Targeting RNA helicase DDX3X with a small molecule inhibitor for breast cancer bone metastasis treatment.

Patients who present with breast cancer bone metastasis only have limited palliative treatment strategies and efficacious drug treatments are needed. In breast cancer patient data, high levels of the RNA helicase DDX3 are associated with poor overall survival and bone metastasis. Consequently, our objective was to target DDX3 in a mouse breast cancer bone metastasis model using a small molecule inhibitor of DDX3, RK-33.

Clinical implementation of artificial-intelligence-assisted detection of breast cancer metastases in sentinel lymph nodes: the CONFIDENT-B single-center, non-randomized clinical trial.

Pathologists' assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm (n = 100) or control arm (n = 90).

Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements.

Exploring timing and delivery of lifestyle advice following an acute cardiac event hospitalization: The cardiac patient's perspective.

Objective: To explore the perspective of cardiac patients regarding the timing and manner of delivering lifestyle advice following an acute cardiac event hospitalization.

Methods: Dutch cardiac patients who experienced a cardiac event hospitalization participated in a semi-structured interview (n = 14) or a cross-sectional survey study (n = 119).

Results: Our findings indicate that cardiac patients are receptive to lifestyle advice throughout the care trajectory.

Patients' preferences for secondary prevention following a coronary event.

Objective: Despite clear evidence on the effectiveness of secondary prevention, patients with coronary artery disease frequently fail to reach guideline-based risk factor targets. Integrating patients' preferences into treatment decisions has been recommended to reduce this gap. However, this requires knowledge about patient treatment preferences.

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported.

RNA helicase DDX3 regulates RAD51 localization and DNA damage repair in Ewing sarcoma.

We previously demonstrated that RNA helicase DDX3X (DDX3) can be a therapeutic target in Ewing sarcoma (EWS), but its role in EWS biology remains unclear. The present work demonstrates that DDX3 plays a unique role in DNA damage repair (DDR). We show that DDX3 interacts with several proteins involved in homologous recombination, including RAD51, RECQL1, RPA32, and XRCC2.

Cardiac rehabilitation for patients with obesity: lessons learned from the OPTICARE XL trial.

Obesity is a known and commonly encountered risk factor for the development of cardiac diseases. Patients with cardiac diseases who also have obesity do not benefit optimally from standard cardiac rehabilitation (CR) programs. Exercises performed during CR are not the best fit for patients with obesity and counselling sessions often do not address their specific needs.

Physical activity and sedentary behaviour changes during and after cardiac rehabilitation: Can patients be clustered?

Objective: To identify clusters of patients according to changes in their physical behaviour during and after cardiac rehabilitation, and to predict cluster membership.

Methods: The study included 533 patients (mean age 57.9 years; 18.

Time Trends in Histopathological Findings in Mammaplasty Specimens in a Dutch Academic Pathology Laboratory.

Unlabelled: Reduction mammaplasties are often performed at a relatively young age. Necessity of routine pathological investigation of the removed breast tissue to exclude breast cancer has been debated. Past studies have shown 0.

RNA Helicase DDX3 Regulates RAD51 Localization and DNA Damage Repair in Ewing Sarcoma.

We previously demonstrated that RNA helicase DDX3X (DDX3) can be a therapeutic target in Ewing sarcoma (EWS), but its role in EWS biology remains unclear. The present work demonstrates that DDX3 plays a unique role in DNA damage repair (DDR). We show that DDX3 interacts with several proteins involved in homologous recombination, including RAD51, RECQL1, RPA32, and XRCC2.

CONFIDENT-trial protocol: a pragmatic template for clinical implementation of artificial intelligence assistance in pathology.

Introduction: Artificial intelligence (AI) has been on the rise in the field of pathology. Despite promising results in retrospective studies, and several CE-IVD certified algorithms on the market, prospective clinical implementation studies of AI have yet to be performed, to the best of our knowledge. In this trial, we will explore the benefits of an AI-assisted pathology workflow, while maintaining diagnostic safety standards.

Deep learning supported mitoses counting on whole slide images: A pilot study for validating breast cancer grading in the clinical workflow.

