Miracle-dz/UniFAR-FTUs huggingface dataset:
Unusual variants of pre‐excitation: From anatomy to ablation: Part I—Understanding the anatomy of the variants of ventricular pre‐excitation

The famous quotation of Winston Churchill, made in his radio broadcast of 1939 regarding Russia's next move, specifically “A riddle wrapped up in a mystery, inside an enigma,” perfectly fits the current understanding of unusual accessory atrioventricular pathways, including the variants producing ventricular pre‐excitation. It was many decades after their original descriptions that we came better to begin to understand most of their structure‐function relationships. Their mysterious pathophysiology was sometimes unveiled after invasive treatments, such as surgical ablation of the atrioventricular conduction axis instead of the accessory pathway itself. Speculations made on this basis have largely been validated by subsequent clinical experience. Most of the names suggested for description of the pathways have stood well the test of time. For some of them, however, this is not the case, with the initial names becoming confusing. In a series of reviews, we re‐visit those accessory pathways producing ventricular pre‐excitation other than classical Wolff‐Parkinson‐White syndrome. To set the scene, in this initial review, we describe the development and anatomy of the normal atrioventricular conduction axis, along with the insulating tissues of the atrioventricular junctions. We have sought to illustrate our explanations by using virtual dissection of computerized tomographic datasets, since they retain the intact heart within the setting of the body. These images illustrate well the value of attitudinally appropriate terminology. Thereafter, we discuss the electrophysiological manifestations of the abnormal anatomical pathways which provide the potential for both accessory atrioventricular and intraventricular conduction.
Preclinical Studies of Neuroplasticity Following Experimental Brain Injury.

A significant challenge in the care of stroke survivors is chronic functional deficits that limit activities of daily living. Despite substantial functional recovery that can occur in the initial weeks following a stroke, over 50% of stroke survivors exhibit hemiparesis 6 months after stroke, which is particularly significant because motor recovery plateaus after 3–6 months. Because of the compelling need to reduce the burden of these chronic deficits, there is great interest in understanding the specific relationships between neuroplasticity and functional recovery. Although fully understanding these mechanisms will necessarily require clinical research in human cohorts, studies utilizing experimental animal models of brain injury are valuable because preclinical studies provide the ability to induce repeatable lesions, to control the specific environmental exposures that animals receive including the amount of rehabilitative training, to test novel therapies or medications, and to examine the structural and functional changes in cortical organization at different time points. Here, we review recent advances that have informed our understanding of neuroplasticity following experimental models of brain injury. Initially, we will review the impact of rehabilitation on functional recovery. Next, we will describe the functional and structural reorganization that is associated with rehabilitation and discuss the functional relevance of specific patterns of reorganization. Finally, we will conclude by describing preclinical evidence for several novel therapies designed to enhance neuroplasticity that span various stages of development towards clinical trials.
Carriage and potential long distance transmission of Listeria monocytogenes by migratory black-headed gulls in Dianchi Lake, Kunming

ABSTRACT Listeria monocytogenes is a high risk pathogen which can cause invasive diseases in humans. We previously reported that black-headed gulls from Dianchi Lake of Kunming carrying L. monocytogenes, while the characteristics of these isolates and the relationship with habitats of migratory gulls have not been explored. In this study, we investigated the prevalence and molecular characteristics of Listeria monocytogenes from black-headed gulls in Dianchi Lake, and phylogenetic analysis based on core genome SNPs was used to determine the genetic relationship of the strains from Dianchi Lake and other regions. Occurrence of L. monocytogenes in black-headed gull feces in 2016, 2017 and 2018 was 1.0%, 1.0% and 0.6% respectively. The predominant serotype of 28 isolates was 4b, while the predominant sequence types were ST145 and ST201. Based on their prevalence and genomic relationships, ST5 and ST87 were likely to be sourced locally while ST145 and ST201 were likely to be non-local. L. monocytogenes may travel along the bird migration route leading to transmission over a large geographical span carried by black-headed gull. Although the prevalence of L. monocytogenes was low, its carriage by the migratory black-headed gulls poses potential public health risks in regions where the migratory birds passage and reside.
Enhanced Adsorptive Properties and Pseudocapacitance of Flexible Polyaniline-Activated Carbon Cloth Composites Synthesized Electrochemically in a Filter-Press Cell

