Miracle-dz/UniFAR-FTUs huggingface dataset:
Accurate Diagnosis of COVID-19 by a Novel Immunogenic Secreted SARS-CoV-2 orf8 Protein

Current commercially available serological tests for COVID-19 patients are detecting antibodies against SARS-CoV-2 nucleoprotein and spike glycoprotein. The antinucleoprotein and antispike antibodies can be accurately detected in patients during the mid or late stage of infection, and therefore, these assays have not been widely used for early diagnosis of COVID-19. In this study, we characterized the secretory property of a SARS-CoV-2 orf8 protein and proposed that orf8 secretion during infection facilitates early mounting of the B cell response. We demonstrated the presence of anti-orf8 antibodies in both symptomatic and asymptomatic patients during the early stage of infection, while the anti-N antibody is not detected. Our serological test detecting anti-orf8 antibodies may facilitate the development of early and accurate diagnosis for COVID-19. ABSTRACT An accurate diagnostic test for early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the key weapon to control the coronavirus disease 2019 (COVID-19) pandemic. We previously reported that the SARS-CoV-2 genome contains a unique orf8 accessory gene absent from other human-pathogenic coronaviruses. Here, we characterized the SARS-CoV-2 orf8 as a novel immunogenic secreted protein and utilized it for the accurate diagnosis of COVID-19. Extracellular orf8 protein was detected in cell culture supernatant and in sera of COVID-19 patients. In addition, orf8 was found highly immunogenic in COVID-19 patients, who showed early seropositivity for anti-orf8 IgM, IgG, and IgA. We hypothesize that orf8 secretion during SARS-CoV-2 infection facilitates early mounting of B cell response. The serological test detecting anti-orf8 IgG antibody can be used for the early and accurate diagnosis of COVID-19. IMPORTANCE Current commercially available serological tests for COVID-19 patients are detecting antibodies against SARS-CoV-2 nucleoprotein and spike glycoprotein. The antinucleoprotein and antispike antibodies can be accurately detected in patients during the mid or late stage of infection, and therefore, these assays have not been widely used for early diagnosis of COVID-19. In this study, we characterized the secretory property of a SARS-CoV-2 orf8 protein and proposed that orf8 secretion during infection facilitates early mounting of the B cell response. We demonstrated the presence of anti-orf8 antibodies in both symptomatic and asymptomatic patients during the early stage of infection, while the anti-N antibody is not detected. Our serological test detecting anti-orf8 antibodies may facilitate the development of early and accurate diagnosis for COVID-19.
Hot Gas Pressure Forming of Ti-55 High Temperature Titanium Alloy Tubular Component

In this paper, hot gas pressure forming (HGPF) of Ti-55 high temperature titanium alloy was studied. The hot deformation behavior was studied by uniaxial tensile tests at temperatures ranging from 750 to 900 °C with strain rates ranging from 0.001 to 0.05 s−1, and the microstructure evolution during tensile tests was characterized by electron backscatter diffraction. Finite element (FE) simulation of HGPF was carried out to study the effect of axial feeding on thickness distribution. Forming tests were performed to validate this process for Ti-55 alloy. Results show that when the temperature was higher than 750 °C, the elongation was large enough for HGPF of Ti-55 alloy. Dynamic recrystallization (DRX) occurred during the tensile deformation, which could refine the microstructure. The thickness uniformity of the formed part could be improved by increasing feeding length. The maximum thinning ratio decreased from 27.7% to 11.5% with the feeding length increasing from 0 to 20 mm. A qualified Ti-55 alloy component was successfully formed at 850 °C, the microstructure was slightly refined after forming, and the average post-form yield strength and peak strength were increased by 8.7% and 6.9%, respectively. Pre-heat treatment at 950 °C before HGPF could obtain Ti-55 alloy tubular component with bimodal microstructure and further improve the post-form strength.
Deciphering the molecular mechanism of stop codon readthrough

Recognition of the stop codon by the translation machinery is essential to terminating translation at the right position and to synthesizing a protein of the correct size. Under certain conditions, the stop codon can be recognized as a coding codon promoting translation, which then terminates at a later stop codon. This event, called stop codon readthrough, occurs either by error, due to a dedicated regulatory environment leading to generation of different protein isoforms, or through the action of a readthrough compound. This review focuses on the mechanisms of stop codon readthrough, the nucleotide and protein environments that facilitate or inhibit it, and the therapeutic interest of stop codon readthrough in the treatment of genetic diseases caused by nonsense mutations.
Production of hydrogen sulfide by the intestinal microbiota and epithelial cells and consequences for the colonic and rectal mucosa.