Introduction: Breast cancer (BC) prognosis is largely influenced by histopathological grade, assessed according to the Nottingham modification of Bloom-Richardson (BR). Mitotic count (MC) is a component of histopathological grading but is prone to subjectivity. This study investigated whether mitoses counting in BC using digital whole slide images (WSI) compares better to light microscopy (LM) when assisted by artificial intelligence (AI), and to which extent differences in digital MC (AI assisted or not) result in BR grade variations.

Effects of a Dedicated Cardiac Rehabilitation Program for Patients With Obesity on Body Weight, Physical Activity, Sedentary Behavior, and Physical Fitness: The OPTICARE XL Randomized Controlled Trial.

Objective: Previously published results of the OPTICARE XL open label randomized controlled trial showed no added value of OPTICARE XL CR, a dedicated cardiac rehabilitation (CR) program for patients with obesity, with respect to health-related quality of life (primary outcome). This clinical trial studied the effects of OPTICARE XL CR on several secondary outcomes, which included body weight, physical activity, sedentary behavior, and physical fitness.

Methods: Patients with coronary artery disease or atrial fibrillation and body mass index ≥ 30 were randomized to OPTICARE XL CR (n = 102) or standard CR (n = 99).

Echocardiographic follow-up after cardiac rehabilitation designed for patients with obesity.

We hypothesize that a novel tailor-made cardiac rehabilitation (CR) program for obesity patients (OPTICARE XL) has better outcomes as compared to usual CR regarding parameters of cardiac function as measured by conventional and advanced transthoracic echocardiography. This is an open-label, randomized controlled trial. Inclusion criteria were: patients referred to CR with a body mass index (BMI) ≥30 kg/m2, and age ≥18 years with either coronary artery disease or nonvalvular atrial fibrillation.

Cost-Effectiveness of a Cardiac Rehabilitation Program Specifically Designed for Patients With Obesity Within the OPTICARE XL Randomized Controlled Trial.

Objective: To assess the cost-effectiveness of a cardiac rehabilitation (CR) program specifically designed for cardiac patients with obesity vs standard CR.

Design: Cost-effectiveness analysis based on observations in a randomized controlled trial.

Setting: Three regional CR centers in the Netherlands.

Effects of menstruation on the onset of acute coronary syndrome in premenopausal women: A case series.

Background: The incidence of cardiovascular disease (CVD) among women is lower before the menopause, which may be due to the atheroprotective effects of female sex hormones, including estrogens. This study explored whether women experienced acute coronary syndrome (ACS) more often during menstruation, when the levels of female sex hormones are low.

Methods: All premenopausal women referred to the local cardiac rehabilitation program after ACS between August 2010 and September 2018 were contacted by telephone to gather information about their menstrual cycle, contraceptive use and whether ACS occurred during menstruation.

Unexploited potential of risk factor treatment in patients with atherosclerotic cardiovascular disease.

Background: Most patients with atherosclerotic cardiovascular disease remain at (very) high risk for recurrent events due to suboptimal risk factor control.

Aims: This study aimed to quantify the potential of maximal risk factor treatment on 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events in patients 1 year after a coronary event.

Methods And Results: Pooled data from six studies are as follows: RESPONSE 1, RESPONSE 2, OPTICARE, EUROASPIRE IV, EUROASPIRE V, and HELIUS.

Mitosis domain generalization in histopathology images - The MIDOG challenge.

The density of mitotic figures (MF) within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of MF by pathologists is subject to a strong inter-rater bias, limiting its prognostic value. State-of-the-art deep learning methods can support experts but have been observed to strongly deteriorate when applied in a different clinical environment.

Assessing Changes in Fear of Movement in Patients attending Cardiac Rehabilitation: Responsiveness of the TSK-NL Heart Questionnaire.

Objectives: The primary objective was to determine the responsiveness of the Dutch version of the 13-item Tampa Scale for Kinesiophobia for cardiac patients (TSK-NL Heart). The secondary objective was to assess changes in kinesiophobia during cardiac rehabilitation.

Methods: Kinesiophobia was measured pre- and post-cardiac rehabilitation using the TSK-NL Heart questionnaire in 109 cardiac patients (61 years; 76% men).

Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy.

Purpose: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown.