of the most effective features for palmprint recognition. However, most existing direction-based palmprint descriptors are hand-craft designed and require strong prior knowledge. In this paper, we propose a discriminant direction binary code (DDBC) learning method for palmprint recognition. Specifically, for each palmprint image, we first calculate the convolutions of the direction-based templates and palmprint and form the informative convolution difference vectors by computing the convolution difference between the neighboring directions. Then, we propose a simple yet effective model to learn feature mapping functions that can project these convolution difference vectors into DDBCs. For all training samples: (1) the variance of the learned binary codes is maximized; (2) the intra-class distance of the binary codes is minimized; and (3) the inter-class distance of the binary codes is maximized. Finally, we cluster the block-wise histograms of DDBC forming the discriminant direction binary palmprint descriptor for palmprint recognition. The experimental results on four challenging contactless palmprint databases clearly demonstrate the effectiveness of the proposed method.
Synthesis and Catalytic Properties of Modified Electrodes by Pulsed Electrodeposition of Pt/PANI Nanocomposite

In this study, the modification of glassy carbon electrodes by potentiostatic pulsed deposition of platinum nanoparticles and potentiostatic pulsed polymerization of polyaniline nanofibers was investigated. During the preparation of the nano-composite materials, the control of the potentiostatic pulsed deposition and potentiostatic pulsed polymerization parameters, such as pulse potential, pulse width time, duty cycle, and platinum precursor concentration allowed the optimization of the size, shape, and distribution of the deposited Pt nanoparticles. It is noteworthy that the polymerization method, cyclic voltammetry method, or potentiostatic pulsed polymerization method show an important effect in the morphology of the deposited polyaniline (PANI) film. The obtained modified electrodes, with highly uniform and well dispersed platinum nanoparticles, exhibit good electrocatalytic properties towards methanol oxidation.
Hepatocellular carcinoma with extrahepatic metastasis: Are there still candidates for transarterial chemoembolization as an initial treatment?

Background and aim Currently, sorafenib is indicated for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM), and many other systemic agents are becoming available. However, a few HCC patients with EHM still undergo transarterial chemoembolization (TACE) for intrahepatic tumor control. We aimed to investigate whether TACE is appropriate for patients with EHM, and if so, which subgroup may benefit from TACE. Methods A total of 186 consecutive HCC patients (median: 55 years, male: 86.0%, hepatitis B virus: 81.7%, Child-Pugh Class A: 83.3%) with EHM (nodal metastasis: 60.8%, distant metastasis: 39.2%) between 2010 and 2014 were analyzed. Initial treatment included sorafenib in 69 patients, and TACE in 117 patients. Results During a median follow-up of 6.6 months (range: 0.2–94.6 months), mortality was observed in 90.3% (168/186). The median survival was better for patients who received TACE than those treated with sorafenib (8.2 months vs. 4.6 months, p < 0.001). However, baseline characteristics varied between patients initially treated with TACE and sorafenib, and the treatment modality was not an independent factor associated with overall survival (hazard ratio: 1.19, 95% confidence interval: 0.81–1.75, p = 0.36). In sub-group analysis, TACE was associated with better survival only among younger patients and those with segmental/lobar portal vein invasion. Conclusion In HCC patients with EHM, TACE was not an independent favorable prognostic factor compared to sorafenib. The concept of intrahepatic control in HCC patients with EHM may need to be reevaluated in the era of promising systemic therapies, although there can be specific subgroups who still benefit from TACE.
Prediction of Discharge Destination after Neurological Rehabilitation in Stroke Patients

Background/Aims: Returning home is one of the most important aims of stroke patients when admitted to rehabilitation. Methods: A single-center prospectively ascertained database study was conducted. Results: Among 1,332 eligible patients (median age = 76.5 years), 828 (62.2%) returned home. Multiple logistic regression revealed 5 independent predictors: independent sitting balance, higher motor and social-cognitive functional independence measure subscores (all on admission to rehabilitation), living with a partner and younger age. The area under the curve (AUC) of this model was 0.86 (95% confidence interval (CI) 0.84–0.88). When age was excluded from the model, the AUC remained virtually the same (AUC = 0.85, 95% CI = 0.83–0.87). Conclusion: The discharge destination could be predicted in a majority of patients with easily available parameters. Availability of a partner as well as parameters linked to severity of the neurological and functional deficit were both important. Age alone adds very little to the predictive power of these variables, therefore access to rehabilitation should not be denied on grounds of age.
Delineation of ecologically distinct units of marine Bacteroidetes in the Northwestern Mediterranean Sea

Bacteroidetes is one of the dominant phyla of ocean bacterioplankton, yet its diversity and population structure is poorly understood. To advance in the delineation of ecologically meaningful units within this group, we constructed near full‐length 16S rRNA gene clone libraries from contrasting marine environments in the NW Mediterranean. Based on phylogeny and the associated ecological variables (depth and season), 24 different Bacteroidetes clades were delineated. By considering their relative abundance (from iTag amplicon sequencing studies), we described the distribution patterns of each of these clades, delimiting them as Ecologically Significant Taxonomic Units (ESTUs). Spatially, there was almost no overlap among ESTUs at different depths. In deep waters there was predominance of Owenweeksia, Leeuwenhoekiella, Muricauda‐related genera, and some depth‐associated ESTUs within the NS5 and NS2b marine clades. Seasonally, multi‐annual dynamics of recurring ESTUs were present with dominance of some ESTUs within the NS4, NS5 and NS2b marine clades along most of the year, but with variable relative frequencies between months. A drastic change towards the predominance of Formosa‐related ESTUs and one ESTU from the NS5 marine clade was typically present after the spring bloom. Even though there are no isolates available for these ESTUs to determine their physiology, correlation analyses identified the environmental preference of some of them. Overall, our results suggest that there is a high degree of niche specialisation within these closely related clades. This work constitutes a step forward in disentangling the ecology of marine Bacteroidetes, which are essential players in organic matter processing in the oceans.
Continuous-time path planning for multi-agents with fuzzy reinforcement learning

There are a lot of applications of multi-agent systems, such as robot navigation, distributed control, data mining, etc. Reinforcement learning (RL) is a popular method used in multi agent path planning. RL algorithm needs an accurate representation of a small and discrete space. In order to plan multi agents in continuous time, this paper approximate the Q-values with the fuzzy logic, such that the modified RL can work in continuous state space. The fuzzy reinforcement learning proposed in this paper uses fuzzy Q-iteration algorithm and a modified Wolf-PH algorithm. The convergence and existence of the algorithm are proven. The continuous time planning algorithm is applied to a cooperative task of two mobile Khepera robots. The experimental results show the effectiveness of the new path planning method for the multi agents in continuous time.