Among bacterial metabolites, hydrogen sulfide (H2S) has received increasing attention. The epithelial cells of the large intestine are exposed to two sources of H2S. The main one is the luminal source that results from specific bacteria metabolic activity towards sulfur-containing substrates. The other source in colonocytes is from the intracellular production mainly through cystathionine beta-synthase (CBS) activity. H2S is oxidized by the mitochondrial sulfide oxidation unit, resulting in ATP synthesis, and thus establishing this compound as the first mineral energy substrate in colonocytes. However, when the intracellular H2S concentration exceeds the colonocyte capacity for its oxidation, it inhibits the mitochondrial respiratory chain, thus affecting energy metabolism. Higher luminal H2S concentration affects the integrity of the mucus layer and displays pro-inflammatory effects. However, a low/minimal amount of endogenous H2S exerts an anti-inflammatory effect on the colon mucosa pointing out the ambivalent effect of H2S depending on its intracellular concentration. Regarding colorectal carcinogenesis, forced CBS expression in late adenoma-like colonocytes increased their proliferative activity, bioenergetics capacity, and tumorigenicity; while genetic ablation of CBS in mice resulted in a reduced number of mutagen-induced aberrant crypt foci. Activation of endogenous H2S production and low H2S extracellular concentration enhance cancerous colorectal cells proliferation. Higher exogenous H2S concentrations markedly reduce mitochondrial ATP synthesis and proliferative capacity in cancerous cells, enhance glycolysis, but do not affect their ATP cell content nor viability. Thus, it appears that, notably through an effect on colonocyte energy metabolism, endogenous and microbiota-derived H2S are involved in the host intestinal physiology and physiopathology.
The Effects of Strength and Conditioning in Physical Education on Athletic Motor Skill Competencies and Psychological Attributes of Secondary School Children: A Pilot Study

Leading global physical activity guidelines advocate that young children need to engage in activities that strengthen musculoskeletal tissues and improve movement skill competency. The purpose of this study was to examine the effects of delivering strength and conditioning as part of the physical education curriculum on athletic motor skill competencies (AMSC), physical performance, and psychosocial factors. Forty-six school children aged 11–14 were included in the study, and sub-divided firstly by sex and then into intervention and control groups. Intervention groups received nine lessons of strength and conditioning based activities over a six-week period, while the control groups continued with traditional physical education curricula. The resistance training skills battery (RTSB) and tuck jump assessment (TJA) assessed AMSC. Standing long jump distance assessed lower limb strength, and online surveys examined motivation, physical self-efficacy and self-esteem. Male and female intervention groups significantly improved RTSB (p > 0.05) whereas no changes were observed in the control groups. No changes were observed in the intervention groups TJA and only trivial and small non-significant changes in standing long jump performance. Significant increases in motivation of the male intervention group occurred. Strength and conditioning integrated in physical education can improve AMSC in short-term interventions.
The age of Clovis—13,050 to 12,750 cal yr B.P.

The Clovis complex dates from 13,050 to 12,750 cal yr B.P. during a time of major environmental change. Thirty-two radiocarbon ages on bone, charcoal, and carbonized plant remains from 10 Clovis sites range from 11,110 ± 40 to 10,820 ± 10 14C years before the present (yr B.P.). These radiocarbon ages provide a maximum calibrated (cal) age range for Clovis of ~13,050 to ~12,750 cal yr B.P. This radiocarbon record suggests that Clovis first appeared at the end of the Allerød and is one of at least three contemporary archaeological complexes in the Western Hemisphere during the terminal Pleistocene. Stemmed projectile points in western North America are coeval and even older than Clovis, and the Fishtail point complex is well established in the southern cone of South America by ~12,900 cal yr B.P. Clovis disappeared ~12,750 cal yr B.P. at the beginning of the Younger Dryas, coincident with the extinction of the remaining North American megafauna (Proboscideans) and the appearance of multiple North American regional archaeological complexes.
Low‐dose ketamine affects blood pressure, but not muscle sympathetic nerve activity, during progressive central hypovolemia without altering tolerance

