Graph neural networks in histopathology: Emerging trends and future directions.

Histopathological analysis of whole slide images (WSIs) has seen a surge in the utilization of deep learning methods, particularly Convolutional Neural Networks (CNNs). However, CNNs often fail to capture the intricate spatial dependencies inherent in WSIs. Graph Neural Networks (GNNs) present a promising alternative, adept at directly modeling pairwise interactions and effectively discerning the topological tissue and cellular structures within WSIs.

PRO-P: evaluating the effect of electronic patient-reported outcome measures monitoring compared with standard care in prostate cancer patients undergoing surgery-study protocol for a randomized controlled trial.

Background: With over 65,000 new cases per year in Germany, prostate cancer (PC) is the most common cancer in men in Germany. Localized PC is often treated by radical prostatectomy and has a very good prognosis. Postoperative quality of life (QoL) is significantly influenced by the side effects of surgery.

Effect of Prior Transurethral Prostate Resection (TURP) or Laser Enucleation (ThuLEP) on Radiotherapy-Induced Toxicity and Quality of Life in Prostate Cancer Patients Undergoing Definitive Radiotherapy.

In our study, the post-radiotherapy quality of life of prostate cancer patients who previously underwent transurethral resection of the prostate (TURP) is compared to those who had thulium laser enucleation of the prostate (ThuLEP) and those who had no prior surgery. It also aims to identify and assess risk factors affecting therapy tolerance in this patient group. We analyzed 132 patients with localized prostate cancer treated with definitive radiotherapy (RT), including 23 who had prior TURP and 19 who previously underwent ThuLEP.

Intracellular spatial transcriptomic analysis toolkit (InSTAnT).

Imaging-based spatial transcriptomics technologies such as Multiplexed error-robust fluorescence in situ hybridization (MERFISH) can capture cellular processes in unparalleled detail. However, rigorous and robust analytical tools are needed to unlock their full potential for discovering subcellular biological patterns. We present Intracellular Spatial Transcriptomic Analysis Toolkit (InSTAnT), a computational toolkit for extracting molecular relationships from spatial transcriptomics data at single molecule resolution.

Immune-Related Adverse Events Can Predict Progression-Free and Overall Survival In Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors.

Background: Different combination therapies using anti - PD-1 / PD-L1 or CTLA-4 immune checkpoint inhibition (ICI) are widely used in patients with metastatic renal cell carcinoma (mRCC). In the absents of established biomarkers, immune-related adverse events (irAEs) have been discussed as potential predictors of response.

Methods: In this retrospective cohort study, data of 134 patients with mRCC undergoing ICI treatment (Nivolumab, Ipilimumab and Nivolumab, Pembrolizumab and Axitinib or Avelumab and Axitinib) between 2015 and 2021 were analyzed.

Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma.

Background: The predictive value of tumor-infiltrating lymphocytes (TILs) in immune-related adverse event (irAE) development remains unknown, although an association between tumor immunogenicity and irAEs has been suggested. We investigated the association between TIL abundance in pretreatment primary and metastasis specimens and the subsequent development of severe irAEs.

Patients And Methods: We retrospectively identified patients with advanced cutaneous melanoma who received first-line anti-programmed cell death protein 1 (PD-1) with or without anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) from 10 hospitals in the Netherlands.

Baseline tumor-infiltrating lymphocyte patterns and response to immune checkpoint inhibition in metastatic cutaneous melanoma.

Introduction: The presence of tumor-infiltrating lymphocytes (TILs) in melanoma has been linked to survival. Their predictive capability for immune checkpoint inhibition (ICI) response remains uncertain. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date and analyzed if this association was independent of known clinical predictors.

Prostate cancer risk assessment and avoidance of prostate biopsies using fully automatic deep learning in prostate MRI: comparison to PI-RADS and integration with clinical data in nomograms.

Objectives: Risk calculators (RCs) improve patient selection for prostate biopsy with clinical/demographic information, recently with prostate MRI using the prostate imaging reporting and data system (PI-RADS). Fully-automated deep learning (DL) analyzes MRI data independently, and has been shown to be on par with clinical radiologists, but has yet to be incorporated into RCs. The goal of this study is to re-assess the diagnostic quality of RCs, the impact of replacing PI-RADS with DL predictions, and potential performance gains by adding DL besides PI-RADS.

Optimizing drug combinations for T-PLL: restoring DNA damage and P53-mediated apoptotic responses.

