Miracle-dz/UniFAR-FTUs huggingface dataset:
Paroxysmal and persistent atrial fibrillation ablation outcomes with the pulmonary vein ablation catheter GOLD duty-cycled phased radiofrequency ablation catheter: quality of life and 12-month efficacy results from the GOLD Atrial Fibrillation Registry

Abstract Aims The GOLD AF Registry has been designed to prospectively assess the population, indications, and outcomes using second-generation phased radiofrequency (RF) ablation (pulmonary vein ablation catheter GOLD) in a global examination of standard-of-care use for the treatment of paroxysmal and persistent atrial fibrillation (AF). Methods and results GOLD AF (NCT02433613) is a prospective, observational, multi-centre registry designed to characterize efficacy and safety of phased RF ablation in patients with AF. The primary endpoint was freedom from AF recurrence at 12-month follow-up after a 90-day blanking period. Ancillary objectives include safety, procedural efficiency, and quality of life (QoL). The QoL assessment using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Heart Rhythm Association (EHRA) Score of AF-related symptoms was collected at baseline and 12 months. In total, 1054 patients were included in this analysis (age 60.6, 67.6% male, 26.5% PersAF). Kaplan–Meier estimate of freedom from AF recurrence was 77.7% at 12 months. Peri-procedural device or procedure-related complications were observed in 26 (2.5%) patients, with a low stroke rate of 0.3%. One-year post-ablation, the EHRA AF Symptom score decreased in 68% of patients. The AFEQT score improvement was observed in 88.4% and 90.4% of patients who completed the questionnaire in-person or interviewed by phone at 12 month follow-up, respectively. Conclusion Phased RF ablation for the treatment of paroxysmal and persistent AF demonstrated a 77.7% freedom from AF recurrence at 12 months in addition to a significant reduction in arrhythmia symptoms and clinically meaningful improved QoL. Low peri-procedural complication rate of <3% was reported.
A wearable freestanding electrochemical sensing system

We devised a strategy for high-fidelity, wearable biomarker data acquisition and sensor integration with consumer electronics. To render high-fidelity wearable biomarker data, understanding and engineering the information delivery pathway from epidermally retrieved biofluid to a readout unit are critical. By examining the biomarker information delivery pathway and recognizing near-zero strained regions within a microfluidic device, a strain-isolated pathway to preserve biomarker data fidelity is engineered. Accordingly, a generalizable and disposable freestanding electrochemical sensing system (FESS) is devised, which simultaneously facilitates sensing and out-of-plane signal interconnection with the aid of double-sided adhesion. The FESS serves as a foundation to realize a system-level design strategy, addressing the challenges of wearable biosensing, in the presence of motion, and integration with consumer electronics. To this end, a FESS-enabled smartwatch was developed, featuring sweat sampling, electrochemical sensing, and data display/transmission, all within a self-contained wearable platform. The FESS-enabled smartwatch was used to monitor the sweat metabolite profiles of individuals in sedentary and high-intensity exercise settings.
Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy

Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules thatinteract with DNA and causecell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, andthey can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specificallytarget cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs). This review is focused on a new generation of polymer-based DDSs with specific chemical functionalities that improve their hydrophilicity, drug loading and cellular interactions.Recentlydesigned multifunctional DDSs used in cancer therapy are highlighted in this review.
The Effect of Nordic Walking Training with Poles with an Integrated Resistance Shock Absorber on the Functional Fitness of Women over the Age of 60