Haemorrhage is the leading cause of battlefield and civilian trauma deaths. Given that a haemorrhagic injury on the battlefield is almost always associated with pain, it is paramount that the administered pain medication does not disrupt the physiological mechanisms that are beneficial in defending against the haemorrhagic insult. Current guidelines from the US Army's Committee on Tactical Combat Casualty Care (CoTCCC) for the selection of pain medications administered to a haemorrhaging soldier are based upon limited scientific evidence, with the clear majority of supporting studies being conducted on anaesthetized animals. Specifically, the influence of low‐dose ketamine, one of three analgesics employed in the pre‐hospital setting by the US Army, on haemorrhagic tolerance in humans is unknown. For the first time in conscious males and females, the findings of the present study demonstrate that the administration of an analgesic dose of ketamine does not compromise tolerance to a simulated haemorrhagic insult. Increases in muscle sympathetic nerve activity during progressive lower‐body negative pressure were not different between trials. Despite the lack of differences for muscle sympathetic nerve activity responses, mean blood pressure and heart rate were higher during moderate hypovolemia after ketamine vs. placebo administration.
Fatty Acid Synthase Is a Key Enabler for Endocrine Resistance in Heregulin-Overexpressing Luminal B-Like Breast Cancer

HER2 transactivation by the HER3 ligand heregulin (HRG) promotes an endocrine-resistant phenotype in the estrogen receptor-positive (ER+) luminal-B subtype of breast cancer. The underlying biological mechanisms that link them are, however, incompletely understood. Here, we evaluated the putative role of the lipogenic enzyme fatty acid synthase (FASN) as a major cause of HRG-driven endocrine resistance in ER+/HER2-negative breast cancer cells. MCF-7 cells engineered to stably overexpress HRG (MCF-7/HRG), an in vitro model of tamoxifen/fulvestrant-resistant luminal B-like breast cancer, showed a pronounced up-regulation of FASN gene/FASN protein expression. Autocrine HRG up-regulated FASN expression via HER2 transactivation and downstream activation of PI-3K/AKT and MAPK-ERK1/2 signaling pathways. The HRG-driven FASN-overexpressing phenotype was fully prevented in MCF-7 cells expressing a structural deletion mutant of HRG that is sequestered in a cellular compartment and lacks the ability to promote endocrine-resistance in an autocrine manner. Pharmacological inhibition of FASN activity blocked the estradiol-independent and tamoxifen/fulvestrant-refractory ability of MCF-7/HRG cells to anchorage-independently grow in soft-agar. In vivo treatment with a FASN inhibitor restored the anti-tumor activity of tamoxifen and fulvestrant against fast-growing, hormone-resistant MCF-7/HRG xenograft tumors in mice. Overall, these findings implicate FASN as a key enabler for endocrine resistance in HRG+/HER2- breast cancer and highlight the therapeutic potential of FASN inhibitors for the treatment of endocrine therapy-resistant luminal-B breast cancer.
Investigating fork rotation and DNA pre-catenation in Saccharomyces cerevisiae