T-prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm associated with marked chemotherapy resistance and continued poor clinical outcomes. Current treatments, that is, the CD52-antibody alemtuzumab, offer transient responses, with relapses being almost inevitable without consolidating allogeneic transplantation. Recent more detailed concepts of T-PLL's pathobiology fostered the identification of actionable vulnerabilities: (1) altered epigenetics, (2) defective DNA damage responses, (3) aberrant cell-cycle regulation, and (4) deregulated prosurvival pathways, including T-cell receptor and JAK/STAT signaling.

Six-Month Real-World Study to Assess the Effectiveness of Ixekizumab After Switching from IL-23 Inhibitors and Other Biologic Therapies: The CorEvitas Psoriasis Registry.

Background: Prior work showed that patients from the CorEvitas Psoriasis Registry who had previously failed a prior biologic and then initiated ixekizumab demonstrated improvements in disease severity and patient-reported outcomes after 6 months. However, newer therapies such as interleukin-23 inhibitors (IL-23i) were not considered. Here, with more recent data including IL-23i, 6-month effectiveness of ixekizumab following a switch from any biologic was assessed as well as whether 6-month effectiveness of ixekizumab was impacted by prior biologic class.

Establishment of primary prostate epithelial and tumorigenic cell lines using a non-viral immortalization approach.

Background: Research on prostate cancer is mostly performed using cell lines derived from metastatic disease, not reflecting stages of tumor initiation or early progression. Establishment of cancer cell lines derived from the primary tumor site has not been described so far. By definition, cancer cells are able to be cultured indefinitely, whereas normal epithelial cells undergo senescence in vitro.

["Pressure kills kidneys": protection of the upper urinary tract through neuro-urological management].

Low compliance is not an independent disease but a severe manifestation resulting from various disorders of the storage and excretory function of the bladder. Reduced distensibility of the detrusor muscle can lead to a pressure load on the upper urinary tract but also to urge-dominant LUTS and urinary tract infections. Neurogenic causes, especially spinal cord injury/spina bifida but also iatrogenic damage or subvesical obstruction, can contribute to the development.

Spot-Based Global Registration for Subpixel Stitching of Single-Molecule Resolution Images for Tissue-Scale Spatial Transcriptomics.

Single-molecule imaging at the tissue scale has revolutionized our understanding of biology by providing unprecedented insight into the molecular expression of individual cells and their spatial organization within tissues. However, achieving precise image stitching at the single-molecule level remains a challenge, primarily due to heterogeneous background signals and dim labeling signals in single-molecule images. This paper introduces Spot-Based Global Registration (SBGR), a novel strategy that shifts the focus from raw images to identified molecular spots for high-resolution image alignment.

Versatile Prepolymer Platform for Controlled Tailoring of Quantum Dot Surface Properties.

Quantum dots (QDs) hold immense promise for bioimaging, yet technical challenges in surface engineering limit their wider scientific use. We introduce poly(pentafluorophenyl acrylate) (PPFPA) as a user-friendly prepolymer platform for creating precisely controlled multidentate polymeric ligands for QD surface engineering, accessible to researchers without extensive synthetic expertise. PPFPA combines the benefits of both bottom-up and prepolymer approaches, offering minimal susceptibility to hydrolysis and side reactions for controlled chemical composition, along with simple synthetic procedures using commercially available reagents.

Cisplatin drives mitochondrial dysregulation in sensory hair cells.

Cisplatin is a chemotherapy drug that causes permanent hearing loss by injuring cochlear hair cells. The mechanisms that initiate injury are not fully understood, but mitochondria have emerged as potential mediators of hair cell cytotoxicity. Using live imaging of hair cells in the zebrafish lateral-line organ expressing a genetically encoded indicator of cumulative mitochondrial activity, we first demonstrate that greater redox history increases susceptibility to cisplatin.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive.

Background: The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive.

Methods: Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified.

Ontologies for increasing the FAIRness of plant research data.

The importance of improving the FAIRness (findability, accessibility, interoperability, reusability) of research data is undeniable, especially in the face of large, complex datasets currently being produced by omics technologies. Facilitating the integration of a dataset with other types of data increases the likelihood of reuse, and the potential of answering novel research questions. Ontologies are a useful tool for semantically tagging datasets as adding relevant metadata increases the understanding of how data was produced and increases its interoperability.