Miracle-dz/UniFAR-FTUs huggingface dataset:
Superiority of MALDI-TOF Mass Spectrometry over Real-Time PCR for SARS-CoV-2 RNA Detection

At present, the RT-PCR test remains the gold standard for early diagnosis of SARS-CoV-2. Nevertheless, there is growing evidence demonstrating that this technique may generate false-negative results. Here, we aimed to compare the new mass spectrometry-based assay MassARRAY® SARS-CoV-2 Panel with the RT-PCR diagnostic test approved for clinical use. The study group consisted of 168 suspected patients with symptoms of a respiratory infection. After simultaneous analysis by RT-PCR and mass spectrometry methods, we obtained discordant results for 17 samples (10.12%). Within fifteen samples officially reported as presumptive positive, 13 were positive according to the MS-based assay. Moreover, four samples reported by the officially approved RT-PCR as negative were positive in at least one MS assay. We have successfully demonstrated superior sensitivity of the MS-based assay in SARS-CoV-2 detection, showing that MALDI-TOF MS seems to be ideal for the detection as well as discrimination of mutations within the viral genome.
Role of Ranolazine in the Prevention and Treatment of Atrial Fibrillation in Patients with Left Ventricular Systolic Dysfunction: A Meta-Analysis of Randomized Clinical Trials

Background: Ranolazine has the potential to prevent atrial fibrillation (AF) and plays a role in rhythm control strategy for atrial fibrillation in various clinical settings. However, data on the use of ranolazine in patients with left ventricular (LV) systolic dysfunction are limited. The aims of this meta-analysis of randomized clinical trials are to investigate the efficacy and safety of ranolazine in AF patients with LV systolic dysfunction. PubMed and the Cochrane Database of Systematic Reviews were searched until July 2020. The efficacy outcomes included the incidence of new-onset AF, the rate of sinus rhythm restoration, and the time until sinus rhythm restoration. Safety endpoints were at death, and any adverse events were reported in the enrolled studies. We initially identified 204 studies and finally retrieved 5 RCTs. Three studies were analyzed in the meta-analysis. Among AF patients with LV systolic dysfunction, our meta-analysis showed that the combination of ranolazine to amiodarone significantly increased the sinus rhythm restoration rate compared to amiodarone alone (risk ratio (RR) 2.87, 95% confidence interval (CI) 2.48–3.32). Moreover, the time to sinus rhythm restoration was 2.46 h shorter in the ranolazine added to amiodarone group (95% CI: 2.27–2.64). No significant adverse events and proarrhythmias in the ranolazine group were identified. In conclusion, in AF patients with LV systolic dysfunction, ranolazine as an add-on therapy to amiodarone potentiates and accelerates the conversion of AF to sinus rhythm. Moreover, ranolazine shows good safety profiles. Further studies to investigate the effectiveness of ranolazine in the prevention of new-onset AF among patients with LV systolic dysfunction are needed.
A case-control comparative study between Toupet-Sleeve and conventional sleeve gastrectomy in patients with preoperative gastroesophageal reflux

Abstract Introduction The aim of that study was to compare outcomes after Toupet-Sleeve (T-Sleeve) and sleeve gastrectomy (SG) as primary bariatric procedures in obese patients presenting with preoperative gastro-esophageal reflux disease (GERD). Material and methods The outcomes of 19 consecutive patients operated between 2017 and 2019 by T-Sleeve were compared to the outcomes of 38 patients operated in 2014 by SG. The two groups were matched by age, sex, ASA classification, BMI, food habits and severity of esophagitis. Postoperative weight loss and evolution of GERD symptoms were the study end-points. Results The preoperative BMI was 43 ± 5 in the T-Sleeve and 42 ± 5 in the SG group (NS). All the procedures were completed by laparoscopy. The operative time was higher in the T-Sleeve group: 89 ± 18 vs. 68 ± 12 min. (p < 0.001). A lower weight loss was observed in the T-Sleeve group. Respectively 1 and 2 years after surgery, the mean BMI were: 32 ± 6 and 34 ± 6 in the T-Sleeve vs. 28 ± 5 (p < 0.006) and 30 ± 6 (p < 0.05) in the SG group and the mean %EWL were: 61 ± 23 and 54 ± 26% in the T-Sleeve vs. 86 ± 25 (p < 0.002) and 75 ± 28% (p < 0.03) in the SG group. Better control of GERD was noted in the T-Sleeve group: the number of patients with complete resolution of GERD symptoms was 17 (89%) vs. 13 (34%) in the SG group (p < 0.001). Conclusion T-Sleeve was an effective procedure for GERD treatment but, the weight loss was significantly much lower than after conventional SG. Studies with longer follow-up are mandatory to validate the T-Sleeve procedure.
Regulatory Light Chains in Cardiac Development and Disease

