Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing efficacy and safety in catheter ablation strategies for atrial fibrillation: protocol of a network meta-analysis of randomised controlled trials

Introduction Atrial fibrillation (AF) is the most common sustained arrhythmia. Catheter ablation (CA) of AF is an increasingly offered therapeutic approach, primary to relieve AF-related symptoms. Despite the development of new ablation approaches, there is no consensus regarding the most efficient ablation strategy. The objective of this network meta-analysis (NMA) is to compare the efficacy and safety of all different CA approaches for the treatment of patients with paroxysmal (PAF) and non-PAF (non-PAF). Methods and analysis We will perform a systematic search to identify randomised controlled trials of different CA approaches for the treatment of PAF and non-PAF, through the final search date of 1 March 2020. Information sources will include major bibliographic databases (MEDLINE, Web of Science and CENTRAL) and clinical trial registries. Our primary outcomes will be the efficacy (recurrence-free survival) and safety of different CA approaches for the treatment of AF. Secondary outcomes will be all-cause mortality and procedural time. An NMA will be performed to determine the relative effects of different catheter ablation approaches (such as pulmonary vein isolation alone or in combination with ablation lines, ablation of complex fractionated atrial electrograms, etc). In PAF, a separate analysis will be performed including different energy sources (such as radiofrequency, cryogenic and laser energy). Risk of bias assessment and sensitivity analyses will be conducted to assess the robustness of the findings to potential bias. Ethics and dissemination No ethical approval will be needed because data are collected from previous studies. The results will be presented through peer-review journals and conference presentation. PROSPERO registration number CRD42020169494.
Influence of VDR and HFE polymorphisms on blood lead levels of occupationally exposed workers

Lead is a ubiquitous heavy metal toxin of significant public health concern. Every individual varies in their response to lead’s toxic effects due to underlying genetic variations in lead metabolizing enzymes or proteins distributed in the population. Earlier studies, including our lab, have attributed the influence of ALAD (δ-Aminolevulinate dehydratase) polymorphism on blood lead retention and ALAD activity. The present study aimed to investigate the influence of VDR (Vitamin D receptor) and HFE (Hemochromatosis) polymorphisms in modulating blood lead levels (BLLs) of occupationally exposed workers. 164 lead-exposed subjects involved in lead alloy manufacturing and battery breaking and recycling processes and 160 unexposed controls with BLLs below 10 µg/dL recruited in the study. Blood lead levels, along with a battery of biochemical assays and genotyping, were performed. Regression analysis revealed a negative influence of BLLs on ALAD activity (p < 0.0001) and a positive influence on smokeless tobacco use (p < 0.001) in lead-exposed subjects. A predicted haplotype of the three VDR polymorphisms computed from genotyping data revealed that T-A-A haplotype increased the BLLs by 0.93 units (p ≤ 0.05) and C-C-A haplotype decreased the BLLs by 7.25 units (p ≤ 0.05). Further analysis revealed that the wild-type CC genotype of HFE H63D presented a higher median BLL, indicating that variant C allele may have a role in increasing the concentration of lead. Hence, the polymorphism of genes associated with lead metabolism might aid in predicting genetic predisposition to lead and its associated effects.
Population demographic history and population structure for Pakistani Nili-Ravi breeding bulls based on SNP genotyping to identify genomic regions associated with male effects for milk yield and body weight

The domestic Nili-Ravi water buffalo (Bubalus bubalis) is the best dairy animal contributing 68% to total milk production in Pakistan. In this study, we identified genome-wide single nucleotide polymorphisms (SNPs) to estimate various population genetic parameters such as diversity, pairwise population differentiation, linkage disequilibrium (LD) distribution and for genome-wide association study for milk yield and body weight traits in the Nili-Ravi dairy bulls that they may pass on to their daughters who are retained for milking purposes. The genotyping by sequencing approach revealed 13,039 reference genome-anchored SNPs with minor allele frequency of 0.05 among 167 buffalos. Population structure analysis revealed that the bulls were grouped into two clusters (K = 2), which indicates the presence of two different lineages in the Pakistani Nili-Ravi water buffalo population, and we showed the extent of admixture of these two lineages in our bull collection. LD analysis revealed 4169 significant SNP associations, with an average LD decay of 90 kb for these buffalo genome. Genome-wide association study involved a multi-locus mixed linear model for milk yield and body weight to identify genome-wide male effects. Our study further illustrates the utility of the genotyping by sequencing approach for identifying genomic regions to uncover additional demographic complexity and to improve the complex dairy traits of the Pakistani Nili-Ravi water buffalo population that would provide the lot of economic benefits to dairy industry.
Neural Decoding of Imagined Speech and Visual Imagery as Intuitive Paradigms for BCI Communication

