IL6 and IL6R as Prognostic Biomarkers in Colorectal Cancer.

Colorectal cancer is the third most diagnosed malignancy worldwide and survival outcomes remain poor. Research is focused on the identification of novel prognostic and predictive biomarkers to improve clinical practice. There is robust evidence in the literature that inflammatory cytokine interleukin-6 (IL6) is elevated systemically in CRC patients and that this phenomenon is a predictor of poor survival outcome.

Complications of cerebrospinal fluid drainage in thoracoabdominal aortic procedures.

Background: Cerebrospinal fluid (CSF) drainage is used to reduce spinal cord ischemia (SCI) in patients undergoing thoracoabdominal aortic procedures. Recent literature has found high rates of complication associated with CSF drainage, which has led to changes in practice. The aim of this study was to investigate rates of CSF drain-related complications in patients undergoing a thoracoabdominal aortic procedure with perioperative placement of a CSF drain.

Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma.

Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, which are associated with resistance to BRAF-targeting therapies. Targeting the RAC1-GTPase pathway, including the upstream activator PREX2 and the downstream effector PI3Kβ, could be a potential strategy for overcoming therapeutic resistance, limiting melanoma recurrence, and suppressing metastatic progression.

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ.

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure.

Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis.

The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to ferroptosis when forming colonies at low density.

KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition.

Pancreatic cancer is characterized by the prevalence of oncogenic mutations in KRAS. Previous studies have reported that altered KRAS gene dosage drives progression and metastasis in pancreatic cancer. Whereas the role of oncogenic KRAS mutations is well characterized, the relevance of the partnering wild-type (WT) KRAS allele in pancreatic cancer is less well understood and controversial.

Interchromosomal segmental duplication drives translocation and loss of histidine-rich protein 3.

Most malaria rapid diagnostic tests (RDTs) detect histidine-rich protein 2 (PfHRP2) and PfHRP3, but deletions of and genes make parasites undetectable by RDTs. We analyzed 19,313 public whole-genome-sequenced field samples to understand these deletions better. deletion only occurred by chromosomal breakage with subsequent telomere healing.

Loss of DOCK2 potentiates Inflammatory Bowel Disease-associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression.

Inflammatory Bowel Disease-associated colorectal cancer (IBD-CRC) is a known and serious complication of Inflammatory Bowel Disease (IBD) affecting the colon. However, relatively little is known about the pathogenesis of IBD-associated colorectal cancer in comparison with its sporadic cancer counterpart. Here, we investigated the function of Dock2, a gene mutated in ~10% of IBD-associated colorectal cancers that encodes a guanine nucleotide exchange factor (GEF).

Reducing Falls in Hospitalized Children and Adolescents with Cancer and Blood Disorders: A Quality Improvement Journey.

Background: Falls in hospitalized pediatric patients represent a serious patient safety concern. Children and adolescents with cancer and blood disorders have inherent risk factors that increase the likelihood of injury from falls. The Hematology/Oncology (HO) and Stem Cell Transplant (SCT) inpatient units at Boston Children's Hospital embarked on a multiyear quality improvement journey to reduce inpatient falls in this population.

Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics.

Background And Aims: The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalised treatments. Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus (HBV) and HDV or HIV co-infection.

Cassini spacecraft reveals global energy imbalance of saturn.

The global energy budget is pivotal to understanding planetary evolution and climate behaviors. Assessing the energy budget of giant planets, particularly those with large seasonal cycles, however, remains a challenge without long-term observations. Evolution models of Saturn cannot explain its estimated Bond albedo and internal heat flux, mainly because previous estimates were based on limited observations.

Lense-Thirring precession after a supermassive black hole disrupts a star.

An accretion disk formed around a supermassive black hole after it disrupts a star is expected to be initially misaligned with respect to the equatorial plane of the black hole. This misalignment induces relativistic torques (the Lense-Thirring effect) on the disk, causing the disk to precess at early times, whereas at late times the disk aligns with the black hole and precession terminates. Here we report, using high-cadence X-ray monitoring observations of a tidal disruption event (TDE), the discovery of strong, quasi-periodic X-ray flux and temperature modulations.

Maternal social environment shapes yolk testosterone allocation and embryonic neural gene expression in tree swallows.

Offspring from females breeding in competitive social environments are often exposed to more testosterone (T) during embryonic development, which can affect traits from growth to behavior in potentially adaptive ways. Despite the important role of maternally derived steroids in shaping offspring development, the molecular mechanisms driving these processes are currently unclear. Here, we use tree swallows (Tachycineta bicolor) to explore the effects of the maternal social environment on yolk T concentrations and genome-wide patterns of neural gene expression in embryos.

The importance of input sequence set to consensus-derived proteins and their relationship to reconstructed ancestral proteins.

A protein sequence encodes its energy landscape-all the accessible conformations, energetics, and dynamics. The evolutionary relationship between sequence and landscape can be probed phylogenetically by compiling a multiple sequence alignment of homologous sequences and generating common ancestors via Ancestral Sequence Reconstruction or a consensus protein containing the most common amino acid at each position. Both ancestral and consensus proteins are often more stable than their extant homologs-questioning the differences between them and suggesting that both approaches serve as general methods to engineer thermostability.

CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake.

Pancreatic ductal adenocarcinoma carries a dismal prognosis, with high rates of metastasis and few treatment options. Hyperactivation of KRAS in almost all tumours drives RAC1 activation, conferring enhanced migratory and proliferative capacity as well as macropinocytosis. Macropinocytosis is well understood as a nutrient scavenging mechanism, but little is known about its functions in trafficking of signalling receptors.

T follicular helper cell profiles differ by malaria antigen and for children compared to adults.

Background: Circulating T-follicular helper (cT ) cells have the potential to provide an additional correlate of protection against ( as they are essential to promote B cell production of long-lasting antibodies. Assessing the specificity of cT subsets to individual malaria antigens is vital to understanding the variation observed in antibody responses and identifying promising malaria vaccine candidates.

Methods: Using spectral flow cytometry and unbiased clustering analysis we assessed antigen-specific cT cell recall responses to malaria vaccine candidates SEA-1A and GARP within a cross-section of children and adults living in a malaria holoendemic region of western Kenya.

Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system.

Imaging reporter genes are indispensable for visualising biological processes in living subjects, particularly in cancer research where they have been used to observe tumour development, cancer cell dissemination, and treatment response. Engineering reporter genes into the germline frequently involves single imaging modality reporters operating over limited spatial scales. To address these limitations, we developed an inducible triple-reporter mouse model (Rosa26) that integrates reporters for complementary imaging modalities, flfluorescence, bioluminescence and positron emission tomography (PET), along with inducible Cre-lox functionality for precise spatiotemporal control of reporter expression.

The Composition and Chemistry of Titan's Atmosphere.

In this review I summarize the current state of knowledge about the composition of Titan's atmosphere and our current understanding of the suggested chemistry that leads to that observed composition. I begin with our present knowledge of the atmospheric composition, garnered from a variety of measurements including -, the , and other ground- and space-based telescopes. This review focuses on the typical vertical profiles of gases at low latitudes rather than global and temporal variations.

Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging.

Purpose: The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and tumor genotype or gene expression-based subtyping remain unknown.

JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors.

Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression of solid tumors. In this study we investigate the effectiveness of inhibiting JAK/STAT3 in diverse CRC models, establish in which contexts high pathway expression is prognostic and perform in depth analysis underlying phenotypes.