The role of regulatory light chains (RLCs) in cardiac muscle function has been elucidated progressively over the past decade. The RLCs are among the earliest expressed markers during cardiogenesis and persist through adulthood. Failing hearts have shown reduced RLC phosphorylation levels and that restoring baseline levels of RLC phosphorylation is necessary for generating optimal force of muscle contraction. The signalling mechanisms triggering changes in RLC phosphorylation levels during disease progression remain elusive. Uncovering this information may provide insights for better management of heart failure patients. Given the cardiac chamber-specific expression of RLC isoforms, ventricular RLCs have facilitated the identification of mature ventricular cardiomyocytes, opening up possibilities of regenerative medicine. This review consolidates the standing of RLCs in cardiac development and disease and highlights knowledge gaps and potential therapeutic advancements in targeting RLCs.
Assessment of 18F-PBR-111 in the Cuprizone Mouse Model of Multiple Sclerosis

The study aims to assess site assessment of the performance of 18F-PBR-111 as a neuroinflammation marker in the cuprizone mouse model of multiple sclerosis (MS). 18F-PBR-111 PET imaging has not been well evaluated in multiple sclerosis applications both in preclinical and clinical research. This study will help establish the potential utility of 18F-PBR-111 PET in preclinical MS research and future animal and future human applications. 18F-PBR-111 PET/CT was conducted at 3.5 weeks (n = 7) and 5.0 weeks (n = 7) after cuprizone treatment or sham control (n = 3) in the mouse model. A subgroup of mice underwent autoradiography with cryosectioned brain tissue. T2 weighted MRI was performed to obtain the brain structural data of each mouse. 18F-PBR-111 uptake was assessed in multiple brain regions with PET and autoradiography images. The correlation between autoradiography and immunofluorescence staining of neuroinflammation (F4/80 and CD11b) was measured. Compared to control mice, significant 18F-PBR-111 uptake in the corpus callosum (p < 0.001), striatum (caudate and internal capsule, p < 0.001), and hippocampus (p < 0.05) was identified with PET images at both 3.5 weeks and 5.0 weeks, and validated with autoradiography. No significant uptake differences were detected between 3.5 weeks and 5.0 weeks assessing these regions as a whole, although there was a trend of increased uptake at 5.0 weeks compared to 3.5 weeks in the CC. High 18F-PBR-111 uptake regions correlated with microglial/macrophage locations by immunofluorescence staining with F4/80 and CD11b antibodies. 18F-PBR-111 uptake in anatomic locations correlated with activated microglia at histology in the cuprizone mouse model of MS suggests that 18F-PBR-111 has potential for in vivo evaluation of therapy response and potential for use in MS patients and animal studies.
Updated Mechanisms of GCN5—The Monkey King of the Plant Kingdom in Plant Development and Resistance to Abiotic Stresses

Histone modifications are the main epigenetic mechanisms that regulate gene expression, chromatin structure, and plant development, among which histone acetylation is one of the most important and studied epigenetic modifications. Histone acetylation is believed to enhance DNA access and promote transcription. GENERAL CONTROL NON-REPRESSIBLE 5 (GCN5), a well-known enzymatic protein responsible for the lysine acetylation of histone H3 and H4, is a universal and crucial histone acetyltransferase involved in gene transcription and plant development. Many studies have found that GCN5 plays important roles in the different development stages of Arabidopsis. In terms of exogenous stress conditions, GCN5 is also involved in the responses to heat stress, cold stress, and nutrient element deficiency by regulating the related gene expression to maintain the homeostasis of some key metabolites (e.g., cellulose) or ions (e.g., phosphate, iron); in addition, GCN5 is involved in the phytohormone pathways such as ethylene, auxin, and salicylic acid to play various roles during the plant lifecycle. Some of the pathways involved by GCN5 also interwind to regulate specific physiological processes or developmental stages. Here, interactions between various developmental events and stress-resistant pathways mediated by GCN5 are comprehensively addressed and the underlying mechanisms are discussed in the plant. Studies with some interacting factors such as ADA2b provided valuable information for the complicated histone acetylation mechanisms. We also suggest the future focuses for GCN5 functions and mechanisms such as functions in seed development/germination stages, exploration of novel interaction factors, identification of more protein substrates, and application of advanced biotechnology-CRISPR in crop genetic improvement, which would be helpful for the complete illumination of roles and mechanisms of GCN5.
Silver Nanoparticles as Modulators of Myogenesis-Related Gene Expression in Chicken Embryos

The present study was conducted to investigate the effects of colloidal nanoparticles of silver (Nano-Ag) on the expression of myogenesis-related genes in chicken embryos. The investigated genes included the members of the myogenic regulatory factors family (MRFs) and myocyte enhancer factor 2A (MEF2A) genes. A total of 200 fertilized broiler eggs (Indian River) were randomly distributed into four groups; non-injected control, injected control with placebo, treatment I in ovo injected with 20 ppm Nano-Ag, and treatment II in ovo injected with 40 ppm Nano-Ag. The eggs were then incubated for 21 days at the optimum temperature and humidity conditions. Breast muscle tissues were collected at the 5th, 8th, and 18th days of the incubation period. The mRNA expression of myogenic determination factor 1 (MYOD1), myogenic factor 5 (MYF5), myogenic factor 6 (MYF6), myogenin (MYOG), and MEF2A was measured at the three sampling points using real-time quantitative PCR, while MYOD1 protein expression was evaluated on day 18 using western blot. Breast muscle tissues were histologically examined on day 18 to detect the changes at the cellular level. Our results indicate that myogenesis was enhanced with the low concentration (20 ppm) of Nano-Ag due to the higher expression of MYOD1, MYF5, and MYF6 at the transcriptional level and MYOD1 at the translational level. Moreover, histological analysis revealed the presence of hyperplasia (31.4% more muscle fibers) in treatment I (injected with 20 ppm). Our findings indicate that in ovo injection of 20 ppm Nano-Ag enhances the development of muscles in chicken embryos compared with the 40-ppm dosage and provide crucial information for the use of silver nanoparticles in poultry production.
Polymerized Albumin Receptor of Hepatitis B Virus for Evading the Reticuloendothelial System

Various strategies, such as optimization of surface chemistry, size, shape, and charge, have been undertaken to develop nanoparticles (NPs) as DDS (drug delivery system) nanocarriers for evading the reticuloendothelial system (RES) in vivo. We previously developed a hollow NP composed of hepatitis B virus (HBV) surface antigen L proteins and lipid bilayers, hereinafter referred to as bio-nanocapsule (BNC), as a nonviral DDS nanocarrier. Such a BNC harbors the HBV-derived human hepatic cell-specific infection mechanism, and intravenously injected BNCs by themselves were shown to avoid clearance by RES-rich organs and accumulate in target tissues. In this study, since the surface modification with albumins is known to prolong the circulation time of nanomedicines, we examined whether the polymerized albumin receptor (PAR) of BNCs contributes to RES evasion in mouse liver. Our results show that NPs conjugated with peptides possessing sufficient PAR activity were captured by Kupffer cells less efficiently in vitro and were able to circulate for a longer period of time in vivo. Comparing with polyethylene glycol, PAR peptides were shown to reduce the recognition by RES to equal content. Taken together, our results strongly suggest that the PAR domain of BNCs, as well as HBV, harbors an innate RES evasion mechanism. Therefore, the surface modification with PAR peptides could be an alternative strategy for improving the pharmacodynamics and pharmacokinetics of forthcoming nanomedicines.
UTM-Chain: Blockchain-Based Secure Unmanned Traffic Management for Internet of Drones

Unmanned aerial systems (UAVs) are dramatically evolving and promoting several civil applications. However, they are still prone to many security issues that threaten public safety. Security becomes even more challenging when they are connected to the Internet as their data stream is exposed to attacks. Unmanned traffic management (UTM) represents one of the most important topics for small unmanned aerial systems for beyond-line-of-sight operations in controlled low-altitude airspace. However, without securing the flight path exchanges between drones and ground stations or control centers, serious security threats may lead to disastrous situations. For example, a predefined flight path could be easily altered to make the drone perform illegal operations. Motivated by these facts, this paper discusses the security issues for UTM’s components and addresses the security requirements for such systems. Moreover, we propose UTM-Chain, a lightweight blockchain-based security solution using hyperledger fabric for UTM of low-altitude UAVs which fits the computational and storage resources limitations of UAVs. Moreover, UTM-Chain provides secure and unalterable traffic data between the UAVs and their ground control stations. The performance of the proposed system related to transaction latency and resource utilization is analyzed by using cAdvisor. Finally, the analysis of security aspects demonstrates that the proposed UTM-Chain scheme is feasible and extensible for the secure sharing of UAV data.
In vitro Assessment of Immunological Synapse Formation by Flow Cytometry

[Abstract] In adaptive immune system, formation of immunological synapse between T cells and antigen presenting cells (dendritic cells, B cells, and macrophages) or target cells (tumor cells and viral-infected cells) is critical for the execution of T cell immune responses via cytokine secretion or direct killing activity. Here, we describe the practical methods that directly measure the number of conjugates as a result of immunological synapse formation between T cells and superantigen-loaded B cells or between cytotoxic T cells and antigen-loaded target cells by dual-color flow cytometry.
A Low Tumor Mutational Burden and PTEN Mutations Are Predictors of a Negative Response to PD-1 Blockade in MSI-H/dMMR Gastrointestinal Tumors

Purpose: This study performed a comprehensive molecular characterization of microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) gastrointestinal (GI) tumors to elucidate predictors of response to PD-1 blockade. Experimental Design: Forty-five patients with MSI-H/dMMR GI tumors, including gastric cancer, colorectal cancer, cholangiocarcinoma, small intestine cancer, pancreatic cancer, and duodenal cancer, receiving PD-1 blockade were analyzed. We conducted the genomic profiling of GI tumors by whole-exome sequencing or targeted next-generation sequencing. The tumor microenvironment was evaluated by transcriptomic analysis and multiplex fluorescence IHC. Results: Patients with low tumor mutational burdens (TMBs) had lower objective response rates (ORRs; 0% vs. 48.8%) and a significantly shorter progression-free survival (PFS; 2.3 vs. 15.6 months; HR, 6.20; P = 0.002) than those with high TMBs. Among common gene alterations in GI tumors, only PTEN mutations, which were mutually exclusive with a low TMB, were significantly associated with a lower ORRs than wild-type PTEN (21.4 vs. 54.8%; odds, 4.45; P = 0.045). Compared with wild-type PTEN, PTEN mutations in the phosphatase domain were associated with significantly lower ORRs (12.5 vs. 54.8%; P = 0.049), shorter PFS (2.6 vs. 15.6 months; HR, 5.04; P < 0.001), lower intratumoral CD8+ T-cell levels, higher intratumoral CD204+ macrophage levels, and PI3K/AKT/mTOR pathway enrichment, whereas PTEN mutations in the C2 domain were not. Conclusions: Low TMBs and PTEN mutations, especially mutations in the phosphatase domain associated with an immunosuppressive environment, were mutually exclusive and might be negative predictors of PD-1 blockade responses in patients with MSI-H/dMMR GI tumors.
Mycobiota Associated with the Vascular Wilt of Poplar

In 2017, a 560-ha area of hybrid poplar plantation in northern Poland showed symptoms of tree decline. The leaves appeared smaller, yellow-brown, and were shed prematurely. Twigs and smaller branches died without distinct cankers. Trunks decayed from the base. The phloem and xylem showed brown necrosis. Ten percent of the trees died 1–2 months after the first appearance of the symptoms. None of these symptoms were typical for known poplar diseases. The trees’ mycobiota were analysed using Illumina sequencing. A total of 69 467 and 70 218 operational taxonomic units (OTUs) were obtained from the soil and wood. Blastocladiomycota and Chytridiomycota occurred only in the soil, with very low frequencies (0.005% and 0.008%). Two taxa of Glomeromycota, with frequencies of 0.001%, occurred in the wood. In the soil and wood, the frequencies of Zygomycota were 3.631% and 0.006%, the frequencies of Ascomycota were 45.299% and 68.697%, and the frequencies of Basidiomycota were 4.119% and 2.076%. At least 400 taxa of fungi were present. The identifiable Zygomycota, Ascomycota, and Basidiomycota were represented by at least 18, 263 and 81 taxa, respectively. Many fungi were common to the soil and wood, but 160 taxa occurred only in soil and 73 occurred only in wood. The root pathogens included species of Oomycota. The vascular and parenchymal pathogens included species of Ascomycota and of Basidiomycota. The initial endophytic character of the fungi is emphasized. Soil, and possibly planting material, may be the sources of the pathogen inoculum, and climate warming is likely to be a predisposing factor. A water deficit may increase the trees’ susceptibility. The epidemiology of poplar vascular wilt reminds grapevine trunk diseases (GTD), including esca, black foot disease and Petri disease.
Grumpy face during adult sleep: A clue to negative emotion during sleep?

