Genetic suppression features ABHD18 as a Barth syndrome therapeutic target.

Cardiolipin (CL) is the signature phospholipid of the inner mitochondrial membrane, where it stabilizes electron transport chain protein complexes. The final step in CL biosynthesis relates to its remodelling: the exchange of nascent acyl chains with longer, unsaturated chains. However, the enzyme responsible for cleaving nascent CL (nCL) has remained elusive.

Resistance mutations and the blood-brain barrier: Key challenges in targeted treatment of brain metastatic non-small cell lung cancer.

Over the past two decades, marked progress has been made in treating non-small cell lung cancer (NSCLC) patients with EGFR-, ALK-, ROS1- and KRAS-targeted inhibitors. NSCLC patients very often develop brain metastases. Despite the continuous development of newer and better inhibitors, the survival outcomes of NSCLC patients with brain metastases remain significantly worse than those of patients without.

Prevalence of germline pathogenic variants in 779 patients with metastatic prostate cancer.

Objective: To assess the prevalence of germline pathogenic variants (gPVs) in genes associated with female breast cancer in Dutch patients with metastatic prostate cancer (mPCa).

Patients And Methods: In this prospective multicentre cohort study (n = 15 centres), germline genetic testing of the genes BRCA1, BRCA2, ATM, CHEK2 and PALB2 was offered to patients with mPCa. We assessed the prevalence of gPVs and compared it to a reference population of 16 823 individuals who underwent genetic testing for non-oncological conditions.

Physical foundations for trustworthy medical imaging: A survey for artificial intelligence researchers.

Artificial intelligence in medical imaging has grown rapidly in the past decade, driven by advances in deep learning and widespread access to computing resources. Applications cover diverse imaging modalities, including those based on electromagnetic radiation (e.g.

Circulating kidney injury molecule-1 (KIM-1) and association with outcome to adjuvant immunotherapy in renal cell carcinoma.

Background: Adjuvant immunotherapy is currently the standard of care for patients with resected renal cell carcinoma (RCC) at increased risk of recurrence, but there are no biomarkers available to guide treatment. Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in renal cell carcinoma.

Patients And Methods: Biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010) were evaluated.

Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells.

Mitosis is a critical phase of the cell cycle and a vulnerable point where cancer cells can be disrupted, causing cell death and inhibiting tumor growth. Challenges such as drug resistance persist in clinical applications. During mitosis, mRNA translation is generally downregulated, while non-canonical translation of specific transcripts continues.

Safety of surveillance endoscopy and EUS of the esophagus after neoadjuvant chemoradiotherapy: Results from the (pre)SANO trial.

Background And Study Aims: Active surveillance has been proposed for patients with esophageal cancer and a clinical complete response after neoadjuvant chemoradiotherapy (nCRT). This strategy involves repeated esophagogastroduodenoscopy (EGD) with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) to detect tumor regrowth or residual disease. The aim of this study was to assess safety of endoscopic procedures during active surveillance.

Impact of deep learning model uncertainty on manual corrections to MRI-based auto-segmentation in prostate cancer radiotherapy.

Background: Deep learning (DL)-based organ segmentation is increasingly used in radiotherapy. While methods exist to generate voxel-wise uncertainty maps from DL-based auto-segmentation models, these maps are rarely presented to clinicians.

Purpose: This study aimed to evaluate the impact of DL-generated uncertainty maps on experienced radiation oncologists during the manual correction of DL-based auto-segmentation for prostate radiotherapy.

Cause-specific mortality after a diagnosis of ductal carcinoma in situ: Associations with screening and socio-economic status.

The lower all-cause mortality in women with Ductal carcinoma in situ (DCIS) compared with the general population has been hypothesized to be due to a "healthy-user effect," but this has not been studied in large cohorts. In a population-based, retrospective cohort study comprising 18,942 women with primary DCIS between 1999 and 2015 in the Netherlands, the cumulative incidence of breast cancer death (BCD) was estimated using death by other cause as a competing risk. The cause-specific mortality risk of women with DCIS was compared with that of the Dutch female population.

Liver metastases treated with MRI-guided SBRT: Outcomes of tolerability, acute toxicity and quality of life from the MOMENTUM study.

Purpose/objective(s): Stereotactic body radiation therapy (SBRT) is a local treatment option for liver metastases. The introduction of Magnetic Resonance Imaging (MRI)-guided SBRT has paved the way for optimal treatment outcomes by improved tumor visualization, daily plan adaptation and margin reduction. The purpose of this study is to review tolerability of MRI-guided liver SBRT and to present early toxicity and quality of life (QoL) outcomes from a prospective multicenter registry.

Absorption of apixaban following metabolic bariatric surgery: is reluctance still warranted?

Background: Absorption of apixaban, a direct oral anticoagulant (DOAC), may be impaired after metabolic and bariatric surgery (MBS). The Dutch guideline advises to switch to vitamin K antagonists (VKA), while patients prefer the use of DOACs. Apixaban is not regularly prescribed after MBS due to a lack of evidence regarding its efficacy and safety.

Aquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions.

