Miracle-dz/UniFAR-FTUs huggingface dataset:
Circular RNA profiling in plasma exosomes from patients with gastric cancer

Gastric cancer (GC) is among the most common cancer types worldwide with high mortality. Recent studies have shown that exosomes play a crucial role in the tumorigenesis of GC. The present study aimed to investigate the circular RNA (circRNA) profile in plasma exosomes from patients with gastric cancer (GC). Peripheral blood samples were collected from 5 patients with GC and 5 healthy donors, and exosomes were isolated from plasma. The high-throughput RNA sequencing (RNA-seq) method was applied to detect the differently expressed circRNAs (DE circRNAs). Subsequently, sequencing results were confirmed by reverse transcription quantitative (RT-q) PCR. The potential roles of DE circRNAs in GC were identified using Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analysis. Furthermore, MiRanda software was used to predict circRNA-micro-RNA (miRNA) interactions. A total of 67,880 circRNAs were identified in all samples and 1,060 significantly DE circRNAs were screened, including 620 upregulated and 440 downregulated ones. These results were further confirmed by RT-qPCR. GO and KEGG analyses revealed that these circRNAs were significantly associated with ‘cell cycle’, ‘cytoskeleton organization’, ‘cellular response to DNA damage’, ‘regulation of GTPase activity’, ‘phosphatidylinositol signaling pathway’, ‘MAPK signaling pathway’, ‘thyroid hormone signaling pathway’, ‘chemokine signaling pathway’ and ‘Wnt signaling pathway’. In addition, a circRNA-miRNA-mRNA interaction network was established. Taken together, these findings may help better understanding the underlying mechanisms of GC and identifying new molecular alterations in GC, and allow the enrichment of the circRNA profiling in human GC.
Vascularization is the next challenge for skin tissue engineering as a solution for burn management

Abstract Skin regeneration represents a promising line of management for patients with skin loss, including burn victims. The current approach of spraying single cells over the defective areas results in variable success rates in different centers. The modern approach is to synthesize a multilayer skin construct that is based on autologous stem cells. One of the main complications with different types of transplants is sloughing due to the absence of proper vascularization. Ensuring proper vascularization will be crucial for the integration of skin constructs with the surrounding tissues. Combination of the right cells with scaffolds of proper physico-chemical properties, vascularization can be markedly enhanced. The material effect, pore size and adsorption of certain proteins, as well as the application of appropriate growth factors, such as vascular endothelial growth factors, can have an additive effect. A selection of the most effective protocols is discussed in this review.
Risk Factors for Candidemia After Open Heart Surgery: Results From a Multicenter Case–Control Study

Abstract Background Candida species are among the most frequent causative agents of health care–associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. Methods This retrospective, matched case–control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. Results Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14–36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73–98.95; P < .001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57–30.67; P = .001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61–20.41; P = .007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91–16.63; P = .002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study. Conclusions Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.
Presenting Symptoms in Sepsis: Is the Mnemonic “SEPSIS” Useful?

Background The mnemonic “SEPSIS” (S = Slurred speech or confusion, E = Extreme shivering or muscle pain, fever, P = Passing no urine all day, S = Severe breathlessness, I = It feels like you are going to die, S = Skin mottled or discolored) has been developed by the World Sepsis Day committee, so as to raise public awareness of the symptomatic presentation of sepsis. However, this mnemonic has not been validated. Methods A retrospective, observational, single-center study was performed. All adult septic patients presenting at the emergency department of Songklanagarind Hospital from 2016 to 2019 were included and followed up until either hospital discharge or death. Results The study included 437 patients, comprising patients with sepsis (n = 250) and those with septic shock (n = 187). Patients presented with symptoms according to the mnemonic as follows: S = 97 (22.2%), E = 240 (54.9%), P = 18 (4.1%), S =181 (41.4%), I = 5 (1.1%), and S = 5 (1.1%). Sixty-five patients (14.9%) did not present with any sepsis-specific symptoms according to the mnemonic. Compared with patients who had at least one mnemonic symptom, a higher proportion of patients without mnemonic symptoms had underlying immunosuppression (24.6% vs 8.3%, P < 0.01) and were diagnosed with intraabdominal infection (38.5% vs 12.1%, P < 0.01). In a multivariable adjusted logistic regression model, vague-presenting symptoms were independently associated with in-hospital mortality (adjusted odds ratio 2.17, 95% confidence interval 1.30−3.61, P = 0.03). Conclusion Two components of the mnemonic “SEPSIS” were rarely reported: it feels like you are going to die and skin mottled or discolored. Using the mnemonic might lead to missed diagnoses, especially in immunosuppression and intraabdominal infection. This mnemonic should be revised for the local context.
Klasea nana (Asteraceae), a New Species from NE Iran

