Miracle-dz/UniFAR-FTUs huggingface dataset:
Poly(beta-amino ester)s as gene delivery vehicles: challenges and opportunities

ABSTRACT Introduction Gene delivery technologies are being developed for an increasing number of biomedical applications, with delivery vehicles including viruses and non-viral materials. Among biomaterials used for non-viral gene delivery, poly(beta-amino ester)s (PBAEs), a class of synthetic, biodegradable polymers, have risen as a leading gene delivery vehicle that has been used for multiple applications in vitro and in vivo. Areas covered This review summarizes the key properties of PBAEs and their development, including a discussion of the advantages and disadvantages of PBAEs for gene delivery applications. The use of PBAEs to improve the properties of other drug delivery vehicles is also summarized. Expert opinion PBAEs are designed to have multiple characteristics that are ideal for gene delivery, including their reversible positive charge, which promotes binding to nucleic acids as well as imparting high buffering capacity, and their rapid degradability under mild conditions. Simultaneously, some of their properties also lead to nanoparticle instability and low transfection efficiency in physiological environments. The ease with which PBAEs can be chemically modified as well as non-covalently blended with other materials, however, allows them to be customized specifically to overcome delivery barriers for varied applications.
Symbiotic germination and development of the myco‐heterotrophic orchid Neottia nidus‐avis in nature and its requirement for locally distributed Sebacina spp.

Summary • Symbiotic germination and development of the fully myco-heterotrophic orchid Neottia nidus-avis were studied in ‘packets’ of seed placed adjacent to, or at varying distances from, adult plants in a Fagus sylvatica woodland. • The distribution and identity of the fungal partner(s) of N. nidus-avis were investigated by internal transcribed spacer (ITS)-restriction fragment length polymorphism (RFLP) and sequence analysis of part of the 28S gene in fungal DNA extracted from adult plants from the UK and Germany, and from seedlings germinated in situ. • Germination commenced in the spring, but only in the presence of a specific fungus, and occurred most frequently in plots containing adults of N. nidus-avis. Seedlings grew best in packets in which a large number of seeds germinated. Adults and seedlings of UK origin contained the same fungal partner whose 28S sequence most closely matched Sebacina dimitica. Plants of German origin contained a closely related, but distinct, fungus. • The results provide the first definitive chronology of the development of N. nidus-avis and establish its critical dependence upon, and specificity for, the locally distributed Sebacina-like fungus that is required for germination and growth.
Pronounced dys-autonomic symptoms announcing a primary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease that involves the nervous system in about 20% of cases. In 25-92% of patients affected by Sjögren's syndrome, neurological symptoms may precede the sicca syndrome. A 65-year-old male presented with a seven-month history of episodes of near-syncope, constipation, anhidrosis, disabling fatigue and asthenia. Physical examination was unremarkable, whilst the ECG revealed sinus bradycardia. Laboratory tests showed lymphopenia and normal inflammatory markers. In order to assess a potential autonomic neuropathy, "Deep Breathing Test" (E/I 1.02), "Lying to Standing Test" (R/R' 0.95), and "Orthostatic Hypotension Tests" (T 120s Systolic reduction >20 mmHg and Diastolic reduction >10 mmHg) were performed, all of which were abnormal. ECG Holter monitoring revealed sinus bradycardia, and right bundle branch block with 24-h blood pressure monitoring revealing a diurnal hypotensive profile. The patient reported a three-month history of worsening dry mouth. On physical examination, the patient had anisocoria in response to light stimulation. Auto-antibody testing was performed to evaluate the presence of any autoimmune disease. The results of these studies included an abnormal elevation of ANA (1:320 speckled pattern), Ro/SS-a (>240U/l), and La/SS-b (162 U/ml) antibodies. The patient was discharged with a diagnosis of "Autonomic Neuropathy Most Likely Due to Primary Sjögren's Syndrome (SS)" and started the immunotherapy. After one month, he reported a significant improvement in his symptoms with a concomitant normalization of his "Orthostatic Hypotension Tests. " This case underlines the potential for dys-autonomic symptoms to precede the onset of sicca syndrome in patients with Sjogren's Syndrome.
Molecular Characterization, Intra-Species Diversity and Abundance of Freshwater Plesiomonas shigelloides Isolates

