Miracle-dz/UniFAR-FTUs huggingface dataset:
Laboratory Diagnosis of COVID-19: Current Issues and Challenges

The COVID-19 outbreak has had a major impact on clinical microbiology laboratories in the past several months. This commentary covers current issues and challenges for the laboratory diagnosis of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19. Appropriate measures are required to keep laboratory staff safe while producing reliable test results. ABSTRACT The COVID-19 outbreak has had a major impact on clinical microbiology laboratories in the past several months. This commentary covers current issues and challenges for the laboratory diagnosis of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19. Appropriate measures are required to keep laboratory staff safe while producing reliable test results. In the analytic stage, real-time reverse transcription-PCR (RT-PCR) assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools. In the postanalytical stage, testing results should be carefully interpreted using both molecular and serological findings. Finally, random-access, integrated devices available at the point of care with scalable capacities will facilitate the rapid and accurate diagnosis and monitoring of SARS-CoV-2 infections and greatly assist in the control of this outbreak.
Dengue Surveillance System in Brazil: A Qualitative Study in the Federal District

Dengue’s increasing trends raise concerns over global health and pose a challenge to the Brazilian health system, highlighting the necessity of a strong surveillance system to reduce morbidity, mortality, and the economic burden of this disease. Although the Brazilian surveillance system reports more dengue cases than any other country, recent studies suggest that non-reported cases are the majority. The aim of the study is to explore the strengths and weaknesses of the Brazilian surveillance system, particularly looking at the functioning of data collection and reporting. This was done through qualitative semi-structured interviews with 17 experts in dengue surveillance, supported by quantitative data from the official notification system. To select the interviewees, purposive and theoretical sampling were used. Data were analyzed through thematic analysis. The research highlighted that a lack of human and technological resources in healthcare units and surveillance departments slows down the notification process and data analysis. Due to a lack of integration in the private sector, the surveillance system fails to detect the socioeconomic profile of the patients. Investments in public healthcare, human and technological resources for surveillance and better integration in the private healthcare system, and vector surveillance may improve dengue surveillance.
TAAR1 agonists attenuate extended‐access cocaine self‐administration and yohimbine‐induced reinstatement of cocaine‐seeking

The trace amine‐associated receptor 1 (TAAR1) negatively modulates dopamine transmission. Our previous studies demonstrated that TAAR1 agonists attenuated cue‐ and drug‐induced cocaine‐seeking and increased the elasticity of the cocaine demand curve, in the short‐access cocaine self‐administration model. Compulsive use of cocaine, which is an essential criterion of cocaine use disorder, can be induced by extended access to cocaine self‐administration.
A retrospective study

Cooled-radiofrequency (CRFA) is a newer technique and may have some theoretical advantages over traditional radiofrequency ablation (TRFA). In this study, we aimed to investigate the efficacy and safety of CRFA for the treatment of lumbar facet joint-mediated pain. In this retrospective study, we evaluated 185 CRFA performed on 105 patients. All patients with axial lower back who received the preliminary diagnosis of lumbar facet joint-mediated pain and refractory to conservative therapy underwent diagnostic medial branch blocks. CRFAwas recommended to those patients who responded favorably to two sets of diagnostic medial branch blocks. Pain scores in numeric rating scale (NRS) were recorded pre-treatment and post-treatment at different time-points. The primary outcome measure was to report descriptive NRS score and average % improvement from baseline at each time point. A significant pain relief was determined by a decrease of≥50% of mean NRS. Secondary outcomemeasure was the time to repeat treatment with subsequent CRFA. Adverse events were also recorded. Primary outcomemeasure determined as the improvement in NRS, for at least 50% or more, was achieved in both 1st (4–8weeks) and 2nd (>2–6months) follow-up (FU) with 60.5% and 53.6% reduction in NRS respectively. Our subgroup analysis comparing the younger (<50) and older (≥50) age groups showed superior pain relief with CRFA in the older (≥50) age group, both in the 1st (4–8 weeks) and 2nd (>2–6months) FU time points (63.4% and 58.4% reduction in NRS, respectively). Cooled-radiofrequency ablation is an effective and safe procedure for the treatment of chronic lumbar facet joint related pain. The duration of pain relief was comparable to traditional radiofrequency ablation as reported in the literature. Abbreviations: CRFA =Cooled radiofrequency neurotomy, FU = Follow up, NRS =Numeric rating scale, RFA = Radiofrequency neurotomy, TRFA = Traditional radiofrequency neurotomy.
Insights into the Synthesis, Secretion and Curing of Barnacle Cyprid Adhesive via Transcriptomic and Proteomic Analyses of the Cement Gland