Inadequate levels of physical activity among older people lead to a gradual decline in self-reliance and consequent dependence on other people. The aim of the study was to evaluate the impact of Nordic walking training with poles with an integrated resistance shock absorber on the functional fitness of older women. Forty-two women (Mage = 64.7 ± 3.15 years) were randomly assigned into the experimental group—training with poles with an integrated resistance shock absorber, EG (n = 21) and the control active group—training with classic poles, CG (n = 21). Functional fitness was measured with the Senior Fitness Test before and after an intervention lasting for 8 weeks (2 training sessions × 75 minutes per week). Two-way ANOVA revealed statistically significant interaction effects for aerobic endurance (F = 14.47, p < 0.001) and upper body strength (F = 5.98, p < 0.05), indicating greater improvement in the experimental group. Nordic walking training both with classic poles and with poles with an integrated resistance shock absorber is beneficial for older people and improves functional fitness over a short time period. However, the poles with an integrated resistance shock absorber provide additional resistance effort during marching, which causes increased muscle activation and results in improved muscle strength and aerobic endurance. Based on these results, it can be concluded that this kind of training could be applied in the complex health programs of seniors.
Potential gains in life expectancy from reducing amenable mortality among people diagnosed with serious mental illness in the United Kingdom

Background To estimate the potential gain in life expectancy from addressing modifiable risk factors for all-cause mortality (excluding suicide and deaths from accidents or violence) across specific serious mental illness (SMI) subgroups, namely schizophrenia, schizoaffective disorders, and bipolar disorders in a Western population. Methods We have used relative risks from recent meta-analyses to estimate the population attribution fraction (PAF) due to specific modifiable risk factors known to be associated with all-cause mortality within SMI. The potential gain in life expectancy at birth, age 50 and age 65 years were assessed by estimating the combined effect of modifiable risk factors from different contextual levels (behavioural, healthcare, social) and accounting for the effectiveness of existing interventions tackling these factors. Projections for annual gain in life expectancy at birth during a two-decade was estimated using the Annual Percentage Change (APC) formula. The predicted estimates were based on mortality rates for year 2014–2015. Results Based on the effectiveness of existing interventions targeting these modifiable risk factors, we estimated potential gain in life expectancy at birth of four (bipolar disorders), six (schizoaffective disorders), or seven years (schizophrenia). The gain in life expectancy at age 50 years was three (bipolar disorders) or five (schizophrenia and schizoaffective disorders) years. The projected gain in life expectancy at age 65 years was three (bipolar disorders) or four (schizophrenia and schizoaffective disorders) years. Conclusions The implementation of existing interventions targeting modifiable risk factors could narrow the current mortality gap between the general and the SMI populations by 24% (men) to 28% (women). These projections represent ideal circumstances and without the limitation of overestimation which often comes with PAFs.
Aspartic Acid Isomerization Characterized by High Definition Mass Spectrometry Significantly Alters the Bioactivity of a Novel Toxin from Poecilotheria

Research in toxinology has created a pharmacological paradox. With an estimated 220,000 venomous animals worldwide, the study of peptidyl toxins provides a vast number of effector molecules. However, due to the complexity of the protein-protein interactions, there are fewer than ten venom-derived molecules on the market. Structural characterization and identification of post-translational modifications are essential to develop biological lead structures into pharmaceuticals. Utilizing advancements in mass spectrometry, we have created a high definition approach that fuses conventional high-resolution MS-MS with ion mobility spectrometry (HDMSE) to elucidate these primary structure characteristics. We investigated venom from ten species of “tiger” spider (Genus: Poecilotheria) and discovered they contain isobaric conformers originating from non-enzymatic Asp isomerization. One conformer pair conserved in five of ten species examined, denominated PcaTX-1a and PcaTX-1b, was found to be a 36-residue peptide with a cysteine knot, an amidated C-terminus, and isoAsp33Asp substitution. Although the isomerization of Asp has been implicated in many pathologies, this is the first characterization of Asp isomerization in a toxin and demonstrates the isomerized product’s diminished physiological effects. This study establishes the value of a HDMSE approach to toxin screening and characterization.
Cyclic-Dependent Damage Evolution in Self-Healing Woven SiC/[Si-B-C] Ceramic-Matrix Composites at Elevated Temperatures

