Independent Validation of a HER2-Low Focused Immunohistochemistry Scoring System for Enhanced Pathologist Precision and Consistency.

For 2 decades, the American Society of Clinial Oncology-College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing criteria have included 0 and 1+ scores, but this distinction was inconsequential. Now, based on the DESTINY Breast-04 Trial (DB-04) results, for patients with metastatic breast cancer it underpins eligibility for trastuzumab-deruxtecan treatment. Discerning 0 from 1+ immunohistochemistry (IHC) staining is challenging, as HER2 low is not a biologically distinct cancer subset, there are no reference standards or controls, and second-tier tests (eg, in situ hybridization) do not apply.

Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma.

In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis.

Development and Validation of a HER2-Low Focused Immunohistochemical Scoring System With High-Interobserver Concordance: The Australian HER2-Low Breast Cancer Concordance Study.

The DESTINY Breast-04 trial revealed survival advantages of trastuzumab deruxtecan for women with metastatic HER2-low breast cancer (1+ or 2+ immunohistochemistry [IHC], without amplification). Although this trial applied the 2018 Americal Society of Clinial Oncology (ASCO)/College of American Pathologists (CAP) HER2 IHC scoring criteria, the subjectivity and imprecision in IHC scoring have raised concerns that patients' treatment may be misaligned. Our group of 9 experienced breast pathologists collated a deidentified set of 60 breast cancer core biopsies from 3 laboratories, evaluated with the Ventana 4B5 HER2 assay and mostly scored locally as HER2 0 or 1+.

Cross-Cutting mHealth Behavior Change Techniques to Support Treatment Adherence and Self-Management of Complex Medical Conditions: Systematic Review.

Background: Mobile health (mHealth) interventions have immense potential to support disease self-management for people with complex medical conditions following treatment regimens that involve taking medicine and other self-management activities. However, there is no consensus on what discrete behavior change techniques (BCTs) should be used in an effective adherence and self-management-promoting mHealth solution for any chronic illness. Reviewing the extant literature to identify effective, cross-cutting BCTs in mHealth interventions for adherence and self-management promotion could help accelerate the development, evaluation, and dissemination of behavior change interventions with potential generalizability across complex medical conditions.

The in situ transcriptomic landscape of breast tumour-associated and normal adjacent endothelial cells.

Background And Aims: Triple Negative Breast Cancer (TNBC) is associated with increased angiogenesis, which is known to aid tumour growth and metastasis. Anti-angiogenic therapies that have been developed to target this feature have mostly generated disappointing clinical results. Further research into targeted approaches is limited by a lack of understanding of the in situ molecular profile of tumour-associated vasculature.

Analgesic effect of the mint terpenoid L-carvone in sheep.

Objective: To determine whether L-carvone increases the voltage threshold response to a noxious electrical stimulus in sheep.

Study Design: Prospective, blinded, randomized, crossover experimental study.

Animals: A group of six healthy adult sheep.

Graphomotor Dysfluency as a Predictor of Disease Progression in Premanifest Huntington's Disease.

Background: Prior studies have relied on conventional observer-based severity ratings such as the Unified Huntington's Disease Rating Scale (UHDRS) to identify early motor markers of decline in Huntington's disease (HD).

Objective: The present study examined the predictive utility of graphomotor measures handwriting and drawing movements.

Methods: Seventeen gene-positive premanifest HD subjects underwent comprehensive clinical, cognitive, motor, and graphomotor assessments at baseline and at follow-up intervals ranging from 9-36 months.

Development and Psychometric Properties of a New Brief, Yet Comprehensive, Behavioral Questionnaire for Huntington's Disease.

Background: Individuals with Huntington's disease (HD) experience motoric, cognitive, and psychiatric dysfunction. These difficulties can cause maladaptive behaviors that can be very distressing to family and caregivers. Capturing these behaviors in clinical and research settings is crucial.

Two symptoms can accurately identify post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome.

Background: Post-exertional malaise (PEM) is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) yet its diverse manifestations make it difficult to recognize. Brief instruments for detecting PEM are critical for clinical and scientific progress.

Objective: To develop a clinical prediction rule for PEM.

Development and measurement properties of the PEM/PESE activity questionnaire (PAQ).

Background: Existing instruments often are inappropriate to measure the effects of post-exertional malaise (PEM) and post-exertional symptom exacerbation (PESE) on activities of daily living (ADLs). A validated questionnaire to measure self-reported ability with ADLs would advance research and clinical practice in conditions like myalgic encephalomyelitis and Long Covid.

Objective: Determine the measurement properties of the PEM/PESE Activity Questionnaire (PAQ).

Salivary Huntingtin protein is uniquely associated with clinical features of Huntington's disease.

