Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability.

The nucleus is a highly organised yet dynamic environment containing distinct membraneless nuclear bodies. This spatial separation enables a subset of components to be concentrated within biomolecular condensates, allowing efficient and discrete processes to occur which regulate cellular function. One such nuclear body, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectural RNA, NEAT1_2.

Dysregulation of the DRAIC/SBK1 Axis Promotes Lung Cancer Progression.

Long non-coding RNAs (lncRNAs) are key regulators of cellular processes that underpin cancer development and progression. DRAIC is a migration inhibitor that has been linked with lung adenocarcinoma progression; however, its mechanisms remain to be studied. Several bioinformatics tools were used to explore the role of DRAIC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).

Meta-analysis of RNA interaction profiles of RNA-binding protein using the RBPInper tool.

Motivation: Recent RNA-centric experimental methods have significantly expanded our knowledge of proteins with known RNA-binding functions. However, the complete regulatory network and pathways for many of these RNA-binding proteins (RBPs) in different cellular contexts remain unknown. Although critical to understanding the role of RBPs in health and disease, experimentally mapping the RBP-RNA interactomes in every single context is an impossible task due the cost and manpower required.

The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer.

Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies.

Platelet-derived microvesicles isolated from type-2 diabetes mellitus patients harbour an altered miRNA signature and drive MDA-MB-231 triple-negative breast cancer cell invasion.

The underlying causes of breast cancer are diverse, however, there is a striking association between type 2 diabetes and poor patient outcomes. Platelet activation is a common feature of both type 2 diabetes and breast cancer and has been implicated in tumourigenesis through a multitude of pathways. Here transcriptomic analysis of type 2 diabetes patient-derived platelet microvesicles revealed an altered miRNA signature compared with normoglycaemic control patients.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

Introduction: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors.

Methods: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected.

Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multigene prognostic signature associated with metastasis.

Background: Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumors at high risk of metastasis would have a significant impact on management.

Complications Following Intramedullary Screw Fixation for Metacarpal Fractures: A Systematic Review.

Purpose: There has been a recent increase in the use of intramedullary screws (IMS) for the surgical treatment of metacarpal fractures. While IMS fixation has been shown to produce excellent functional outcomes, postoperative complications have yet to be fully explored in a comprehensive way. This systematic review quantified the incidence, treatment, and results of complications following IMS fixation for metacarpal fractures.

Return to Sport After Anterior Cruciate Ligament Reconstruction Requires Evaluation of >2 Functional Tests, Psychological Readiness, Quadriceps/Hamstring Strength, and Time After Surgery of 8 Months.

Purpose: The purpose of this study was to examine the factors commonly used to determine readiness for return to sport (RTS) in the ACL reconstruction (ACL-R) patient population and assess which were most influential to successfully returning to sport and avoiding re-tear.

Methods: The PUBMED, EMBASE and Cochrane Library databases were queried for studies related to RTS in ACL-R. Inclusion and exclusion criteria were applied to identify studies with greater than 1-year outcomes detailing the rate of return and re-tear given a described RTS protocol.

Decosus: An R Framework for Universal Integration of Cell Proportion Estimation Methods.

The assessment of the cellular heterogeneity and abundance in bulk tissue samples is essential for characterising cellular and organismal states. Computational approaches to estimate cellular abundance from bulk RNA-Seq datasets have variable performances, often requiring benchmarking matrices to select the best performing methods for individual studies. However, such benchmarking investigations are difficult to perform and assess in typical applications because of the absence of gold standard/ground-truth cellular measurements.

Dysregulation of the miR-30c/DLL4 axis by circHIPK3 is essential for KSHV lytic replication.

Non-coding RNA (ncRNA) regulatory networks are emerging as critical regulators of gene expression. These intricate networks of ncRNA:ncRNA interactions modulate multiple cellular pathways and impact the development and progression of multiple diseases. Herpesviruses, including Kaposi's sarcoma-associated herpesvirus, are adept at utilising ncRNAs, encoding their own as well as dysregulating host ncRNAs to modulate virus gene expression and the host response to infection.

SFPQ promotes an oncogenic transcriptomic state in melanoma.

The multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes.

ACSNI: An unsupervised machine-learning tool for prediction of tissue-specific pathway components using gene expression profiles.

Determining the tissue- and disease-specific circuit of biological pathways remains a fundamental goal of molecular biology. Many components of these biological pathways still remain unknown, hindering the full and accurate characterization of biological processes of interest. Here we describe ACSNI, an algorithm that combines prior knowledge of biological processes with a deep neural network to effectively decompose gene expression profiles (GEPs) into multi-variable pathway activities and identify unknown pathway components.

The Genomic Landscape of Actinic Keratosis.

Actinic keratoses (AKs) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression from normal skin to skin with AK to skin with invasive cSCC is challenging because of the massive UVR-induced mutational burden characteristic at all stages of this progression. In this study, we report the largest AK whole-exome sequencing study to date and perform a mutational signature and candidate driver gene analysis on these lesions.

The role of CAF derived exosomal microRNAs in the tumour microenvironment of melanoma.

Exosomes play a crucial role in the crosstalk between cancer associated fibroblasts (CAFs) and cancer cells, contributing to carcinogenesis and the tumour microenvironment. Recent studies have revealed that CAFs, normal fibroblasts and cancer cells all secrete exosomes that contain miRNA, establishing a cell-cell communication network within the tumour microenvironment. For example, miRNA dysregulation in melanoma has been shown to promote CAF activation via induction of epithelial-mesenchymal transition (EMT), which in turn alters the secretory phenotype of CAFs in the stroma.

Platelet microparticle delivered microRNA-Let-7a promotes the angiogenic switch.

Platelet microparticle (PMP)-induced angiogenesis plays a key role in tumour metastasis and has been proposed to contribute towards cardiovascular disease by enhancing atherosclerotic plaque vulnerability. However, the mechanisms underlying PMP induced angiogenesis are ill defined. Recent reports demonstrate that PMPs deliver micro-RNAs (miRNAs) to recipient cells, controlling gene expression.

Diagnosis of Partial Anomalous Pulmonary Venous Connection with Intact Interatrial Septum by Echocardiography.

This case illustrates the complementary use of transthoracic echocardiography and transesophageal echocardiography in the diagnosis of partial anomalous pulmonary venous connection. The transthoracic echocardiogram suggested the presence of anomalous pulmonary venous return by demonstrating right heart volume overload and evidence of an intact atrial septum. Transesophageal echocardiography was required to confirm these findings and provide a firm anatomic diagnosis before surgery.

Enoxaparin associated with hugh abdominal wall hematomas: a report of two cases.

Enoxaparin is a low-molecular-weight heparin used for prophylaxis against deep venous thrombosis. Indications include hip and knee replacement surgery, risk of deep venous thrombosis during abdominal surgery, and prevention of ischemic complications of unstable angina and non-Q-wave myocardial infarction. Its efficacy in the prevention of the above complications has been previously studied; however, the liberal use of enoxaparin is not without incident.

Echocardiography allows safer venous cannulation during excision of large right atrial masses.

Background: Excision of large right atrial masses requires bicaval cannulation and cardiopulmonary bypass. Safe venous cannulation can be accomplished only by knowing the exact intracavitary location and extension of the mass to avoid fragmentation. Transthoracic echocardiography and intraoperative transesophageal echocardiography, although helpful, cannot always define the exact intracavitary relationships of the tumor.

Somatostatinoma: atypical presentation of a rare pancreatic tumor.

Somatostatinomas are rare neuroendocrine tumors that can result in a variety of symptoms depending on the secretion of other peptides in association with or in response to somatostatin. The rarity and variable clinical presentation of these tumors present problems in diagnosis and management. This report details the treatment of a 66-yr-old male who had a somatostatinoma with an atypical location and presentation.

Alternative conduits for coronary revascularization: a novel approach for harvest of the lesser saphenous vein.

Previous use of the greater saphenous vein limits the subsequent availability of conduit for coronary artery bypass grafting (CABG). One readily available alternative conduit is the lesser saphenous vein (LSV). During a 4-year period, 34 LSVs were explored in 23 patients using a novel surgical approach.

Isolation of Enterobacter aerogenes susceptible to beta-lactam antibiotics despite high level beta-lactamase production.

This report describes a patient with nosocomial meningitis from whom four distinct isolates of Enterobacter aerogenes were recovered over a complicated course of chemotherapy. The initial isolate was susceptible to expanded spectrum beta-lactams despite constitutive production of high levels of beta-lactamase. Resistant isolates recovered during antibiotic therapy had lost a 42,000 outer membrane protein.

Pericardial cells for graft seeding: isolation, culture and identification.

The purpose of this study was to determine the feasibility of using the pericardium as a source of endothelial cells. Nineteen pieces of fresh pericardium were obtained from nine mongrel dogs. Cells were prepared by collagenase digestion of the pericardium for 24 minutes followed by centrifugation.