Brain-computer interface (BCI) is oriented toward intuitive systems that users can easily operate. Imagined speech and visual imagery are emerging paradigms that can directly convey a user’s intention. We investigated the underlying characteristics that affect the decoding performance of these two paradigms. Twenty-two subjects performed imagined speech and visual imagery of twelve words/phrases frequently used for patients’ communication. Spectral features were analyzed with thirteen-class classification (including rest class) using EEG filtered in six frequency ranges. In addition, cortical regions relevant to the two paradigms were analyzed by classification using single-channel and pre-defined cortical groups. Furthermore, we analyzed the word properties that affect the decoding performance based on the number of syllables, concrete and abstract concepts, and the correlation between the two paradigms. Finally, we investigated multiclass scalability in both paradigms. The high-frequency band displayed a significantly superior performance to that in the case of any other spectral features in the thirteen-class classification (imagined speech: 39.73 ± 5.64%; visual imagery: 40.14 ± 4.17%). Furthermore, the performance of Broca’s and Wernicke’s areas and auditory cortex was found to have improved among the cortical regions in both paradigms. As the number of classes increased, the decoding performance decreased moderately. Moreover, every subject exceeded the confidence level performance, implying the strength of the two paradigms in BCI inefficiency. These two intuitive paradigms were found to be highly effective for multiclass communication systems, having considerable similarities between each other. The results could provide crucial information for improving the decoding performance for practical BCI applications.
NMR in Organometallic Chemistry

Preface XI Abbreviations XIII 1 Introduction 1 2 Routine Measuring and Relaxation 7 3 COSY and HMQC 2-D Sequences 19 4 Overhauser Effects and 2-D NOESY 39 5 Diffusion Constants via NMR Measurements 55 6 Chemical Shifts 63 7 Coupling Constants 207 8 Dynamics 279 9 Preface to the Problems 311 10 Organometallic Introduction 313 11 NMR Problems 319 12 Solutions to the Problems and Comments 361 Index 389
Short-duration splice promoting compound enables a tunable mouse model of spinal muscular atrophy

We describe drug treatment paradigms that allow investigation of cellular and molecular pathogenesis at different stages of spinal muscular atrophy in a mouse model. Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality. SMA results from insufficient survival motor neuron (SMN) protein due to alternative splicing. Antisense oligonucleotides, gene therapy and splicing modifiers recently received FDA approval. Although severe SMA transgenic mouse models have been beneficial for testing therapeutic efficacy, models mimicking milder cases that manifest post-infancy have proven challenging to develop. We established a titratable model of mild and moderate SMA using the splicing compound NVS-SM2. Administration for 30 d prevented development of the SMA phenotype in severe SMA mice, which typically show rapid weakness and succumb by postnatal day 11. Furthermore, administration at day eight resulted in phenotypic recovery. Remarkably, acute dosing limited to the first 3 d of life significantly enhanced survival in two severe SMA mice models, easing the burden on neonates and demonstrating the compound as suitable for evaluation of follow-on therapies without potential drug–drug interactions. This pharmacologically tunable SMA model represents a useful tool to investigate cellular and molecular pathogenesis at different stages of disease.
Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells

Enrichment of angiomotin (AMOT) in the ectoplacental cone of E7.5 murine placenta prompted our investigation on the role of AMOT in trophoblast differentiation. We show here that AMOT levels increased in mouse placenta during gestation and also upon induction of differentiation in trophoblast stem cell ex vivo. Proteomic data unravelling AMOT‐interactome in trophoblast cells indicated a majority of AMOT interactors to be involved in protein translation. In‐depth analysis of AMOT‐interactome led to identification of eukaryotic translation initiation factor 4A (eIF4A) as the most plausible AMOT interactor. Loss of function of AMOT enhanced, whereas, gain in function resulted in decline of global protein synthesis in trophoblast cells. Bioinformatics analysis evaluating the potential energy of AMOT‐eIF4A binding suggested a strong AMOT‐eIF4A interaction using a distinct groove encompassing amino acid residue positions 238 to 255 of AMOT. Co‐immunoprecipitation of AMOT with eIF4A reaffirmed AMOT‐eIF4A association in trophoblast cells. Deletion of 238 to 255 amino acids of AMOT resulted in abrogation of AMOT‐eIF4A interaction. In addition, 238 to 255 amino acid deletion of AMOT was ineffective in eliciting AMOT's function in reducing global protein synthesis. Interestingly, AMOT‐dependent sequestration of eIF4A dampened its loading to the m7‐GTP cap and hindered its interaction with eIF4G. Furthermore, enhanced AMOT expression in placenta was associated with intrauterine growth restriction in both rats and humans. These results not only highlight a hitherto unknown novel function of AMOT in trophoblast cells but also have broad biological implications as AMOT might be an inbuilt switch to check protein synthesis in developmentally indispensable trophoblast cells.
Mortality Patterns Among Industrial Workers Exposed to Chloroprene and Other Substances: Extended Follow-Up.

OBJECTIVES To update the U.S. portion of an historical cohort mortality study of workers with potential exposure to chloroprene (CD) and vinyl chloride (VC) with focus on lung and liver cancer. METHODS Subjects were 6,864 workers from two sites with vital status determined through 2017 for 99% of subjects and cause of death for 97.2% of deaths. Historical exposures to CD and VC were estimated quantitatively. We performed external and internal mortality comparisons. RESULTS External comparisons revealed mostly deficits in deaths; internal comparisons revealed no consistent evidence of exposure-response relationships with CD or VC. CONCLUSIONS Our update continues to support the conclusion that the risk of death from lung or liver cancer is unrelated to exposure to CD or VC at levels experienced by workers in the two U.S. sites.
Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B Signaling Controls Excitability and Long-Term Depression in Oval Nucleus of the BNST

Dysregulation of proteins involved in synaptic plasticity is associated with pathologies in the CNS, including psychiatric disorders. The bed nucleus of the stria terminalis (BNST), a brain region of the extended amygdala circuit, has been identified as the critical hub responsible for fear responses related to stress coping and pathologic systems states. Here, we report that one particular nucleus, the oval nucleus of the BNST (ovBNST), is rich in brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptor. Whole-cell patch-clamp recordings of neurons from male mouse ovBNST in vitro showed that the BDNF/TrkB interaction causes a hyperpolarizing shift of the membrane potential from resting value, mediated by an inwardly rectifying potassium current, resulting in reduced neuronal excitability in all major types of ovBNST neurons. Furthermore, BDNF/TrkB signaling mediated long-term depression (LTD) at postsynaptic sites in ovBNST neurons. LTD of ovBNST neurons was prevented by a BDNF scavenger or in the presence of TrkB inhibitors, indicating the contribution to LTD induction. Our data identify BDNF/TrkB signaling as a critical regulator of synaptic activity in ovBNST, which acts at postsynaptic sites to dampen excitability at short and long time scales. Given the central role of ovBNST in mediating maladaptive behaviors associated with stress exposure, our findings suggest a synaptic entry point of the BDNF/TrkB system for adaptation to stressful environmental encounters.
Usefulness of controlled attenuation parameter and liver stiffness measurement for detecting increased arterial stiffness in asymptomatic populations in China

