Landscape analysis of environmental data sources for linkage with SEER cancer patients database.

One of the challenges associated with understanding environmental impacts on cancer risk and outcomes is estimating potential exposures of individuals diagnosed with cancer to adverse environmental conditions over the life course. Historically, this has been partly due to the lack of reliable measures of cancer patients' potential environmental exposures before a cancer diagnosis. The emerging sources of cancer-related spatiotemporal environmental data and residential history information, coupled with novel technologies for data extraction and linkage, present an opportunity to integrate these data into the existing cancer surveillance data infrastructure, thereby facilitating more comprehensive assessment of cancer risk and outcomes.

Targeting axonal guidance dependencies in glioblastoma with ROBO1 CAR T cells.

Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers of post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived GBM models and independent lines of validation. Specific genetic dependencies were found consistent across recurrent tumor models, accompanied by increased mutational burden and differential transcript and protein expression compared to its primary GBM predecessor.

An exploratory analysis of the impact of area-level exposome on geographic disparities in aggressive prostate cancer.

Numbers of aggressive prostate cancer (aPC) cases are rising, but only a few risk factors have been identified. In this study, we introduce a systematic approach to integrate geospatial data into external exposome research using aPC cases from Pennsylvania. We demonstrate the association between several area-level exposome measures across five Social Determinants of Health domains (SDOH) and geographic areas identified as having elevated odds of aPC.

The Association Between a Neighborhood Adverse Childhood Experiences Index and Body Mass Index Among New York City Youth.

The role of neighborhood factors in the association between adverse childhood experiences (ACEs) and body mass index (BMI) has not been widely studied. A neighborhood ACEs index (NAI) captures neighborhood environment factors associated with ACE exposure. This study examined associations between BMI and an NAI among New York City (NYC) youth.

Evaluating the Effects of Food Deserts and Food Swamps in an Urban Burn Patient Population.

Poverty is a known risk factor for burn injury and is associated with residency in food deserts and food swamps. Our aim was to determine the prevalence of residency in food deserts and food swamps and to investigate the relationship between food environment, comorbidities, and wound healing in patients with burns. We performed a retrospective chart review of all patients with burns aged ≥ 18 seen in the emergency department or admitted to the burn service at an American Burn Association-verified urban academic center between January 2016 and January 2022.

Outer membrane vesicles as a platform for the discovery of antibodies to bacterial pathogens.

Bacterial outer membrane vesicles (OMVs) are nanosized spheroidal particles shed by gram-negative bacteria that contain biomolecules derived from the periplasmic space, the bacterial outer membrane, and possibly other compartments. OMVs can be purified from bacterial culture supernatants, and by genetically manipulating the bacterial cells that produce them, they can be engineered to harbor cargoes and/or display molecules of interest on their surfaces including antigens that are immunogenic in mammals. Since OMV bilayer-embedded components presumably maintain their native structures, OMVs may represent highly useful tools for generating antibodies to bacterial outer membrane targets.

Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6.

Mucin-16 (MUC16) is a target for antibody-mediated immunotherapy in pancreatic ductal adenocarcinoma (PDAC) among other malignancies. The MUC16-specific monoclonal antibody AR9.6 has shown promise for PDAC immunotherapy and imaging.

Capturing emergency dispatch address points as geocoding candidates to quantify delimited confidence in residential geolocation.

Background: In response to citizens' concerns about elevated cancer incidence in their locales, US CDC proposed publishing cancer incidence at sub-county scales. At these scales, confidence in patients' residential geolocation becomes a key constraint of geospatial analysis. To support monitoring cancer incidence in sub-county areas, we presented summary metrics to numerically delimit confidence in residential geolocation.

Sequence tolerance of immunoglobulin variable domain framework regions to noncanonical intradomain disulfide linkages.

Most immunoglobulin (Ig) domains bear only a single highly conserved canonical intradomain, inter-β-sheet disulfide linkage formed between Cys23-Cys104, and incorporation of rare noncanonical disulfide linkages at other locations can enhance Ig domain stability. Here, we exhaustively surveyed the sequence tolerance of Ig variable (V) domain framework regions (FRs) to noncanonical disulfide linkages. Starting from a destabilized V domain lacking a Cys23-Cys104 disulfide linkage, we generated and screened phage-displayed libraries of engineered Vs, bearing all possible pairwise combinations of Cys residues in neighboring β-strands of the Ig fold FRs.

Applications of High-Throughput DNA Sequencing to Single-Domain Antibody Discovery and Engineering.

Next-generation DNA sequencing (NGS) technologies have made it possible to interrogate antibody repertoires to unprecedented depths, typically via sequencing of cDNAs encoding immunoglobulin variable domains. In the absence of heavy-light chain pairing, the variable domains of heavy chain-only antibodies (HCAbs), referred to as single-domain antibodies (sdAbs), are uniquely amenable to NGS analyses. In this chapter, we provide simple and rapid protocols for producing and sequencing multiplexed immunoglobulin variable domain (VH, V or V) amplicons derived from a variety of sources using the Illumina MiSeq platform.

