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The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

The use of unconventional DNA sources has increased because the acquisition of traditional samples can be invasive, destructive, or impossible. Mollusks are one group for which novel genetic sources are crucial, but methodology remains relatively undeveloped. Many species are important ecologically and in aquaculture production. However, mollusks have the highest number of extinctions of any taxonomic group. Traditionally, mollusk shell material was used for morphological research and only recently has been used in DNA studies. In the present article, we review the studies in which shell DNA was extracted and found that effective procedures consider taxon-specific biological characteristics, environmental conditions, laboratory methods, and the study objectives. Importantly, these factors cannot be considered in isolation because of their fundamental, sometimes reciprocal, relationships and influence in the long-term preservation and recovery of shell DNA. Successful recovery of shell DNA can facilitate research on pressing ecological and evolutionary questions and inform conservation strategies to protect molluscan diversity.

Background: Food insecurity (FI) has been associated with poor access to health care. It is unclear whether this association is beyond that predicted by income, education, and health insurance. FI may serve as a target for intervention given the many programs designed to ameliorate FI. We examined the association of FI with being up-to-date to colorectal cancer and breast cancer screening guidelines. Methods: Nine NCI-designated cancer centers surveyed adults in their catchment areas using demographic items and a two-item FI questionnaire. For the colorectal cancer screening sample (n = 4,816), adults ages 50–75 years who reported having a stool test in the past year or a colonoscopy in the past 10 years were considered up-to-date. For the breast cancer screening sample (n = 2,449), female participants ages 50–74 years who reported having a mammogram in the past 2 years were up-to-date. We used logistic regression to examine the association between colorectal cancer or breast cancer screening status and FI, adjusting for race/ethnicity, income, education, health insurance, and other sociodemographic covariates. Results: The prevalence of FI was 18.2% and 21.6% among colorectal cancer and breast cancer screening participants, respectively. For screenings, 25.6% of colorectal cancer and 34.1% of breast cancer participants were not up-to-date. In two separate adjusted models, FI was significantly associated with lower odds of being up-to-date with colorectal cancer screening [OR, 0.7; 95% confidence interval (CI), 0.5–0.99)] and breast cancer screening (OR, 0.6; 95% CI, 0.4–0.96). Conclusions: FI was inversely associated with being up-to-date for colorectal cancer and breast cancer screening. Impact: Future studies should combine FI and cancer screening interventions to improve screening rates.

To understand data privacy in retailing, one must consider a myriad of consumer, retailer, and regulatory tensions, trade-offs, and compromises. Scholarly research on consumer data privacy in retailing remains a fruitful area of inquiry precisely because it confronts these critical tensions. As a scholarly domain, data privacy research investigates questions and contexts that are fraught with persistent conflicts and paradoxes. Despite some important advances, many pressing questions remain, leaving various tensions unresolved too. In this editorial, we review the role of data privacy in retailing, attending to focal consumer and retailer tensions. We also provide an overview of the unique contributions offered by the articles in this issue, stressing the novel insights they provide for retail theory and practice. This overview exposes three promising research directions that offer particular promise for informing the critical data privacy tensions that we identify and for expanding the relevance of data privacy research to encompass a broader set of retail implications. These research directions in turn may motivate future scholarly inquiry in retailing, inform retail management, and suggest public policy options.

Unprecedented, exponential growth in the amount of consumer data collected by retailers across various customer touchpoints has made safeguarding data privacy a key priority. Data privacy in retail contexts requires convergence among three key stakeholders—consumer, retailer, and regulatory—each of which has unique roles and viewpoints. With a global perspective and a multimethod data collection approach, combining in-depth expert interviews, a large-scale consumer survey across four countries, and global case studies, this research identifies three emergent themes for understanding the convergence of these three stakeholders’ interests: (1) big data as a driver of customer relationship performance, (2) profound impacts of regulation, and (3) privacy protection as a proactive retail strategy. These themes underscore the complex interrelations among consumers, retailers, and regulatory forces. The delineated research opportunities in turn may foster deeper understanding of these stakeholders, their perspectives, and their convergence.

Despite growing evidence of significant racial disparities in the experience and treatment of chronic pain, the mechanisms by which these disparities manifest have remained relatively understudied. The current study examined the relationship between past experiences of racial discrimination and pain-related outcomes (self-rated disability and depressive symptomatology) and tested the potential mediating roles of pain catastrophizing and perceived injustice related to pain. Analyses consisted of cross-sectional path modeling in a multiracial sample of 137 individuals with chronic low back pain (Hispanics: n = 43; blacks: n = 43; whites: n = 51). Results indicated a positive relationship between prior discriminatory experiences and severity of disability and depressive symptoms. In mediation analyses, pain-related appraisals of injustice, but not pain catastrophizing, were found to mediate these relationships. Notably, the association between discrimination history and perceived injustice was significantly stronger in black and Hispanic participants and was not statistically significant in white participants. The findings suggest that race-based discriminatory experiences may contribute to racial disparities in pain outcomes and highlight the specificity of pain-related, injustice-related appraisals as a mechanism by which these experiences may impair physical and psychosocial function. Future research is needed to investigate temporal and causal mechanisms suggested by the model through longitudinal and clinical intervention studies. Perspective More frequent prior experiences of racial discrimination are associated with greater depressive symptomatology and pain-related disability in individuals with chronic low back pain. These associations are explained by the degree of injustice perception related to pain, but not pain catastrophizing, and were stronger among black and Hispanic participants.

The language system is perhaps the most unique feature of the human brain's cognitive architecture. It has long been a quest of cognitive neuroscience to understand the neural components that contribute to the hierarchical pattern processing and advanced rule learning required for language. The most important goal of this research is to understand how language becomes impaired when these neural components malfunction or are lost to stroke, and ultimately how we might recover language abilities under these circumstances. Additionally, understanding how the language system develops and how it can reorganize in the face of brain injury or dysfunction could help us to understand brain plasticity in cognitive networks more broadly. In this chapter we will discuss the earliest features of language organization in infants, and how deviations in typical development can-but in some cases, do not-lead to disordered language. We will then survey findings from adult stroke and aphasia research on the potential for recovering language processing in both the remaining left hemisphere tissue and in the non-dominant right hemisphere. Altogether, we hope to present a clear picture of what is known about the capacity for plastic change in the neurobiology of the human language system.

Curcumin, a natural polyphenol derived from the spice turmeric (Curcuma longa), contains antioxidant, anti-inflammatory, and anti-cancer properties. However, curcumin bioavailability is inherently low due to poor water solubility and rapid metabolism. Here, we further refined for use curcumin incorporated into “biomimetic” nanolipoprotein particles (cNLPs) consisting of a phospholipid bilayer surrounded by apolipoprotein A1 and amphipathic polymer scaffolding moieties. Our cNLP formulation improves the water solubility of curcumin over 30-fold and produces nanoparticles with ~350 µg/mL total loading capacity for downstream in vitro and in vivo applications. We found that cNLPs were well tolerated in AG05965/MRC-5 human primary lung fibroblasts compared to cultures treated with curcumin solubilized in DMSO (curDMSO). Pre-treatment with cNLPs of quiescent G0/G1-phase MRC-5 cultures improved cell survival following 137Cs gamma ray irradiations, although this finding was reversed in asynchronously cycling log-phase cell cultures. These findings may be useful for establishing cNLPs as a method to improve curcumin bioavailability for administration as a radioprotective and/or radiomitigative agent against ionizing radiation (IR) exposures in non-cycling cells or as a radiosensitizing agent for actively dividing cell populations, such as tumors.

This study expands the literature on body image among lesbian and bisexual women by examining the relationship between self-perceived gendered personality traits and expressions (i.e., sense of self in relation to cultural constructions of femininity and masculinity) and body satisfaction, a key body image construct. We used data from Wave 3 (2010-12) of the Chicago Health and Life Experiences of Women (CHLEW) study. The CHLEW includes a novel measure of gender expression, with masculinity and femininity as distinct but overlapping constructs. In the large analytic sample (N=553), we found both similarities and differences in the association between femininity/masculinity and body image in lesbian and bisexual women. Bisexual women reported significantly lower body satisfaction than lesbian women. Higher masculinity was associated with greater body satisfaction in the full sample, but the association was stronger for bisexual than lesbian women. Femininity was positively associated with body satisfaction only for bisexual women. These findings suggest that masculinity and femininity play different roles in body satisfaction for lesbian and bisexual women and highlight the importance of disaggregating sexual identity in studies of SMW’s health. Clinicians should routinely ask about sexual identity and gender expression, especially when presenting concerns involve body image or disordered eating.

