IGLV3-21-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia.

We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a high-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors.

MiNEN, amphicrine carcinomas, and conventional carcinomas with neuroendocrine differentiation: diagnostic criteria, open questions, and future perspectives.

Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNEN) represent a heterogeneous group of bidirectionally differentiated epithelial malignancies that are, in most cases, highly aggressive. They are defined by the presence of morphologically distinct, yet clonally related, neuroendocrine and non-neuroendocrine components, each comprising at least 30% of the tumor mass according to current guidelines. Tumors that fall within the differential diagnostic spectrum of MiNEN include amphicrine carcinomas-characterized by the co-expression of neuroendocrine and non-neuroendocrine features within the same tumor cell-as well as conventional carcinomas that lack neuroendocrine morphology but exhibit immunohistochemical expression of neuroendocrine markers.

Functional synapses between neurons and small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate. Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer. Cancer-to-neuron synapses have been reported in gliomas, but whether peripheral tumours can form such structures is unknown.

Protocol: Faecal microbiota transfer in liver cancer to overcome resistance to atezolizumab/bevacizumab - a multicentre, randomised, placebo-controlled, double-blind phase II trial (the FLORA trial).

Introduction: Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade.

Extensive Vulvar Involvement as the Initial Presentation of Granulomatosis with Polyangiitis in a Young Woman.

Introduction: Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis, rarely affecting the genitourinary tract. Vulvar involvement is extremely uncommon and often misdiagnosed.

Case Presentation: A 21-year-old female patient presented with a one-month history of necrotic vulvar lesions and skin ulcerations.

Linear magnetic nanoparticle structures as key feature in magnetic particle imaging.

Objective: Magnetic particle imaging (MPI) opens huge possibilities in image-guided therapy. Its effectiveness is strongly influenced by the quality of the magnetic nanoparticles (MNP) used as tracers. Besides MNP optimization following different synthesis routes, MNP assembly into linear structures can significantly enhance their performance in MPI.

Urinary catheters: state of the art and future perspectives - a narrative review.

Catheter associated urinary tract infection (CAUTI) is the most frequent healthcare associated infection, arising from microbial adhesion to catheter surfaces, biofilm development, and the growing problem of antimicrobial resistance. Many publications have addressed CAUTI epidemiology, biofilm biology, or biomaterials for catheters in isolation, yet there is little literature that connects these areas into a coherent translational perspective. This review seeks to fill that gap by combining an overview of biofilm pathophysiology with recent advances in material based innovations for catheter design, including nanostructured and responsive coatings, sensor enabled systems, additive manufacturing, and three dimensional printing.

AI Algorithm for Lung Adenocarcinoma Pattern Quantification (PATQUANT): International Validation and Advanced Risk Stratification Superior to Conventional Grading.

The morphological patterns of lung adenocarcinoma (LUAD) are recognized for their prognostic significance, with ongoing debate regarding the optimal grading strategy. This study aimed to develop a clinical-grade, fully quantitative, and automated tool for pattern classification/quantification (PATQUANT), to evaluate existing grading strategies, and determine the optimal grading system. PATQUANT was trained on a high-quality dataset, manually annotated by expert pathologists.

The X-Age Project to construct a Chinese aging clock.

The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age-related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual's physiological and molecular state, across diverse Chinese cohorts.

Social media and cytopathology (#cytopath) education: developing a curated online resource index and exploring the evolution of e-learning.

In recent years, social media (SoMe) has revolutionized medical education within the field of pathology; however, its performance in cytopathology has not been explored in detail. This systematic review aims to analyze SoMe trends, hashtag metrics, and online resources within cytopathology over the period of 7 years. A systematic review of 4 databases (PubMed, Medline, Embase, and Scopus) was conducted between January 1st, 2017, and December 22nd, 2022, in order to identify relevant English-language articles about SoMe and cytopathology.

Single-cell analysis of Barrett's esophagus and carcinoma reveals cell types conferring risk via genetic predisposition.

Inherited genetic variants contribute to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but it is unknown which cell types are involved in this process. We performed single-cell RNA sequencing of BE, EAC, and paired normal tissues and integrated genome-wide association data to determine cell-type-specific genetic risk and cellular processes that contribute to BE and EAC. The analysis reveals that EAC development is driven to a greater extent by local cellular processes than BE development and suggests that one cell type of BE origin (intestinal metaplasia cells) and cellular processes that control the differentiation of columnar cells are of particular relevance for EAC development.

Global burden of osteoarthritis in middle-aged adults (40-59 years): estimates from the global burden of disease 2021 study.

Objectives: Osteoarthritis (OA) is a leading cause of chronic pain and disability worldwide, traditionally viewed as a disease of aging. However, emerging evidence highlights its increasing prevalence among middle-aged adults (40-59 years), a population critical to socioeconomic stability. This study is designed to assess the burden of OA among middle-aged adults.

