Miracle-dz/UniFAR-FTUs huggingface dataset:
Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates

Minimal myelination is proposed to be a contributing factor to the preferential nigral neuronal loss in Parkinson's disease (PD). Similar to nigral dopaminergic neurons, sympathetic neurons innervating the heart have long, thin axons which are unmyelinated or minimally myelinated. Interestingly, cardiac sympathetic loss in PD is heterogeneous across the heart, yet the spatial relationship between myelination and neurodegeneration is unknown. Here, we report the mapping of myelin basic protein (MBP) expression across the left ventricle of normal rhesus macaques (n = 5) and animals intoxicated with systemic 6-OHDA (50 mg/kg iv) to model parkinsonian cardiac neurodegeneration (n = 10). A subset of 6-OHDA-treated rhesus received daily dosing of pioglitazone (5 mg/kg po; n = 5), a PPARγ agonist with neuroprotective properties. In normal animals, MBP-immunoreactivity (-ir) was identified surrounding approximately 14% of axonal fibers within nerve bundles of the left ventricle, with more myelinated nerve fibers at the base level of the left ventricle than the apex (p < 0.014). Greater MBP-ir at the base was related to a greater number of nerve bundles at that level relative to the apex (p < 0.05), as the percent of myelinated nerve fibers in bundles was not significantly different between levels of the heart. Cardiac sympathetic loss following 6-OHDA was associated with decreased MBP-ir in cardiac nerve bundles, with the percent decrease of MBP-ir greater in the apex (84.5%) than the base (52.0%). Interestingly, cardiac regions and levels with more MBP-ir in normal animals showed attenuated sympathetic loss relative to areas with less MBP-ir in 6-OHDA + placebo (r = −0.7, p < 0.014), but not in 6-OHDA + pioglitazone (r = −0.1) subjects. Our results demonstrate that myelination is present around a minority of left ventricle nerve bundle fibers, is heterogeneously distributed in the heart of rhesus macaques, and has a complex relationship with cardiac sympathetic neurodegeneration and neuroprotection.
Biological and Molecular Characterization of a Jumbo Bacteriophage Infecting Plant Pathogenic Ralstonia solanacearum Species Complex Strains

A jumbo phage infecting Ralstonia solanacearum species complex strains, designated RsoM2USA, was isolated from soil of a tomato field in Florida, United States, and belongs to the family Myoviridae. The phage has a long latent period of 270 min and completed its infection cycle in 360 min with a burst size of approximately 32 particles per cell. With a genome size of 343,806 bp, phage RsoM2USA is the largest Ralstonia-infecting phage sequenced and reported to date. Out of the 486 ORFs annotated for RsoM2USA, only 80 could be assigned putative functions in replication, transcription, translation including 44 tRNAs, and structure with the main structural proteins experimentally confirmed. Phylogenetic analyses placed RsoM2USA in the same clade as Xanthomonas phage XacN1, prompting a proposal of a new genus for the two jumbo phages. Jumbo phage RsoM2USA is a lytic phage and has a wide host range, infecting each of the three newly established Ralstonia species: R. solanacearum, R. pseudosolanacearum, and R. syzygii, and significantly reduced the virulence of its susceptible R. solanacearum strain RUN302 in tomato plants, suggesting that this jumbo phage has the potential to be developed into an effective control against diseases caused by R. solanacearum species complex strains.
Identification of the Molecular Subgroups in Idiopathic Pulmonary Fibrosis by Gene Expression Profiles