Electrochemical polymerization is known to be a suitable route to obtain conducting polymer-carbon composites uniformly covering the carbon support. In this work, we report the application of a filter-press electrochemical cell to polymerize polyaniline (PAni) on the surface of large-sized activated carbon cloth (ACC) by simple galvanostatic electropolymerization of an aniline-containing H2SO4 electrolyte. Flexible composites with different PAni loadings were synthesized by controlling the treatment time and characterized by means of Scanning Electron microscopy (SEM), X-Ray Photoelectron Spectroscopy (XPS), physical adsorption of gases, thermogravimetric analysis (TGA), cyclic voltammetry and direct current (DC) conductivity measurements. PAni grows first as a thin film mostly deposited inside ACC micro- and mesoporosity. At prolonged electropolymerization time, the amount of deposited PAni rises sharply to form a brittle and porous, thick coating of nanofibrous or nanowire-shaped structures. Composites with low-loading PAni thin films show enhanced specific capacitance, lower sheet resistance and faster adsorption kinetics of Acid Red 27. Instead, thick nanofibrous coatings have a deleterious effect, which is attributed to a dramatic decrease in the specific surface area caused by strong pore blockage and to the occurrence of contact electrical resistance. Our results demonstrate that mass-production restrictions often claimed for electropolymerization can be easily overcome.
Supplementation with Synbiotics and/or Branched Chain Amino Acids in Hepatic Encephalopathy: A Pilot Randomised Placebo-Controlled Clinical Study

Introduction: Hepatic encephalopathy (HE) is common in patients with cirrhosis and is characterised by reduced hepatic ammonia clearance. This is accompanied by alterations in gut bacteria that may be ameliorated with synbiotics (pro- and prebiotics). Branched chain amino acids (BCAAs) are thought to have a role in the detoxification of ammonia. We investigated the effects of the administration of synbiotics and/or BCAAs in treating HE. Methods: Participants with overt HE were randomised in a blinded placebo-controlled study to receive synbiotics, BCAAs, or a combination of BCAAs and Synbiotics. Relevant biochemical and nutritional data and depression and anxiety scores (DASS-21) were collected at entry, 4 weeks, and on completion, at 8 weeks. The Trail Making Test (TMT) and Inhibitory Control Test (ICT) were used to assess cognitive function in patients withHE. Results were analysed using linear mixed effects regression analyses. Results: Sixty-one participants were enrolled and 49 who returned for at least 1 follow-up review were included in the intention to treat analysis. The mean age was 55.8 ± 6.1 years and 86% were males. Despite evidence of a placebo effect, there was significant improvement in TMT B and ICT weighted lures in participants who received combined synbiotics/BCAAs treatment compared to placebo at study completion (p ≤ 0.05). Cognitive improvement occurred without a significant change in ammonia levels. Conclusion: To our knowledge, this is the first study reporting that combined synbiotics and BCAAs improve HE, and that may be beneficial in the management of HE. A larger study is needed to confirm these results.
Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.

Parathyroid hormone (PTH)-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in the urine including its potential relationship with the renal function. Herein, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot, we could detect a single protein band, corresponding to intact PTHrP in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot-blot, and its quantification with two specific ELISA kits showed that, in comparison to control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as PTHrP to creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in the rat urine, and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.
The Effect of Dietary Supplementation of Crocetin for Myopia Control in Children: A Randomized Clinical Trial

The prevalence of myopia has been increasing in recent years. The natural carotenoid crocetin has been reported to suppress experimental myopia in mice. We evaluated the effects of crocetin on myopia suppression in children. A multicenter randomized double-blind placebo-controlled clinical trial was performed with 69 participants aged 6 to 12 years, whose cycloplegic spherical equivalent refractions (SER) were between −1.5 and −4.5 diopter (D). The participants were randomized to receive either a placebo or crocetin and followed up for 24 weeks. Axial length (AL) elongation and changes in SER were evaluated for 24 weeks. Both written informed assent from the participants and written informed consent from legal guardians were obtained in this study because the selection criteria of this trial included children aged between 6 and 12 years old. This trial was approved by the institutional review boards. A mixed-effects model was used for analysis, using both eyes. Two participants dropped out and 67 children completed this trial. The change in SER in the placebo group, −0.41 ± 0.05 D (mean ± standard deviation), was significantly more myopic compared to that in the crocetin group, −0.33 ± 0.05 D (p = 0.049). The AL elongation in the placebo group, 0.21 ± 0.02 mm, was significantly bigger than that in the crocetin group, 0.18 ± 0.02 mm (p = 0.046). In conclusion, dietary crocetin may have a suppressive effect on myopia progression in children, but large-scale studies are required in order to confirm this effect.
MicroRNA-361: A Multifaceted Player Regulating Tumor Aggressiveness and Tumor Microenvironment Formation

MicroRNA-361-5p (miR-361) expression frequently decreases or is lost in different types of cancers, and contributes to tumor suppression by repressing the expression of its target genes implicated in tumor growth, epithelial-to-mesenchymal transition (EMT), metastasis, drug resistance, glycolysis, angiogenesis, and inflammation. Here, we review the expression pattern of miR-361 in human tumors, describe the mechanisms responsible for its dysregulation, and discuss how miR-361 modulates the aggressive properties of tumor cells and alter the tumor microenvironment by acting as a novel tumor suppressor. Furthermore, we describe its potentials as a promising diagnostic or prognostic biomarker for cancers and a promising target for therapeutic development.
End-Users and Caregivers’ Involvement in Health Interventional Research Carried Out in Geriatric Facilities: A Systematic Review

Public involvement (PI) is of great interest. However, little is known about this topic in the design, development, and/or implementation of health interventions in geriatric facilities. This study aimed to provide a critical overview of the involvement of caregivers and end-users in interventions in these facilities, based on Rifkin’s analytical framework. This systematic review, supplemented by a questionnaire to the corresponding authors, covered non-drug intervention reports targeting nurses, doctors, residents, and their relatives. Articles were published in Pubmed, Medline, Scopus, and Cinahl, from January 2016 to April 2018. Ninety-seven articles were included. The review shows a low level or partial PI in geriatric facilities where it exists. These results are further supported by the authors’ responses to the questionnaire. PI remains uncommon in geriatric institutions and consists of a consumerist model, suggesting the need for improved practices. More efforts are needed to experiment with recommendations to meet the challenges of PI and enhance the public ownership of interventions. The protocol was registered on Prospero under the number CRD42018098504.
Response to commentaries on our review of Fast Mapping in adults

ABSTRACT We thank all the commentators for their thoughts on our review of Fast Mapping (FM) in adults, where we questioned the evidence that FM is a distinct learning mechanism, and urged caution over the excitement generated by the original report of FM in adults with amnesia using the fast mapping paradigm (FMP) . While some commentators remain convinced that there is good evidence to support a FM process in adults, most reported a skepticism similar to ours. Here we respond to the main comments, and clarify some of the terms of debate.
Forced Degradation Studies to Identify Critical Process Parameters for the Purification of Infectious Measles Virus

