Identification of a conserved subset of cold tumors responsive to immune checkpoint blockade.

Background: The efficacy of immune checkpoint blockade (ICB) depends on restoring immune recognition of cancer cells that have evaded immune surveillance. Transforming growth factor-beta (TGFβ) is associated with immune-poor, so-called cold tumors whereas loss of its signaling promotes DNA misrepair that could stimulate immune response.

Methods: We analyzed transcriptomic data from IMvigor210, The Cancer Genome Atlas, and Tumor Immune Syngeneic MOuse data sets to evaluate the predictive value of high βAlt, a score representing low expression of a signature consisting of TGFβ targets and high expression of genes involved in error-prone DNA repair.

Low dose DNA methyltransferase inhibitors potentiate PARP inhibitors in homologous recombination repair deficient tumors.

Background: Poly (ADP-Ribose) polymerase inhibitors are approved for treatment of tumors with BRCA1/2 and other homologous recombination repair (HRR) mutations. However, clinical responses are often not durable and treatment may be detrimental in advanced cancer due to excessive toxicities. Thus we are seeking alternative therapeutics to enhance PARP-directed outcomes.

Association of Menopause With Functional Outcomes and Disease Biomarkers in Women With Multiple Sclerosis.

Background And Objective: The impact of menopause on the brain is not well understood. Hormonal changes, including puberty and pregnancy, influence the onset and course of multiple sclerosis (MS). After menopause, a worsening of MS disease trajectory measured on the clinician-rated Expanded Disability Status Scale (EDSS) was reported in some, but not all, studies.

The role of race/ethnicity and age in clinical trial knowledge among patients with gynecologic malignancy.

Purpose: To identify whether race/ethnicity plays a role in knowledge of clinical trials among patients with a gynecologic malignancy.

Patients And Methods: A cross-sectional survey was conducted at a tertiary medical center. Participants were adults (≥18 years old), with gynecologic malignancy, and literate in English, Spanish or Chinese.

Teletherapy to address language disparities in deaf and hard-of-hearing children: study protocol for an inclusive multicentre clinical trial.

Introduction: Children who are deaf or hard-of-hearing (DHH) are at risk for speech and language delay. Language outcomes are worse in DHH children from lower socioeconomic backgrounds, due in part to disparities in access to specialised speech-language therapy. Teletherapy may help improve access to this specialised care and close this language gap.

Neuropsychological and social predictors of participation in a deep brain stimulation study of Parkinson's disease and dystonia.

Objectives: Participation is essential to DBS research, yet circumstances that affect diverse participation remain unclear. Here we evaluate factors impacting participation in an adaptive DBS study of Parkinson's disease (PD) and dystonia.

Methods: Twenty participants were implanted with a sensing-enabled DBS device (Medtronic Summit RC+S) that allows neural data streaming in naturalistic settings and encouraged to stream as much as possible for the first five months after surgery.

Virtual versus usual in-office care for multiple sclerosis: The VIRTUAL-MS multi-site randomized clinical trial study protocol.

Background: Multiple sclerosis (MS) affects nearly 1 million people and is estimated to cost $85.4 billion in the United States annually. People with MS have significant barriers to receiving care and telemedicine could substantially improve access to specialized, comprehensive care.

Pragmatic phase II clinical trial to improve depression care in a real-world diverse MS cohort from an academic MS centre in Northern California: MS CATCH study protocol.

Introduction: Depression occurs in over 50% of individuals living with multiple sclerosis (MS) and can be treated using many modalities. Yet, it remains: under-reported by patients, under-ascertained by clinicians and under-treated. To enhance these three behaviours likely to promote evidence-based depression care, we engaged multiple stakeholders to iteratively design a first-in-kind digital health tool.

Incidence of Fit Test Failure During N95 Respirator Reuse and Extended Use.

Importance: The COVID-19 pandemic resulted in a widespread acute shortage of N95 respirators, prompting the Centers for Disease Control and Prevention to develop guidelines for extended use and limited reuse of N95s for health care workers (HCWs). While HCWs followed these guidelines to conserve N95s, evidence from clinical settings regarding the safety of reuse and extended use is limited.

Objective: To measure the incidence of fit test failure during N95 reuse and compare the incidence between N95 types.

Type 2 diabetes impairs annulus fibrosus fiber deformation and rotation under disc compression in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model.

Understanding the biomechanical behavior of the intervertebral disc is crucial for studying disease mechanisms and developing tissue engineering strategies for managing disc degeneration. We used synchrotron small-angle X-ray scattering to investigate how changes to collagen behavior contribute to alterations in the disc's ability to resist compression. Coccygeal motion segments from 6-month-old lean Sprague-Dawley rats ( ) and diabetic obese University of California Davis type 2 diabetes mellitus (UCD-T2DM) rats ( , diabetic for days) were compressed during simultaneous synchrotron scanning to measure collagen strain at the nanoscale (beamline 7.

Impact of San Francisco's New Street crisis response Team on Service use among people experiencing homelessness with mental and substance use disorders: A mixed methods study protocol.

Mobile crisis services for people experiencing distress related to mental health or substance use are expanding rapidly across the US, yet there is little evidence to support these specific models of care. These new programs present a unique opportunity to expand the literature by utilizing implementation science methods to inform the future design of crisis systems. This mixed methods study will examine the effectiveness and acceptability of the Street Crisis Response Team (SCRT), a new 911-dispatched multidisciplinary mobile crisis intervention piloted in San Francisco, California.