During DNA replication, the intertwining between the two strands of the parental DNA double helix needs to be resolved. This is achieved in two ways: by the action of topoisomerases ahead of the replication fork or by fork rotation and precatenation of the newly replicated DNA helixes. However, the factors that influence fork rotation and pre-catenation remain unknown. In this thesis, I used classical genetics and high-resolution two-dimensional agarose gel electrophoresis to identify the replisome-associated factors important for fork rotation and DNA pre-catenation during DNA replication in the yeast Saccharomyces cerevisiae. The results indicate that fork rotation and precatenation are impeded by two non-essential evolutionarily conserved replisome components: the Timeless and Tipin homologs, Tof1 and Csm3. Tof1/Csm3 are required for maintaining genome integrity during unperturbed and perturbed DNA replication. Similarly, checkpoint activation is also thought to stabilize the replisome in both unchallenged and challenged cells. However, none of the checkpoint kinases were found to alter the frequency of fork rotation during DNA replication in our study. Finally, constitutive DNA damage was found to be dramatically increased on newly replicated chromatids in the absence of Top2 and/or Tof1 as a consequence of excessive fork rotation and DNA pre-catenation during DNA replication in both western blot and ChIp-Seq experiments. This led to the activation of the DNA damage checkpoint and extensive DNA repair. These results suggest that although fork rotation and pre-catenation facilitate DNA unwinding under certain chromosomal contexts, excessive fork rotation and precatenation lead to defects on the newly replicated chromatids and therefore must be inhibited by Tof1/Csm3. In conclusion, I showed that Tof1/Timeless and Csm3/Tipin proteins regulate DNA replication and prevent chronic genome instability by minimizing pre-catenation during DNA replication.
The Antibacterial Efficacy and Mechanism of Plasma-Activated Water Against Salmonella Enteritidis (ATCC 13076) on Shell Eggs

Eggs are one of the most commonly consumed food items. Currently, chlorine washing is the most common method used to sanitize shell eggs. However, chlorine could react with organic matters to form a potential carcinogen, trihalomethanes, which can have a negative impact on human health. Plasma-activated water (PAW) has been demonstrated to inactivate microorganisms effectively without compromising the sensory qualities of shell eggs. For this study, various amounts (250, 500, 750, or 1000 mL) of PAW were generated by using one or two plasma jet(s) at 60 watts for 20 min with an air flow rate at 6 or 10 standard liters per minute (slm). After being inoculated with 7.0 log CFU Salmonella Enteritidis, one shell egg was placed into PAW for 30, 60, or 90 s with 1 or 2 acting plasma jet(s). When 2 plasma jets were used in a large amount of water (1000 mL), populations of S. Enteritidis were reduced from 7.92 log CFU/egg to 2.84 CFU/egg after 60 s of treatment. In addition, concentrations of ozone, hydrogen peroxide, nitrate, and nitrite in the PAW were correlated with the levels of antibacterial efficacy. The highest concentrations of ozone (1.22 ppm) and nitrate (55.5 ppm) were obtained with a larger water amount and lower air flow rate. High oxidation reduction potential (ORP) and low pH values were obtained with longer activation time, more plasma jet, and a lower air flow rate. Electron paramagnetic resonance (EPR) analyses demonstrated that reactive oxygen species (ROS) were generated in the PAW. The observation under the scanning electron microscope (SEM) revealed that bacterial cells were swollen, or even erupted after treatment with PAW. These results indicate that the bacterial cells lost control of cell permeability after the PAW treatment. This study shows that PAW is effective against S. Enteritidis on shell eggs in a large amount of water. Ozone, nitrate, and ROS could be the main causes for the inactivation of bacterial cells.
Gelatin Microsphere for Cartilage Tissue Engineering: Current and Future Strategies

The gelatin microsphere (GM) provides an attractive option for tissue engineering due to its versatility, as reported by various studies. This review presents the history, characteristics of, and the multiple approaches to, the production of GM, and in particular, the water in oil emulsification technique. Thereafter, the application of GM as a drug delivery system for cartilage diseases is introduced. The review then focusses on the emerging application of GM as a carrier for cells and biologics, and biologics delivery within a cartilage construct. The influence of GM on chondrocytes in terms of promoting chondrocyte proliferation and chondrogenic differentiation is highlighted. Furthermore, GM seeded with cells has been shown to have a high tendency to form aggregates; hence the concept of using GM seeded with cells as the building block for the formation of a complex tissue construct. Despite the advancement in GM research, some issues must still be addressed, particularly the improvement of GM’s ability to home to defect sites. As such, the strategy of intraarticular injection of GM seeded with antibody-coated cells is proposed. By addressing this in future studies, a better-targeted delivery system, that would result in more effective intervention, can be achieved.
Translation and Validation of the Modified A-DIVA Scale to European Portuguese: Difficult Intravenous Access Scale for Adult Patients