OBJECTIVES: To investigate factors associated with residual sleepiness in patients who were highly adherent to continuous positive airway pressure (CPAP). Nocturnal inactivity, comorbidities, concomitant medications, and, in particular, white matter (WM) differences using diffusion magnetic resonance imaging (MRI) were explored using a continuous-time random-walk (CTRW) model. METHODS: Twenty-seven male patients (30–55 years of age) with obstructive sleep apnea (OSA) received CPAP as the only treatment (CPAP ≥ 6hr./night) for at least 30 days. Based on the Psychomotor Vigilance Task (PVT) results, participants were divided into a non-sleepy group (lapses ≤ 5; n = 18) and a sleepy group (lapses > 5; n = 9). Mean nocturnal inactivity (sleep proxy) was measured using actigraphy for one week. Diffusion-weighted imaging (DWI) with high b-values, as well as diffusion tensor imaging (DTI), was performed on a 3 Tesla MRI scanner. The DWI dataset was analyzed using the CTRW model that yielded three parameters: temporal diffusion heterogeneity α, spatial diffusion heterogeneity β, and an anomalous diffusion coefficient D(m). The differences in α, β, D(m), and the combination of α and β between the two groups were investigated by a whole-brain analysis using tract-based spatial statistics (TBSS), followed by a regional analysis on individual fiber tracts using a standard parcellation template. Results from the CTRW model were compared with those obtained from DTI. The three CTRW parameters were also correlated with the clinical assessment scores, Epworth Sleepiness Scale (ESS), PVT lapses, and PVT mean reaction time (MRT) in specific fiber tracts. RESULTS: There were no differences between groups in mean sleep duration, comorbidities, and the number or type of medications, including alerting and sedating medications. In the whole-brain DWI analysis, the sleepy group showed higher α (17.27% of the WM voxels) and D(m) (17.14%) when compared to the non-sleepy group (P < 0.05), whereas no significant difference in β was observed. In the regional fiber analysis, the sleepy and non-sleepy groups showed significant differences in α, β, or their combinations in a total of twelve fiber tracts, whereas similar differences were not observed in DTI parameters, when age was used as a covariate. Additionally, moderate to strong correlations between the CTRW parameters (α, β, or D(m)) and the sleepiness assessment scores (ESS, PVT lapses, or PVT MRT) were observed in specific fiber tracts (|R| = 0.448–0.654, P = 0.0003–0.019). CONCLUSIONS: The observed differences in the CTRW parameters between the two groups indicate that WM alterations can be a possible mechanism to explain reversible versus residual sleepiness observed in OSA patients with identical high level of CPAP use. The moderate to strong correlations between the CTRW parameters and the clinical scores suggest the possibility of developing objective and quantitative imaging markers to complement clinical assessment of OSA patients.

Background: Two decades ago, there was almost no research on alcohol use among sexual minority women (SMW, e.g., lesbian, bisexual). Since then, a growing body of scientific literature documents substantial sexual orientation-related disparities in alcohol use and alcohol-related problems. Research has identified multiple risk factors associated with high-risk/hazardous drinking among SMW. However, this research has almost exclusively used cross-sectional designs, limiting the ability to draw conclusions about processes through which sexual minority status affects alcohol use. Longitudinal designs, although very rare in research on alcohol use among SMW, are important for testing mediational mechanisms and necessary to understanding how changes in social determinants impact alcohol use. Aim: To describe the processes and lessons learned in conducting a 20-year longitudinal study focused on alcohol use among SMW. Methods: The Chicago Health and Life Experiences of Women (CHLEW) study includes five waves of data collection (2000–present) with an age and racially/ethnically diverse sample of 815 SMW (ages 18–83) originally recruited in the Chicago Metropolitan Area in Illinois, a midwestern state in the United States (U.S.). Measures and focus have evolved over the course of the study. Results: The CHLEW study is the longest-running and most comprehensive study of SMW’s drinking in the U.S. or elsewhere. Findings reported in more than 50 published manuscripts have contributed to understanding variations in SMW’s risk for hazardous/harmful drinking based on sexual identity, age, race/ethnicity, sex/gender of partner, and many other factors. Conclusions: By describing the process used in conducting this long-term study, its major findings, and the lessons learned, we hope to encourage and support other researchers in conducting longitudinal research focused on SMW’s health. Such research is critically important in understanding and ultimately eliminating sexual orientation-related health disparities.

Background Intimate partner violence (IPV) is one of the leading causes of pregnancy-related death. Prenatal health care providers can offer critical screening and support to pregnant people who experience IPV. During the COVID-19 shelter-in-place order, mobile apps may offer such people the opportunity to continue receiving screening and support services. Objective We aimed to examine cases of IPV that were reported on a prenatal care app before and during the implementation of COVID-19 shelter-in-place mandates. Methods The number of patients who underwent voluntary IPV screening and the incidence rate of IPV were determined by using a prenatal care app that was disseminated to patients from a single, large health care system. We compared the IPV screening frequencies and IPV incidence rates of patients who started using the app before the COVID-19 shelter-in-place order, to those of patients who started using the app during the shelter-in-place order. Results We found 552 patients who started using the app within 60 days prior to the enforcement of the shelter-in-place order, and 407 patients who used the app at the start of shelter-in-place enforcement until the order was lifted. The incidence rates of voluntary IPV screening for new app users during the two time periods were similar (before sheltering in place: 252/552, 46%; during sheltering in place: 163/407, 40%). The overall use of the IPV screening tool increased during the shelter-in-place order. A slight, nonsignificant increase in the incidence of physical, sexual, and psychological violence during the shelter-in-place order was found across all app users (P=.56). Notably, none of the patients who screened positively for IPV had mentions of IPV in their medical charts. Conclusions App-based screening for IPV is feasible during times when in-person access to health care providers is limited. Our results suggest that the incidence of IPV slightly increased during the shelter-in-place order. App-based screening may also address the needs of those who are unwilling or unable to share their IPV experiences with their health care provider.

