Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2-positive early breast cancer (EBC).

Background: In human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across four neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO, and NSABP B-41.

Patients And Methods: We compared tumor and immune gene expression changes during neoadjuvant treatment and their association with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index.

Results: Analysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-enriched at baseline (50.

Designing Positive Psychology Interventions for Social Media: Cross-Sectional Web-Based Experiment With Young Adults With Cancer.

Background: Young adults (ages 18-39 years) with cancer face unique risks for negative psychosocial outcomes. These risks could be lessened with positive psychology interventions adapted for social media if intervention messages encourage intentions to do the activities and positive message reactions and if young adults with cancer perceive few downsides.

Objective: This study aimed to assess whether social media messages from evidence-based positive psychology interventions encouraged intentions to do the intervention activities and intended positive message reactions, overall and among sociodemographic or cancer characteristic subgroups.

A structure-based mechanism for initiation of AP-3 coated vesicle formation.

Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question.

Protein stability models fail to capture epistatic interactions of double point mutations.

There is strong interest in accurate methods for predicting changes in protein stability resulting from amino acid mutations to the protein sequence. Recombinant proteins must often be stabilized to be used as therapeutics or reagents, and destabilizing mutations are implicated in a variety of diseases. Due to increased data availability and improved modeling techniques, recent studies have shown advancements in predicting changes in protein stability when a single-point mutation is made.

Message development for a communication campaign to support health warning labels on cigars: a qualitative study.

Background: Communication campaigns for health warning labels (HWLs) are an evidence-based strategy to reduce tobacco use. No research has examined campaign messages to support graphic HWLs for little cigars and cigarillos (LCCs).

Methods: We developed four message types for graphic LCC HWLs: (1) Explanatory (2) Testimonial (3) Inquisitive and (4) Recommendation, depicting colon, lung, and esophageal cancer.

Intestinal E. coli-produced yersiniabactin promotes profibrotic macrophages in Crohn's disease.

Inflammatory bowel disease (IBD)-associated fibrosis causes significant morbidity. Mechanisms are poorly understood but implicate the microbiota, especially adherent-invasive Escherichia coli (AIEC). We previously demonstrated that AIEC producing the metallophore yersiniabactin (Ybt) promotes intestinal fibrosis in an IBD mouse model.

L. extract exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells and a transgenic mouse model of endometrial cancer.

Introduction: Endometrial cancer is the most common malignancy of the female reproductive system in the United States. is a versatile, nutrient-dense, low-calorie vegetable that contains various bioactive metabolites that have shown a variety of biologic functions beneficial to health. The metabolites from extracts or extracts exhibit significant anti-tumorigenic activity in some pre-clinical models of cancer.

A Content Analysis of Cancer-Related Changes in Perceptions of Self, Relationships, and Health Among LGBTQI+ Cancer Survivors Across the Life Course: Findings From OUT: The National Cancer Survey.

Background: The LGBTQI+ population makes up at least 7.6% of the US population. LGBTQI+ populations are at increased risk of experiencing LGBTQI+-related discrimination and cis-heteronormativity in healthcare leading to poorer health outcomes throughout the cancer care continuum.

Evaluating the intersection of climate vulnerability and cancer burden in North Carolina.

Climate-related extreme weather events disrupt healthcare systems and exacerbate health disparities, particularly affecting individuals diagnosed with cancer. This study explores the intersection of climate vulnerability and cancer burden in North Carolina (NC). Using county-level data from the US Climate Vulnerability Index (CVI) and the NC Department of Health and Human Services, we analyzed cancer incidence and mortality rates from 2017-2021.

Validation and expansion of Baveno VII criteria for cACLD and CSPH based on liver stiffness and platelet count: Correlation with risk of hepatic decompensation and death.

Background And Aims: Recently proposed "Rule-of-Five" criteria define compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) using liver stiffness (LS) and platelet count. We aimed to validate these criteria by determining whether they are associated with risk of adverse outcomes.

Approach And Results: Patients without prior hepatic decompensation or HCC who underwent LS and platelet measurements (n = 17,076) were categorized as follows: no cACLD (LS: 2.

Evi1 governs Kdm6b-mediated histone demethylation to regulate the Laptm4b-driven mTOR pathway in hematopoietic progenitor cells.

Ecotropic viral integration site 1 (EVI1/MECOM) is frequently upregulated in myeloid malignancies. Here, we present an Evi1-transgenic mouse model with inducible expression in hematopoietic stem/progenitor cells (HSPCs). Upon induction of Evi1 expression, mice displayed anemia, thrombocytopenia, lymphopenia, and erythroid and megakaryocyte dysplasia with a significant expansion of committed myeloid progenitor cells, resembling human myelodysplastic syndrome/myeloproliferative neoplasm-like (MDS/MPN-like) disease.

Iron Oxide Nanoparticles Induce Macrophage Secretion of ATP and HMGB1 to Enhance Irradiation-Led Immunogenic Cell Death.

ATP (adenosine triphosphate) and HMGB1 (high mobility group box 1 protein) are key players in treatments that induce immunogenic cell death (ICD). However, conventional therapies, including radiotherapy, are often insufficient to induce ICD. In this study, we explore a strategy using nanoparticle-loaded macrophages as a source of ATP and HMGB1 to complement radiation-induced intrinsic and adaptive immune responses.

Systematic review of interventions to promote colorectal cancer screening: Benchmarking effect sizes and screening rates.

Objective: The effectiveness of behavioral interventions is typically evaluated relative to control conditions using null hypothesis significance testing (i.e., < .

An RNAi screen of Rab GTPase genes in reveals that somatic cells of the reproductive system depend on for morphogenesis but not stem cell niche maintenance.

Membrane trafficking is a crucial function of all cells and is regulated at multiple levels from vesicle formation, packaging, and localization to fusion, exocytosis, and endocytosis. Rab GTPase proteins are core regulators of eukaryotic membrane trafficking, but developmental roles of specific Rab GTPases are less well characterized, potentially because of their essentiality for basic cellular function. gonad development entails the coordination of cell growth, proliferation, and migration-processes in which membrane trafficking is known to be required.

Design of a Water-Soluble CD20 Antigen with Computational Epitope Scaffolding.

The poor solubility of integral membrane proteins in water frequently hinders studies with these proteins, presenting challenges for structure determination and binding screens. For instance, the transmembrane protein CD20, which is an important target for treating B-cell malignancies, is not soluble in water and cannot be easily screened against potential protein binders with techniques like phage display or yeast display. Here, we use protein design to create a water-soluble mimic of the CD20 dimer ("soluble CD20").

HIV-1 single transcription start site mutants display complementary replication functions that are restored by reversion.

HIV-1 transcription initiates at two positions, generating RNAs with either 1G or 3G 5' ends. The replication fates of these RNAs di\er, with viral particles encapsidating almost exclusively 1G RNAs and 3G RNAs retained in cells where they are enriched on polysomes and among spliced viral RNAs. Here, we studied replication properties of virus promoter mutants that produced only one RNA 5' isoform or the other: separately, in combination, and during spreading infection.

Outcomes and Trends in Axillary Management of Stage cN3b Breast Cancer Patients.

Background: There is limited data regarding sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for cN3b patients, who present with both axillary and ipsilateral internal mammary node involvement. We examined trends in the use of SLNB in cN3b patients and survival by axillary procedure for those with nodal pathologic complete response (nPCR).

Methods: Adult women with nonmetastatic cN3b invasive breast carcinoma between 2012 and 2021 were selected from the National Cancer Database.

Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro , facilitating the identification of kinase vulnerabilities to target therapeutically.