Bcl6 reactivity is associated with a distinct immune landscape and spatial transcriptome in COVID-19.

The regulation of follicular (F) and germinal center (GC) immune reactivity in human lymph nodes (LNs), particularly during the acute stages of viral infection, remains poorly understood: We have analyzed lung-draining lymph nodes (LD-LNs) from COVID-19 autopsies using multiplex imaging and spatial transcriptomics to examine the immune landscape with respect to follicular immune reactivity. We identified three groups of donors based on the Bcl6 prevalence of their Reactive Follicles (RFs): RF-Bcl6no/low, RF-Bcl6int, and RF-Bcl6high. A distinct B/TFH immune landscape, associated with increased prevalence of proliferating B-cell and TFH-cell subsets, was found in RF-Bcl6high LD-LNs.

Imaging mass cytometry dataset of small-cell lung cancer tumors and tumor microenvironments.

Objectives: Small cell lung cancer (SCLC) accounts for approximately 15% of lung tumors and is marked by aggressive growth and early metastatic spread. In this study, we used two SCLC mouse models with differing tumor mutation burdens (TMB). To investigate tumor composition, spatial architecture, and interactions with the surrounding microenvironment, we acquired multiplexed images of mouse lung tumors using imaging mass cytometry (IMC).

Deletion of ABIN1-LIR motifs impairs hepatic lipid homeostasis and mitophagy via AMPK-TFEB axis in mice.

The A20 binding inhibitor of nuclear factor-kappa B (NF-κB)-1 (ABIN-1) serves as a ubiquitin sensor and autophagy receptor, crucial for modulating inflammation and cell death. Our previous in vitro investigation identified the LC3-interacting region (LIR) motifs 1 and 2 of ABIN-1 as key mitophagy regulators. This study aimed to explore the in vivo biological significance of ABIN1-LIR domains using a novel CRISPR-engineered ABIN1-ΔLIR1/2 mouse model, which lacks both LIR motifs.

Anti-tumorigenic properties by trichothiodystrophy mutations in melanocytic cells.

Germline mutations in the DNA repair helicase XPD can cause the diseases xeroderma pigmentosum (XP) and trichothiodystrophy (TTD). XP patients bear an increased risk of skin cancer including melanoma. This is not observed for TTD patients despite DNA repair defects.

Neural interaction explainable AI predicts drug response across cancers.

Personalized treatment selection is crucial for cancer patients due to the high variability in drug response. While actionable mutations can increasingly inform treatment decisions, most therapies still rely on population-based approaches. Here, we introduce neural interaction explainable AI (NeurixAI), an explainable and highly scalable deep learning framework that models drug-gene interactions and identifies transcriptomic patterns linked with drug response.

CD63 is a diagnostic marker of prostate cancer and a prognostic marker of biochemical progression following radical prostatectomy.

Aims: We aimed to analyze CD63, a cell surface protein that has been associated with tumor aggressiveness in several cancers, including breast, colorectal, and lung cancer, as well as melanoma, in prostate cancer.

Methods: CD63 expression was analyzed immunohistochemically in a cohort of primary prostate cancers from 281 patients. The results were correlated with clinico-pathologic parameters, including biochemical recurrence.

Thymus-like phenotype in benign lymphoepithelial neoplasms of salivary glands: clinicopathological and molecular characterization and reappraisal of relationship to non-sebaceous lymphadenoma.

Benign lymphoepithelial tumors of salivary glands had been restricted to sebaceous and non-sebaceous (NSLA) lymphadenomas. However, salivary neoplasms recapitulating carcinoma showing thymus-like elements (CASTLE) have been the subject of recent case reports. We reviewed clinicopathological, immunohistochemical, and molecular findings in 20 salivary gland tumors with thymus-like phenotype (18 histologically benign and two with malignant component).

Interdisciplinary evidence-based tumor board simulation training in surgical medical education.

Purpose: Evidence-based medicine (EBM), precision medicine and interdisciplinarity are becoming increasingly important in medical education. The purposeful connection between EBM and interdisciplinary work is given in the context of a tumor board, since therapy decisions are discussed here in an interdisciplinary team based on current evidence-based guidelines. To date, there has been little focus on either topic.

Current practice of pathologic response assessment following chemoimmunotherapy for non-small cell lung cancer (NSCLC) in Germany: first real-world data from the multicentre Re-GraDE study.

Background: Given that pathologists now frequently assess pathologic response following neoadjuvant or perioperative chemoimmunotherapy for NSCLC, we set up a multicentre study to evaluate the current practice of regression grading in Germany (Re-GraDE NSCLC).

Methods: 133 cases of NSCLC resection specimens following chemoimmunotherapy (IO) were collected from 9 high-volume lung cancer centres in Germany. Case characteristics were obtained from pathology reports/electronic medical records.