Oncolytic measles virus (MV) is a promising treatment for cancer but titers of up to 1011 infectious particles per dose are needed for therapeutic efficacy, which requires an efficient, robust, and scalable production process. MV is highly sensitive to process conditions, and a substantial fraction of the virus is lost during current purification processes. We therefore conducted forced degradation studies under thermal, pH, chemical, and mechanical stress to determine critical process parameters. We found that MV remained stable following up to five freeze–thaw cycles, but was inactivated during short-term incubation (< 2 h) at temperatures exceeding 35 °C. The infectivity of MV declined at pH < 7, but was not influenced by different buffer systems or the ionic strength/osmolality, except high concentrations of CaCl2 and MgSO4. We observed low shear sensitivity (dependent on the flow rate) caused by the use of a peristaltic pump. For tangential flow filtration, the highest recovery of MV was at a shear rate of ~5700 s−1. Our results confirm that the application of forced degradation studies is important to identify critical process parameters for MV purification. This will be helpful during the early stages of process development, ensuring the recovery of high titers of active MV particles after purification.
Randomized Controlled Trial on the Effects of Morning versus Evening Primary Vaccination on Episodes of Hypoxemia and Bradycardia in Very Preterm Infants

Background: Hypoxemia and bradycardia occur frequently in preterm infants, but are incompletely understood. They are more prevalent during infections and following immunization. Data on adults suggested an increased immune response if subjects slept following vaccination, suggesting an interaction between circadian rhythm and the immune system. Whether this holds true for preterm infants with their less well-established circadian rhythm is unclear. Objective: Do infants born at 26–30 weeks’ gestation and having received their first routine hexavalent vaccination in the morning have a lower cardiorespiratory event rate (CER) after vaccination than those receiving it in the evening? Methods: Twenty-six infants were randomized to an evening versus morning vaccination group in a pilot and main study with 10 and 16 participants, respectively. Pulse oximeter saturation, actigraphy, and rectal temperature were obtained for 24 h before and after vaccination. Blood samples for vaccination titers were taken before vaccination and during a follow-up examination in our outpatient clinic; another blood sample was taken 24 h after vaccination to determine inflammatory markers. Results: Vaccination led to an increase in CER in both groups, but there was no difference in CER between the morning and evening groups. Vaccination titers for Bordetella pertussis were increased in both groups, with no difference in inflammatory markers 24 h after vaccination. Body temperature increased in both groups after vaccination. Participants in the evening group slept longer after vaccination. Conclusions: We did not identify a difference in CER between morning and evening vaccination but could confirm increased body temperatures and vaccination titers following vaccination.
Arrhythmia mechanisms and spontaneous calcium release: Bi-directional coupling between re-entrant and focal excitation

Spontaneous sub-cellular calcium release events (SCRE) are conjectured to promote rapid arrhythmias associated with conditions such as heart failure and atrial fibrillation: they can underlie the emergence of spontaneous action potentials in single cells which can lead to arrhythmogenic triggers in tissue. The multi-scale mechanisms of the development of SCRE into arrhythmia triggers, and their dynamic interaction with the tissue substrate, remain elusive; rigorous and simultaneous study of dynamics from the nanometre to the centimetre scale is a major challenge. The aim of this study was to develop a computational approach to overcome this challenge and study potential bi-directional coupling between sub-cellular and tissue-scale arrhythmia phenomena. A framework comprising a hierarchy of computational models was developed, which includes detailed single-cell models describing spatio-temporal calcium dynamics in 3D, efficient non-spatial cell models, and both idealised and realistic tissue models. A phenomenological approach was implemented to reproduce SCRE morphology and variability in the efficient cell models, comprising the definition of analytical Spontaneous Release Functions (SRF) whose parameters may be randomly sampled from appropriate distributions in order to match either the 3D cell models or experimental data. Pro-arrhythmogenic pacing protocols were applied to initiate re-entry and promote calcium overload, leading to the emergence of SCRE. The SRF accurately reproduced the dynamics of SCRE and its dependence on environment variables under multiple different conditions. Sustained re-entrant excitation promoted calcium overload, and led to the emergence of focal excitations after termination. A purely functional mechanism of re-entry and focal activity localisation was demonstrated, related to the unexcited spiral wave core. In conclusion, a novel approach has been developed to dynamically model SCRE at the tissue scale, which facilitates novel, detailed multi-scale mechanistic analysis. It was revealed that complex re-entrant excitation patterns and SCRE may be bi-directionally coupled, promoting novel mechanisms of arrhythmia perpetuation.
The pathogenicity of duck hepatitis A virus types 1 and 3 on ducklings

Duck hepatitis A virus (DHAV) is one of the pathogens that cause fatal duck viral hepatitis (DVH) in ducklings, which is an acute and contagious disease with a high mortality rate. Despite a continuing official duck vaccination program, DHAV infection remains a major threat to the duck industry. Considerable changes were observed in the epidemiology of DHAV-1/-3 in China over time. Therefore, comparing the pathogenicity of different DHAV serotypes can provide a theoretical basis for the diagnosis and prevention of DVH. In this study, we systematically investigated the effects of infection with DHAV-1/-3 field strains on clinical signs, gross lesions, histopathological changes, viral RNA detection, enzymatic systems, and metabolite concentrations. The results demonstrated that the major macroscopic and microscopic lesions in ducks infected with DHAV-1/-3 in the liver, brain, spleen, pancreas, and kidneys exhibited no significant differences. After 24 h of infection, DHAV quickly appeared in blood and major organs. Significant changes in clinical chemical markers together with histopathological lesions and viral RNA detection indicated that the liver is the major target organ for both viruses, resulting in impaired of liver integrity and function. In addition, we found that both viruses were able to invade both central and peripheral immune organs. Also lipase plasma activity was substantially affected by DHAV-1/-3, indicating that the integrity and function of the pancreas was compromised. However, there was no significant difference in pathogenicity between DHAV-1 and -3. The results of this study provide new insights into the pathogenesis of DHAV-1/3, two viruses that cause serious depression, metabolic disorders, and immunosuppression.
Accurate identification of myocardial viability after myocardial infarction with novel manganese chelate‐based MR imaging

We developed a novel manganese (Mn2+) chelate for magnetic resonance imaging (MRI) assessment of myocardial viability in acute and chronic myocardial infarct (MI) models, and compared it with Gadolinium‐based delay enhancement MRI (Gd3+‐DEMRI) and histology. MI was induced in 14 rabbits by permanent occlusion of the left circumflex coronary artery. Gd3+‐DEMRI and Mn2+ chelate‐based delayed enhancement MRI (Mn2+ chelate‐DEMRI) were performed at 7 days (acute MI, n = 8) or 8 weeks (chronic MI, n = 6) after surgery with sequential injection of 0.15 mmol/kg Gd3+ and Mn2+ chelate. The biodistribution of Mn2+ in tissues and blood was measured at 1.5 and 24 h. Blood pressure, heart rate (HR), left ventricular (LV) function, and infarct fraction (IF) were analyzed, and IF was compared with the histology. The Mn2+ chelate group maintained a stable hemodynamic status during experiment. For acute and chronic MI, all rabbits survived without significant differences in HR or LV function before and after injection of Mn2+ chelate or Gd3+ (p > 0.05). Mn2+ chelate mainly accumulated in the kidney, liver, spleen, and heart at 1.5 h, with low tissue uptake and urine residue at 24 h after injection. In the acute MI group, there was no significant difference in IF between Mn2+ chelate‐DEMRI and histology (22.92 ± 2.21% vs. 21.79 ± 2.25%, respectively, p = 0.87), while Gd3+‐DEMRI overestimated IF, as compared with histology (24.54 ± 1.73%, p = 0.04). In the chronic MI group, there was no significant difference in IF between the Mn2+ chelate‐DEMRI, Gd3+‐DEMRI, and histology (29.50 ± 11.39%, 29.95 ± 9.40%, and 29.00 ± 10.44%, respectively, p > 0.05), and all three were well correlated (r = 0.92–0.96, p < 0.01). We conclude that the use of Mn2+ chelate‐DEMRI is reliable for MI visualization and identifies acute MI more accurately than Gd3+‐DEMRI.