HIV-1 integration into host chromosomes, essential for viral replication, is catalysed by viral integrase (IN). IN recurrently targets intronic regions of transcriptionally active genes, but a detailed understanding of this process is still unclear. Here, using ex vivo activated human primary CD4T cells, we find that genomic RNA:DNA hybrids (R-loops) preferentially map to intronic regions of active genes that are typical HIV-1 integration sites.

Radiological T-staging in prostate Cancer: Towards a universal MRI-based scoring system.

Magnetic resonance imaging (MRI) is recommended for local prostate cancer tumor (T) staging. While MRI offers superior anatomical resolution compared to digital rectal examination, its accuracy in distinguishing organ-confined (T2) from locally advanced (T3a) tumors remains low. This narrative review critically examines the current MRI-based T-staging performance, its limitations, and the clinical implications of image scoring systems to assess local tumor extent.

Di--Substituted Fluorinated Benzenesulfonamides as Potent and Selective Anticancer Inhibitors of Carbonic Anhydrase IX and XII.

The development of selective drug candidate molecules for cancer-related carbonic anhydrase isozymes IX and XII is challenging due to high homology binding sites among 12 catalytically active isozymes. Starting from the trifluorinated benzenesulfonamide with cyclooctylamino substituent at the position, we designed and synthesized di--substituted fluorinated benzenesulfonamides with up to 10-fold affinity improvement for CAIX, resulting in low picomolar binders. The resulting CAIX-targeting compounds showed up to 1000-fold selectivity over off-target CA isozymes.

Genetic and Epigenetic Reprogramming of Transposable Elements Drives ecDNA-Mediated Metastatic Prostate Cancer.

Extrachromosomal DNAs (ecDNAs), which replicate and segregate in a non-Mendelian manner, serve as vectors for accelerated tumor evolution. By integrating chromatin accessibility, whole-genome sequencing, and Hi-C-based genome topology data from a cohort of metastatic Castration-Resistant Prostate Cancer (mCRPC) cases, we show that epigenetically activated repeat DNA, amplified in ecDNAs, drive oncogene overexpression. Specifically, we identify a subgroup of mCRPCs (20%) characterized by clusters of accessible LINE1 repeat DNA elements flanking the androgen receptor (AR) gene.

Consensus on the definition, components, timeframe and grading of composite outcome of postoperative pulmonary complication-protocol for an international mixed-method consensus study (PrECiSIOn).

Introduction: Postoperative pulmonary complications (PPCs) represent a significant cause of postoperative morbidity and even mortality. However, there is a lack of consensus regarding this composite endpoint, the definition of the individual components, classification and optimal outcome measures. This study aims to refine the PPCs composite framework by evaluating its construct validity, assessing the necessity and risks of a composite measure and exploring the feasibility of differentiating severity categories.

Prostate Volume and PSA-Density Estimation by Transabdominal Ultrasound: Prospective Evidence of Comparative Accuracy to MRI and Transrectal Ultrasound in Prostate Cancer Early Diagnostics.

Background: Prostate-specific antigen (PSA) density is an easily available predictor for clinically significant PCa. While transrectal ultrasound (TRUS) is utilized for PSA density (PSAD) estimation, transabdominal ultrasound (TAUS) is a more accessible, noninvasive alternative that can be used to decide if follow-up diagnostics are necessary. This study aims to compare prostate volume (PV) and PSAD across TAUS, TRUS and MRI, comparing the clinical utility of TAUS and TRUS for PSAD-based risk stratification.

Diagnostic accuracy of CT for identifying high-risk colon cancer: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis aimed to assess the diagnostic accuracy of CT in differentiating high-risk from low-risk colon cancer, with a focus on staging parameters and the impact of CT slice thickness.

Materials And Methods: A systematic search of Ovid MEDLINE and Embase.com was conducted from January 1, 2015, to September 24, 2024, to identify studies evaluating CT-based staging accuracy using histopathology as the reference standard.

TRIM24 as a therapeutic target in endocrine treatment-resistant breast cancer.

While Estrogen receptor alpha (ERα)+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since ERα is still the main driver in most therapy-resistant tumors, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we position TRIM24 as a therapeutic target in endocrine resistance, given its role as a key component of the ERα transcriptional complex.

Prospective validation of an artificial intelligence assessment in a cohort of applicants seeking financial compensation for asbestosis (PROSBEST).

Background: Asbestosis, a rare pneumoconiosis marked by diffuse pulmonary fibrosis, arises from prolonged asbestos exposure. Its diagnosis, guided by the Helsinki criteria, relies on exposure history, clinical findings, radiology, and lung function. However, interobserver variability complicates diagnoses and financial compensation.

Multiparametric magnetic resonance imaging for radiotherapy response evaluation in high-risk soft tissue sarcoma: A pilot study.

Background And Purpose: Soft tissue sarcomas (STS) are rare mesenchymal tumors for which no clinically validated quantitative magnetic resonance imaging (qMRI) parameters exist yet.This study explores repeatability and association with histopathology of qMRI parameters during and after neo-adjuvant angiogenesis inhibition (oral pazopanib) and radiotherapy for localized, high-risk STS.

Materials And Methods: For fifteen patients, qMRI parameters, including apparent diffusion coefficient (ADC), volume transfer constant (K) and T relaxation times were acquired twice at baseline (B1 and B2), twice during neo-adjuvant treatment and pre-surgery.