Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cardiac Gap Junction has Discrete Functions in Electrotonic and Ephaptic Coupling

Connexin43‐formed gap junctions have long been thought to contribute to cardiac conduction in the mammalian ventricle by providing direct electrotonic connectivity between the cytoplasms of neighboring cardiomyocytes. However, accumulating data from studies of non‐mammalian hearts, Connexin 43 (Cx43) knockout mice and human Cx43 mutations have raised questions as to whether gap junctions are the sole means by which electrical coupling between cardiomyocytes is accomplished. Computational and experimental work over the last decade have indicated that intercellular propagation of action potentials in the heart may involve both electrotonic and ephaptic contributions—in what has been dubbed “mixed‐mode” conduction. Interestingly, the Cx43 gap junction may provide a common structural platform in mammals that facilitates the operation of these two mechanisms. In addition to gap junction channels functioning in an electrotonic role, the perinexus region at the edge of gap junctions may be provide a niche for voltage‐gated sodium channels from neighboring cells to be in sufficiently close proximity to enable ephaptic transmission of action potential. A novel role has recently been identified in this potential ephaptic mechanism for inter‐membrane adhesion mediated by the beta subunit (beta1/Scn1b) of the sodium channel. The new perspective of the operational redundancy that is built into cardiac electrical connectivity could provide new understanding of arrhythmia mechanisms and holds the promise for new approach to anti‐arrhythmic therapy. Anat Rec, 302:93–100, 2019. © 2018 Wiley Periodicals, Inc.
Theranostic molecular profiling of pleomorphic ductal carcinoma of the breast

Pleomorphic ductal carcinoma (PDC) is a very rare subtype of invasive ductal carcinoma of no‐special type (NST), characterized by the presence of highly atypical/bizarre (>6‐fold variation in nuclear size) and multinucleated (giant) neoplastic cells comprising >50% of the tumor cell population (Figure 1A). PDC is typically triple‐negative breast cancer (TNBC), associated with an aggressive clinical course and a poor outcome.2–4 So far, no single study explored novel predictive biomarkers for the precision medicine purposes in the patients with PDC. Formalin‐fixed paraffin‐embedded tissue samples of the six PDC patients (four primary and two metastatic cases) were sequenced for 592‐genes using NextSeq platform (Illumina, La Jolla, CA, USA). Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations; high TML was considered when it was ≥17 mutations/Mb. Microsatellite instability (MSI) status was explored by the direct analysis of known MSI loci in the target regions of the sequenced genes. Cases were considered microsatellite instable (MSI‐H) if they exhibited ≥46 altered microsatellite loci (the threshold was established by comparing to the PCR‐based MSI FA result from ~2100 cases). Copy number variations (CNVs) were determined by comparing the depth of sequencing of genomic loci with a diploid control. Calculated gains ≥6 copies were considered amplified. ArcherDx FusionPlex Assay was used to detect gene fusions (52 gene targets). Immunohistochemistry was used to detect expression of PD‐L1 (SP142 antibody, Ventana) in tumor cells (TC) and immune cells (IC). PD‐L1 positivity in TC was defined as 2+ intensity in ≥5% of tumor cells. PD‐L1 status
Controllable Synthesis and Catalytic Performance of Gold Nanoparticles with Cucurbit[n]urils (n = 5–8)

A series of gold nanoparticles (AuNPs) was prepared in situ with different cucurbit[n]urils (CB[n]s) in an alkaline aqueous solution. The nanoparticle sizes can be well controlled by CB[n]s (n = 5, 6, 7, 8) with different ring sizes. The packing densities of CB[5–8] and free surface area on AuNPs were determined. A direct relationship was found between the ring size and packing density of CB[n]s with respect to the AuNP-catalyzed reduction of 4-nitrophenol in the presence of NaBH4. The larger particle size and higher surface coverage of bigger CB[n]-capped AuNPs significantly decreased the catalytic activity. Furthermore, this work could lead to new applications that utilize AuNPs under an overlayer of CB[n]s for catalysis, sensing, and drug delivery.
Reliability and Validity of the Lithuanian Version of CASP-19: A Quality of Life Questionnaire for the Elderly

