The pairwise interaction between transcription factors (TFs) plays an important role in enhancer-promoter loop formation. Although thousands of TFs in the human genome have been found, only a few TF pairs have been demonstrated to be related to loop formation. It is still a challenge to determine which TF pairs could be involved in the enhancer-promoter regulation network. This work describes a computational framework to identify TF pairs in enhancer-promoter regulation. By integrating different levels of data derived from Promoter Capture Hi-C, chromatin immunoprecipitation sequencing (ChIP-seq) of histone marks, RNA-seq, protein-protein interaction (PPI), and TF motif, we identified 361 significant TF pairs and constructed a TF interaction network. From the network, we found several hub-TFs, which may have important roles in the regulation of long-range interactions. Our studies extended TF pairs identified in other experimental and computational approaches. These findings will help the further study of long-range interactions between enhancers and promoters.

Introduction Patients with unresectable non-small cell lung cancer (NSCLC) may benefit from chemotherapy, tyrosine kinase inhibitor (TKI) therapy, or both. TKI therapy may be administered to the subset of patients who harbor the epidermal growth factor receptor (EGFR) mutation. EGFR mutation testing now plays a vital role in the diagnostic work-up of advanced NSCLC patients to determine which patients are more likely to benefit from TKI therapy. The role of surgery in these patients is mostly limited to obtaining an adequate biopsy for histological, immunohistochemical, and EGFR analysis using the least invasive methods possible. It is thought that larger volume samples, such as those obtained from traditional surgical lung biopsies (SLBs), have better yield than small volume samples, such as those obtained from transthoracic needle lung biopsies (TTNLBs), for EGFR analysis. Aim The aim of this was to determine which biopsy procedures provide superior yield for EGFR mutation analysis among primary NSCLC patients at the Eric Williams Medical Sciences Complex (EWMSC) and whether these tissue yields are in keeping with international recommendations. Methods This is a retrospective, observational study using patient data obtained from the Lung Malignancy Unit, which is based at the EWMSC. The study population was limited to primary NSCLC patients presenting to the EWMSC from January 2014 to June 2017 whose biopsy samples were sent for EGFR testing. Relevant patient data were entered onto a spreadsheet using Microsoft Excel. Patients were classified as having had either an SLB, bronchial biopsy (BB), TTNLB, or some other biopsy procedure. All samples were sent for histological analysis, followed by immunohistochemistry and finally EGFR testing. All EGFR mutation analysis was performed at a single laboratory in the USA. A minimum of 200 tumor cells or 10% tumor content defined an adequate sample for EGFR mutation analysis. Samples that yielded a positive or negative result were considered adequate samples in this study. The number of adequate and inadequate samples for each procedure group was tabulated and the yield was determined as the percentage of adequate samples obtained for each procedure group. Results SLBs had superior yield (95.6%) compared to BBs (88.5%) and TTNLB (85%) in obtaining adequate samples for EGFR analysis. Conclusion SLBs demonstrated superior yield in attaining adequate tissue samples for EGFR mutation analysis compared to BBs and TTNLBs.

Face mask detection had seen significant progress in the domains of Image processing and Computer vision, since the rise of the Covid-19 pandemic. Many face detection models have been created using several algorithms and techniques. The proposed approach in this paper uses deep learning, TensorFlow, Keras, and OpenCV to detect face masks. This model can be used for safety purposes since it is very resource efficient to deploy. The SSDMNV2 approach uses Single Shot Multibox Detector as a face detector and MobilenetV2 architecture as a framework for the classifier, which is very lightweight and can even be used in embedded devices (like NVIDIA Jetson Nano, Raspberry pi) to perform real-time mask detection. The technique deployed in this paper gives us an accuracy score of 0.9264 and an F1 score of 0.93. The dataset provided in this paper, was collected from various sources, can be used by other researchers for further advanced models such as those of face recognition, facial landmarks, and facial part detection process.

The thiol-containing compound Dithiothreitol (DTT) has been shown to be toxic to cultured cells by inducing the generation of reactive oxygen species that ultimately cause cell death. However, its effects on multicellular organisms and the environment have not been investigated yet in detail. In this work, we tested the toxicity of DTT to the model insect Drosophila melanogaster. We show that DTT is lethal to D. melanogaster by topical application but not through feeding. DTT treatment triggers the transcription of the canonical apoptosis regulators grim, hid and rpr at low amounts. The amplitude of this induction declines with elevating DTT amounts. By live microscopy, we observe apoptotic cells especially in the gut of DTT treated flies. In parallel, low DTT amounts also activate the expression of the cuticle barrier component gene snsl. This indicates that a physical defence response is launched upon DTT contact. This combined measure is seemingly successful in preventing fly death. The expression of a number of known detoxification genes including cyp6a2, cyp6a8, cyp12d1 and GstD2 is also enhanced through DTT contact. The degree of upregulation of these genes is proportional to the applied DTT amounts. Despite this effort, flies exposed to high amounts of DTT eventually die. Together, D. melanogaster is able to sense DTT toxicity and adjust the defence response successfully at least at low concentrations. This is the first time to analyse the molecular consequences of DTT exposure in a multicellular organism. Our work provides a new model to discuss the physiological response of animals against thiol toxins and to resurvey the effect of redox agents on the environment.