Klasea nana Ranjbar & Negaresh sp. nova (Asteraceae) is described and illustrated. It is confined to the Khorasan Province in northeastern Iran and closely resembles K. latifolia, but differs from it by having a shorter habit, smaller basal leaves, and arachnoid phyllaries.
The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy

With advances in medical technology, the number of people over the age of 60 is on the rise, and thus, increasing the prevalence of age-related pathologies within the aging population. Neurodegenerative disorders, cancers, metabolic and inflammatory diseases are some of the most prevalent age-related pathologies affecting the growing population. It is imperative that a new treatment to combat these pathologies be developed. Although, still in its infancy, the CRISPR-Cas9 system has become a potent gene-editing tool capable of correcting gene-mediated age-related pathology, and therefore ameliorating or eliminating disease symptoms. Deleting target genes using the CRISPR-Cas9 system or correcting for gene mutations may ameliorate many different neurodegenerative disorders detected in the aging population. Cancer cells targeted by the CRISPR-Cas9 system may result in an increased sensitivity to chemotherapeutics, lower proliferation, and higher cancer cell death. Finally, reducing gene targeting inflammatory molecules production through microRNA knockout holds promise as a therapeutic strategy for both arthritis and inflammation. Here we present a review based on how the expanding world of genome editing can be applied to disorders and diseases affecting the aging population.
Deposição e distribuição de calda de pulverização em plantas de feijoeiro (Phaseolus vulgaris) e capim-braquiária (Brachiaria decumbens)

An experiment was carried out at the NuPAM-FCA/UNESP, Botucatu Campus, Sao Paulo, Brazil, to estimate the deposition and distribution of a marker solution on the P. vulgaris and B. decumbens plants, using a sprayer simulator under a controlled environment. The treatments were: nozzle fan jet XR Teejet (XR110.02VS) + surfactant (Aterbane BR - 0.5% v/v); nozzle Conejet (TXVK-4) + surfactant (Aterbane BR - 0.5% v/v); nozzle fan jet XR Teejet (XR110.02VS) and nozzle Conejet (TXVK-4). A solution of NaCl (0.5%) + Orange Poliglow colour (0.5%) + mancozeb (0.5%) was applied in all treatments. The experimental units consisted of pots with two B. decumbens target plants underneath one P. vulgaris target plant. Droplet distribution over B. decumbens leaves was evaluated with black light, and deposition by electric conductivity of the sprayer solution collected by washing the targets in deionized water. The spraying nozzles, XR Teejet and Conejet, did not show deposition difference on P. vulgaris leaves, under equal spray solution conditions. However, the nozzle with fan jet XR Teejet (XR110.02VS) and the nozzle Conejet (TXVK-4) provided, respectively, 67.1% and 61.5% increase on the leaf area deposition and 106,4% and 66.9% increase dry weight increase, when compared to the nozzle with fan jet XR Teejet (XR110.02VS) + surfactant (Aterbane BR - 0.5% v/v) and the nozzle Conejet (TXVK-4) + surfactant (Aterbane BR - 0.5% v/v). Nozzle Conejet provided higher uniform distribution, when compared to nozzle XR Teejet.
FROM D. MELANOGASTER TO INSECT PARASITOIDS: DIFFERENT PROCESSES, CONSERVED MOLECULAR MECHANISMS

Several parasitic wasps, when ovipositing in host insects, inject factors that disrupt their physiology, development and immune reaction. Among these factors, the polydnaviruses (PDVs), obligate symbionts of the parasitoids, play a pivotal role in successful parasitism. We have shown that the genome of the polydnavirus associated with Toxoneuron nigriceps (TnBV) codes for truncated forms of Cactus/IκB-like proteins. In Drosophila, Cactus regulates the nuclear import of various NF-κB/Rel proteins, which are transcription factors controlling embryonic dorso-ventral patterning and antimicrobial response. Insect immune response shares many components with the mammalian innate immunity, including the intracellular signaling pathways that activate NF-κB. The viral cactus-like proteins may act as dominant inhibitors leading to the cytoplasmic retention of NF-κB/Rel proteins, thus providing a molecular mechanism accounting for the impairment of insect immune response induced by parasitoids. We discuss the role of Cactus/IκB molecules as an example of the reiterated use of intracellular signaling pathways conserved during evolution.
Efficacy of tolvaptan for fluid management after cardiovascular surgery: A systematic review and meta-analysis of randomized control trials

The purpose of this study was to systematically search the literature and analyze evidence from randomized controlled trials (RCTs) comparing tolvaptan with conventional diuretics for postoperative fluid management in cardiac surgery patients. An electronic search of PubMed, Scopus, BioMed Central, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases was carried out up to 1st December 2019. Four RCTs were included. Tolvaptan was co-administered with conventional diuretics in all the studies. The mean postoperative urine output was significantly greater in patients receiving tolvaptan as compared to controls (MD=0.39; 95% CI: 0.17 to 0.61; P=0.006, I2=48%). Body weight of patients on tolvaptan returned to pre-operative levels significantly earlier (MD=-1.57; 95% CI: -2.48 to -0.66; P=0.007, I2=50%). There was statistical significant difference in the highest postoperative serum sodium levels (MD=2.34; 95% CI: -1.65 to 3.03; p<0.00001, I2=0%), lowest serum sodium levels (MD=2.05; 95% CI: 1.41 to 2.68; p<0.00001, I2=0%) and mean serum sodium levels (MD=1.69; 95% CI: 0.98 to 2.40; p<0.00001, I2=0%) between the tolvaptan and control groups. Lowest serum potassium was significantly higher with tolvaptan as compared to the control group (MD=0.10; 95% CI: 0.01 to 0.18; P=0.03, I2=19%). There was no significant difference in the length of ICU stay or incidence of arrhythmias between the two groups. The quality of the included studies was not high. Within the limitations of our study, our results indicate that co-administration of tolvaptan with low dose of conventional diuretics significantly increases urine output while maintaining electrolyte balance in postoperative cardiac surgery patients. Faster return of body weight to pre-operative levels is evident with tolvaptan. Further high-quality RCTs are required to confirm this evidence.
Measurements of scleral thickness and corneal optic densitometry in patients with systemic lupus erythematosus

Abstract Background: This study aimed to evaluate the scleral thickness and corneal parameters of patients with systemic lupus erythematosus (SLE). Methods: Forty-seven eyes of 47 SLE patients and 44 eyes of healthy controls were included in this cross-sectional study. Anterior segment optical coherence tomography (AS-OCT) was used to measure the corneal and scleral thickness. Scleral thickness (ST) was measured based upon the segmentation at 1000 to 5000 μm from the scleral spur. Pentacam HR was used to measure corneal parameters. Results: There was no statistically significant difference between SLE group and control group according to age and sex (P > .05). The ST measurements at all distances from scleral spur were found to be thicker in patients with SLE (P < .05). Central corneal thickness (CCT), cornea volume (CV), corneal densitometry (CD), and peripheral corneal thickness (PCT) measurements were similar between the groups (P > .05). Conclusion: ST was thicker in SLE patients compared with healthy controls. AS-OCT seems helpful in selecting optimal sites for pharmaceutical or surgical intervention in SLE patients, since it shows thickness variations in anterior sclera.
Impact of NDF degradability of corn silage on the milk yield potential of dairy cows

Abstract The neutral detergent fibre (NDF) degradability of corn silage samples, measured in vitro (ivNDFd) by a filter bag system, was used to examine (i) the relationship between the ivNDFd and that calculated from acid detergent lignin (L) content (NDFd) and (ii) the impact of ivNDFd variations on the predicted milk yield (MY) of dairy cows fed corn silage based diets. A total of 173 samples of corn silage were collected during a period of three years (2001-03) in different dairy farms of the Po Valley (Northern Italy). Each sample was analysed for chemical composition and was also tested in triplicate for the ivNDFd using the DaisyII incubator (Ankom, Tech. Co., Fairport, NY, USA) with incubation time of 48hs. Moreover, the NDFd of samples was calculated from the L contents, while the measured ivNDFd values were used to estimate the NEl, the potential dry matter intakes (DMI) and to predict the MY of cows. Corn silage samples of the three years were similar for NDF and starch contents (44.2 and 30.7% DM, on average, respectively) while samples from 2003, in comparison with 2001 and 2002, had lower crude protein (6.9 vs 8.3-8.4% DM, P<0.01) and L contents (3.3 vs 3.6-3.9% DM, P<0.01) and higher ivNDFd values (53.3 vs 45.6-47.8%, P<0.01). The relationship between ivNDFd and NDFd was weak (R2=0.09, not significant). The MY predicted from the NEl content and DMI of corn silage (5.5 MJ/kg DM and 8.9 kg/d) minus the maintenance energy costs, was 11.5 kg/d on average (coefficient of variation 20%). Our simulations indicate that a variation of ivNDFd by +1.0% changes the NEl of corn silage to have an expected variation in milk yield of +0.15 kg/d. If the ivNDFd is also used to predict the corn silage DMI then a +1.0% variation in ivNDFd of corn silage produces an overall +0.23 kg/d MY variation. The present results indicate that ivNDFd is highly variable in corn silage populations and differences in this nutritional parameter have an appreciable impact on the predicted milk yield from dairy cows.
In silico screening of known small molecules to bind ACE2 specific RBD on Spike glycoprotein of SARS-CoV-2 for repurposing against COVID-19

Background: Human coronavirus (SARS-CoV-2) is causing a pandemic with significant morbidity and mortality. As no effective novel drugs are available currently, drug repurposing is an alternative intervention strategy. Here we present an in silico drug repurposing study that implements successful concepts of computer-aided drug design (CADD) technology for repurposing known drugs to interfere with viral cellular entry via the spike glycoprotein (SARS-CoV-2-S), which mediates host cell entry via the hACE2 receptor. Methods: A total of 4015 known and approved small molecules were screened for interaction with SARS-CoV-2-S through docking studies and 15 lead molecules were shortlisted. Additionally, streptomycin, ciprofloxacin, and glycyrrhizic acid (GA) were selected based on their reported anti-viral activity, safety, availability and affordability. The 18 molecules were subjected to molecular dynamics (MD) simulation. Results: The MD simulation results indicate that GA of plant origin may be repurposed for SARS-CoV-2 intervention, pending further studies. Conclusions: Repurposing is a beneficial strategy for treating COVID-19 with existing drugs. It is aimed at using docking studies to screen molecules for clinical application and investigating their efficacy in inhibiting SARS-CoV-2-S. SARS-CoV-2-S is a key pathogenic protein that mediates pathogen-host interaction. Hence, the molecules screened for inhibitory properties against SARS-CoV-2-S can be clinically used to treat COVID-19 since the safety profile is already known.
Switching from originator infliximab to biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving clinical remission (the IFX-SIRIUS study I)

