Applying theories, models, and frameworks to help genetic counselors and students achieve clinical and professional goals.

Some genetic counselors (GCs) may find theories, models, and frameworks (TMFs) useful in clinical skills selection and when reflecting on or evaluating genetic counseling practice. This paper aims to demonstrate how TMFs can be used to postulate how different skills may impact patients'/clients' decisions, behaviors, and outcomes and consider how multiple TMFs can inform the use of various skills or strategies to achieve different goals. Additionally, we provide examples of TMFs that may help GCs in nonclinical aspects of their work, such as implementing and evaluating new interventions or service delivery models.

Vaping, Smoking and Lung Cancer Risk.

Nicotine exposure through the use of electronic delivery systems (vaping) has been found to elevate the risk of certain conditions of the lungs, e.g., vaping associated lung injury, EVALI).

Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

Purpose: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.

Methods: This is an investigator-initiated, multicenter, phase I trial.

Evaluating a web-based training curriculum for disseminating best practices for the care of newborns with neonatal opioid withdrawal syndrome in a rural hospital, the NOWS-NM Program.

Background: The incidence of neonatal opiate withdrawal syndrome (NOWS) in the US has grown dramatically over the past two decades. Many rural hospitals not equipped to manage these patients transfer them to hospitals in bigger cities.

Methods: We created a curriculum, the NOWS-NM Program, a web-based curriculum training in best practices.

Anti-PD-(L)1 plus BRAF/MEK inhibitors (triplet therapy) after failure of immune checkpoint inhibition and targeted therapy in patients with advanced melanoma.

Background: Effective treatment options are limited for patients with advanced melanoma who have progressed on immune checkpoint inhibitors (ICI) and targeted therapies (TT). Preclinical models support the combination of ICI with TT; however, clinical trials evaluating the efficacy of triplet combinations in first-line setting showed limited advantage compared to TT only.

Methods: We conducted a retrospective, multicenter study, that included patients with advanced melanoma who were treated with BRAF/MEK inhibitors in combination with an anti-PD-(L)1 antibody (triplet therapy) after failure of at least one anti-PD-(L)1-based therapy and one TT in seven major melanoma centers between February 2016 and July 2022.

Racial and Ethnic Disparities in Intensity of Care at the End of Life for Patients With Lung Cancer: A 13-Year Population-Based Study.

Purpose: Lung cancer is the leading cause of cancer death in the United States. Disparities in lung cancer mortality among racial and ethnic minorities are well documented. Less is known as to whether racial and ethnic minority patients with lung cancer experience higher rates of intensity of care at the end of life (EOL) compared with non-Hispanic White (NHW) patients.

A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma.

Background And Objective: Checkpoint inhibitor therapy (CPI) has demonstrated survival benefits in urothelial carcinoma (UC); however, not all patients benefit from CPI due to resistance. Combining sitravatinib, a multitargeted receptor tyrosine kinase inhibitor of TYRO3, AXL, and MERTK (TAM) receptors and VEGFR2, with CPI may improve antitumor responses. Our objective was to assess the efficacy and safety of sitravatinib plus nivolumab in patients with advanced/metastatic UC.

Food insecurity among adult females with a history of breast cancer compared to adult females without cancer in the USA.

Purpose: To determine the prevalence of food insecurity (FI) among females with a history of breast cancer compared to females without cancer in the USA and the sociodemographic characteristics that may explain their FI.

Methods: Using the 2019 National Health Interview (NHIS) survey that included the US Department of Agriculture's (USDA's) 10-item Household Food Security Survey Module, participants with high/moderate food security were considered food secure and low/very low food security were considered food insecure. Analyses accounted for complex survey design and included descriptive statistics, bivariate analyses, and multivariate regression analyses.

Workflow for Evaluating Normalization Tools for Omics Data Using Supervised and Unsupervised Machine Learning.

To achieve high quality omics results, systematic variability in mass spectrometry (MS) data must be adequately addressed. Effective data normalization is essential for minimizing this variability. The abundance of approaches and the data-dependent nature of normalization have led some researchers to develop open-source academic software for choosing the best approach.

Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.

Background: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.

Methods: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level.

Becoming less beige with age.

The production of beige adipocytes following cold exposure is blocked as mice get older and leads to changes in the expression of metabolic genes.

Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer.

Background: Gastric cancer is one of the most common cancers. Peritoneal carcinomatosis (PC) appears to be the most common pattern of recurrence, and more than half of the GC patients eventually die from PC. Novel strategies for the management of patients with PC are urgently needed.

Outcomes of Second-Line Therapies in Patients With Metastatic de Novo and Treatment-Emergent Neuroendocrine Prostate Cancer: A Multi-Institutional Study.

Background: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments.

Patients And Methods: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution.

MLH1-methylated endometrial cancer under 60 years of age as the "sentinel" cancer in female carriers of high-risk constitutional MLH1 epimutation.

Objective: Universal screening of endometrial carcinoma (EC) for mismatch repair deficiency (MMRd) and Lynch syndrome uses presence of MLH1 methylation to omit common sporadic cases from follow-up germline testing. However, this overlooks rare cases with high-risk constitutional MLH1 methylation (epimutation), a poorly-recognized mechanism that predisposes to Lynch-type cancers with MLH1 methylation. We aimed to determine the role and frequency of constitutional MLH1 methylation among EC cases with MMRd, MLH1-methylated tumors.

Porous Silicon Nanocarriers Boost the Immunomodulation of Mitochondria-Targeted Bovine Serum Albumins on Macrophage Polarization.

The development of nanosystems with intrinsic immunomodulatory effects on macrophage polarization is important for the macrophage-targeted immunotherapy. Here, mitochondria-targeted bovine serum albumins (BSAs) via the conjugation of fluorescent, lipophilic, and cationic rhodamine 110 molecules can efficiently enhance the gene expression of the proinflammatory phenotype of macrophages and correspondingly inhibit the gene expression of their anti-inflammatory phenotype. On this basis, porous silicon nanocarriers can further boost the immunomodulation of these mitochondria-targeted BSAs or , accompanied by the secretion of proinflammatory mediators including tumor necrosis factor α, nitric oxide, and reactive oxygen species (ROS).

Bridging the to gap: Using the Chick Embryo Model to Accelerate Nanoparticle Validation and Qualification for studies.

We postulate that nanoparticles (NPs) for use in therapeutic applications have largely not realized their clinical potential due to an overall inability to use results to predict NP performance . The avian embryo and associated chorioallantoic membrane (CAM) has emerged as an preclinical model that bridges the gap between and , enabling rapid screening of NP behavior under physiologically relevant conditions and providing a rapid, accessible, economical, and more ethical means of qualifying nanoparticles for use. The CAM is highly vascularized and mimics the diverging/converging vasculature of the liver, spleen, and lungs that serve as nanoparticle traps.

Involvement of Rho-Associated Coiled-Coil Containing Kinase (ROCK) in BCR-ABL1 Tyrosine Kinase Inhibitor Cardiovascular Toxicity.

Background: Second- and third-generation BCR-ABL1 tyrosine kinase inhibitors (TKIs) are associated with cardiovascular adverse events (CVAEs) in patients with Philadelphia chromosome-positive (Ph+) leukemia.

Objectives: We hypothesized that second- and third-generation BCR-ABL1 TKIs may cause CVAEs through the activation of Rho-associated coiled-coil containing kinase (ROCK).

Methods: Peripheral blood mononuclear cells from 53 Ph+ patients on TKIs and 15 control patients without Ph+ leukemia were assessed for ROCK activity through capillary electrophoresis (median follow-up = 26 months [Q1-Q3: 5-37 months]).

PFKFB4 facilitates palbociclib resistance in oestrogen receptor-positive breast cancer by enhancing stemness.

Background: ER breast cancer (ER BC) is the most common subtype of BC. Recently, CDK4/6 inhibitors combined with aromatase inhibitors have been approved by FDA as the first-line therapy for patients with ER BC, and showed promising therapeutic efficacy in clinical treatment. However, resistance to CDK4/6 inhibitors is frequently observed.

Human skin dermis-derived fibroblasts are a kind of functional mesenchymal stromal cells: judgements from surface markers, biological characteristics, to therapeutic efficacy.

Background: Human mesenchymal stromal cells (MSCs) have been widely advocated to clinical use. Human skin dermis-derived fibroblasts shared similar cellular morphology and biological characteristics to MSCs, while it still keeps elusive whether fibroblasts are functionally equivalent to MSCs for therapeutic use.

Methods: We isolated various fibroblasts derived from human foreskins (HFFs) and human double-fold eyelids (HDF) and MSCs derived from human umbilical cords (UC-MSCs), and then comprehensively investigated their similarities and differences in morphology, surface markers, immunoregulation, multilineage differentiation, transcriptome sequencing, and metabolomics, and therapeutic efficacies in treating 2,4,6-Trinitrobenzenesulfonic acid (TNBS) induced colitis and carbontetrachloride (CCL) induced liver fibrosis.

A long-term anti-inflammation markedly alleviated high-fat diet-induced obesity by repeated administrations of overexpressing IL10 human umbilical cord-derived mesenchymal stromal cells.

Objectives: Obesity is a chronic process and could activate various inflammatory responses, which in turn aggravates obesity and related metabolic syndrome. Here we explored whether long-term inhibition of inflammation could successfully alleviate high-fat diet (HFD)-induced obesity.

Methods: We constructed stable overexpressing interleukin 10 (IL10) human umbilical cord-derived mesenchymal stromal cells (HUCMSCs) which repeatedly were applied to obesity mice with HFD feeding to obtain a long-term anti-inflammation based on the prominent anti-inflammation effects of IL10 and immunomodulatery effects of HUCMSCs.

Gene-Modified Stem Cells for Spinal Cord Injury: a Promising Better Alternative Therapy.

Stem cell therapy holds great promise for the treatment of spinal cord injury (SCI), which can reverse neurodegeneration and promote tissue regeneration via its pluripotency and ability to secrete neurotrophic factors. Although various stem cell-based approaches have shown certain therapeutic effects when applied to the treatment of SCI, their clinical efficacies have been disappointing. Thus, it is an urgent need to further enhance the neurological benefits of stem cells through bioengineering strategies including genetic engineering.

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538).

A Multi-step Approach to Adapting a Mind-Body Resiliency Intervention for Fear of Cancer Recurrence and Uncertainty in Survivorship (IN FOCUS).

Background: For cancer survivors, there is a paucity of fear of recurrence (FOR) interventions that integrate empirically supported mind-body and psychological skills for managing FOR and are delivered in scalable formats.

Objective: To adapt an evidence-based resiliency intervention to address FOR among cancer survivors.

Methods: A multidisciplinary team of researchers, clinicians, and patient stakeholders followed an iterative intervention adaptation process (ORBIT).