Measuring Huntingtin (HTT) protein in peripheral cells represents an essential step in biomarker discovery for Huntington's Disease (HD), however to date, investigations into the salivary expression of HTT has been lacking. In the current study, we quantified total HTT (tHTT) and mutant HTT (mHTT) protein in matched blood and saliva samples using single molecule counting (SMC) immunoassays: 2B7-D7F7 (tHTT) and 2B7-MW1 (mHTT). Matched samples, and clinical data, were collected from 95 subjects: n = 19 manifest HD, n = 34 premanifest HD (PM), and n = 42 normal controls (NC).

Anosognosia in HD: Comparison of self-report and caregiver ratings with objective performance measures.

Introduction: Individuals with Huntington's disease (HD) commonly experience anosognosia, a lack of awareness of deficits. Thus, it is important to examine the accuracy of patient vs caregiver ratings on the basis of objective performance-based measures.

Methods: The Anosognosia Scale (AS) was given to 33 patients with manifest HD and their caregivers.

Exploring the Potential of PEG-Heparin Hydrogels to Support Long-Term Ex Vivo Culture of Patient-Derived Breast Explant Tissues.

Breast cancer is a complex, highly heterogenous, and dynamic disease and the leading cause of cancer-related death in women worldwide. Evaluation of the heterogeneity of breast cancer and its various subtypes is crucial to identify novel treatment strategies that can overcome the limitations of currently available options. Explant cultures of human mammary tissue have been known to provide important insights for the study of breast cancer structure and phenotype as they include the context of the surrounding microenvironment, allowing for the comprehensive exploration of patient heterogeneity.

CUB Domain-Containing Protein 1 (CDCP1) is a rational target for the development of imaging tracers and antibody-drug conjugates for cancer detection and therapy.

An antibody-drug conjugate (ADC) is a targeted therapy consisting of a cytotoxic payload that is linked to an antibody which targets a protein enriched on malignant cells. Multiple ADCs are currently used clinically as anti-cancer agents significantly improving patient survival. Herein, we evaluated the rationale of targeting the cell surface oncoreceptor CUB domain-containing protein 1 (CDCP1) using ADCs and assessed the efficacy of CDCP1-directed ADCs against a range of malignant tumors.

Escherichia coli probiotic exhibits in vitro growth-limiting effects on clinical feline uropathogenic E coli isolates.

Objective: To characterize uropathogenic Escherichia coli (UPEC) in cases of clinical feline urinary tract infection (UTI) and subclinical bacteriuria and investigate the in vitro effects of E coli strain Nissle 1917 on isolate growth.

Animals: 40 cats with positive E coli culture results for urine collected during routine evaluation.

Procedures: Characterization of UPEC isolates was performed by PCR-based phylotype analysis and serotyping.

Spatial expression of the FGFR2b splice isoform and its prognostic significance in endometrioid endometrial carcinoma.

Endometrial carcinoma (EC) is the most common gynecological malignancy and fibroblast growth factor receptor 2 (FGFR2) is a frequently dysregulated receptor tyrosine kinase. FGFR2b and FGFR2c are the two main splice isoforms of FGFR2 and are normally localized in epithelial and mesenchymal cells, respectively. Previously, we demonstrated that FGFR2c mRNA expression was associated with aggressive tumor characteristics, shorter progression-free survival (PFS), and disease-specific survival (DSS) in endometrioid ECs (EECs).

The Repeatable Battery for the Assessment of Neuropsychological Status, While Useful for Measuring Cognitive Changes in Manifest Huntington Disease, May Show Limited Utility in Premanifest Disease.

Background: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief, standardized neuropsychological test that assesses several areas of cognitive function. Recent studies, although sparse, have examined the use of the RBANS to detect cognitive deficits in individuals with manifest Huntington disease (HD); however, no studies have investigated its utility to detect cognitive deficits in individuals with premanifest HD (PreHD), where cognitive symptoms are thought to be more subtle.

Objective: To assess cognitive deficits in individuals with HD, particularly in individuals with PreHD, using an easily administered, brief but comprehensive, neuropsychological test.

Isotypic analysis of anti-p53 serum autoantibodies and p53 protein tissue phenotypes in colorectal cancer.

The presence of IgA- and IgM-specific autoantibody (AAb) isotypes and their relationship to p53 tissue expression patterns are not well understood. This study aims to investigate the clinical utility of the anti-p53 AAb isotypes and tissue positivity in colorectal cancer (CRC). We analyzed anti-p53 IgG, IgM, and IgA AAbs in sera of 99 CRC patients and 99 non-cancer control subjects.

Escherichia coli pathotype contamination in raw canine diets.

Objective: To investigate the prevalence of Escherichia coli contamination and E coli virulence gene signatures consistent with known E coli pathotypes in commercially available conventional diets and raw-meat-based diets (RMBDs).

Sample: 40 diets in total (19 conventionally cooked kibble or canned diets and 21 RMBDs) obtained from retail stores or online distributors.

Procedures: Each diet was cultured for E coli contamination in 3 separate container locations using standard microbiological techniques.