Abstract Background: The introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) into clinical practice has dramatically improve the clinical outcomes of individuals with rheumatoid arthritis (RA). However, bDMARDs are associated with high costs, which has resulted in restricted treatment access and a burden on medical insurance finances. Although biosimilars offer cost-saving, their effectiveness and safety must be established in Post-Marketing Surveillance (PMS). Infliximab (IFX), a chimeric monoclonal antibody to TNF-alpha, is the first bDMARD; its biosimilar, CT-P13, is the first biosimilar DMARD approved for RA treatment in Japan. We will evaluate whether switching from originator IFX to CT-P13 is not inferior for maintaining non-clinical relapse to continued treatment with originator IFX in RA patients achieving clinical remission. Methods/design: This study is an interventional, multicenter, open-label, single-arm against historical control and noninferiority clinical trial with a 24-week follow-up. Eighty RA patients who are treated by originator IFX for ≥24 weeks and are achieving clinical remission will be included. Patients will be switched to CT-P13 with the unchanged dosing regimen. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the ratio of patients who experience a nonclinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of many biomarkers such as cytokines and chemokines. Discussion: The study results are expected to show the noninferiority of switching to CT-P13 over the continuation of originator IFX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS to accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will explore whether parameters at baseline can predict a nonclinical relapse after switching from originator IFX to CT-P13 by integrating multilateral assessments, i.e., clinical disease activity indices, MSUS findings, and serum biomarkers. Trial registration: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on October 11, 2019 as jRCTs071190030.
Δ-9-Tetrahydrocannabinol Enhances Breast Cancer Growth and Metastasis by Suppression of the Antitumor Immune Response1

In the current study, we tested the central hypothesis that exposure to Δ-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component in marijuana, can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response. We demonstrated that the human breast cancer cell lines MCF-7 and MDA-MB-231 and the mouse mammary carcinoma 4T1 express low to undetectable levels of cannabinoid receptors, CB1 and CB2, and that these cells are resistant to Δ9-THC-induced cytotoxicity. Furthermore, exposure of mice to Δ9-THC led to significantly elevated 4T1 tumor growth and metastasis due to inhibition of the specific antitumor immune response in vivo. The suppression of the antitumor immune response was mediated primarily through CB2 as opposed to CB1. Furthermore, exposure to Δ9-THC led to increased production of IL-4 and IL-10, suggesting that Δ9-THC exposure may specifically suppress the cell-mediated Th1 response by enhancing Th2-associated cytokines. This possibility was further supported by microarray data demonstrating the up-regulation of a number of Th2-related genes and the down-regulation of a number of Th1-related genes following exposure to Δ9-THC. Finally, injection of anti-IL-4 and anti-IL-10 mAbs led to a partial reversal of the Δ9-THC-induced suppression of the immune response to 4T1. Such findings suggest that marijuana exposure either recreationally or medicinally may increase the susceptibility to and/or incidence of breast cancer as well as other cancers that do not express cannabinoid receptors and are resistant to Δ9-THC-induced apoptosis.
Preventing COVID‐19 Amid Public Health and Urban Planning Failures in Slums of Indian Cities

The COVID‐19 pandemic has brought renewed attention to the lack of urban planning and its public health implications in developing countries. Slum communities face the dual challenges of chronically poor residential environments and the acute effects of a pandemic and the preventive measures that follow. In this paper, I assess the effectiveness and implications of social distancing, frequent handwashing, and lockdown in the context of slums in Indian cities, where overcrowding, lack of access to water and sanitation, and dependence on daily wages for sustenance and livelihood are common. Using data from multiple sources, I demonstrate that not only will these measures be hard to achieve in slums in the short term due to specific characteristics of these habitats, but they will bring new challenges in the long term due to disproportionate impacts on the urban poor. Lessons learned from this pandemic will require us to rethink public health responses and urban planning practices that could better prepare our cities for future pandemics.