Pancreatic ductal adenocarcinoma (PDAC) is one of the top five deadliest forms of cancer with very few treatment options. The 5-year survival rate for PDAC is 10% following diagnosis. Preclinical murine models have been developed that leverage key driver mutations and have significantly contributed to our understanding of PDAC. One such genetically engineered mouse model (GEMM) that has emerged as an important tool is the KPC mouse (LSL-KrasG12D/+;LSL-Trp53R172H/+; p48-Cre) that spontaneously develops pancreatic tumors at ~14-16 weeks of age. Cadherin-11 (Cdh11), a cell-to-cell adhesion molecule has been suggested to play a role in development of the desmoplastic stroma in PDAC, that leads to difficulties in drug accessibility and has been hypothesized to contribute to chemotherapeutic resistance and correlate with poor prognosis. However, the mechanisms by which Cdh11 deficiency in the stromal microenvironment of PDAC-bearing KPC mice influences tumor infiltrating immune cells, has yet to be fully understood. Single-cell RNA sequencing (scRNAseq) of the immune (CD45+) compartment of tumor bearing Cdh11 proficient (KPC/Cdh11+/+), tumor bearing Cdh11 deficient (KPC/Cdh11+/-), non-tumor bearing Cdh11 deficient (Cdh11+/-) and wildtype (Cdh11+/+) mice was performed. We observed a sharp decrease in the presence of myeloid/monocyte lineage cells (CD14+) in KPC/Cdh11+/- tumors and also an increase in T, B and plasma cells, compared to KPC/Cdh11+/+ tumors. Genes upregulated in infiltrating T- and NK cells specific to a Cdh11 deficient background include Cd8a, Nkg7, Maf. Additionally, genes found to be upregulated in B cell clusters in Cdh11 deficient mice include those related to B cell differentiation/activation such as Lgals1, Id2, Itgb1, Rgs1. The increase in B and T cell infiltration was specific to the Cdh11 deficient background, since both pancreata from KPC/Cdh11+/+and Cdh11+/- mice had elevated levels of infiltration. Immunohistochemical validation of these findings has confirmed these changes in tumor infiltrating immune cells. Additionally of note, an increase in antibody-producing plasma cells was observed specifically in a Cdh11 deficient background. Igkc, an immunoglobulin found to be enriched in plasma cells was highly expressed in this group of immune cells. We also observed that KPC/Cdh11+/-had significantly more Igkc expressing cells than KPC/Cdh11+/+. Future work is needed to clearly define the role of Cdh11 in modulating B, T and plasma cell behavior and subsequent contributions to PDAC outcome. This study received funding by LDRD 19-SI-003. This work was conducted under the auspices of the USDOE by LLNL (DE-AC52-07NA27344), LLNL-ABS-820889. This work was supported by AACR-AstraZeneca Fellowship in Immunooncology Research, grant 17-40-12-PERA; The Ruesch Center for the Cure of Gastrointestinal Cancers grant award; NIH R01 CA170653; and NIH Cancer Center Support Grant P30 CA051008. Citation Format: Kelly A. Martin, Aimy Sebastian, Nicholas Hum, Ivana Peran, Stephen Byers, Elizabeth Wheeler, Matthew Coleman, Gabriela Loots. Loss of cadherin 11 in pancreatic cancer induces altered immune cell infiltration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2516.