Barnacles represent one of the model organisms used for antifouling research, however, knowledge regarding the molecular mechanisms underlying barnacle cyprid cementation is relatively scarce. Here, RNA-seq was used to obtain the transcriptomes of the cement glands where adhesive is generated and the remaining carcasses of Megabalanus volcano cyprids. Comparative transcriptomic analysis identified 9060 differentially expressed genes, with 4383 upregulated in the cement glands. Four cement proteins, named Mvcp113k, Mvcp130k, Mvcp52k and Mvlcp1-122k, were detected in the cement glands. The salivary secretion pathway was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed genes, implying that the secretion of cyprid adhesive might be analogous to that of saliva. Lysyl oxidase had a higher expression level in the cement glands and was speculated to function in the curing of cyprid adhesive. Furthermore, the KEGG enrichment analysis of the 352 proteins identified in the cement gland proteome partially confirmed the comparative transcriptomic results. These results present insights into the molecular mechanisms underlying the synthesis, secretion and curing of barnacle cyprid adhesive and provide potential molecular targets for the development of environmentally friendly antifouling compounds.
Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation

Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß, but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis. Here we evaluate the potential biological activities of recombinant sIFNAR2 without the mediation of IFN-ß in human cells. Recombinant sIFNAR2 down-regulated the production of IL-17 and IFN-ɣ and reduced the cell proliferation rate. Moreover, it showed a strong antiviral activity, fully protecting the cell monolayer after being infected by the virus. Specific inhibitors completely abrogated the antiviral activity of IFN-ß, but not that of the recombinant sIFNAR2, and there was no activation of the JAK-STAT signaling pathway. Consequently, r-sIFNAR2 exerts immunomodulatory, antiproliferative and antiviral activities without IFN-ß mediation, and could be a promising treatment against viral infections and immune-mediated diseases.
The COVID-19 pandemic and research shutdown: staying safe and productive.

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has caused severe disease outcomes and widespread infections not seen in terms of its case fatality rate and global economic impact since the 1918-1919 Spanish flu; the latter leading to 675,000 deaths in the United States (US) (50 million worldwide).
A Micro-Optic Stalk (μOS) System to Model the Collective Migration of Retinal Neuroblasts

Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes of replacement neural stem cells. The system scales with the microstructure of the Drosophila optic stalk, which is a pre-cursor to the optic nerve, to produce signaling fields spatially comparable to in vivo RNB stimuli. Experiments used the micro-optic stalk system, or μOS, to demonstrate the preferred sizing and directional migration of collective, motile RNB groups in response to changes in exogenous concentrations of fibroblast growth factor (FGF), which is a key factor in development. Our data highlight the importance of cell-to-cell contacts in enabling cell cohesion during collective RNB migration and point to the unexplored synergy of invertebrate cell study and microfluidic platforms to advance regenerative strategies.
Surgical Treatment of Femoral Neck Fractures: A Brief Review

Hip fracture is a cause for concern in the geriatric population. It is one of the leading causes of traumatic injury in this demographic and correlates to a higher risk of all-cause morbidity and mortality. The Garden classification of femoral neck fractures (FNF) dictates treatment via internal fixation or hip replacement, including hemiarthroplasty or total hip arthroplasty. This review summarizes existing literature that has explored the difference in outcomes between internal fixation, hemiarthroplasty, and total hip arthroplasty for nondisplaced and displaced FNF in the geriatric population, and more specifically highlights the risks and benefits of a cemented vs. uncemented approach to hemiarthroplasty.
A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design

The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl2 concentrations, whereas zeta potential depends only on the Alg and CaCl2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (−9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm−1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model (R2 between 0.956–0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.
Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke

Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS.
Effect of Tack Cure on Polymerization Shrinkage of Resin-Based Luting Cements.

OBJECTIVES To evaluate the effect of tack cure on polymerization shrinkage (PS) of resin-based luting cements. METHODS AND MATERIALS One composite resin cement, Duo-Link (Duolink); two self-adhesive resin cements, RelyX U200 (U200) and G-CEM LinkAce (GCem); and one resin-modified glass ionomer cement, RelyX Luting Plus (Luting+), were used for measuring PS in light-cure (LC group), self-cure (SC group), and two tack-cure modes that were light cured (TC-LC group) or self-cured (TC-SC group) after tack cure. PS was measured by a modified bonded disc method for 1600 seconds and analyzed with two-way analysis of variance and Tukey honestly significant difference test. To investigate the effect of tack cure on light cure or self-cure, data were analyzed with an independent-samples t-test with tack cure as a variable. The significance level was 5%. RESULTS Regarding cure mode, Duolink showed a significantly lower PS in the TC-SC group compared with the other groups. Luting+ showed a significantly lower PS in the TC-SC group than in the SC group. U200 showed a significantly lower PS in the self-cure groups compared with that in the light-cure groups. The PS of GCem was not affected by cure mode. Regarding cements, Luting+ showed the highest PS, followed by GCem, Duolink, and U200 (p<0.05). Self-cure of Duolink and Luting+ was negatively affected by tack cure, while light cure was not affected. U200 and GCem were not affected by tack cure either in the self-cure or light-cure groups. CONCLUSION For the tested cements, tack cure decreased the PS of Duolink and Luting+ when they were self-cured after tack cure. When the cements were light cured after tack cure, PS was not affected by tack cure in any cement.
Characterization of Applied Forces and Torques During Rigid Bronchoscopy Intubation

Background: Rigid bronchoscopy intubation poses a significant risk of complication to patients from mechanical trauma. Despite the importance of precision in forces exerted by surgeons during intubation, no prior study has analyzed the overall forces and torques involved in rigid bronchoscopy intubation, and whether existing training modalities accurately replicate them. Methods: A bronchoscope was equipped with a 6-axis load sensor to measure forces and torques applied during rigid bronchoscopy intubation. The device was applied to measure intubation forces in low-fidelity manikins and patients by interventional pulmonologists. Results: Axial and lateral forces were measured during rigid bronchoscope intubation from the mouth to the mid-trachea. The mean axial/lateral forces recorded during manikin trials were 6.93/18.06 N, whereas those recorded during patient trials were 4.57/9.43 N. Average axial and lateral force application was therefore 51.6% and 92.6% higher in manikin, respectively. Applied axial torque averaged across all human trials was 130.5 N-mm compared with 78.3 N-mm for manikin trials, 40% lower in manikin than in human. Lateral torque application during manikin intubation showed greater variation in between trials and a greater range of SDs within trials. Conclusion: This was the first application of a rigid bronchoscope measurement device designed to measure forces applied at the handle. Force and torque discrepancies between manikin training and patient applications were found, indicating a possible mismatch between the haptic feedback received by physicians during rigid training and application. This inconsistency could be resolved via novel haptic training modalities and help increase atraumatic intubations.
Comparative Proteomic Analysis by iTRAQ Reveals that Plastid Pigment Metabolism Contributes to Leaf Color Changes in Tobacco (Nicotiana tabacum) during Curing