Background Idiopathic Pulmonary Fibrosis (IPF) is one of the most common idiopathic interstitial pneumonia, which can occur all over the world. The median survival time of patients is about 3-5 years, and the mortality is relatively high. Objective To reveal the potential molecular characteristics of IPF and deepen the understanding of the molecular mechanism of IPF. In order to provide some guidance for the clinical treatment, new drug development, and prognosis judgment of IPF. Although the preliminary conclusion of this study has certain guiding significance for the treatment of IPF and so on, it needs more accurate analytical approaches and large sample clinical trials to verify. Methods 220 patients with IPF were divided into different subgroups according to the gene expression profiles, which were obtained from the Gene Expression Omnibus (GEO) database. In addition, these subgroups present different expression forms and clinical features. Therefore, weighted gene coexpression analysis (WGCNA) was used to seek the differences between subtypes. And six subgroup-specific WGCNA modules were identified. Results Combined with the characteristics of WGCNA and KEGG enrichment modules, the autophagic pathway was only upregulated in subgroup I and enriched significantly. The differentiation pathways of Th1 and Th2 cells were only upregulated and enriched in subgroup II. At the same time, combined with clinical information, IPF patients in subgroup II were older and more serious, which may be closely related to the differentiation of Th1 and Th2 cells. In contrast, the neuroactive ligand-receptor interaction pathway and Ca+ signaling pathway were significantly upregulated and enriched in subgroup III. Although there was no significant difference in prognosis between subgroup I and subgroup III, their intrinsic biological characteristics were very different. These results suggest that the subtypes may represent risk factors of age and intrinsic biological characteristics and may also partly reflect the severity of the disease. Conclusion In conclusion, current studies have improved our understanding of IPF-related molecular mechanisms. At the same time, because the results show that patients from different subgroups may have their own unique gene expression patterns, it reminds us that patients in each subgroup should receive more personalized treatment.
The 10-Repeat 3′-UTR VNTR Polymorphism in the SLC6A3 Gene May Confer Protection Against Parkinson’s Disease: A Meta-analysis

The dopamine transporter (DAT) is encoded by the SLC6A3 gene and plays an important role in the regulation of the neurotransmitter dopamine. The SLC6A3 gene contains several repetition alleles (3–11 repeats) of a 40-base pair variable number of tandem repeats (VNTR) in the 3′-untranslated region (3′-UTR), which may affect DAT expression levels. The 10-repeat (10R) allele could play a protective role against PD. However, inconsistent findings have been reported. Methods: A comprehensive meta-analysis was performed to accurately estimate the association between the 10R allele of the 3′-UTR VNTR in SLC6A3 and PD among four different genetic models. Results: This meta-analysis included a total of 3,142 patients and 3,496 controls. We observed a significant difference between patients and controls for the allele model (10R vs. all others: OR = 0.860, 95% CI: 0.771–0.958, P = 0.006), pseudodominant model (10R/10R + 10R/9R vs. all others: OR = 0.781, 95% CI: 0.641–0.952, P = 0.014) and pseudorecessive model (10R/10R vs. all others: OR = 0.858, 95% CI: 0.760–0.969, P = 0.013) using a fixed effects model. No significant differences were observed under the pseudocodominant model (10R/9R vs. all others: OR = 1.079, 95% CI: 0.945–1.233, P = 0.262). By subgroup analysis, the 10R, 10R/10R and 10R/9R genotypes were found to be significantly different from PD in Asian populations. Conclusion: Our findings suggest that the SLC6A3 10R may be a protective factor in susceptibility to PD.
Synthesis, characterization, and docking studies of novel cyanopyridone analogs with serotonin 5-HT1B receptor agonists

Abstract The medications in use for treating migraine are directed either towards inhibiting the characteristic migraine pain or towards preventing it from occurring. In this pursuit, ergotamine and sumatriptan class of 5-HT1B receptor agonists have been proved to be extremely effective. Further research into this field led us to design cyanopyridone derivatives that were synthesized through cyclization of 2-cyano-N-phenylacetamides with malonitrile and 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde. The synthesized cyanopyridones analogs, when docked with active site of 5-HT1B receptor, showed better binding affinity compared to standard antimigraine medications. Additionally, in silico ADME prediction for drug-likeness and pharmacokinetics revealed that all compounds are safer and can be used as antimigraine medicine. The structure of the synthesized compounds has been elucidated on the basis of spectral analysis. Graphical Abstract
Effect of Acupuncture on Simple Obesity and Serum Levels of Prostaglandin E and Leptin in Sprague-Dawley Rats