Negative facial expressions and frowns have been studied (albeit more rarely than smiles) in fetus’ and neonate’ sleep, but they have not been investigated during adult sleep. Video polysomnography (including corrugator muscle electromyography and face‐focussed video) was used to study negative facial expressions in sleeping adults, including healthy subjects and patients with/out parasomnia. Frowns were observed during sleep in 89/91 (97.8%) adults during normal (29 healthy subjects) and abnormal sleep (29 patients without parasomnia, 15 patients with disorders of arousal and 18 patients with rapid eye movement [REM] sleep behaviour disorder [RBD]). In healthy subjects, the following events occurred in decreasing frequency: isometric corrugator activations, brief frowns, and then prolonged frowns and raised eyebrows (both similarly rare). Frowns predominated in REM sleep, and had a lower frequency in non‐REM sleep. In healthy subjects, frowns were elementary and not associated with other face movements to the point of composing negative expressions. In contrast, frowns were occasionally associated with overt negative facial expressions in REM sleep in patients with RBD and a young patient with night terrors. They included mostly painful expressions and rarely sadness and anger in connection with apparently negative behaviours (shouts, painful moaning, and speeches). Frowns persist during normal sleep (mostly in REM sleep) in adults, but overt negative facial expressions are restricted to patients with parasomnia. Whether elementary frowns translate a negative dream emotion should be determined, but overt negative facial expressions during RBD could be used as a direct access to dream emotions.
Development and Content Validation of an Instrument to Measure Medication Self-Management in Older Adults

Background: For older adults, the capacity to self-manage medications may be limited by several factors. However, currently available tools do not permit a comprehensive assessment of such limitations. The Domain Specific Limitation in Medication Management Capacity (DSL-MMC) was developed to address this need. This study aimed to establish the face and content validity of the DSL-MMC. Methods: The DSL-MMC tool consisted of 4 domains and 12 sub-domains with 42 items including: 1. physical abilities (vision, dexterity, hearing); 2. cognition (comprehension, memory, executive functioning); 3. medication regimen complexity (dosing regimen, non-oral administration, polypharmacy); and 4. access/caregiver (prescription refill, new prescription, caregiver). Pharmacists assessed each item for relevance, importance, readability, understandability, and representation. Items with content validity index (CVI) scores of <0.80 for relevance were examined for revision or removal. Results: Twelve pharmacists participated in the study. CVI scores for relevance and importance of domains were 1.0; of the sub-domains, two were below 0.80. Among the 42 items, 35 (83%) and 30 (71%) maintained CVI scores above 0.80 for relevance and importance, respectively. Five items were removed, three were merged and seven were modified due to low CVI scores and/or feedback. Conclusion: The DSL-MMC has been validated for content.
The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos

Ras-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor acting downstream of RAS signaling. Rreb1 has been implicated in cancer and Noonan-like RASopathies. However, little is known about its role in mammalian non-disease states. Here, we show that Rreb1 is essential for mouse embryonic development. Loss of Rreb1 led to a reduction in the expression of vasculogenic factors, cardiovascular defects, and embryonic lethality. During gastrulation, the absence of Rreb1 also resulted in the upregulation of cytoskeleton-associated genes, a change in the organization of F-ACTIN and adherens junctions within the pluripotent epiblast, and perturbed epithelial architecture. Moreover, Rreb1 mutant cells ectopically exited the epiblast epithelium through the underlying basement membrane, paralleling cell behaviors observed during metastasis. Thus, disentangling the function of Rreb1 in development should shed light on its role in cancer and other diseases involving loss of epithelial integrity.