Introduction: Ageing is associated with several physical, psychological, and behavioral changes. These changes are closely related with general health problems and quality of life in old age. The CASP-19 multidimensional instrument was specially designed to measure quality of life in the elderly. The different language versions of this scale have been used in more than 20 countries. However, Lithuanian translation was not available. The objective of our study was to test psychometric properties of the Lithuanian version of the CASP-19 questionnaire. Materials and methods: A cross-sectional study was performed with ambulatory men and women aged 60 and older, living in a community in Vilnius, Lithuania. Exclusion criteria were current acute illness, malignant tumor, and Mini-Mental State Examination (MMSE) score < 25 points. Psychometric properties of CASP-19 were tested using reliability and validity methods. Results: The study sample consisted of 132 participants, 28 (21.8%) of them were men and 103 (78.2%) women. Analysis of psychometric properties of the Lithuanian version of CASP-19 showed high internal consistency (Cronbach’s alpha 0.85), good agreement between test-retest measures with an ICC of 0.82 (95% CI 0.79–0.85) and good convergent and divergent construct validity. Conclusions: The psychometric properties indicated that the Lithuanian version of CASP-19 was reliable and valid. As such, it might be used to evaluate quality of life in elderly people.
Exchanging knowledge across international borders: building a new network for the RCGP’s global members

The Royal College of General Practitioners (RCGP) has a growing and diverse global membership of 3048 members (Box 1) based across 86 countries outside the UK. This represents approximately 6% of the total membership of the RCGP. In March 2017, it launched a new International and Overseas Network (ION) to link its global members with 'knowledge, support and inspiration' in their professional practice,1 and to improve its professional global connections. Networks can be described as 'complex adaptive systems' with multiple non-linear interactions between members of the system.2–3 Network structures vary along a continuum. At one end is a network defined as a diffuse decentralised structure comprising individuals (sometimes called communities of practice) or informal alliances of organisations. At the other end is a hierarchical network organisation with a centralised hub and spoke structure and clear governance systems comprising either organisations or individuals. 3–5 Box 1. ### Definitions of international and overseas member of the RCGP | International member (IM) | A GP who has passed an RCGP international membership exam at any one of nine accredited exam sites and has chosen to apply for membership. They are classified as international members and use the post-nominals MRCGP[INT]. | || | Overseas member (OM) | A GP who has passed the RCGP membership exam in the UK and has chosen to apply for membership, which they retain after leaving the UK to work in another country. They are classified as overseas members and can use the post nominals MRCGP. | When the RCGP was founded in 1952, it began as an informal network but was developed into the formal institutionalised network that is now the largest medical royal college in the UK. This history helps in understanding the development of the ION, the profession, and similar associations in the countries where the RCGP's global members are working. All professional networks function at two levels: formal and informal. The formal network is built around the membership body itself with systems, processes, and structures to adhere to, whereas the informal networks are clustered around smaller, closely linked groups of individual professionals. Millar and Choi6 argue that formal networks are essential to transfer explicit knowledge but …
Pre-Operative Frailty Status Is Associated with Cardiac Rehabilitation Completion: A Retrospective Cohort Study

While previous investigations have demonstrated the benefit of cardiac rehabilitation (CR) on outcomes after cardiac surgery, the association between pre-operative frailty and post-operative CR completion is unclear. The purpose of this retrospective cohort study was to determine if pre-operative frailty scores impacted CR completion post-operatively and if CR completion influenced frailty scores in 114 cardiac surgery patients. Frailty was assessed with the use of the Clinical Frailty Scale (CFS), the Modified Fried Criteria (MFC), the Short Physical Performance Battery (SPPB), and the Functional Frailty Index (FFI). A Mann-Whitney test was used to compare frailty scores between CR completers and non-completers and changes in frailty scores from baseline to 1-year post-operation. CR non-completers were more frail than CR completers at pre-operative baseline based on the CFS (p = 0.01), MFC (p < 0.001), SPPB (p = 0.007), and the FFI (p < 0.001). A change in frailty scores from baseline to 1-year post-operation was not detected in either group using any of the four frailty assessments. However, greater improvements from baseline to 1-year post-operation in two MFC domains (cognitive impairment and low physical activity) and the physical domain of the FFI were found in CR completers as compared to CR non-completers. These data suggest that pre-operative frailty assessments have the potential to identify participants who are less likely to attend and complete CR. The data also suggest that frailty assessment tools need further refinement, as physical domains of frailty function appear to be more sensitive to change following CR than other domains of frailty.
Modulation of resting‐state brain functional connectivity by exposure to acute fourth‐generation long‐term evolution electromagnetic field: An fMRI study

By now, the neurophysiological effect of electromagnetic field (EMF) exposure and its underlying regulating mechanisms are not well manifested. In this study, we aimed to investigate whether acute long‐term evolution (LTE) EMF exposure could modulate brain functional connectivity using regional homogeneity (ReHo) method and seed‐based analysis on resting‐state functional magnetic resonance imaging (fMRI). We performed the LTE‐EMF exposure experiment and acquired the resting‐state brain activities before and after EMF exposure. Then we applied ReHo index to characterize the localized functional connectivity and seed‐based method to evaluate the inter‐regional functional connectivity. Statistical comparisons were conducted to identify the possible evidence of brain functional connectivity modulation induced by the acute LTE‐EMF exposure. We found that the acute LTE‐EMF exposure modulated localized intra‐regional connectivity (p < 0.05, AlphaSim corrected, voxel size ≥ 18) and inter‐regional connectivity in some brain regions (p < 0.05, AlphaSim corrected, voxel size ≥ 18). Our results may indicate that the approaches relying on network‐level inferences could provide deeper insight into the acute effect on human functional activity induced by LTE‐EMF exposure. Bioelectromagnetics. 40:42–51, 2019. © 2018 Wiley Periodicals, Inc.
Research on the Irrational Behavior of Consumers’ Safe Consumption and Its Influencing Factors

Frequent food safety incidents in recent years have greatly reduced consumers’ trust, and consumers’ demand for safe food has been on the rise. However, there is an inconsistency between the consumers’ willingness and actual purchasing behaviors. Some consumers who have a willingness to purchase safe food ultimately do not produce actual purchasing behaviors, resulting in an “irrational behavior” in the safe food consumer market. In order to better study this phenomenon and identify its inherent logic, we chose to use pork (a typical representative of safety-certified agricultural products) as the object, based on a survey on 844 consumers in the Jiangsu Province and Anhui Province analyzed in July 2017 by RPL (Random Parameters Logit) and binary Logit regression methods from two aspects, i.e. consumer preference for different attributes of safety-certified products and factors affecting safe consumption. The research results show that consumers have a significant preference for pork that has additional attributes such as green food certification, organic food certification, origin information and “No Additives and Veterinary Drug Residue Labeling”; labeling such information on the pork can effectively improve consumers’ trust. Consumers’ inconsistency of purchase intention with purchasing behaviors of safety-certified pork is affected by many factors, such as gender, age, annual household income, the degree of trust in agricultural product quality and a safety certification mark, understanding of safety-certified pork, and the degree of concern on pork quality and safety issues. These factors have all contributed, to varying degrees, to the rising of “irrational behavior” of consumers’ safe consumption, lead to an irrational state of consumption that consumers with a safely certified pork purchase will not necessarily buy a safety-certified pork. Based on the results of two empirical analyses, it can be concluded that pricing and age are the two main influencing factors that lead to the “irrational behavior” of consumers’ safe consumption.
Investigating the permeation properties of contact lenses and its influence on tear electrolyte composition.

The health of the cornea is paramount; the aim of this study was to assess the permeation of essential tear electrolytes through a range of commercial contact lenses. Donor/receiver conductivity measurements were recorded using a dual-chamber diffusion system which allowed material permeability profiles and coefficients to be calculated. Water structuring properties of the contact lenses were measured by differential scanning calorimetry. Freezing water was subdivided into "ice-like" water (free, non-bound and has a melting point close to that of pure water) and polymer-associated water (free but loosely bound to the polymer matrix). Each material interacts differently with each of the three salts, for example; lotrafilcon B (34% equilibrium water content [EWC]) shows a higher and larger range of receiver concentrations post KCl, NaCl, CaCl2 permeation (76, 59 and 42 mM, respectively) compared with the lower and tighter range exhibited by lotrafilcon A (22% EWC) (36, 22, and 18 mM, respectively). Additionally, in terms of the relationship between permeation and water structure, balafilcon A (34% EWC) has a high KCl permeation (P60 258 × 10-8 cm2 /s) and ice-like water (14%), but narafilcon A (44% EWC) has a low ion permeation (P60 3.9 × 10-8 cm2 /s) and significantly less ice-like water (4%). The permeation trends for the silicone hydrogel materials could not be fully explained by water content and structuring. Composition and, in particular, the microstructure and morphology of these materials must impart a greater influence on permeation capability. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: 2018.
Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis

Abstract Objective To assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA). Design Systematic review and meta-analysis of randomised, placebo controlled trials. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018. Eligibility criteria for selecting studies and methods Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology. Results Three eligible trials involving 10 447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I2=0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I2=0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I2=32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely. Conclusions Dual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.
Focused ultrasound transiently increases membrane conductance in isolated crayfish axon.

