Creating pragmatic, rapid-cycle, evidence-based innovation: The Kaiser Permanente Northern California Delivery Science and Applied Research (DARE) program.

Introduction: Ongoing crises in the quality, affordability, sustainability, value, and equity of U.S. healthcare call for rapid, massive-scale innovations across multiple specialties.

300,000 quitters and counting; A systematic approach to tobacco cessation.

Objective: To describe Kaiser Permanente Northern California's (KPNC) systematic implementation of universal tobacco screening, evidence-based interventions, and performance measures to achieve long-term smoking cessation success.

Methods: We outline seven key components of KPNC's tobacco screening and intervention program that contributed to a significant decline in smoking prevalence. We also report changes in the prevalence of current smokers within KPNC from 2014 to 2023 using linear regression analyses.

Barriers and facilitators to high-volume evidence-based innovation and implementation in a large, community-based learning health system.

Background: Broad-scale, rapid health care change is critically needed to improve value-based, effective health care. Health care providers and systems need to address common barriers and facilitators across the evidence to implementation pathway, across diverse specialties. However, most evidence translation / implementation research evaluates single topic areas, and may be of limited value for informing comprehensive efforts.

Training the next generation of delivery science researchers: 10-year experience of a post-doctoral research fellowship program within an integrated care system.

Introduction: Learning health systems require a workforce of researchers trained in the methods of identifying and overcoming barriers to effective, evidence-based care. Most existing postdoctoral training programs, such as NIH-funded postdoctoral T32 awards, support basic and epidemiological science with very limited focus on rigorous delivery science methods for improving care. In this report, we present the 10-year experience of developing and implementing a Delivery Science postdoctoral fellowship embedded within an integrated health care delivery system.

Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study.

Objectives: In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients' referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme.

Changes in COVID-19 Vaccine Intent Among a Diverse Population of Older Adults, June 2021-February 2022.

Introduction COVID-19 vaccination rates remain suboptimal in the United States. Clinicians and policymakers need to better understand how likely vaccine-hesitant individuals are to ultimately accept vaccination and what is associated with such changes. This study's aims were to 1) describe changes between vaccine intentions and actual uptake from June 2021 through February 2022, and 2) identify modifiable factors associated with vaccine uptake among those with initial hesitancy.

Strategies Facilitating Video Visit Implementation by a Medical Group Serving a Diverse Population.

IntroductionVideo visits have created new opportunities to enhance access to care, but limited information exists on strategies medical groups can employ to facilitate video visit use by higher-risk patients. Our objective was to identify generalizable strategies to facilitate successful delivery of video visits by systems serving highly diverse patient populations. MethodsThe authors conducted a qualitative study of physicians and staff members in a large group practice with 4.

Effect of Electronic and Mail Outreach From Primary Care Physicians for COVID-19 Vaccination of Black and Latino Older Adults: A Randomized Clinical Trial.

Importance: COVID-19 morbidity is highest in Black and Latino older adults. These racial and ethnic groups initially had lower vaccination uptake than others, and rates in Black adults continue to lag.

Objectives: To evaluate the effect of outreach via electronic secure messages and mailings from primary care physicians (PCPs) on COVID-19 vaccination uptake among Black and Latino older adults and to compare the effects of culturally tailored and standard PCP messages.

A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.

Mitochondrial genome and its regulator TFAM modulates head and neck tumourigenesis through intracellular metabolic reprogramming and activation of oncogenic effectors.

Mitochondrial transcriptional factor A (TFAM) acts as a key regulatory to control mitochondrial DNA (mtDNA); the impact of TFAM and mtDNA in modulating carcinogenesis is controversial. Current study aims to define TFAM mediated regulations in head and neck cancer (HNC). Multifaceted analyses in HNC cells genetically manipulated for TFAM were performed.

DDX3 modulates the tumor microenvironment via its role in endoplasmic reticulum-associated translation.

Using antibody arrays, we found that the RNA helicase DDX3 modulates the expression of secreted signaling factors in oral squamous cell carcinoma (OSCC) cells. Ribo-seq analysis confirmed amphiregulin () as a translational target of DDX3. AREG exerts important biological functions in cancer, including promoting cell migration and paracrine effects of OSCC cells and reprogramming the tumor microenvironment (TME) of OSCC in mice.

Development of a healthcare system COVID Hotspotting Score in California: an observational study with prospective validation.

Objective: To examine the value of health systems data as indicators of emerging COVID-19 activity.

Design: Observational study of health system indicators for the COVID Hotspotting Score (CHOTS) with prospective validation.

Setting And Participants: An integrated healthcare delivery system in Northern California including 21 hospitals and 4.

Racial Disparities in COVID-19 Testing and Outcomes : Retrospective Cohort Study in an Integrated Health System.

Background: Racial disparities exist in outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objective: To evaluate the contribution of race/ethnicity in SARS-CoV-2 testing, infection, and outcomes.