Lung cancer is the second most diagnosed type of cancer and is the leading cause of cancer-related deaths in both men and women. An estimated 235,760 new cases of lung cancer and 131,880 lung cancer deaths are expected this year accounting for 12% of new cancer cases and 22% of cancer deaths in the United States. Exosomes are secreted vesicles that contain selectively packaged biomaterials (protein, lipids, and RNA) and serve as a form of extracellular communication between cells in the tumor microenvironment. Previous studies have shown the effects of cancer-derived exosomes on specific cell types or gross tumor response in vivo yet, the competitive nature and dynamics of exosomal uptake in the tumor microenvironment remains largely unknown. This work seeks to identify molecular responses induced by cancer-derived exosomes on cells residing in the tumor microenvironment. In order to control tumor cell exposure to cancer-derived exosomes, heterogeneous ex vivo cultures derived from subcutaneous Lewis lung carcinoma (LLC) tumors in C57BL6 mice were exposed to fluorescently dyed LLC exosomes for up to 72 hours. Flow cytometric analysis was performed to identify preferential uptake of cancer exosomes into the stromal subpopulations of tumor cells. Increased uptake was observed throughout the duration of the exposure and preferential uptake was observed into neutrophils, macrophages, and endothelial cells while cancer cells, fibroblasts, and lymphocytes were underrepresented in the exosome uptaken population. Additionally, single cell RNA-sequencing was performed 24 hours post-exosomal exposure to identify transcriptional changes promoted by cancer exosome uptake. We found tumor-derived cancer cells to up-regulate transcripts associated with proliferation and down-regulated genes associated with interferon signaling in response to exosome uptake. These preliminary findings suggest that cancer-derived exosomes have targeted effects on specific cell types in the tumor microenvironment. Specifically in cancer cells, exosomal uptake can elicit protumor (cancer proliferation and immune suppression via decreased interferon signaling) effects that may serve as mediators of disease progression. An understanding of both cancer and host-derived exosomal response to disease progression may identify novel biomarkers and potential therapeutic targets previously undiscovered using canonical discovery methods. This study received funding from LLNL LDRD grant 21-LW-028. This work was conducted under the auspices of the USDOE by LLNL (DE-AC52-07NA27344). LLNL-ABS-829271 Citation Format: Nicholas R. Hum, Nicole F. Leon, Aimy Sebastian, Kelly A. Martin, Gabriela G. Loots. Molecular characterization of the effects of cancer-derived exosomes on murine lung cancer tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3136.

Driven by data proliferation, digital technologies have transformed the marketing landscape. In parallel, significant privacy concerns have shaken consumer–firm relationships, prompting changes in both regulatory interventions and people’s own privacy-protective behaviors. With a comprehensive analysis of digital technologies and data strategy informed by structuration theory and privacy literature, the authors consider privacy tensions as the product of firm–consumer interactions, facilitated by digital technologies. This perspective in turn implies distinct consumer, regulatory, and firm responses related to data protection. By consolidating various perspectives, the authors propose three tenets and seven propositions, supported by interview insights from senior managers and consumer informants, that create a foundation for understanding the digital technology implications for firm performance in contexts marked by growing privacy worries and legal ramifications. On the basis of this conceptual framework, they also propose a data strategy typology across two main strategic functions of digital technologies: data monetization and data sharing. The result is four distinct types of firms, which engage in disparate behaviors in the broader ecosystem pertaining to privacy issues. This article also provides directions for research, according to a synthesis of findings from both academic and practical perspectives.

BACKGROUND Intimate partner violence (IPV) is one of the leading causes of pregnancy-related death. Prenatal health care providers can offer critical screening and support to pregnant people who experience IPV. During the COVID-19 shelter-in-place order, mobile apps may offer such people the opportunity to continue receiving screening and support services. OBJECTIVE We aimed to examine cases of IPV that were reported on a prenatal care app before and during the implementation of COVID-19 shelter-in-place mandates. METHODS The number of patients who underwent voluntary IPV screening and the incidence rate of IPV were determined by using a prenatal care app that was disseminated to patients from a single, large health care system. We compared the IPV screening frequencies and IPV incidence rates of patients who started using the app before the COVID-19 shelter-in-place order, to those of patients who started using the app during the shelter-in-place order. RESULTS We found 552 patients who started using the app within 60 days prior to the enforcement of the shelter-in-place order, and 407 patients who used the app at the start of shelter-in-place enforcement until the order was lifted. The incidence rates of voluntary IPV screening for new app users during the two time periods were similar (before sheltering in place: 252/552, 46%; during sheltering in place: 163/407, 40%). The overall use of the IPV screening tool increased during the shelter-in-place order. A slight, nonsignificant increase in the incidence of physical, sexual, and psychological violence during the shelter-in-place order was found across all app users (P=.56). Notably, none of the patients who screened positively for IPV had mentions of IPV in their medical charts. CONCLUSIONS App-based screening for IPV is feasible during times when in-person access to health care providers is limited. Our results suggest that the incidence of IPV slightly increased during the shelter-in-place order. App-based screening may also address the needs of those who are unwilling or unable to share their IPV experiences with their health care provider.

Cancer-associated fibroblasts (CAFs) are a prominent stromal cell type in solid tumors and molecules secreted by CAFs play an important role in tumor progression and metastasis. CAFs coexist as heterogeneous populations with potentially different biological functions. Although CAFs are a major component of the breast cancer stroma, molecular and phenotypic heterogeneity of CAFs in breast cancer is poorly understood. In this study, we investigated CAF heterogeneity in triple-negative breast cancer (TNBC) using a syngeneic mouse model, BALB/c-derived 4T1 mammary tumors. Using single-cell RNA sequencing (scRNA-seq), we identified six CAF subpopulations in 4T1 tumors including: 1) myofibroblastic CAFs, enriched for &alpha, smooth muscle actin and several other contractile proteins, 2) &lsquo, inflammatory&rsquo, CAFs with elevated expression of inflammatory cytokines, and 3) a CAF subpopulation expressing major histocompatibility complex (MHC) class II proteins that are generally expressed in antigen-presenting cells. Comparison of 4T1-derived CAFs to CAFs from pancreatic cancer revealed that these three CAF subpopulations exist in both tumor types. Interestingly, cells with inflammatory and MHC class II-expressing CAF profiles were also detected in normal breast/pancreas tissue, suggesting that these phenotypes are not tumor microenvironment-induced. This work enhances our understanding of CAF heterogeneity, and specifically targeting these CAF subpopulations could be an effective therapeutic approach for treating highly aggressive TNBCs.