Abstract In recent studies, vibration-controlled transient elastography (FibroScan) has been reported as an alternative noninvasive approach for measuring liver steatosis and fibrosis. The present study aimed to investigate the feasibility of FibroScan controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) in the detection of increased arterial stiffness in asymptomatic populations in China. A retrospective cohort recruiting 4747 asymptomatic patients with no underlying causes of liver disease and having FibroScan and brachial-ankle pulse wave velocity (baPWV) during wellness check-up was covered. Nonalcoholic fatty liver disease (NAFLD) was defined as a CAP ≥238 dB/m. NAFLD with significant fibrosis was defined as an LSM ≥7.3 kPa in the presence of NAFLD. Increased arterial stiffness was determined as a BaPWV ≥1.4m/second. Among the 4747 study participants, 1596 subjects (33.6%) suffered from increased arterial stiffness. The prevalence of increased arterial stiffness progressively increased across CAP quartiles and LSM quartiles in NAFLD (23.5%, 30.8%, 38.3%, 43.7%, P < .001 and 33.1%, 36.8%, 40.4%, 48.2%, P < .001, respectively). After conventional cardiovascular risk factors were adjusted (age, sex, overweight, diabetes mellitus, hypertension, hypercholesterolemia, and current smoking habits), multivariate logistic regression analysis revealed that CAP (odd ratio [OR] = 1.005; 95% confidence interval [CI]: 1.003–1.006; P < .001), NAFLD (OR = 1.427; 95% CI: 1.212–1.681; P < .001), LSM in NAFLD (OR = 1.073; 95% CI: 1.023–1.125; P = .003), and significant fibrosis in NAFLD (OR = 1.480; 95% CI: 1.090–2.010; P = .012) were independently associated with increased arterial stiffness. Furthermore, in a multivariate logistic regression analysis, OR (95% CI) for the maximal vs. the minimal quartile of CAP was 1.602 (1.268–2.024), and that of LSM in NAFLD was 1.362 (1.034–1.792) after adjustment for the above-mentioned risk factors. Notably, NAFLD and significant fibrosis in NAFLD were significantly correlated only with increased arterial stiffness in subjects without hypertension or diabetes mellitus after adjustment for the above-mentioned risk factors. CAP-defined NAFLD and LSM-defined significant fibrosis in NAFLD showed significant and independent relationships with increased arterial stiffness even after adjustment for conventional cardiovascular risk factors, which can be conducive to stratifying relative risk of subjects having undergone screening assessment for cardiovascular disease.
A Novel Surface-Exposed Polypeptide Is Successfully Employed as a Target for Developing a Prototype One-Step Immunochromatographic Strip for Specific and Sensitive Direct Detection of Staphylococcus aureus Causing Neonatal Sepsis

Neonatal sepsis is a life-threatening condition and Staphylococcus aureus is one of its major causes. However, to date, no rapid and sensitive diagnostic tool has been developed for its direct detection. Bioinformatics analyses identified a surface-exposed 112-amino acid polypeptide of the cell wall protein NWMN_1649, a surface protein involved in cell aggregation and biofilm formation, as being a species-specific and highly conserved moiety. The polypeptide was cloned, purified, and used to immunize mice to raise specific immunoglobulins. The purified antibodies were conjugated to gold nano-particles and used to assemble an immunochromatographic strip (ICS). The developed prototype ICS detected as low as 5 µg purified polypeptide and 102 CFU/mL S. aureus within 15 min. The strip showed superior ability to directly detect S. aureus in neonatal sepsis blood specimens without prior sample processing. Moreover, it showed no cross-reaction in specimens infected with two other major causes of neonatal sepsis; coagulase-negative staphylococci and Klebsiella pneumoniae. The selected NWMN_1649-derived polypeptide demonstrates success as a promising biomolecule upon which a prototype ICS has been developed. This ICS provides a rapid, direct, sensitive, and specific option for the detection of S. aureus causing neonatal sepsis. Such a tool is urgently needed especially in resources-limited countries.
The deubiquitinase USP36 Regulates DNA replication stress and confers therapeutic resistance through PrimPol stabilization

Abstract PrimPol has been recently identified as a DNA damage tolerant polymerase that plays an important role in replication stress response. However, the regulatory mechanisms of PrimPol are not well defined. In this study, we identify that the deubiquitinase USP36 interferes with degradation of PrimPol to regulate the replication stress response. Mechanistically, USP36 is deubiquitinated following DNA replication stress, which in turn facilitates its upregulation and interaction with PrimPol. USP36 deubiquitinates K29-linked polyubiquitination of PrimPol and increases its protein stability. Depletion of USP36 results in replication stress-related defects and elevates cell sensitivity to DNA-damage agents, such as cisplatin and olaparib. Moreover, USP36 expression positively correlates with the level of PrimPol protein and poor prognosis in patient samples. These findings indicate that the regulation of PrimPol K29-linked ubiquitination by USP36 plays a critical role in DNA replication stress and chemotherapy response.
Evolutive Models for the Geometry and Heat Conductivity of an Intumescent EVA-ATH Composite during Its Thermal Degradation

Reliable predictions from numerical simulations in fire safety applications require knowledge of the combustible materials’ properties in their initial and thermally degraded states. The thermal conductivity of the sheath material of electrical cables, present in massive amounts in industrial plants, is addressed here. An evolutive conceptual model is proposed for the morphology of this intumescent polymer composite during its thermal degradation. It accounts for the multiscale structure and anisotropy observed during a thorough characterization based on tomographic images of samples at representative stages of the degradation. The evolution of the geometrical characteristics during the process is linked to chemical advancement parameters according to a reasoned scenario based on physical arguments and balance considerations. The anisotropic thermal conductivity tensor can be deduced from the geometry by a nested application of classical models. Ultimately, the conductivity is obtained as an analytic function of the chemical advancement and temperature. The model predictions were validated by comparisons with direct numerical solutions of thermal problems in the fully described geometry provided by the tomographies, and with measurements from the literature. The methodology and conceptual tools can be of interest for the treatment of other materials and in other contexts of application.
The importance of food systems and the environment for nutrition

ABSTRACT Global and local food system transformation is necessary in order to ensure the delivery of healthy, safe, and nutritious foods in both sustainable and equitable ways. Food systems are complex entities that affect diets, human health, and a range of other outcomes including economic growth, natural resource and environmental resiliency, and sociocultural factors. However, food systems contribute to and are vulnerable to ongoing climate and environmental changes that threaten their sustainability. Although there has been increased focus on this topic in recent years, many gaps in our knowledge persist on the relation between environmental factors, food systems, and nutritional outcomes. In this article, we summarize this emerging field and describe what innovative nutrition research is needed in order to bring about food policy changes in the era of climate disruption and environmental degradation.
Extracellular Vesicles Derived from Kefir Grain Lactobacillus Ameliorate Intestinal Inflammation via Regulation of Proinflammatory Pathway and Tight Junction Integrity

The aim of this study was to demonstrate the anti-inflammatory effect of Lactobacillus kefirgranum PRCC-1301-derived extracellular vesicles (PRCC-1301 EVs) on intestinal inflammation and intestinal barrier function. Human intestinal epithelial cells (IECs) Caco-2 were treated with PRCC-1301 EVs and then stimulated with dextran sulfate sodium (DSS). Real-time RT-PCR revealed that PRCC-1301 EVs inhibited the expression of pro-inflammatory cytokines in Caco-2 cells. PRCC-1301 EVs enhanced intestinal barrier function by maintaining intestinal cell integrity and the tight junction. Loss of Zo-1, claudin-1, and occludin in Caco-2 cells and the colitis tissues was recovered after PRCC-1301 EVs treatment, as evidenced by immunofluorescence analysis. Acute murine colitis was induced using 4% DSS and chronic colitis was generated in piroxicam-treated IL-10-/- mice. PRCC-1301 EVs attenuated body weight loss, colon shortening, and histological damage in acute and chronic colitis models in mice. Immunohistochemistry revealed that phosphorylated NF-κB p65 and IκBα were reduced in the colon tissue sections treated with PRCC-1301 EVs. Our results suggest that PRCC-1301 EVs may have an anti-inflammatory effect on colitis by inhibiting the NF-κB pathway and improving intestinal barrier function.