Tobacco (Nicotiana tabacum), is a world’s major non-food agricultural crop widely cultivated for its economic value. Among several color change associated biological processes, plastid pigment metabolism is of trivial importance in postharvest plant organs during curing and storage. However, the molecular mechanisms involved in carotenoid and chlorophyll metabolism, as well as color change in tobacco leaves during curing, need further elaboration. Here, proteomic analysis at different curing stages (0 h, 48 h, 72 h) was performed in tobacco cv. Bi’na1 with an aim to investigate the molecular mechanisms of pigment metabolism in tobacco leaves as revealed by the iTRAQ proteomic approach. Our results displayed significant differences in leaf color parameters and ultrastructural fingerprints that indicate an acceleration of chloroplast disintegration and promotion of pigment degradation in tobacco leaves due to curing. In total, 5931 proteins were identified, of which 923 (450 up-regulated, 452 down-regulated, and 21 common) differentially expressed proteins (DEPs) were obtained from tobacco leaves. To elucidate the molecular mechanisms of pigment metabolism and color change, 19 DEPs involved in carotenoid metabolism and 12 DEPs related to chlorophyll metabolism were screened. The results exhibited the complex regulation of DEPs in carotenoid metabolism, a negative regulation in chlorophyll biosynthesis, and a positive regulation in chlorophyll breakdown, which delayed the degradation of xanthophylls and accelerated the breakdown of chlorophylls, promoting the formation of yellow color during curing. Particularly, the up-regulation of the chlorophyllase-1-like isoform X2 was the key protein regulatory mechanism responsible for chlorophyll metabolism and color change. The expression pattern of 8 genes was consistent with the iTRAQ data. These results not only provide new insights into pigment metabolism and color change underlying the postharvest physiological regulatory networks in plants, but also a broader perspective, which prompts us to pay attention to further screen key proteins in tobacco leaves during curing.
EAT-18 is an essential auxiliary protein interacting with the non-alpha nAChR subunit EAT-2 to form a functional receptor

Nematode parasites infect approximately 1.5 billion people globally and are a significant public health concern. There is an accepted need for new, more effective anthelmintic drugs. Nicotinic acetylcholine receptors on parasite nerve and somatic muscle are targets of the cholinomimetic anthelmintics, while glutamate-gated chloride channels in the pharynx of the nematode are affected by the avermectins. Here we describe a novel nicotinic acetylcholine receptor on the nematode pharynx that is a potential new drug target. This homomeric receptor is comprised of five non-α EAT-2 subunits and is not sensitive to existing cholinomimetic anthelmintics. We found that EAT-18, a novel auxiliary subunit protein, is essential for functional expression of the receptor. EAT-18 directly interacts with the mature receptor, and different homologs alter the pharmacological properties. Thus we have described not only a novel potential drug target but also a new type of obligate auxiliary protein for nAChRs.
Pentraxin 3 (PTX3): A Molecular Marker of Endothelial Dysfunction in Chronic Migraine

Even though endothelial dysfunction is known to play a role in migraine pathophysiology, studies regarding levels of endothelial biomarkers in migraine have controversial results. Our aim was to evaluate the role of pentraxin 3 (PTX3) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) as potential biomarkers of endothelial dysfunction in chronic migraine (CM). We performed a case-control study including 102 CM patients and 28 control subjects and measured serum levels of markers of endothelial dysfunction (PTX3 and sTWEAK) and inflammation [high-sensitivity C-reactive protein (hs-CRP)] as well as brachial artery flow-mediated dilation (FMD) during interictal periods. Interictal serum levels of PTX3 and sTWEAK were higher in CM patients than in controls (1350.6 ± 54.8 versus 476.1 ± 49.4 pg/mL, p < 0.001 and 255.7 ± 21.1 versus 26.4 ± 2.6 pg/mL, p < 0.0001; respectively). FMD was diminished in CM patients compared to controls (9.6 ± 0.6 versus 15.2 ± 0.9%, p < 0.001). Both PTX3 and sTWEAK were negatively correlated with FMD (r = −0.508, p < 0.001 and r = −0.188, p = 0.033; respectively). After adjustment of confounders, PTX3 remained significantly correlated to FMD (r = −0.250, p = 0.013). Diagnosis of CM was 68.4 times more likely in an individual with levels of PTX3 ≥ 832.5 pg/mL, suggesting that PTX3 could be a novel biomarker of endothelial dysfunction in CM.