Despite the important roles of freshwater gastropods in aquatic ecosystems, the taxonomic status of many taxa is unclear, which is compounded by a lack of information on species population genetic structuring, distribution, and dispersal patterns. The objective of this study was to address the biogeography of the freshwater snail Planorbella trivolvis (Gastropoda: Planorbidae) in the western United States. We amplified two genetic markers (16S, COI) from individuals belonging to western USA populations and downloaded genetic data from GenBank. We utilized minimum spanning networks to assess the genetic patterns and performed Analysis of Molecular Variance and linear regression analyses to determine how geographic distance and watershed identity contributed to the observed genetic structuring. For both markers, we found that the majority of genetic variation was associated within and among populations, rather than among watersheds. Correspondingly, there was no significant effect of geographic distance on genetic distance, suggesting that long-distance dispersal was promoting gene flow between populations. The genetic similarity could reflect avian-mediated dispersal of snails along the Pacific Flyway, a major waterfowl migratory corridor. Further analysis of the population structuring across North America revealed East-West genetic structuring, suggesting that across longitudinal gradients P. trivolvis experiences significant genetic isolation.

Here we introduce an Accelerator Mass Spectrometry (AMS)-based high precision method for quantifying the number of cancer cells that initiate metastatic tumors, in xenograft mice. Quantification of 14C per cell prior to injection into animals, and quantification of 14C in whole organs allows us to extrapolate the number of cancer cells available to initiate metastatic tumors. The 14C labeling was optimized such that 1 cancer cell was detected among 1 million normal cells. We show that ~1–5% of human cancer cells injected into immunodeficient mice form subcutaneous tumors, and even fewer cells initiate metastatic tumors. Comparisons of metastatic site colonization between a highly metastatic (PC3) and a non-metastatic (LnCap) cell line showed that PC3 cells colonize target tissues in greater quantities at 2 weeks post-delivery, and by 12 weeks post-delivery no 14C was detected in LnCap xenografts, suggesting that all metastatic cells were cleared. The 14C-signal correlated with the presence and the severity of metastatic tumors. AMS measurements of 14C-labeled cells provides a highly-sensitive, quantitative assay to experimentally evaluate metastasis and colonization of target tissues in xenograft mouse models. This approach can potentially be used to evaluate tumor aggressiveness and assist in making informed decisions regarding treatment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer with very few treatment options. Less than 10 percent of patients diagnosed with PDAC survive 5 years post diagnosis. Mutations in CDKN2A, SMAD4, KRAS and P53 have been well linked to the development of PDAC. Preclinical murine models have been developed that leverage key driver mutations and have significantly contributed to our understanding of PDAC. One such genetically engineered mouse model (GEMM) that has emerged as an important tool in PDAC investigations is the KPC mouse (LSL-KrasG12D/+LSL-Trp53R172H/+Pdx-1-Cre) that spontaneously develops pancreatic tumors at ~14-16 weeks of age. Cadherin-11 (Cdh11), a cell-to-cell adhesion molecule, is highly expressed in desmoplastic stroma, a characteristic of PDAC, that leads to difficulties in drug accessibility and has been hypothesized to contribute to chemotherapeutic resistance. However, the mechanisms by which Cdh11 deficiency in the stromal microenvironment of PDAC-bearing mice (KPC) influences therapeutic outcomes, has yet to be fully understood. Single-cell RNA sequencing (scRNAseq) of both the non-immune (CD45-) and immune (CD45+) cellular compartments of tumor bearing (KPC/Cdh11+/+), tumor bearing Cdh11 deficient (KPC/Cdh11+/-), non-tumor bearing Cdh11 deficient (Cdh11-/+) and wildtype (KP) were performed. We observed changes in the abundance and types of infiltrating immune cells (T-cells, B-cells, myeloid lineage cells) of KPC/Cdh11+/- tumors when compared to tumors harvested from KPC/Cdh11+/+ mice. KPC/Cdh11+/+ pancreata had significantly more myeloid cells while KPC/Cdh11+/- tumors favored an increase in the numbers of infiltrating B- and T- cells. Genes upregulated in infiltrating T-cells specific to KPC/Cdh11+/+ mice include Spp1, Ifi30, Apoe, Ifitm3, Fn1. The increase in B and T cell infiltration was specific to the Cdh11-/+ deficient background, since both pancreata from KPC/Cdh11+/- and Cdh11-/+ mice had elevated levels of infiltration, compared to the KPC group. We also observed a decrease in the number of antigen-presenting cancer associated fibroblasts (apCAFs) in Cdh11-/+ and KPC/Cdh11+/- pancreata, denoted by the lack of CD74+ fibroblasts. Further validation of these findings will help to define the role of Cdh11-/+ in modulating B and T-cell behavior in addition to providing insight into Cdh11-/+ as a therapeutic target for PDAC through altering the tumor microenvironment. Citation Format: Kelly A. Martin, Aimy Sebastian, Nicholas Hum, Ivana Peran, Stephen Byers, Elizabeth K. Wheeler, Matthew A. Coleman, Gabriela Loots. Loss of Cadherin-11 in PDAC induces altered immune cell infiltration and remodels stromal landscape [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2741.

The study purpose was to examine demographic, healthcare, and contextual correlates of smoking among sexual minority women (SMW).Data were from the Chicago Health and Life Experiences of Women study (2010-2012, N = 726).The rate of current smoking was 29.6%, with 29.5% and 40.9% former or nonsmokers, respectively. A history of ever smoking was associated with lower educational levels, having a partner who smokes, heavy drinking, illicit drug use, and a bisexual identity. Statistically significant correlates of former versus current smoker included higher education, having a nonsmoking partner, being from the newest recruited cohort, and less illicit drug use. A past-year quit attempt among current smokers was associated with higher levels of illicit drug use, longer time until first cigarette, and being from the original cohort.The study results highlight key correlates of smoking behaviors among SMW and make an important contribution to the literature on smoking disparities. Additional research is needed to inform smoking cessation prevention and control efforts to reduce known and persistent smoking disparities among SMW.

Although marketers increasingly rely on customer data, firms have little insight into the ramifications of such data use and do not know how to prevent negative effects. Data management efforts may heighten customers’ vulnerability worries or create real vulnerability. Using a conceptual framework grounded in gossip theory, the authors link customer vulnerability to negative performance effects. Three studies show that transparency and control in firms’ data management practices can suppress the negative effects of customer data vulnerability. Experimental manipulations reveal that mere access to personal data inflates feelings of violation and reduces trust. An event study of data security breaches affecting 414 public companies also confirms negative effects, as well as spillover vulnerabilities from rival firms’ breaches, on firm performance. Severity of the breach hurts the focal firm but helps the rival firm, which provides some insight into mixed findings in prior research. Finally, a field study with actual customers of 15 companies across three industries demonstrates consistent effects across four types of customer data vulnerability and confirms that violation and trust mediate the effects of data vulnerabilities on outcomes.