Molecular signatures of Plesiomonas shigelloides strain specific to pathogenic and nonpathogenic variants are not well established till present. There is a need for intra-species barcoding of P. shigelloides to aid infection control. This study aims at characterizing and assessing intra-species diversity and abundance of P. shigelloides isolated from three freshwaters in the Eastern Cape Province. The study used a Plesiomonas-specific PCR to characterize the isolates. Intra-species (dis)similarities were assessed using ERIC-PCR and (GTG)5-PCR techniques. The DNA fingerprints produced were electrophoresed, digitized, and documented via computer-assisted pattern analysis. The fingerprints were analyzed using neighbor-joining clustering (NJC) based on Euclidean similarity index. Results revealed 80%, 83.64%, and 80% of the water samples from Tyhume, Kat, and Kubusie rivers, respectively, positive for P. shigelloides isolation. The prevalence of P. shigelloides from sites ranged from 13.5% to 88.9%. NJC delineated 48 isolates to 8 clades (ERIC-fingerprints) and 34 isolates into 7 clades ((GTG)5-fingerprints). The relative abundance of unique strains ranged from 6.3% to 22.9% via the two methods. Both fingerprinting approaches have strain-differentiating potential for P. shigelloides, however ERIC-PCR possessed higher resolution (D = 37.46) advantage over (GTG)5-PCR (D = 29.64). In conclusion, the study achieved intra-species diversity and abundance of P. shigelloides from aquatic milieu and provide further opportunity for intra-species-specific barcoding.
Analysis of molecular markers as IL-12, IL-22 and IFN-γ in correlation with a clinical course in patients with psoriasis.

OBJECTIVES As a chronic, recurrent, immunologically mediated systemic disease and a common cause of dermatological problems, psoriasis is often a subject of scientific research. Skin changes located on the hands can cause difficulties and limitations in the performance of professional activities, especially manual ones. The main role in pathogenesis is played by immunological factors - improper functioning of the components of the immune system, among others, T lymphocytes and cytokines like interleukin-12 (IL-12), interleukin-22 (IL-22) and interferon gamma (IFN-γ). MATERIAL AND METHODS The obtained tissue and blood were destined for RNA isolation. The RNA was then subjected to a reverse transcription reaction. The relative gene expression level was evaluated by the real-time polymerase chain reaction for IL-12B, IL-22 and IFN-γ genes, and presented as the relative quantification (RQ) value, relative to the reference gene GAPDH. In addition, a correlation analysis of the expression level of selected genes with the clinical course of the disease, as assessed by the Psoriasis Area and Severity Index (PASI), the Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI) scores was performed. RESULTS Statistical analysis confirmed a significant increase in RQ values for IL-12B, IL-22 and IFN-γ in the group of psoriatic patients vs. the control group. A positive correlation was also found between BSA and PASI and RQ for the IL-12B gene. CONCLUSIONS Increased expression levels of IL-12B, IL-22 and IFN-γ genes in psoriatic skin confirm that selected cytokines play an important role in the initiation and sustenance of psoriasis.
Decoding of standard and non-standard visuomotor associations from parietal cortex

Objective. Neural signals can be decoded and used to move neural prostheses with the purpose of restoring motor function in patients with mobility impairments. Such patients typically have intact eye movement control and visual function, suggesting that cortical visuospatial signals could be used to guide external devices. Neurons in parietal cortex mediate sensory-motor transformations, encode the spatial coordinates for reaching goals, hand position and movements, and other spatial variables. We studied how spatial information is represented at the population level, and the possibility to decode not only the position of visual targets and the plans to reach them, but also conditional, non-spatial motor responses. Approach. The animals first fixated one of nine targets in 3D space and then, after the target changed color, either reached toward it, or performed a non-spatial motor response (lift hand from a button). Spiking activity of parietal neurons was recorded in monkeys during two tasks. We then decoded different task related parameters. Main results. We first show that a maximum-likelihood estimation (MLE) algorithm trained separately in each task transformed neural activity into accurate metric predictions of target location. Furthermore, by combining MLE with a Naïve Bayes classifier, we decoded the monkey’s motor intention (reach or hand lift) and the different phases of the tasks. These results show that, although V6A encodes the spatial location of a target during a delay period, the signals they carry are updated around the movement execution in an intention/motor specific way. Significance. These findings show the presence of multiple levels of information in parietal cortex that could be decoded and used in brain machine interfaces to control both goal-directed movements and more cognitive visuomotor associations.
A randomized controlled trial of central executive training (CET) versus inhibitory control training (ICT) for ADHD.