Cycle-dependent damage evolution in self-healing, 2.5D woven Hi-NicalonTM SiC/[Si-B-C] and 2D woven Hi-NicalonTM SiC/[SiC-B4C] ceramic-matrix composites (CMCs) at 600 and 1200 °C was investigated. The cycle-dependent damage parameters of internal friction, dissipated energy, Kachanov’s damage parameter, and broken fiber fraction were obtained to describe damage development in self-healing CMCs. The relationships between cycle-dependent damage parameters and multiple fatigue damage mechanisms were established. The experimental fatigue damage development of self-healing Hi-NicalonTM SiC/[Si-B-C] and Hi-NicalonTM SiC/[SiC-B4C] composites was predicted for different temperatures, peak stresses, and loading frequencies. The cycle-dependent damage evolution of self-healing Hi-NicalonTM SiC/[Si-B-C] and Hi-NicalonTM SiC/[SiC-B4C] composites depends on temperature, testing environment, peak stress, and loading frequency. For the Hi-NicalonTM SiC/[Si-B-C] composite, temperature is a governing parameter for the fatigue process. At an elevated temperature of 600 °C in an air atmosphere, the internal frictional parameter of Hi-NicalonTM SiC/[Si-B-C] composite decreases first and then increases with applied cycle number; however, at an elevated temperature of 1200 °C in an air atmosphere, the internal frictional parameter of Hi-NicalonTM SiC/[Si-B-C] composite decreases with applied cycle number, and the interface shear stress at 1200 °C is much lower than that at 600 °C. For Hi-NicalonTM SiC/[SiC-B4C] composite at 1200 °C, loading frequency is a governing parameter for the fatigue process. The degradation rate of interface shear stress is much higher at the loading frequency of 0.1 Hz than that at the loading frequency of 1 Hz.
Frequency of Aortic Arch Variants in Patients with Large Vessel Stroke in the Anterior Circulation

Background: The presence of aortic arch variants (AAV) may complicate catheterization and prolong procedure times during endovascular stroke treatment. Hence, it is of great importance to know the prevalence of such variants in stroke patients in order to anticipate possible difficulties during catheterization. As the prevalence of such variants in stroke patients has not been investigated yet, we assessed the prevalence of AAV in patients, who received acute endovascular stroke treatment for large vessel occlusion in the anterior circulation. Methods: We retrospectively analyzed computed tomography angiograms of 248 patients with acute stroke in the anterior circulation, who received endovascular stroke treatment, for the prevalence of a bovine arch, a direct origin of the left vertebral artery, and an aberrant right subclavian artery. We then compared the prevalence of AAV in our stroke cohort with a control cohort of 808 patients. Results: AAV were found in 152 of all 1056 (14.4%) patients. There were AAV in 40/248 (16.1%) patients in the stroke group and 112/808 (13.9%) patients in the control group (p=0.374). The prevalence of AAV in the stroke and control cohort was as follows: bovine arch: 8.9% (22/248) versus 8.3% (67/808) (p=0.774); direct origin of the left vertebral artery from the aortic arch: 7.3% (18/248) versus 4.6% (37/808) (p=0.097); aberrant right subclavian artery: 0.8% (2/248) versus 1.2% (10/808) (p=0.742). Conclusion: The prevalence of aortic arch variants in patients with stroke in the anterior circulation is comparable to the prevalence in cohorts without stroke.
Evaluation of the Prognostic Value of FDG PET/CT Parameters for Patients With Surgically Treated Head and Neck Cancer: A Systematic Review.