Activated carbon block (ACB)-based point-of-use (PoU) drinking water filters are widely used to remove residual disinfectant, heavy metals, and disinfection by-products (DBPs) from household tap water. The filters are not designed to remove bacteria, which can grow in the filter. Based on previous research, we hypothesized that more biofilm would form in PoU filters due to the presence of chlorinated phenolic DBPs, resulting in higher bacterial concentrations in filtered water. Therefore, studies were conducted by operating a manifold system with three sets of ACB PoU filters that received chloraminated tap water spiked with (50 and 100 ng L−1 added) and without (0 ng L−1 added) pentachlorophenol (PCP) as a surrogate chlorinated phenolic DBP. After processing 85% of the manufacturer's recommended water volume, effluent heterotrophic plate counts plateaued at levels up to 100 times greater than influent counts. The upstream filter fabric developed a significant biofilm that lightened with increasing PCP concentration; however, the overall biofilm mass was not different between treatments. Influent, effluent, and fabric samples had distinct bacterial community structures, and the structure of effluent communities was more similar to that of fabric communities than that of influent communities. The bacterial community structure changed across the filter primarily due to the filter environment itself, while PCP effects were subtle yet significant. The relative abundance of Mycobacterium increased within fabric biofilms when PCP was added, and the absolute abundance was estimated to increase in the effluent relative to the influent. In conclusion, ACB PoU filters significantly alter the bacterial abundance and composition of drinking water.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinomas (PDAC) are characterized by fibrosis and an abundance of cancer-associated fibroblasts (CAFs). We investigated strategies to disrupt interactions among CAFs, the immune system, and cancer cells, focusing on adhesion molecule cadherin 11 (CDH11), which has been associated with other fibrotic disorders and is expressed by activated fibroblasts. METHODS: We compared levels of CDH11 mRNA in human pancreatitis and pancreatic cancer tissues and cells, compared with normal pancreas, and measured levels of CDH11 protein in human and mouse pancreatic lesions and normal tissues. We crossed p48-Cre;LSL-Kras(G12D/+);LSL-Trp53(R172H/+) (KPC) mice with CDH11-knockout mice and measured survival times of offspring. Pancreata were collected and analyzed by histology, immunohistochemistry, and (single-cell) RNA sequencing; RNA and proteins were identified by imaging mass cytometry. Some mice were given injections of PD1 antibody or gemcitabine and survival was monitored. Pancreatic cancer cells from KPC mice were subcutaneously injected into Cdh11(+/+) and Cdh11(−/−) mice and tumor growth was monitored. Pancreatic cancer cells (mT3) from KPC mice (C57BL/6), were subcutaneously injected into Cdh11(+/+) (C57BL/6J) mice and mice were given injections of antibody against CDH11, gemcitabine, or small molecule inhibitor of CDH11 (SD133) and tumor growth was monitored. RESULTS: Levels of CDH11 mRNA and protein were significantly higher in CAFs than in pancreatic cancer epithelial cells, human or mouse pancreatic cancer cell lines, or immune cells. KPC/Cdh11(+/−) and KPC/Cdh11(−/−) mice survived significantly longer than KPC/Cdh11(+/+) mice. Markers of stromal activation entirely surrounded pancreatic intraepithelial neoplasias in KPC/Cdh11(+/+) mice and incompletely in KPC/Cdh11(+/−) and KPC/Cdh11(−/−) mice, whose lesions also contained fewer FOXP3(+) cells in the tumor center. Compared with pancreatic tumors in KPC/Cdh11(+/+) mice, tumors of KPC/Cdh11(+/−) mice had increased markers of antigen processing and presentation; more lymphocytes and associated cytokines; decreased extracellular matrix components; and reductions in markers and cytokines associated with immunosuppression. Administration of the PD1 antibody did not prolong survival of KPC mice with 0, 1, or 2 alleles of Cdh11. Gemcitabine extended survival only of KPC/Cdh11(+/−) and KPC/Cdh11(−/−) mice or reduced subcutaneous tumor growth in mT3 engrafted Cdh11(+/+) mice given in combination with the CDH11 antibody. A small molecule inhibitor of CDH11 reduced growth of pre-established mT3 subcutaneous tumors only if T and B cells were present in mice. CONCLUSIONS: Knockout or inhibition of CDH11, which is expressed by CAFs in the pancreatic tumor stroma, reduces growth of pancreatic tumors, increases their response to gemcitabine, and significantly extends survival of mice. CDH11 promotes immunosuppression and extracellular matrix deposition, and might be developed as a therapeutic target for pancreatic cancer.

This paper captures the current state of privacy scholarship in marketing and related disciplines. We examine theoretical perspectives and empirical findings about data and information privacy grouped according to privacy’s role in society, the psychology of privacy, and the economics of privacy. Although a coherent subset of research themes provide deep understanding, theoretical and empirical findings show this narrow focus also has constrained our view of privacy to consumer, organizational, ethical, or legal silos. In response, we take a necessary step toward expanding the privacy domain across these borders, emphasizing the compelling synergies that span multiple interests. We conclude by highlighting future research themes that embody a multidimensional approach, which blends the many interconnected concerns that feature in contemporary privacy questions in marketing. Since internal and external stakeholders are affected in multiple and potentially unforeseen ways by data privacy issues, additional work in this space remains critical and needed.

Purpose To investigate white matter (WM) structural alterations using diffusion tensor imaging (DTI) in obstructive sleep apnea (OSA) patients, with or without residual sleepiness, following adherent continuous positive airway pressure (CPAP) treatment. Possible quantitative relationships were explored between the DTI metrics and two clinical assessments of somnolence. Materials and Methods Twenty-nine male patients (30–55 years old) with a confirmed diagnosis of OSA were recruited. The patients were treated with CPAP therapy only. The Psychomotor Vigilance Task (PVT) and Epworth Sleepiness Scale (ESS) were performed after CPAP treatment and additionally administered at the time of the magnetic resonance imaging (MRI) scan. Based on the PVT results, the patients were divided into a nonsleepy group (lapses ≤5) and a sleepy group (lapses >5). DTI was performed at 3T, followed by an analysis using tract-based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (λ23) between the two groups. Results A higher MD (P 0.17). The alterations in FA or MD of individual fiber tracts occurred mainly in the internal/external capsule, corona radiata, corpus callosum, and sagittal stratum regions. The FA and MD values correlated with the PVT and ESS assessments from all patients (R ≥ 0.517, P < 0.05). Conclusion Global and regional WM alterations, as revealed by DTI, can be a possible mechanism to explain why OSA patients with high levels of CPAP use can have differing responses to treatment. Compromised myelin sheath, indicated by increased radial diffusivity, can be involved in the underlying WM changes. Evidence level: 1 J. MAGN. RESON. IMAGING 2017;45:1371–1378