Re-WRAP (Remyelination for women at risk of axonal loss and progression): A phase II randomized placebo-controlled delayed-start trial of bazedoxifene for myelin repair in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a major cause of disability in young and middle-aged people, and myelin repair therapies are needed to slow or potentially reverse this damage. Bazedoxifene (BZA) is a selective estrogen receptor modulator identified in a novel high-throughput unbiased screen for its remyelinating potential, and its remyelinating effects were demonstrated in pre-clinical models.

Methods: This is a single-center, double blind, randomized, controlled, delayed-start Phase 2 clinical trial (NCT04002934) investigating the remyelinating effects of BZA relative to placebo.

Deep-learning-based biomarker of spinal cartilage endplate health using ultra-short echo time magnetic resonance imaging.

Background: T2* relaxation times in the spinal cartilage endplate (CEP) measured using ultra-short echo time magnetic resonance imaging (UTE MRI) reflect aspects of biochemical composition that influence the CEP's permeability to nutrients. Deficits in CEP composition measured using T2* biomarkers from UTE MRI are associated with more severe intervertebral disc degeneration in patients with chronic low back pain (cLBP). The goal of this study was to develop an objective, accurate, and efficient deep-learning-based method for calculating biomarkers of CEP health using UTE images.

ISSLS Prize in Bioengineering Science 2023: Age- and sex-related differences in lumbar intervertebral disc degeneration between patients with chronic low back pain and asymptomatic controls.

Purpose: Clinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging.

Methods: T1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.

HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status.

The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH.

Emergency department visits and emergency-to-inpatient admissions for abnormal uterine bleeding in the USA nationwide.

Background: Abnormal uterine bleeding (AUB) is a common but understudied gynaecological problem, and data are lacking on emergency department (ED) visits and associated ED-to-inpatient admissions for AUB. This project aims to further understanding of the burden of AUB on patients and the healthcare system by establishing the number and characteristics of women with AUB in the ED and evaluating predictors of AUB-related inpatient hospitalisation in the USA.

Methods: This is a cross-sectional study of women presenting to the ED with non-malignant AUB in the 2016 US Nationwide Emergency Department Sample (NEDS).

A Measurement-Based Protocol Improves Interrater Agreement and Accuracy of Right Ventricular Systolic Pressure Assessment by Echocardiography in Children: A Call for Quality Improvement.

Background: Echocardiographic measurements carry the promise of improving interrater (IR) agreement over subjective assessment. The aim of this study was to assess the effect of implementing a measurement-based protocol on IR agreement and accuracy in reporting of right ventricular (RV) systolic pressure in children. The effect of this reporting protocol on IR agreement in reporting RV dilation, hypertrophy, and systolic function was also evaluated.

The contributions of cartilage endplate composition and vertebral bone marrow fat to intervertebral disc degeneration in patients with chronic low back pain.

Purpose: The composition of the subchondral bone marrow and cartilage endplate (CEP) could affect intervertebral disc health by influencing vertebral perfusion and nutrient diffusion. However, the relative contributions of these factors to disc degeneration in patients with chronic low back pain (cLBP) have not been quantified. The goal of this study was to use compositional biomarkers derived from quantitative MRI to establish how CEP composition (surrogate for permeability) and vertebral bone marrow fat fraction (BMFF, surrogate for perfusion) relate to disc degeneration.

Paraspinal Muscle in Chronic Low Back Pain: Comparison Between Standard Parameters and Chemical Shift Encoding-Based Water-Fat MRI.

Background: Paraspinal musculature (PSM) is increasingly recognized as a contributor to low back pain (LBP), but with conventional MRI sequences, assessment is limited. Chemical shift encoding-based water-fat MRI (CSE-MRI) enables the measurement of PSM fat fraction (FF), which may assist investigations of chronic LBP.

Purpose: To investigate associations between PSM parameters from conventional MRI and CSE-MRI and between PSM parameters and pain.

Different α-synuclein prion strains cause dementia with Lewy bodies and multiple system atrophy.

The α-synuclein protein can adopt several different conformations that cause neurodegeneration. Different α-synuclein conformers cause at least three distinct α-synucleinopathies: multiple system atrophy (MSA), dementia with Lewy bodies (DLB), and Parkinson's disease (PD). In earlier studies, we transmitted MSA to transgenic (Tg) mice and cultured HEK cells both expressing mutant α-synuclein (A53T) but not to cells expressing α-synuclein (E46K).

Association Between the Frequent Use of Perineal Talcum Powder Products and Ovarian Cancer: a Systematic Review and Meta-analysis.

Background: Risk of ovarian cancer in women with frequent perineal talcum powder product is not well understood. Prior systematic reviews focused on ever use. The purpose of this study is to estimate the association between frequent (at least 2 times per week) perineal talcum powder use and ovarian cancer.

Validation of Anticorrelated TGFβ Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy.

Purpose: Loss of TGFβ signaling increases error-prone alternative end-joining (alt-EJ) DNA repair. We previously translated this mechanistic relationship as TGFβ and alt-EJ gene expression signatures, which we showed are anticorrelated across cancer types. A score representing anticorrelation, βAlt, predicts patient outcome in response to genotoxic therapy.

Mammary Tumor-Derived Transplants as Breast Cancer Models to Evaluate Tumor-Immune Interactions and Therapeutic Responses.

In breast cancer, the type and distribution of infiltrating immune cells are associated with clinical outcome. Moreover, cancers with abundant tumor-infiltrating lymphocytes (TIL) are more likely to respond to immunotherapy, whereas those in which CD8 T cells are completely absent (deserts) or excluded are less likely to respond. Detailed understanding of this biology is limited by a lack of preclinical breast cancer models that recapitulate TIL distributions and their associated biology.