Importance Head and neck squamous cell cancer (HNSCC) represents the seventh most frequent cancer worldwide. More than half of the patients diagnosed with HNSCC are treated with primary surgery. Objective To report the available evidence on the value of quantitative parameters of fluorodeoxyglucose F 18-labeled positron emission tomography and computed tomography (FDG-PET/CT) performed before surgical treatment of HNSCC to estimate overall survival (OS), disease-free survival (DFS), and distant metastasis (DM) and to discuss their limitations. Evidence Review A systematic review of the English-language literature in PubMed/MEDLINE and ScienceDirect published between January 2003 and February 15, 2019, was performed between March 1 and July 27, 2019, to identify articles addressing the association between preoperative FDG-PET/CT parameters and oncological outcomes among patients with HNSCC. Articles included those that addressed the following: (1) cancer of the oral cavity, oropharynx, hypopharynx, or larynx; (2) surgically treated (primary or for salvage); (3) pretreatment FDG-PET/CT; (4) quantitative or semiquantitative evaluation of the FDG-PET/CT parameters; and (5) the association between the value of FDG-PET/CT parameters and clinical outcomes. Quality assessment was performed using the Oxford Centre for Evidence-Based Medicine level of evidence. Findings A total of 128 studies were retrieved from the databases, and 36 studies met the inclusion criteria; these studies comprised 3585 unique patients with a median follow-up of 30.6 months (range, 16-53 months). Of these 36 studies, 32 showed an association between at least 1 FDG-PET/CT parameter and oncological outcomes (OS, DFS, and DM). The FDG-PET/CT volumetric parameters (metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) were independent prognostic factors in most of the data, with a higher prognostic value than the maximum standard uptake value (SUVmax). For example, in univariate analysis of OS, the SUVmax was correlated with OS in 5 of 11 studies, MTV in 11 of 12 studies, and TLG in 6 of 9 studies. The spatial distribution of metabolism via textural indices seemed promising, although that factor is currently poorly evaluated: only 3 studies analyzed data from radiomics indices. Conclusions and Relevance The findings of this study suggest that the prognostic effectiveness of FDG-PET/CT parameters as biomarkers of OS, DFS, and DM among patients with HNSCC treated with surgery may be valuable. The volumetric parameters (MTV and TLG) seemed relevant for identifying patients with a higher risk of postsurgical disease progression who could receive early therapeutic intervention to improve their prognosis. However, further large-scale studies including exclusively surgery-treated patients stratified according to localization and further analysis of the textural indices are required to define a reliable FDG-PET/CT-based prognostic model of mortality and recurrence risk for these patients.
A technical review and guide to RNA fluorescence in situ hybridization

RNA-fluorescence in situ hybridization (FISH) is a powerful tool to visualize target messenger RNA transcripts in cultured cells, tissue sections or whole-mount preparations. As the technique has been developed over time, an ever-increasing number of divergent protocols have been published. There is now a broad selection of options available to facilitate proper tissue preparation, hybridization, and post-hybridization background removal to achieve optimal results. Here we review the technical aspects of RNA-FISH, examining the most common methods associated with different sample types including cytological preparations and whole-mounts. We discuss the application of commonly used reagents for tissue preparation, hybridization, and post-hybridization washing and provide explanations of the functional roles for each reagent. We also discuss the available probe types and necessary controls to accurately visualize gene expression. Finally, we review the most recent advances in FISH technology that facilitate both highly multiplexed experiments and signal amplification for individual targets. Taken together, this information will guide the methods development process for investigators that seek to perform FISH in organisms that lack documented or optimized protocols.
A Gecko-Inspired Soft Passive Gripper

This paper presents a soft passive gripper consisting of six fluidic soft bending actuators arranged in a star-shaped manner. The actuators are oriented such that, upon pressurization, they bend against gravity. Gripping is realized by a commercial tape with mushroom-shaped adhesive structures that is glued to the bottom patches of the gripper. In this way, the object is released by peeling away the actuators from the object’s surface. In contrast to active grippers, which require continuous pressurization during gripping and holding, the presented passive gripper only requires energy for the release process. However, due to its working principle, the gripper is restricted to only flat objects or objects with at least one flat surface.
Novel, Non–Gene-Destructive Knock-In Reporter Mice Refute the Concept of Monoallelic Gata3 Expression

Key Points New Gata3 reporter mice allow noninvasive monitoring of Th2 polarization. Gata3-driven fluorescent marker expression highlights ILC2 progenitor cells. Patterns of reporter expression disprove claims of monoallelic Gata3 expression. Accurately tuned expression levels of the transcription factor GATA-3 are crucial at several stages of T cell and innate lymphoid cell development and differentiation. Moreover, several lines of evidence suggest that Gata3 expression might provide a reliable molecular marker for the identification of elusive progenitor cell subsets at the earliest stages of T lineage commitment. To be able to faithfully monitor Gata3 expression noninvasively at the single-cell level, we have generated a novel strain of knock-in reporter mice, termed GATIR, by inserting an expression cassette encoding a bright fluorescent marker into the 3′-untranslated region of the endogenous Gata3 locus. Importantly, in contrast to three previously published strains of Gata3 reporter mice, GATIR mice preserve physiological Gata3 expression on the targeted allele. In this study, we show that GATIR mice faithfully reflect endogenous Gata3 expression without disturbing the development of GATA-3–dependent lymphoid cell populations. We further show that GATIR mice provide an ideal tool for noninvasive monitoring of Th2 polarization and straightforward identification of innate lymphoid cell 2 progenitor populations. Finally, as our reporter is non–gene-destructive, GATIR mice can be bred to homozygosity, not feasible with previously published strains of Gata3 reporter mice harboring disrupted alleles. The availability of hetero- and homozygous Gata3 reporter mice with an exceptionally bright fluorescent marker, allowed us to visualize allelic Gata3 expression in individual cells simply by flow cytometry. The unambiguous results obtained provide compelling evidence against previously postulated monoallelic Gata3 expression in early T lineage and hematopoietic stem cell subsets.
Draft Genome Sequence of Desulfovibrio sulfodismutans ThAc01, a Heterotrophic Sulfur-Disproportionating Member of the Desulfobacterota

Here, we describe the genome of Desulfovibrio sulfodismutans ThAc01, a Desulfobacterota member first isolated from freshwater mud and the first strain reported to be capable of growth via sulfur disproportionation. As such, this genome expands our understanding of the diversity of sulfur-disproportionating microorganisms. ABSTRACT Here, we describe the genome of Desulfovibrio sulfodismutans ThAc01, a Desulfobacterota member first isolated from freshwater mud and the first strain reported to be capable of growth via sulfur disproportionation. As such, this genome expands our understanding of the diversity of sulfur-disproportionating microorganisms.
Mutation spectrum of PAX6 and clinical findings in 95 Chinese patients with aniridia

Purpose Aniridia is a rare congenital panocular disease caused by mutations in PAX6. The purposes of this study were to clarify the mutation features of PAX6 in a cohort of Chinese patients with aniridia and to describe their clinical characteristics. Methods We recruited 95 patients from 65 unrelated families clinically diagnosed with aniridia. All patients underwent ophthalmic examinations. Sanger sequencing and multiplex ligation probe amplification of PAX6 were performed to detect intragenic variants and copy number variations (CNVs). Results We identified 58 disease-causing mutations in PAX6 in 63 families; the detection rate was 96.9%. The 58 mutations included frameshift indels (27.6%), splice site changes (25.9%), nonsense mutations (20.7%), CNVs (19.0%), missense mutations (3.4%), run-on mutations (1.7%), and a synonymous mutation (1.7%). Clinical examinations revealed that 71 patients had complete or almost complete iris loss, 16 patients showed partial iris loss, and six patients had a full iris but with an abnormal structure. Conclusions The results confirmed that mutations in PAX6 are the predominant cause of aniridia, and the majority are loss-of-function mutations that usually result in classical aniridia. In contrast, missense mutations, run-on mutations, and small numbers of splicing mutations mostly lead to atypical aniridia and an intrafamilial phenotypic variability of iris hypoplasia.