OBJECTIVE Executive function deficits are well-established in ADHD. Unfortunately, replicated evidence indicates that executive function training for ADHD has been largely unsuccessful. We hypothesized that this may reflect insufficient targeting, such that extant protocols do not sufficiently and specifically target the neurocognitive systems associated with phenotypic ADHD behaviors/impairments. METHOD Children with ADHD ages 8-12 (M = 10.41, SD = 1.46; 12 girls; 74% Caucasian/Non-Hispanic) were randomized with allocation concealment to either central executive training (CET; n = 25) or newly developed inhibitory control training (ICT; n = 29). Detailed data analytic plans were preregistered. RESULTS Both treatments were feasible/acceptable based on training duration, child-reported ease of use, and parent-reported high satisfaction. CET was superior to ICT for improving its primary intervention targets: phonological and visuospatial working memory (d = 0.70-0.84). CET was also superior to ICT for improving go/no-go (d = 0.84) but not stop-signal inhibition. Mechanisms of change analyses indicated that CET-related working memory improvements produced significant reductions in the primary clinical endpoints (objectively assessed hyperactivity) during working memory and inhibition testing (indirect effects: β ≥ -.11; 95% CIs exclude 0.0). CET was also superior to ICT on 3 of 4 secondary clinical endpoints (blinded teacher-rated ADHD symptoms; d = 0.46-0.70 vs. 0.16-0.42) and 2 of 4 feasibility/acceptability clinical endpoints (parent-reported ADHD symptoms; d = 0.96-1.42 vs. 0.45-0.65). CET-related gains were maintained at 2-4 month follow-up; ICT-related gains were maintained for attention problems but not hyperactivity/impulsivity per parent report. CONCLUSIONS Results support the use of CET for treating executive function deficits and targeting ADHD behavioral symptoms in children with ADHD. Findings for ICT were mixed at best and indicate the need for continued development/study. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Microbiology of Orinotyri, a ewe's milk cheese from the Greek mountains

The microflora of five batches of Orinotyri, a cheese made from raw ewe's milk, was studied in ten day and three-month-old cheese. Mean log counts of 7·94 for Enterobacteriaceae and 7.41 for coliforms in fresh cheese were reduced (P<0·05) by 3·02 and 2·76 log units, respectively, during ripening. It also seems that high cheese pH (means: ten days, 6·31; three months, 5·79) did not favour the growth of yeasts. These organisms were found at low levels only in fresh cheese. Lactic acid bacteria numbers of the cheese at ten days decreased significantly (P<0·05) in the three-month-old cheese, but they were still present at high levels (mean log counts: lactobacilli, 5·78; lactococci, 8·24; enterococci, 6·20). Enterococci predominated in the fresh cheese, but they were outnumbered by lactococci in three-month-old cheese. Enterococcus faecalis and Lactococcus lactis subsp. lactis were the most frequently isolated species. Acid production by Lc. lactis subsp. lactis strains varied considerably and the same was observed for their caseinolytic, lipolytic and peptidolytic activities. The results suggest the possibility of choosing strains for industrial fermentation.
Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers

PURPOSE The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research. METHODS All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives. RESULTS Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region. CONCLUSION As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA.
New phytoconstituents, anti-microbial and cytotoxic activities of Acacia etbaica Schweinf

