Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states.

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature.

Data collation for climate-cooling gas dimethylsulfide in Antarctic snow, sea ice and underlying seawater.

Dimethylsulfide (DMS) is a climatically active volatile sulfur compound found in Earth's oceans and atmosphere that plays an important role in cloud formation. DMS originates from its precursor dimethylsulfoniopropionate (DMSP), which is produced by several classes of phytoplankton. Concentrations of DMS and DMSP in Antarctic sea ice, snow and underlying seawater are not well documented and there is currently no dataset available to find the existing data.

C2H2-zinc-finger transcription factors bind RNA and function in diverse post-transcriptional regulatory processes.

Cys2-His2 zinc-finger proteins (C2H2-ZNFs) constitute the largest class of DNA-binding transcription factors (TFs) yet remain largely uncharacterized. Although certain family members, e.g.

Host range of a parasitoid wasp is linked to host susceptibility to its mutualistic viral symbiont.

Parasitoid wasps are one of the most species-rich groups of animals on Earth, due to their ability to successfully develop as parasites of nearly all types of insects. Unlike most known parasitoid wasps that specialize towards one or a few host species, Diachasmimorpha longicaudata is a generalist that can survive within multiple genera of tephritid fruit fly hosts, including many globally important pest species. Diachasmimorpha longicaudata has therefore been widely released to suppress pest populations as part of biological control efforts in tropical and subtropical agricultural ecosystems.

Role of the Innate Immune Response in Glomerular Disease Pathogenesis: Focus on Podocytes.

Accumulating evidence indicates that inflammatory and immunologic processes play a significant role in the development and progression of glomerular diseases. Podocytes, the terminally differentiated epithelial cells, are crucial for maintaining the integrity of the glomerular filtration barrier. Once injured, podocytes cannot regenerate, leading to progressive proteinuric glomerular diseases.

Simultaneous Heart and Kidney Transplantation: A Systematic Review and Proportional Meta-Analysis of Its Characteristics and Long-Term Variables.

Patients with end-stage heart disease who undergo a heart transplant frequently have simultaneous kidney insufficiency, therefore simultaneous heart and kidney transplantation is an option and it is necessary to understand its characteristics and long-term variables. The recipient characteristics and operative and long-term variables were assessed in a meta-analysis. A total of 781 studies were screened, and 33 were thoroughly reviewed.

Sensitivity of air quality to vehicle ammonia emissions in the United States.

The US Environmental Protection Agency (EPA) estimates on-road vehicles emissions using the Motor Vehicle Emission Simulator (MOVES). We developed updated ammonia emission rates for MOVES based on road-side exhaust emission measurements of light-duty gasoline and heavy-duty diesel vehicles. The resulting nationwide on-road vehicle ammonia emissions are 1.

Parasitoid wasps.

Parasitoids - insects that parasitize other insects - have fascinating biologies that have made them darlings of the science fiction genre, owing to their wide array of innovative and often gruesome strategies for living off other organisms. These insects do not sting, but rather lay eggs on or inside their hosts, typically another insect or spider. Unlike parasites, which feed off a host without killing it, parasitoids kill their hosts - and they typically do it slowly.

Metastatic Merkel Cell Carcinoma After Simultaneous Pancreas-Kidney Transplantation: Fatal Outcomes.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes.

Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and treatment-free remissions.

In the phase 2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refractory [R/R] disease) received ibrutinib 560 mg and venetoclax 400 mg both once daily. High complete remission (CR) and measurable residual disease negative (MRD-negative) CR rates were previously reported. With median survivor follow-up now exceeding 7 years, we report long-term results.

Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.

Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis.

Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter.

Messenger RNA precursors (pre-mRNA) generally undergo 3' end processing by cleavage and polyadenylation (CPA), which is specified by a polyadenylation site (PAS) and adjacent RNA sequences and regulated by a large variety of core and auxiliary CPA factors. To date, most of the human CPA factors have been discovered through biochemical and proteomic studies. However, genetic identification of the human CPA factors has been hampered by the lack of a reliable genome-wide screening method.

Subclinical vascular composites predict clinical cardiovascular disease, stroke, and dementia: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background And Aims: Subclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) followed 6814 participants (45-84 years of age) from baseline in 2000-2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supineblood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound.

Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Heart Failure after Transcatheter Aortic Valve Implantation: Application of the Most Impactful Strain Imaging Techniques.

• LBBB is the most common TAVI-induced conduction abnormality. • Strain imaging can assist with determining the etiology of heart failure after TAVI. • Strain imaging can help predict response to CRT.

Challenging our understanding of B-cell lymphomagenesis and risk: Paediatric high-grade B-cell lymphoma, not otherwise specified with a DDX3X::MLLT10 fusion and an IGH deletion.

We report a unique case of high-grade B-cell lymphoma, not otherwise specified in a 5-year-old child. Whole-genome sequencing revealed a DDX3X::MLLT10 fusion, usually seen in T-cell acute lymphoblastic leukaemia (ALL). This suggests the novel idea that MLLT10 fusions are capable of driving B-cell malignancies.

Liposomal encapsulation of amoxicillin via microfluidics with subsequent investigation of the significance of PEGylated therapeutics.

With an increasing concern of global antimicrobial resistance, the efforts to improve the formulation of a narrowing library of therapeutic antibiotics must be confronted. The liposomal encapsulation of antibiotics using a novel and sustainable microfluidic method has been employed in this study to address this pressing issue, via a targeted, lower-dose medical approach. The study focusses upon microfluidic parameter optimisation, formulation stability, cytotoxicity, and future applications.

Functional characterization of bracovirus genes that encode nucleocapsid components.

Understanding how bracoviruses (BVs) function in wasps is of broad interest in the study of virus evolution. This study characterizes most of the bracovirus (MdBV) genes whose products are nucleocapsid components. Results indicate several genes unknown outside of nudiviruses and BVs are essential for normal capsid assembly.