(1) Background: In Portugal, no accurate and reliable predictive instruments are known that could assist healthcare professionals in recognizing patients with difficult venous access. Thus, this study aimed to translate and validate the Modified A-DIVA scale to European Portuguese. (2) Methods: A methodological and cross-sectional study was conducted in two phases: translation of the Modified A-DIVA scale to European Portuguese following six stages proposed by Beaton and collaborators, and assessment of its psychometric properties in a non-probability sample of 100 patients who required peripheral intravenous catheterization in a Portuguese hospital. (3) Results: The European version of the Modified A-DIVA scale (A-DM scale) showed excellent inter-rater accordance scores, k = 0.593 (95% CI, 0.847 to 0.970), p < 0.0005. The A-DM scale’s criterion and construct validity was assessed through predictive, convergent, and correlational analysis with variables identified in the literature as associated with difficult peripheral intravenous access, with moderate to large magnitudes and statistical significance. (4) Conclusions: The A-DM scale is a reliable and valid instrument that can support healthcare professionals and researchers in the early identification of patients at risk of difficult peripheral intravenous access. Future validation studies are needed to test the A-DM scale’s applicability across clinical settings and in different patient cohorts.
Adult survival and reproductive rate are linked to habitat preference in territorial, year‐round resident Song Sparrows Melospiza melodia

Individual animal fitness can be strongly influenced by the ability to recognise habitat features which may be beneficial. Many studies focus on the effects of habitat on annual reproductive rate, even though adult survival is typically a greater influence on fitness and population growth in vertebrate species with intermediate to long lifespans. Understanding the effects of preferred habitat on individuals over the annual cycle is therefore necessary to predict its influences on individual fitness. This is particularly true in species that are resident and territorial year-round in the temperate zone, which may face potential trade-offs between habitat that maximises reproduction and that which maximises non-breeding season (‘over-winter’) survival. We used a 37-year study of Song Sparrows Melospiza melodia residing territorially year-round on a small island to examine what habitat features influenced adult over-winter survival, how site-specific variation in adult survival versus annual reproductive rate influenced long-term habitat preference, and if preferred sites conferred on average higher individual fitness. Habitat features such as area of shrub cover and exposure to intertidal coastline predicted adult over-winter survival independent of individual age or sex, population size, or winter weather. Long-term habitat preference (measured as occupation rate) was better predicted by site-specific annual reproductive rate than by expected over-winter survival, but preferred sites maximised fitness on average over the entire annual cycle,. Although adult over-winter survival had a greater influence on population growth (λ) than reproductive rate, the influence of reproductive rate on λ increased in preferred sites because site-specific variation in reproductive rate was higher than variation in expected over-winter survival. Because preferred habitats tended to have higher mean site-specific reproductive and adult survival rates, territorial birds in this population do not appear to experience seasonal trade-offs in preferred habitat, but are predicted to incur substantial fitness costs of settling in less-preferred sites. This article is protected by copyright. All rights reserved.
Post-surgical management of cataract: Light and dark in the 2020s

Cataract surgery is the most frequently performed elective surgery worldwide. Although considered a safe procedure, potentially sight-threatening adverse events are possible. Among these, post-surgical inflammation and infections are the most relevant. Anti-inflammatory drugs, such as corticosteroids, and topical antibiotics are the pillars for the treatment of inflammation and for the prevention of infections. However, uncertainties remain regarding the duration of both topical antibiotic prophylaxis and corticosteroid treatment. LEADER7, a recent international clinical study conducted with the new fixed combination of levofloxacin and dexamethasone eye drops in patients undergoing uncomplicated cataract surgery, found that 1-week topical antibiotic prophylaxis is just as effective as the 2-week course commonly used in clinical practice. The study also showed that treatment for 1 week with dexamethasone results in complete resolution of inflammatory signs and symptoms in over 85% of patients, for whom further prolongation of corticosteroid treatment is, therefore, not necessary. This new treatment strategy can represent a significant step forward to reduce the unjustified use of prophylactic antibiotics after cataract surgery, limiting the emergence of bacterial resistance, as well as representing an opportunity to optimize the use and safety of the corticosteroid treatment.