NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.

Current models for the study of neuroendocrine tumours (NETs) are severely limited. While (e.g.

Stroke emboli from patients with atrial fibrillation enriched with neutrophil extracellular traps.

Background: Recent literature has demonstrated remarkable heterogeneity in the composition of acute ischemic stroke (AIS) emboli, which may impact susceptibility to therapy.

Objectives: In this study, we explored differences in proteomic composition of retrieved embolic material from patients with stroke with and without atrial fibrillation (AF) (AF+ and AF-, respectively).

Methods: The full proteome of retrieved thromboembolic material from 24 patients with AIS was obtained by mass spectrometry.

Histone content, and thus DNA content, is associated with differential in vitro lysis of acute ischemic stroke clots.

Background: Fibrin, von Willebrand factor, and extracellular DNA from neutrophil extracellular traps all contribute to acute ischemic stroke thrombus integrity.

Objectives: In this study, we explored how the proteomic composition of retrieved thromboemboli relates to susceptibility to lysis with distinct thrombolytics.

Methods: Twenty-six retrieved stroke thromboemboli were portioned into 4 segments, with each subjected to 1 hour of in vitro lysis at 37 °C in 1 of 4 solutions: tissue plasminogen activator (tPA), tPA + von Willebrand factor-cleaving ADAMTS-13, tPA + DNA-cleaving deoxyribonuclease (DNase) I, and all 3 enzymes.

Loss of ATG4B and ATG4A results in two-stage cell cycle defects in pancreatic ductal adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) exhibits elevated levels of autophagy, which promote tumor progression and treatment resistance. ATG4B is an autophagy-related cysteine protease under consideration as a potential therapeutic target, but it is largely unexplored in PDAC. Here, we investigated the clinical and functional relevance of ATG4B expression in PDAC.

Multi-Omic Analysis of CIC's Functional Networks Reveals Novel Interaction Partners and a Potential Role in Mitotic Fidelity.

encodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CIC's interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, as well as novel interactions between CIC and cell cycle regulators and RNA processing factors.

CT hyperdense cerebral artery sign reflects distinct proteomic composition in acute ischemic stroke thrombus.

Background: Hyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior studies have correlated HCAS with histopathological composition of cerebral thrombus, it is unknown whether and to what extent HCAS is also associated with distinct clot protein composition.

Methods: Thromboembolic material from 24 patients with AIS were retrieved via mechanical thrombectomy and evaluated with mass spectrometry in order to characterize their proteomic composition.

Bilateral Primary Iliopsoas Abscess with Bilateral Hip Septic Arthritis - A Rare Case Report.

Introduction: Iliopsoas abscess is an uncommon condition, often with insidious and nonspecific symptoms. Patients often present with a limp, fever, weight loss, and flank or abdominal pain. An iliopsoas abscess can be either primary or secondary depending on the presence or absence of an underlying disease.

Single-Stage Revision With Fluconazole Monotherapy in Fungal Prosthetic Knee Joint Infections.

Fungal prosthetic joint infection is rare, and two-stage revision is usually advocated. We present our experience with 2 cases of fungal prosthetic knee joint infection presenting 25 months and 3 years after index surgery. Both patients were managed with single-stage revision arthroplasty and fluconazole monotherapy.

Transcriptomic analysis of CIC and ATXN1L reveal a functional relationship exploited by cancer.

Aberrations in Capicua (CIC) have recently been implicated as a negative prognostic factor in a multitude of cancer types through activation of the MAPK signalling cascade and derepression of oncogenic ETS transcription factors. The Ataxin-family protein ATXN1L has previously been reported to interact with CIC in developmental and disease contexts to facilitate the repression of CIC target genes. To further investigate this relationship, we performed functional in vitro studies utilizing ATXN1L and CIC human cell lines and characterized a reciprocal functional relationship between CIC and ATXN1L.

Techniques for the Detection of Autophagy in Primary Mammalian Cells.

Autophagy is a lysosomal catabolic pathway responsible for the degradation of cytoplasmic constituents. Autophagy is primarily a survival pathway for recycling cellular material in times of nutrient starvation, and in response to hypoxia, endoplasmic reticulum stress, and other stresses, regulated through the mammalian target of rapamycin pathway. The proteasomal pathway is responsible for degradation of proteins, whereas autophagy can degrade cytoplasmic material in bulk, including whole organelles such as mitochondria (mitophagy), bacteria (xenophagy), or lipids (lipophagy).

Monitoring Autophagic Flux by Using Lysosomal Inhibitors and Western Blotting of Endogenous MAP1LC3B.

Assays that monitor autophagic flux, or degradative completion of autophagy, are crucial for the assessment of the dynamic autophagy process in a variety of systems. Such assays help to distinguish between an increase in autophagosomes resulting from induced autophagic activity versus an increase in autophagosomes due to reduced lysosomal turnover. The majority of flux assays use autophagy protein MAP1LC3B (microtubule-associated proteins 1A/1B light chain 3B, here referred to as LC3B) as a marker for autophagy, and most are based on the use of reporters.

The Drosophila TIPE family member Sigmar interacts with the Ste20-like kinase Misshapen and modulates JNK signaling, cytoskeletal remodeling and autophagy.

TNFAIP8 and other mammalian TIPE family proteins have attracted increased interest due to their associations with disease-related processes including oncogenic transformation, metastasis, and inflammation. The molecular and cellular functions of TIPE family proteins are still not well understood. Here we report the molecular and genetic characterization of the Drosophila TNFAIP8 homolog, CG4091/sigmar.

Treatment of Large Recurrent Bilateral Xanthomatosis of Achilles Tendon- A Case Report.

Introduction: Xanthomas of the Achilles tendon are a rare interesting orthopaedic condition. There are very few articles dealing with the treatment of recurrent xanthomatosis of tendoachilles. Here we report this patient with bilateral recurrent xanthomatosis of tendoachilles.

Mutations in CIC and IDH1 cooperatively regulate 2-hydroxyglutarate levels and cell clonogenicity.

The majority of oligodendrogliomas (ODGs) exhibit combined losses of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH1-R132H or IDH2-R172K). Approximately 70% of ODGs with 1p19q co-deletions harbor somatic mutations in the Capicua Transcriptional Repressor (CIC) gene on chromosome 19q13.2.

Autophagy inhibition augments the anticancer effects of epirubicin treatment in anthracycline-sensitive and -resistant triple-negative breast cancer.

Purpose: Triple-negative breast cancers (TNBC) are defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (ERBB2/HER2). Although initially responsive to chemotherapy, most recurrent TNBCs develop resistance, resulting in disease progression. Autophagy is a lysosome-mediated degradation and recycling process that can function as an adaptive survival response during chemotherapy and contribute to chemoresistance.

High glycolic poly (DL lactic co glycolic acid) nanoparticles for controlled release of meropenem.

Nanospheres of low molecular weight poly lactic co glycolic acid (PLGA) with high glycolic acid content (10:90) and polylactic acid (PLA) are synthesized and loaded with meropenem, a broad spectrum antibiotic. The loading efficiency of the drug is 82 and 70% in PLGA 10:90 and PLA respectively. The rate of drug release is higher with PLGA 10:90 (3.

Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer.

The drug fluorouracil (5-FU) is a widely used antimetabolite chemotherapy in the treatment of colorectal cancer. The gene uridine monophosphate synthetase (UMPS) is thought to be primarily responsible for conversion of 5-FU to active anticancer metabolites in tumor cells. Mutation or aberrant expression of UMPS may contribute to 5-FU resistance during treatment.

Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers.

Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution.

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma.

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations.

A simple solution for wound coverage by skin stretching.

Viscoelastic properties of skin, ie, creep and stress relaxation, allow it to stretch beyond its normal state within a short period of time. Presented here is a technique of "wound coverage by skin stretching" that uses this principle. Kirschner wires were passed through the skin edges on either side of the wound margins.

Alternative expression analysis by RNA sequencing.

In alternative expression analysis by sequencing (ALEXA-seq), we developed a method to analyze massively parallel RNA sequence data to catalog transcripts and assess differential and alternative expression of known and predicted mRNA isoforms in cells and tissues. As proof of principle, we used the approach to compare fluorouracil-resistant and -nonresistant human colorectal cancer cell lines. We assessed the sensitivity and specificity of the approach by comparison to exon tiling and splicing microarrays and validated the results with reverse transcription-PCR, quantitative PCR and Sanger sequencing.

Fecal polymerase chain reaction for Mycobacterium tuberculosis IS6110 to distinguish Crohn's disease from intestinal tuberculosis.

Background: We have previously shown that amplification of Mycobacterium tuberculosis specific DNA (TB PCR) from feces reliably diagnosed intestinal tuberculosis. This study was undertaken to determine how well this test would distinguish intestinal tuberculosis from Crohn's disease in a country endemic for tuberculosis.

Methods: Consecutive patients with diagnoses of Crohn's disease and intestinal tuberculosis were enrolled, and the diagnoses confirmed by follow up.

Low levels of faecal lactobacilli in women with iron-deficiency anaemia in south India.

Fe deficiency in women contributes significantly to maternal and child morbidity in India. The intestinal bacterial flora may facilitate absorption of Fe from the caecum and proximal colon. The present study investigated the possibility that intestinal microbiota of anaemic young women may differ from that of women with normal Hb levels.