Asian American Enclaves and Healthcare Accessibility: An Ecologic Study Across Five States.

Introduction: Access to primary care has been a long-standing priority for improving population health. Asian Americans, who often settle in ethnic enclaves, have been found to underutilize health care. Understanding geographic primary care accessibility within Asian American enclaves can help to ensure the long-term health of this fast-growing population.

Ethnic enclaves and colon cancer stage at diagnosis among New Jersey Hispanics.

Ethnic enclaves are neighborhoods with high concentrations of individuals of the same ethnic origin. Researchers have hypothesized that residence in ethnic enclaves may contribute to cancer outcomes through detrimental or protective pathways. A limitation of previous work, however, is their cross-sectional approach whereby an individual's residence at the time of diagnosis was used to capture residence in an ethnic enclave at a single point in time.

Isolation and characterization of a VHH targeting the Acinetobacter baumannii cell surface protein CsuA/B.

Acinetobacter baumannii is a Gram-negative bacterial pathogen that exhibits high intrinsic resistance to antimicrobials, with treatment often requiring the use of last-resort antibiotics. Antibiotic-resistant strains have become increasingly prevalent, underscoring a need for new therapeutic interventions. The aim of this study was to use A.

Disparities in geospatial patterns of cancer care within urban counties and structural inequities in access to oncology care.

Objective: To examine geospatial patterns of cancer care utilization across diverse populations in New Jersey-a state where most residents live in urban areas.

Data Sources/study Setting: We used data from the New Jersey State Cancer Registry from 2012 to 2014.

Study Design: We examined the location of cancer treatment among patients 20-65 years of age diagnosed with breast, colorectal, or invasive cervical cancer and investigated differences in geospatial patterns of care by individual and area-level (e.

Geographic diffusion of digital mammography in the United States.

Background: Examining temporal and spatial diffusion of a new technology, such as digital mammography, can provide important insights into potential disparities associated with access to new medical technologies and how quickly these technologies are adopted. Although digital mammography is currently a standard technology in the United States for breast cancer screening, its adoption and geographic diffusion, as medical facilities transitioned from film to digital units, has not been explored well.

Methods: This study evaluated the geographic diffusion of digital mammography facilities from 2001 to 2014 in the contiguous United States (excluding Alaska and Hawaii) and estimated the geographic accessibility to this new technology for women aged ≥45 years at the census tract level within a 20-minute drivetime by population density, rural/urban residence, and race/ethnicity.

Disparities in Cutaneous T-Cell Lymphoma Incidence by Race/Ethnicity and Area-Based Socioeconomic Status.

Cutaneous T-cell lymphoma (CTCL) is a rare type of extranodal non-Hodgkin lymphoma (NHL). This study uses population-based data from the New Jersey (NJ) State Cancer Registry to examine geographic variation in CTCL incidence and evaluates whether CTCL risk varies by race/ethnicity and census tract socioeconomic status (SES). The study included 1163 cases diagnosed in NJ between 2006 and 2014.

Changes in geographic accessibility to mammography by state and rural-urban status, United States, 2006-2022.

Although mammography is widely available in the United States, differences in accessibility in rural and urban areas and changes over time are not well described. In this study, we estimated the number and proportion of women aged 45-84 years who had limited travel time-based geographic accessibility to mammography by urban-rural status and state in the contiguous United States in 2006 and 2022. The proportion of women aged 45-84 years with limited accessibility to mammography did not substantially change from 2006 (12.

Evolution of endovascular stroke centers and disparities in access to stroke care in four Northeastern states: 2015-2019.

Objectives: Disparities exist throughout our healthcare system, especially related to access to care. Advanced stroke care for strokes is only available at selected endovascular centers (ESCs) in the United States. Although the number of ESCs increase each year, this does not necessarily reflect increased access to care.

Programmable Attenuation of Antigenic Sensitivity for a Nanobody-Based EGFR Chimeric Antigen Receptor Through Hinge Domain Truncation.

Epidermal growth factor family receptor (EGFR) is commonly overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR)-T therapy, but as EGFR is also expressed at lower levels in healthy tissues a therapeutic strategy must balance antigenic responsiveness against the risk of on-target off-tumor toxicity. Herein, we identify several camelid single-domain antibodies (also known as nanobodies) that are effective EGFR targeting moieties for CARs (EGFR-sdCARs) with very strong reactivity to EGFR-high and EGFR-low target cells. As a strategy to attenuate their potent antigenic sensitivity, we performed progressive truncation of the human CD8 hinge commonly used as a spacer domain in many CAR constructs.