Design: Retrospective cohort study (1 February 2020 to 31 May 2020).

Evaluation of Attention Switching and Duration of Electronic Inbox Work Among Primary Care Physicians.

Importance: Primary care physicians (PCPs) report multitasking during workdays while processing electronic inbox messages, but scant systematic information exists on attention switching and its correlates in the health care setting.

Objectives: To describe PCPs' frequency of attention switching associated with electronic inbox work, identify potentially modifiable factors associated with attention switching and inbox work duration, and compare the relative association of attention switching and other factors with inbox work duration.

Design, Setting, And Participants: This cross-sectional study of the work of 1275 PCPs in an integrated group serving 4.

Establishment of a Null Murine Oral Carcinoma Cell Line and the Identification of Genetic Alterations Associated with This Carcinoma.

Head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC), ranks sixth in cancer incidence worldwide. To generate OSCC cells lines from human or murine tumors, greatly facilitates investigations into OSCC. This study describes the establishing of a mouse palatal carcinoma cell line (designated MPC-1) from a spontaneous tumor present in a heterozygous gene loss C57BL/6 mouse.

Detection of Oral Dysplastic and Early Cancerous Lesions by Polarization-Sensitive Optical Coherence Tomography.

Detection of oral dysplastic and early-stage cancerous lesions is difficult with the current tools. Half of oral cancers are diagnosed in a late stage. Detection of early stromal change to predict malignant transformation is a new direction in the diagnosis of early-stage oral cancer.

Quantification of structural and microvascular changes for diagnosing early-stage oral cancer.

Changes in mucosal microvascular networks, called intraepithelial papillary capillary loops (IPCL), are an important key factor for diagnosing early-stage oral cancer Nevertheless, there are a lack of tools to quantify these changes objectively. This is the first study to quantify the IPCL changes to differentiate benign or malignant oral lesions by the optical coherence tomography (OCT) technique. K14-EGFP-miR-211-GFP transgenic mice were inducted by 4-Nitroquinoline-1-oxide to produce oral carcinogenesis in different stages, including normal, premalignancy and cancer.

The -ZBTB7A Oncogenic Axis Suppresses TRAIL-R2 Associated Drug Sensitivity in Oral Carcinoma.

has been shown a potent oncogenic miRNA in the pathogenesis of oral squamous cell carcinoma (OSCC). The zinc finger and BTB domain containing 7A protein (ZBTB7A) is a transcriptional regulator that is involved in a great diversity of physiological and oncogenic regulation. However, the modulation of ZBTB7A in OSCC remains unclear.

Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis.

Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies.

Establishment of syngeneic murine model for oral cancer therapy.

Oral carcinoma (OSCC) is one of the most important causes of cancer death worldwide. OSCC cell lines and preclinical rodent models are crucial to addressing the mechanisms of OSCC and helping the development of new therapeutic strategies and interventions. The establishment of murine OSCC cell lines and syngeneic models are necessary to allow concordant investigation of both in vitro and in vivo pathogenesis.

Determination of Pyruvate Metabolic Fates Modulates Head and Neck Tumorigenesis.

Even with increasing evidence for roles of glycolytic enzymes in controlling cancerous characteristics, the best target of candidate metabolic enzymes for lessening malignancy remains under debate. Pyruvate is a main glycolytic metabolite that could be mainly converted into either lactate by Lactate Dehydrogenase A (LDHA) or acetyl-CoA by Pyruvate Dehydrogenase E1 component α subunit (PDHA1) catalytic complex. In tumor cells, accumulating lactate is produced whereas the conversion of pyruvate into mitochondrial acetyl-CoA is less active compared with their normal counterparts.

MicroRNA miR-31 targets SIRT3 to disrupt mitochondrial activity and increase oxidative stress in oral carcinoma.

MicroRNA miR-31 is implicated in the neoplastic process of various malignancies including oral squamous cell carcinoma (OSCC). Silent information regulator 3 (Sirtuin3 or SIRT3) is a NAD-dependent deacetylase that regulates metabolic process. Suppressor role of SIRT3 has been found in neoplasms.

Establishing of mouse oral carcinoma cell lines derived from transgenic mice and their use as syngeneic tumorigenesis models.

Background: The survival of OSCC patient needs to be further improved. miR-211 is oncogenic in OSCC and its upregulation is associated with tumor progression and poor patient survival. K14-EGFP-miR-211 transgenic mice also exhibit augmented potential for OSCC induction.

miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A.

Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress.

Combination of structural and vascular optical coherence tomography for differentiating oral lesions of mice in different carcinogenesis stages.

Differentiating between early malignancy and benign lesions in oral cavities is difficult using current optical tools. As has been shown in previous studies, microvascular changes in squamous epithelium can be regarded as a key marker for diagnosis. We propose the combination of structural and vascular optical coherence tomography (OCT) imaging for the investigation of disease related changes.