ZNF143 is a transcriptional regulator of nuclear-encoded mitochondrial genes that acts independently of looping and CTCF.

Gene expression is orchestrated by transcription factors, which function within the context of a three-dimensional genome. Zinc-finger protein 143 (ZNF143/ZFP143) is a transcription factor that has been implicated in both gene activation and chromatin looping. To study the direct consequences of ZNF143/ZFP143 loss, we generated a ZNF143/ZFP143 depletion system in mouse embryonic stem cells.

Associations of intraoperative end-tidal CO levels with postoperative outcome-secondary analysis of a worldwide observational study.

Background: Patients receiving intraoperative ventilation during general anesthesia often have low end-tidal CO (etCO). We examined the association of intraoperative etCO levels with the occurrence of postoperative pulmonary complications (PPCs) in a conveniently-sized international, prospective study named 'Local ASsessment of Ventilatory management during General Anesthesia for Surgery' (LAS VEGAS).

Methods: Patients at high risk of PPCs were categorized as 'low etCO' or 'normal to high etCO' patients, using a cut-off of 35 mmHg.

Muscle atrophy and organ enlargement associated with quality of life during systemic therapy for melanoma: findings from an AI-based body composition analysis.

Introduction: Health-related quality of life (HRQoL) is emerging as an endpoint, adjunct to survival, in cancer treatment. For this reason, the European Organization for Research and Treatment of Cancer (EORTC) has developed standardized quality-of-life questionnaires to collect patient-reported outcome measurement (PROM), which so far have been widely used in clinical trials to evaluate the impact of new drugs on cancer patients. However, while these questionnaires comprehensively describe patient functions, little is known about their association with patient characteristics.

Heterogeneity in response to neoadjuvant radiotherapy between soft tissue sarcoma histotypes: associations between radiology and pathology findings.

Objective: To investigate imaging biomarkers of tumour response by describing changes in imaging and pathology findings after neoadjuvant radiotherapy (nRT) and exploring their correlations.

Materials And Methods: Tumour diameter, volume, and tumour-to-muscle signal intensity (SI) ratio were collected before and after radiotherapy in a cohort of 107 patients with intermediate/high-grade STS and were correlated with post-radiotherapy pathology findings (percentage of necrosis, viable cells, and fibrosis) using Spearman Rank test. Pathological complete response (pCR) was defined as no residual viable cells present, whereas the presence of < 10% viable cells was defined as near-complete pathologic response (near-pCR).

Win Ratio approach for the composite outcome of postoperative pulmonary complications: Secondary analysis of a harmonised and pooled database of three randomised clinical trials.

Background: The win ratio analysis method might provide new insight on the impact of positive end-expiratory pressure (PEEP) on clinical outcomes.

Objective: The aim is to re-analyse the results of the 'Re-evaluation of the effects of high PEEP with recruitment manoeuvres vs. low PEEP without recruitment manoeuvres during general anaesthesia for surgery' (REPEAT) study using the win ratio analysis.

An antibiotic that mediates immune destruction of senescent cancer cells.

Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells.

Identification of a sorting motif for Tspan3 to MHCII compartments in human B cells.

Tetraspanins are four-transmembrane proteins that play fundamental roles in the immune system by enabling processes like migration, proliferation, signaling and protein trafficking. While the importance of cell surface tetraspanins has been established, the function of intracellular tetraspanins is less well understood. Here, we investigated the role of tetraspanin 3 (Tspan3) in lymphocytes.

Advances in peripheral T cell lymphomas: pathogenesis, genetic landscapes and emerging therapeutic targets.

Peripheral T cell lymphomas (PTCLs) are a biologically diverse and aggressive group of non-Hodgkin lymphomas that originate from mature T cells, often presenting with complex clinical and morphological features. This review explores the challenges in diagnosing and classifying PTCLs, focusing on the intricate biology of the more common nodal entities. Advances in molecular diagnostics, such as mutational and gene expression profiling, have improved our understanding.

Tissue-probe contact assessment during robotic surgery using single-fiber reflectance spectroscopy.

The introduction of robotic surgery has improved minimally invasive surgery, and now robotic surgery is used in several areas of surgical oncology. Several optical techniques can be used to discriminate cancer from healthy tissue based on their optical properties. These technologies can also be employed with a small fiber-optic probe during minimally invasive surgery; however, for acquiring reliable measurements, some optical techniques require the fiber-optic probe to be in direct contact with the tissue.

An early economic evaluation of active surveillance for low-risk ductal carcinoma .