We report a novel phenomenon produced by focused ultrasound (US) that may be important for understanding its effects on cell membranes. When a US burst (2.1 MHz, 1-mm focal diameter, 0.1-1 MPa) was focused on a motor axon of the crayfish neuromuscular junction, it consistently produced a fast hyperpolarization, which was followed or superseded by subthreshold depolarizations or action potentials in a stochastic manner. The depolarization persisted in the presence of voltage-gated channel blockers [1 µM TTX ( INa), 50 µM ZD7288 ( Ih), and 200 µM 4-aminopyridine ( IK)] and typically started shortly after the onset of a 5-ms US burst, with a mean latency of 3.35 ± 0.53 ms (SE). The duration and amplitude of depolarizations averaged 2.13 ± 0.87 s and 10.1 ± 2.09 mV, with a maximum of 200 s and 60 mV, respectively. The US-induced depolarization was always associated with a decrease in membrane resistance. By measuring membrane potential and resistance during the US-induced depolarization, the reversal potential of US-induced conductance ( gus) was estimated to be -8.4 ± 2.3 mV, suggesting a nonselective conductance. The increase in gus was 10-100 times larger than the leak conductance; thus it could significantly influence neuronal activity. This change in conductance may be due to stimulation of mechanoreceptors. Alternatively, US may perturb the lateral motion of phospholipids and produce nanopores, which then increase gus. These results may be important for understanding mechanisms underlying US-mediated modulation of neuronal activity and brain function. NEW & NOTEWORTHY We report a specific increase in membrane conductance produced by ultrasound (US) on neuronal membrane. When a 5-ms US tone burst was focused on a crayfish motor axon, it stochastically triggered either depolarization or a spike train. The depolarization was up to 60 mV in amplitude and 200 s in duration and therefore could significantly influence neuronal activity. Depolarization was still evoked by US burst in the presence of Na+ and Ca2+ channel blockers and had a reversal potential of -8.4 ± 2.3 mV, suggesting a nonselective permeability. US can be applied noninvasively in the form of a focused beam to deep brain areas through the skull and has been shown to modulate brain activity. Understanding the depolarization reported here should be helpful for improving the use of US for noninvasive modulation and stimulation in brain-related disease.
Characterization and Beige Adipogenic Potential of Human Embryo White Adipose Tissue-Derived Stem Cells

Background/Aims: Brown and beige adipocytes are widely recognized as potential therapeutic targets to treat obesity and related metabolic disorders, and the recruitment of brown and beige adipocytes is an essential aspect that requires attention. Although many methods of activating brown adipocytes or generating beige adipocytes have been reported, the limited number and sources are the biggest challenges. The number of white adipocytes is much greater than the number of brown adipocytes, both in human adults and fetuses. Unfortunately, human adult white adipose tissue-derived stem cell (aWAsc) has little beige adipogenic potential. However, the characteristics and beige adipogenic potential of human embryo-derived white adipose stem cells (eWAsc) still need to be investigated. Methods: To analyze the characteristics and functionality of eWAsc, we analyzed the markers of adipose precursor cells by flow cytometry. Then, differentiation and browning/beiging were induced, and the identifying markers were analyzed by real-time PCR and immunoblot. In addition, more in-depth exploration was performed using RNA-SEQ on eWAsc and aWAsc. Results: eWAsc was isolated from human embryonic white adipose tissue, and aWAsc was isolated from adult white adipose tissue by collagenase treatment. eWAsc has extreme advantages in adipogenesis capacity and browning/beiging ability in comparison to aWAsc, indicating that eWAsc may possess some special regulatory factors to promote the generation of functional brown/beige adipocytes. Greater exploration was enabled by RNA-SEQ, revealing a large number of differences at the transcriptional levels, including 1263 differentially expressed genes, 657 down- and 605 upregulated, in eWAsc compared to aWAsc. Pathway analysis revealed enrichment in cell cycle, TGF-β signaling pathway, DNA replication, and Hippo signaling pathways. Interestingly, the expression levels of C/EBPα, FGF1 and FST gene, which are related to the maturation of adipocytes, Hippo signaling pathway and TGF-β signaling pathway, were significantly higher in eWAsc than in aWAsc. These may be potential candidates and possible regulatory targets for recruiting beige adipocytes in human adipose tissue. Conclusion: Overall, we have demonstrated the molecular characteristics and excellent beige adipogenic potential of eWAsc, providing a new reference for studying human adipocytes.
Serum amyloid A in equine health and disease

Summary Serum amyloid A (SAA) is the major acute phase protein in horses. It is produced during the acute phase response (APR), a nonspecific systemic reaction to any type of tissue injury. In the blood of healthy horses, SAA concentration is very low, but it increases dramatically with inflammation. Due to the short half‐life of SAA, changes in its concentration in blood closely reflect the onset of inflammation and, therefore, measurement of SAA useful in the diagnosis and monitoring of disease and response to treatment. Increases in SAA concentration have been described in equine digestive, reproductive and respiratory diseases and following surgical procedures. Moreover, SAA has proven useful for detection of some subclinical pathologies that can disturb training and competing in equine athletes. Increasing availability of diagnostic tests for both laboratory and field use adds to SAA's applicability as a reliable indicator of horses’ health status. This review article presents the current information on changes in SAA concentrations in the blood of healthy and diseased horses, focussing on clinical application of this biomarker.