Aim The study is aimed at investigating the curative effect of acupuncture on simple obesity and its influence on serum levels of prostaglandin E and leptin in Sprague-Dawley (SD) rats. Methods In the study, there are 50 male SD rats. We took 10 as healthy controls and fed 40 with a diet of high fat for 8 weeks. After the 40 rat model was established successfully, we fed 10 rats in the model group with a normal diet and treated 10 rats in the acupuncture group by acupuncture. During the experiment, the body fat and body length of rats were measured weekly, and Lee's index was calculated. After the treatment, the levels of leptin, prostaglandin E, C-reactive protein (CRP), triacylglycerol (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were detected, and the liver fat morphology was observed by electron microscope. Results Acupuncture significantly downregulated the serum levels of CRP, TG, CHO, LDL, leptin, and prostaglandin E and upregulated the serum levels of HDL in rats with simple obesity. Conclusion On basis of these results, it was found that acupuncture could boost fat metabolism and weight loss by inhibiting the production of leptin and prostaglandin E.
Soluble Epoxide Hydrolase Inhibitors Regulate Ischemic Arrhythmia by Targeting MicroRNA-1

Background: Soluble epoxide hydrolase inhibitors (sEHis) inhibit the degradation of epoxyeicosatrienoic acids (EETs) in cells, and EETs have antiarrhythmic effects. Our previous experiments confirmed that t-AUCB, a preparation of sEHis, inhibited ischemic arrhythmia by negatively regulating microRNA-1 (miR-1), but its specific mechanism remained unclear. Aim: This study aimed to examine the role of serum response factor (SRF) and the PI3K/Akt/GSK3β pathway in t-AUCB-mediated regulation of miR-1 and the interaction between them. Methods/Results: We used SRF small interfering RNA (siSRF), SRF small hairpin (shSRF) RNA sequence adenovirus, PI3K/Akt/GSK3β pathway inhibitors, t-AUCB, and 14,15-EEZE (a preparation of EETs antagonists) to treat mouse cardiomyocytes overexpressing miR-1 and mice with myocardial infarction (MI). We found that silencing SRF attenuated the effects on miR-1 and its target genes KCNJ2 and GJA1 in the presence of t-AUCB, and inhibition of the PI3K/Akt/GSK3β pathway antagonized the effects of t-AUCB on miR-1, KCNJ2, and GJA1, which were associated with PI3Kα, Akt, and Gsk3β but not PI3Kβ or PI3Kγ. Moreover, the PI3K/Akt/GSK3β pathway was involved in the regulation of SRF by t-AUCB, and silencing SRF inhibited the t-AUCB-induced increases in Akt and Gsk3β phosphorylation. Conclusions: Both the SRF and the PI3K/Akt/GSK3β pathway are involved in the t-AUCB-mediated regulation of miR-1, and these factors interact with each other.
Genomic and pathogenic investigations of Streptococcus suis serotype 7 population derived from a human patient and pigs

ABSTRACT Streptococcus suis is one of the important emerging zoonotic pathogens. Serotype 2 is most prevalent in patients worldwide. In the present study, we first isolated one S. suis serotype 7 strain GX69 from the blood culture of a patient with septicemia complicated with pneumonia in China. In order to deepen the understanding of S. suis serotype 7 population characteristics, we investigated the phylogenetic structure, genomic features, and virulence of S. suis serotype 7 population, including 35 strains and 79 genomes. Significant diversities were revealed in S. suis serotype 7 population, which were clustered into 22 sequence types (STs), five minimum core genome (MCG) groups, and six lineages. Lineages 1, 3a, and 6 were mainly constituted by genomes from Asia. Genomes of Lineages 2, 3b, and 5a were mainly from Northern America. Most of genomes from Europe (41/48) were clustered into Lineage 5b. In addition to strain GX69, 13 of 21 S. suis serotype 7 representative strains were classified as virulent strains using the C57BL/6 mouse model. Virulence-associated genes preferentially present in highly pathogenic S. suis serotype 2 strains were not suitable as virulence indicators for S. suis serotype 7 strains. Integrative mobilizable elements were widespread and may play a critical role in disseminating antibiotic resistance genes of S. suis serotype 7 strains. Our study confirmed S. suis serotype 7 is a non-negligible pathotype and deepened the understanding of the population structure of S. suis serotype 7, which provided valuable information for the improved surveillance of this serotype.
The Waiting Room Assessment to Virtual Emergency Department pathway: Initiating video-based telemedicine in the pediatric emergency department

The COVID-19 pandemic has presented pediatric emergency departments with unique challenges, resulting in a heightened demand for adapted clinical pathways. In response to this need, the Montreal Children's Hospital pediatric emergency department introduced the WAVE (Waiting Room Assessment to Virtual Emergency Department) pathway, a video-based telemedicine pathway for selected non-critical patients, aiming to reduce safety issues related to emergency department overcrowding, while providing timely care to all children presenting and registering at our emergency department. The objective of the WAVE pilot phase was to evaluate the feasibility and acceptability of telemedicine in our pediatric emergency department, which was previously unfamiliar with this mode of care delivery. During the six-week, three-evening per week deployment, we conducted 18 five-hour telemedicine shifts. In total, 27 patients participated in the WAVE pathway. Results from this pilot phase met four of five a priori feasibility and acceptability criteria. Overall, participating families were satisfied with this novel care pathway and reported no disruptive technological barriers.
Retrospective diagnosis of lymphatic tuberculosis in frozen samples using two genetic amplification methods, Xpert® MTB/RIF ULTRA and Abbott RealTime MTB Assay

Objectives The main objective of the present study is to assess the sensitivity and specificity of a retrospective diagnostic of lymphatic tuberculosis (LTB), testing frozen samples using gene amplification PCR methods. The secondary objective was to compare the results of two different commercial tuberculosis gene amplification methods for this purpose. Material and methods We retrospectively studied 38 frozen samples, previously processed for mycobacterial culture between January 2014 and August 2019. The results of the previous cultures were: 21 samples positive for Mycobacterium tuberculosis complex (MTB) (5 being smear positive), 7 samples culture positive for Mycobacterium avium-intracellulare complex and 10 samples which were mycobacterial culture negative and discarded for LTB diagnosis, used as controls. The samples were processed using two gene amplification methods: Xpert® MTB/RIF Ultra (Cepheid) and Abbott RealTime MTB Assay (Abbott). Results Compared to initial culture results the sensitivity and specificity of Xpert® MTB/RIF Ultra were 57.1% and 100% and 52.3 % and 92.5%, respectively for the Abbott RealTime MTB assay. The differences were not statistically significant. In addition, there were no differences according to the period of freezing. Conclusions Gene amplification of frozen samples confirmed the diagnosis of lymphatic TB in almost 60% of cases, allowing retrospective diagnosis in initially non suspected cases. Both gene amplification techniques tested were equally useful.
The impact of post-slaughter natural antioxidants application on the physical and chemical characteristics of broiler chicken meat

Experiments assessing the efficiency of natural antioxidants rosemary (ROS), small red bean (SRB), sunflower seeds (SFS) and ginger (GGR) extracts compared to the synthetic antioxidant (BHT) on characteristics of chicken meat were studied. The initial experiment evaluated the effect of the addition of antioxidants at 10 and 20 mg to lipids extracted from different tissues (breast, thigh, adipose and skin tissue) during the Schaal oven te st 62.8 o C. Antioxidants at 10 and 20 mg significantly reduced TBARS, CD and CT values in all extracted lipids compared to the non - treated samples . However, no significant differences were found between both levels. Among the antioxidants, ROS significantl y reduced TBARS values in fat from all the chicken portions over 7 days. In the subsequent experiments, the impact of antioxidants on physical and chemical characteristics of raw and freshly cooked meat was investigated. In addition, the impact of the app lication of natural antioxidants on warmed - over characteristics in cooked chicken meat was evaluated. Raw meat samples treated with SFS had the lowest TBARS values, while in meat freshly cooked, ROS treatment had the lowest TBARS values. The a ddition of an tioxidants reduced the degradation of phospholipids and formation of CDs and CTs in both raw and freshly cooked meat s compared to the non - treated samples . Antioxidant treatments had a significantly lower drip loss and pH values , but did not affect cooking loss and shear force. Natural antioxidants significantly increased the colour stability and yielded more fatty acids in chicken meat. Natural antioxidants significantly reduced (p ≤ 0.05) the formation of TBARS, CD and CT in both LTLO and HTHO samples, whi le their effect was much greater in LTLO samples compared to HTHO meat samples. Reheating process had a significant an effect on TBARS, CD and CT accumulation of most treatments either cooked by LTLO or HTHO methods ( p ≤ 0.05). In conclusion, the results suggest that natural antioxidants may have the ability to inhibit the lipid oxidation and enhance meat quality. The impact of natural antioxidants was similar to that of BHT.
Eosinophilic endotype of chronic obstructive pulmonary disease: similarities and differences from asthma

Approximately 25% to 40% of patients with chronic obstructive pulmonary disease (COPD) have the eosinophilic endotype. It is important to identify this group accurately because they are more symptomatic and are at increased risk for exacerbations and accelerated decline in forced expiratory volume in the 1st second. Importantly, this endotype is a marker of treat ment responsiveness to inhaled corticosteroid (ICS), resulting in decreased mortality risk. In this review, we highlight differences in the biology of eosinophils in COPD compared to asthma and the different definitions of the COPD eosinophilic endotype based on sputum and blood eosinophil count (BEC) with the corresponding limitations. Although BEC is useful as a biomarker for eosinophilic COPD endotype, optimal BEC cut-offs can be combined with clinical characteristics to improve its sensitivity and specificity. A targeted approach comprising airway eosinophilia and appropriate clinical and physiological features may improve identification of subgroups of patients who would benefit from biologic therapy or early use of ICS for disease modification.
Emergency Response Protocols for Overseas Outreach Settings: Global Smile Foundation Strategy

Non-governmental organizations (NGOs) aim to alleviate unmet global disease burden and promote collaboration between visiting and host countries. Well-executed emergency response protocols are foundational to providing safe and quality care in an unpredictable global setting. Global Smile Foundation (GSF) instituted a protocol in 2012 based on over three decades of cleft care experience. Here, we update this protocol and provide information on how to address special circumstances such as humanitarian crises and disease outbreaks. The GSF response protocol was developed in conjunction with surgeons, anesthesiologists, nurses, and administrators to ensure all team members are adequately prepared to respond to emergency situations in global outreach. This protocol provides information on pre-departure preparation, onsite setup, operative precautions, and post-departure debriefings. Emphasis is placed on a standardized, reproducible workflow that accounts for necessary site-specific adjustments. Strategies include emergency simulations, site-specific safety checklists, standardized operating room protocols, and well-defined individual responsibilities. The authors also provide anticipatory guidance in addressing unexpected circumstances, such as disease outbreak and natural disaster, during global outreach. In conclusion, a proactive and systematic approach to emergency response and prevention is vital to minimizing morbidity and mortality during surgical outreach initiatives. The GSF protocol represents a reproducible approach that other organizations can adopt and adapt to their unique needs.
Efficacy and safety of bivalirudin without post-procedure infusion in patients with coronary heart disease during elective percutaneous coronary intervention: a real-world study

To the Editor: Antithrombotic therapy is essential to prevent adverse ischemic events during and after percutaneous coronary intervention (PCI). Anticoagulation during PCI is most commonly achieved with heparin or bivalirudin. Bivalirudin does not activate platelets, does not bind to plasma proteins and has linear pharmacokinetics with a short half-life of 25 min. These characteristics indicate that bivalirudin may be an ideal anticoagulation drug for PCI. Prior trials whichwere about patients with acute myocardial infarction (AMI) undergoing primary PCI showed that a bivalirudin-based anticoagulation strategy decreased the risk of major bleeding, but it was associated with an increased risk of acute stent thrombosis (ST) compared with a heparin-based strategy. It was considered that short half-life of bivalirudin and delayed onset of platelet P2Y12 receptor inhibitor in AMI patients led to a blank period of antithrombotic therapy after primary PCI. Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary interventionin acute myocardial infarction: the BRIGHT randomized clinical trial, using a high-dose infusion of bivalirudin for 3 to 4 h after PCI, the results showed that compared with the heparin or heparin combined with platelet glycoprotein IIb/IIIa receptor antagonist (GPI), bivalirudin did not increase acute ST and reduced the occurrence of net adverse clinical events (NACE). However, for patients with coronary heart disease (CHD) who choose elective PCI, there is still no clear evidence of the benefit of post-procedure infusion of bivalirudin for 3 to 4 h. Therefore, our study validates the efficacy and safety of bivalirudin without post-procedure infusion contrasting to heparin during elective PCI.