Duchenne muscular dystrophy (DMD) is a severe congenital disease associated with mutation of the dystrophin gene. Supplementation of dystrophin using recombinant adeno-associated virus (rAAV) has promise as a treatment for DMD, although vector-related general toxicities, such as liver injury, neurotoxicity, and germline transmission, have been suggested in association with the systemic delivery of high doses of rAAV. Here, we treated normal or dystrophic dogs with rAAV9 transduction in conjunction with multipotent mesenchymal stromal cell (MSC) injection to investigate the therapeutic effects of an rAAV expressing microdystrophin (μDys) under conditions of immune modulation. Bone-marrow-derived MSCs, rAAV-CMV-μDys, and a rAAV-CAG-luciferase (Luc) were injected into the jugular vein of a young dystrophic dog to induce systemic expression of μDys. One week after the first injection, the dog received a second intravenous injection of MSCs, and on the following day, rAAV was intravenously injected into the same dog. Systemic injection of rAAV9 with MSCs pretreatment improves gene transfer into normal and dystrophic dogs. Dystrophic phenotypes significantly improved in the rAAV-μDys-injected dystrophic dog, suggesting that an improved rAAV-μDys treatment including immune modulation induces successful long-term transgene expression to improve dystrophic phenotypes.

We developed an orally administered, engineered, bacterium-based, RNA interference-mediated therapeutic method to significantly reduce the symptoms in the most frequently used animal model of inflammatory bowel disease. This bacterium-mediated RNA interference strategy was based on the genomically stable, non-pathogenic E. coli MDS42 strain, which was engineered to constitutively produce invasin and the listeriolysin O cytolysin. These proteins enabled the bacteria first to invade the colon epithelium and then degrade in the phagosome. This allowed the delivery of a plasmid encoding small hairpin RNA (shRNA) targeting tumor necrosis factor (TNF) into the cytoplasm of the target cells. The expression levels of TNF and other cytokines significantly decreased upon this treatment in dextran sulfate sodium (DSS)-induced colitis, and the degree of inflammation was significantly reduced. With further safety modifications this method could serve as a safe and side effect-free alternative to biologicals targeting TNF or other inflammatory mediators.

We aimed to identify specific circular RNAs (circRNAs) involved in bone repair of trauma-induced osteonecrosis of femoral head (TIONFH) and to explore the potential mechanism. CircRNA sequencing on the blood sample collected from patients with and without TIONFH was performed to select cirRNAs that were significantly differentially expressed, followed by qRT-PCR confirmation. Furthermore, the functions of one selected circRNA and the potential mechanisms in bone repair of TIONFH were validated based on the bone marrow mesenchymal stem cells (BMSCs) and osteoclast-like cells (OLCs) through CCK-8, flow cytometry, transwell assay, luciferase reporter assay, and western blot. A total of 234 upregulated and 148 downregulated differentially expressed circRNAs were identified, and qRT-PCR showed that circRNA_25487 was significantly upregulated in the peripheral blood of TIONFH patients. Luciferase reporter assay confirmed the binding effect between miR-134-3p and circRNA_25487. CircRNA_25487 suppression and miR-134-3p overexpression could promote cell proliferation and invasion while inhibited apoptosis of BMSCs and OLCs. miR-134-3p could target p21. CircRNA_25487 inhibited bone repair in TIONFH by sponging miR-134-3p to upregulate the expression of p21.

Type 2 diabetes mellitus (T2DM) is an important public health problem. The knowledge of bacterial communities in the gut of Vietnamese patients with T2DM and non diabetic controls is still insufficient. We report in this article the 16S rDNA amplicon data of the gut microbiomes of Vietnamese patients with T2DM and nondiabetic controls carried out using the Illumina sequencing. This work included 7 patients and 7 controls. A total of 1,627,646 reads were obtained and a total of 13 phyla, 25 classes, 94 genera were revealed. The top three dominant bacterial phyla in all subjects were Firmicutes, Bacteroidetes and Proteobacteria. Significant differences in the relative abundances of the phylum Firmicutes and class Clostridia between patients and controls were observed, suggesting that the reducing of phylum Firmicutes and class Clostridia in the gut may be linked to obesity and T2DM. All sequencing libraries were deposited in the NCBI SRA as BioProject PRJNA668251. The datasets are needed to determine the association between the bacterial composition of the gut and the pathogenesis of T2DM in Vietnamese patients.

Tragia involucrata L. have been utilized as traditional medicine in Indian subcontinent for the treatment of numerous illnesses such as inflammation, pain and skin infection. In this current study we sought to assess the anxiolytic, sedative and analgesic activity of Tragia involucrata L. leaves extract.

Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro-microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro-microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. In vivo studies further revealed that the hierarchical macro-microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro-microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.

Sea squirt, as a highly invasive species and main biofouling source in marine aquaculture, has seriously threatened the biodiversity and aquaculture economy. On the other hand, a conductive biomaterial with excellent biocompatibility, and appropriate mechanical property from renewable resources is urgently required for tissue engineering patches. To meet these targets, we presented a novel and robust strategy for sustainable development aiming at the marine pollution via recycling and upgrading the waste biomass-sea squirts and serving as a renewable resource for functional bio-scaffold patch in tissue engineering. We firstly demonstrated that the tunic cellulose derived natural self-conductive scaffolds successfully served as functional cardiac patches, which significantly promote the maturation and spontaneous contraction of cardiomyocytes both in vitro and enhance cardiac function of MI rats in vivo. We believe this novel, feasible and "Trash to Treasure" strategy to gain cardiac patches via recycling the waste biomass must be promising and beneficial for marine environmental bio-pollution issue and sustainable development considering the large-scale consumption potential for tissue engineering and other applications.

Establishing the frequency and nature of arrhythmias in hemodialysis (HD) is an important step in improving outcomes of these patients. We undertook this systematic review and meta-analysis to characterize arrhythmia frequency in maintenance HD patients.

Increased left ventricular mass index (LVMI) is associated with mortality in end-stage renal disease. LVMI regression may improve outcomes. Allopurinol has reduced LVMI in randomized controlled trials in chronic kidney disease, diabetes, and ischemic heart disease. This study investigated whether allopurinol would regress LVMI in hemodialysis patients.

A novel SARS-like coronavirus (severe acute respiratory syndrome-related coronavirus-2, SARS-CoV-2) outbreak has recently become a worldwide pandemic. Researchers from various disciplinary backgrounds (social to natural science, health and medicine, etc.) have studied different aspects of the pandemic. The current situation has revealed how the ongoing development of nanotechnology and nanomedicine can accelerate the fight against the novel viruses. A comprehensive solution to this and future pandemic outbreaks includes preventing the spread of the virus through anti-viral personal protective equipment (PPE) and anti-viral surfaces, plus efforts to encourage behavior to minimize risks. Studies of previously introduced anti-viral biomaterials and their optimization to fight against SARS-CoV-2 is the foundation of most of the recent progress. The identification of non-symptomatic patients and symptomatic patients is vital. Reviewing published research highlights the pivotal roles of nanotechnology and biomaterials in the development and efficiency of detection techniques, e.g., by applying nanotechnology and nanomedicine as part of the road map in the treatment of coronavirus disease 2019 (COVID-19) patients. In this review, we discuss efforts to deploy nanotechnology, biomaterials, and stem cells in each step of the fight against SARS-CoV-2, which may provide a framework for future efforts in combating global pandemics.

Time-of-flight magnetic resonance angiography (MRA) is limited by clip-induced artifacts after cerebral aneurysmal clipping. Recently, ultrashort echo time was shown to reduce metal artifacts. We assessed the pointwise encoding time reduction with radial acquisition (PETRA) sequence in subtraction-based MRA as an ultrashort echo time method during follow-up for clipping surgery.

The HOX genes are master regulators of embryogenesis that are also involved in hematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles in hematopoiesis and leukemogenesis.

Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project 'Treat to Target Italia' was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations.

Current clinical and histological classifications are unable to determine the risk of vulvar squamous cell carcinoma (VSCC) in high-grade vulvar intraepithelial neoplasia (VIN), making prognostic biomarkers highly needed. We studied host-cell DNA methylation markers in high-grade squamous intraepithelial lesion (HSIL) and differentiated VIN (dVIN) without VSCC, in HSIL and dVIN adjacent to VSCC and in human papillomavirus (HPV) positive and negative VSCC, relative to control vulvar tissues. A series of 192 formalin-fixed paraffin-embedded vulvar samples, including VSCC (n = 58), VIN adjacent to VSCC (n = 30), VIN without VSCC during follow-up (n = 41) and normal vulvar tissues (n = 63), were tested for 12 DNA methylation markers with quantitative multiplex methylation-specific PCR (qMSP). HPV status was determined by p16INK4A immunohistochemistry and high-risk HPV PCR analysis. Logistic regression analyses were used to determine methylation patterns and methylation marker performance for VIN and VSCC detection. Methylation markers showed significantly higher methylation levels with increasing severity of disease. VIN adjacent to VSCC showed a similar methylation-high pattern as VSCC, while VIN without VSCC displayed a heterogeneous methylation pattern. Vulvar carcinogenesis is associated with increased DNA methylation. Higher DNA methylation levels in VIN seem to reflect higher cancer risk, emphasizing the high potential of DNA methylation biomarkers in the diagnostic workup of VIN. As a next step, longitudinal studies are needed to verify the prognostic value of methylation biomarkers as a clinical tool for stratification of cancer risk in women with VIN.

Lung ultrasound (LUS) has received considerable interest in the clinical evaluation of patients with COVID-19. Previously described LUS manifestations for COVID-19 include B-lines, consolidations, and pleural thickening. The interrater reliability (IRR) of these findings for COVID-19 is unknown.

Spexin (SPX) is a peptide hormone that regulates body weight, adipose tissue metabolism, and food intake.