Abstract Acacia etbaica is wild plant growing in the desert of Egypt, and it has folkloric medicinal uses. Phytochemical investigation of Acacia etbaica extracts led to the isolation and identification of seven compounds. Among these compounds are three new simple phenolics: Resacetophenone-6-methyl [1], Resorcinol [2], Resorcinol-O- β -Glucoside [3]; phenolic ester; and other four known compounds: Methylparaben [4]; two chromones, Noreugenin [5], Eugenin [6]; and one cyclitol: pinitol [7]. Compounds [1–3] isolated and identified for the first time from natural origin. In contrast, compounds [4–6] isolated for the first time from the family Fabaceae. The biological investigation was conducted on plant extracts and showed that the methylene chloride extract had a strong efficacy against Bacillus subtilis and good activity against Candida albicans. In contrast, the n-butanol extract showed extreme cytotoxic activity against Mammary gland breast cancer (MCF-7), and strong activity against Hepatocellular carcinoma (HEPG-2), and Colorectal carcinoma (HCT-116) cell lines. Graphical Abstract
Role of promoting inflammation of Krüppel-like factor 6 in acute kidney injury

Abstract Background Krüppel-like factor 6 (KLF6) is a transcription factor that participate in various pathophysiological processes, but its contribution in ischemia acute kidney injury (AKI) is lacking so far. The study aimed to investigate the expression and the role of KLF6 in kidney ischemia–reperfusion (IR) injury. Method Microarray data were collected from GSE58438 and GSE52004. The rat IR model was established to evaluate the mRNA and protein expression of KLF6 and inflammatory cytokines in serum and kidney tissues. SiRNA-KLF6 was transfected with HK-2 cells, and then a cell-based hypoxia-reoxygenation (HR) model was established. Results Bioinformatics showed KLF6 mRNA in kidney tissue is up-regulated in 3 h after IR in rat kidney, which involved in cell activation, leukocyte activation, and response to hydrogen peroxide after IR. The rat IR model results showed that KLF6 expression was peaking at 6 h, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α was increased both in serum and kidney tissues, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed that KLF6 knock-down reduced the pro-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) KLF6 may play a role in promoting inflammation in AKI.
Anti-Inflammatory Effects of the Novel PIM Kinase Inhibitor KMU-470 in RAW 264.7 Cells through the TLR4-NF-κB-NLRP3 Pathway

PIM kinases, a small family of serine/threonine kinases, are important intermediates in the cytokine signaling pathway of inflammatory disease. In this study, we investigated whether the novel PIM kinase inhibitor KMU-470, a derivative of indolin-2-one, inhibits lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 cells. We demonstrated that KMU-470 suppressed the production of nitric oxide and inducible nitric oxide synthases that are induced by LPS in RAW 264.7 cells. Furthermore, KMU-470 inhibited LPS-induced up-regulation of TLR4 and MyD88, as well as the phosphorylation of IκB kinase and NF-κB in RAW 264.7 cells. Additionally, KMU-470 suppressed LPS-induced up-regulation at the transcriptional level of various pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. Notably, KMU-470 inhibited LPS-induced up-regulation of a major component of the inflammasome complex, NLRP3, in RAW 264.7 cells. Importantly, PIM-1 siRNA transfection attenuated up-regulation of NLRP3 and pro-IL-1β in LPS-treated RAW 264.7 cells. Taken together, these findings indicate that PIM-1 plays a key role in inflammatory signaling and that KMU-470 is a potential anti-inflammatory agent.
Mechanical characteristics of metal nanoparticle thin film on flexible substrate exposed to saline solution

The robust and reliable mechanical characteristics of metal nanoparticle (NP) thin films on flexible substrates are important because they operate under tensile, bending, and twisting loads. Furthermore, in wearable printed electronics applications, salty solutions such as sweat and seawater can affect the mechanical reliabilities of devices. In this paper, we investigated the effect of sodium chloride (NaCl) solutions on silver (Ag) NP thin films on flexible polymer substrate. After exposure to NaCl solution of Ag NP thin film, we observed the aggregation behavior between Ag NPs and formation of larger pores in the film due to the removal of organic capping layer from the surface of Ag NPs. The average porosity and 5% deviation strains of Ag NP thin films on the polyimide substrate were dramatically increased and decreased from 2.99% to 9.64% and from 3.94% to 0.87%, respectively, after exposure to NaCl solution for 1 h. Also, we verified a drastic deterioration of the surface adhesion of the Ag NP thin film to the substrate by exposure to NaCl solution. We could observe crack propagation and delamination by in-situ scanning electron microscope imaging. In addition, passivation effect by a parylene layer for preventing the permeation of the saline solution was investigated.
A comprehensive individual patient data meta‐analysis of the effects of cardiac contractility modulation on functional capacity and heart failure‐related quality of life

Cardiac contractility modulation, also referred to as CCM™, has emerged as a promising device treatment for heart failure (HF) in patients not indicated for cardiac resynchronization therapy. We performed a comprehensive individual patient data meta‐analysis of all non‐confounded prospective randomized controlled trials of CCM vs. control that have measured functional capacity and/or quality of life questionnaires in patients with HF.
Phytol Down-Regulates Expression of Some Cancer Stem Cell Markers and Decreases Side Population Proportion in Human Embryonic Carcinoma NCCIT Cells

Abstract Cancer stem cells (CSCs), a subgroup of cancer cells, have self-renewal capacity and differentiation potential and drive tumor growth. CSCs are highly-resistant to conventional chemo-radio therapy. Phytochemicals were shown to be able to eliminate CSCs. Phytol is a diterpene alcohol with demonstrated anticancer effects. The current study compared the effect of phytol with retinoic acid (RA) as a well-known inducers of CSC differentiation and cisplatin, a common chemotherapy drug, on CSC markers in human embryonic carcinoma NCCIT cells. NCCIT cells were exposed to 10 mM RA for 14 day to induce differentiation. Moreover, NCCIT cells were treated with IC50 dose of cisplatin (12 µM) and phytol (40 µM) for 7 day. Real-time PCR showed that phytol was more effective that RA and cisplatin in down-regulating the CSC markers OCT4, NANOG, SOX2, ALDH1, ABCB1, CD44 and CD133. Percentage of SP (13%) and ABCB1+ (0.34%) in NCCIT cells decreased to 7% and 0.1% respectively after treatment with phytol. A very small proportion of NCCIT cells were positive for CD44 (0.2%) and CD133 (0.48%) and this fraction did not change significantly after treatment with three agents. In conclusion, phytol has the greatest inhibitory effect on CSC population and markers than RA and cisplatin.
Effect of nitrate concentration in nutrient solution on hemagglutinin content of Nicotiana benthamiana leaves in a viral vector-mediated transient gene expression system

Viral vector-mediated transient expression enables rapid biopharmaceutical protein production using whole plants. In recent years, plant growth conditions have received close attention as factors influencing the content of recombinant protein. In particular, because nitrogen is an important resource used in protein synthesis, nitrogen supplied to the root zone may influence accumulation of recombinant proteins. We tested whether fertilization of Nicotiana benthamiana with high-nitrate nutrient solution during plant growth prior to Agrobacterium-mediated delivery (agroinfiltration) of a tobamoviral vector resulted in high recombinant influenza hemagglutinin (HA) content per unit of leaf fresh weight and/or per plant. Nutrient solution containing 60 mM nitrate yielded 40% higher HA content per unit of leaf fresh weight, and comparable HA content per plant, relative to nutrient solution containing 12 or 36 mM nitrate. There were positive correlations among HA, total soluble protein (TSP), and soluble reduced-nitrogen content, suggesting that fertilization with the high-nitrate nutrient solution increased soluble reduced nitrogen and subsequently provided high TSP and HA. Although the increased HA content per unit of leaf fresh weight was offset by reduced leaf fresh weight on a per plant basis, nitrate-enriched fertilization represents an easily applicable technique to obtain a given amount of HA from smaller leaf biomass, thereby potentially reducing downstream processing costs for HA vaccine production using viral vector-mediated transient expression systems.