Perform early economic evaluation comparing active surveillance (AS) to surgery for women with low-risk ductal carcinoma , a precursor of invasive breast cancer. A 10-year incremental costs (€) and quality-adjusted life years (QALYs) were compared between a simulated cohort of women undergoing breast conserving surgery ± radiotherapy, and a cohort with a low-risk subgroup undergoing AS using a semi-Markov model. Scenario and headroom analyses evaluated a better-performing biomarker to select low-risk women for AS.

Incorporating patient-specific prior clinical knowledge to improve clinical target volume auto-segmentation generalisability for online adaptive radiotherapy of rectal cancer: A multicenter validation.

Background & Purpose: Deep learning (DL) based auto-segmentation has shown to be beneficial for online adaptive radiotherapy (OART). However, auto-segmentation of clinical target volumes (CTV) is complex, as clinical interpretations are crucial in their definition. The resulting variation between clinicians and institutes hampers the generalizability of DL networks.

Cost-effectiveness of a nurse-led sexual rehabilitation intervention for women treated with radiotherapy for gynaecological cancer in a randomized trial.

Purpose: To compare the cost-effectiveness of a nurse-led sexual rehabilitation intervention with standard care in women treated with external beam radiotherapy, with or without brachytherapy, for gynaecological cancers.

Methods: Eligible women were randomly assigned to the intervention (n = 112) or standard care (n = 117). Primary endpoint was sexual functioning at 12-months post-radiotherapy, assessed by the Female Sexual Function Index (FSFI).

JBP1 and JBP3 have conserved structures but different affinity to base-J.

Base-J (β-D-glucopyranosyloxymethyluracil) is an unusual kinetoplastid-specific DNA modification, recognized by base-J containing DNA (J-DNA) binding proteins JBP1 and JBP3. Recognition of J-DNA by both JBP1 and JBP3 takes place by a conserved J-DNA binding domain (JDBD). Here we show that JDBD-JBP3 has about 1,000-fold weaker affinity to base-J than JDBD-JBP1 and discriminates between J-DNA and unmodified DNA with a factor ∼5, whereas JDBD-JBP1 discriminates with a factor ∼10,000.

Translating Between Radiation Dose and Late Toxicity for Lymphoma Survivors: Implications on Toxicity Counseling and Survivorship.

Radiation therapy (RT) is an important modality in the modern management of lymphoma. RT has long been recognized as a cause of late toxicity in lymphoma survivors, including serious morbidity and increased mortality from second cancers and cardiovascular disease. Many studies have quantified the relationships between radiation dose to normal tissues and the risk of late toxicities.

Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics.

The spatiotemporal configuration of genes with distal regulatory elements is believed to be crucial for transcriptional control, but full mechanistic understanding is lacking. We combine simultaneous live tracking of pairs of genomic loci and nascent transcripts with molecular dynamics simulations to assess the gene and its enhancer. We find that both loci exhibit more constrained mobility than control sequences due to stalled cohesin at CCCTC-binding factor sites.

Prognostic value of radiologic and pathological response in colorectal cancer liver metastases upon systemic induction treatment: subgroup analysis of the CAIRO5 trial.

Background: RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM).

Patients And Methods: Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

Perturbation of mRNA splicing in liver cancer: insights, opportunities and challenges.

Perturbation of mRNA splicing is commonly observed in human cancers and plays a role in various aspects of cancer hallmarks. Understanding the mechanisms and functions of alternative splicing (AS) not only enables us to explore the complex regulatory network involved in tumour initiation and progression but also reveals potential for RNA-based cancer treatment strategies. This review provides a comprehensive summary of the significance of AS in liver cancer, covering the regulatory mechanisms, cancer-related AS events, abnormal splicing regulators, as well as the interplay between AS and post-transcriptional and post-translational regulations.

The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements.

The farnesoid X receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with the retinoid X receptor (RXR). FXR is expressed as four isoforms (α1-α4) that drive transcription from IR-1 (inverted repeat-1) response elements (REs). Recently, we found that FXR isoforms α2/α4 also activate transcription from non-canonical ER-2 (everted repeat-2) REs, mediating most metabolic effects of general FXR activation.

Measurement variability of radiologists when measuring brain tumors.

Background: In oncology trials, response evaluation criteria are pivotal in developing new treatments. This study examines the influence of measurement variability in brain lesions on response classification, considering long-standing cut-offs for progression and response were determined before the era of submillimeter resolutions of medical imaging.

Methods: We replicate a key study using modern radiological tools.

Androgen receptor inhibition increases MHC Class I expression and improves immune response in prostate cancer.

Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression.