Search

The introduction of effective human papillomavirus (HPV) vaccination, screening, and treatment programs has led the World Health Organization to call for the global elimination of cervical cancer. Assessing progress toward this goal is supported through monitoring vaccination coverage and its impact. We performed a targeted review to assess the characteristics of HPV-related data systems from seven high-income countries (HICs) that represented varied approaches, including Australia, Canada, France, Italy, Scotland, Sweden, and the United States (US). Included data systems focused on preventive and early detection measures: HPV vaccination and cervical screening programs, as well as HPV-related disease outcomes. Differences were observed in approach to development of data systems, along with variation in geographical scope and methods of data collection. A challenge exists in how to best follow-up the ongoing global-scale elimination efforts in a comprehensive manner. These sources provide a wealth of information regarding the strengths and limitations of, and notable variation among, current data systems used in HICs. This review can inform improvements to existing prevention programs and the implementation of new programs in other countries, and thus support optimization of cervical cancer prevention policy.

Aim: Whole-genome methylation sequencing carries both DNA methylation and structural variant information (single nucleotide variant [SNV]; copy number variant [CNV]); however, limited data is available on the reliability of obtaining this information simultaneously from low-input DNA using various library preparation and sequencing protocols. Methods: A HapMap NA12878 sample was sequenced with three protocols (EM-sequencing, QIA-sequencing and Swift-sequencing) and their performance was compared on CpG methylation measurement and SNV and CNV detection. Results: At low DNA input (10–25 ng), EM-sequencing was superior in almost all metrics except CNV detection where all protocols were similar. EM-sequencing captured the highest number of CpGs and true SNVs. Conclusion: EM-sequencing is suitable to detect methylation, SNVs and CNVs from single sequencing with low-input DNA.

Children exposed to parental opioid use disorder are at an elevated risk of maltreatment. We study whether parents’ access to medication-assisted opioid treatment programs (OTPs) affects the well-being of their children. An administrative decision to lift a moratorium on access to these programs in Indiana created the opportunity for this study. We show that after a county opened an OTP, methadone dispensing increased and emergency department visits related to opioid overdose decreased there, offering evidence of the success of these programs. We also show that the opening of these OTPs did not have significant effects on reports of child maltreatment, but that out-of-home foster care placements were reduced by 22 percent. Our findings are consistent with past research showing that child welfare cases involving parental substance use tend to be complex and tend to have longer times to parent/child reunification than child welfare cases in which substance use is not present. We argue that expanding access to opioid treatment programs may help reduce foster care placements.

Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities; however, data on the economic burden of cCMVi during early childhood are scarce. The primary objective of the study was to describe longitudinal patterns of health care resource utilization (HCRU) and direct medical costs among infants with cCMVi compared to infants unexposed to cCMVi.A retrospective cohort study was performed using data on infants born between 2013 and 2017, as captured in the database of Maccabi Healthcare Services, a 2.5 million-member health care organization in Israel. cCMVi cases were identified by physician diagnosis and/or dispensed valganciclovir within 90 days after birth. Infants born to mothers CMV-seronegative throughout pregnancy were selected for comparison (unexposed controls). Infants were retrospectively followed up through December 31, 2018, or 4 years of age (Y4). HCRU included physician visits, hospital admissions, audiology tests/procedures, imaging, and valganciclovir treatment. Direct medical costs, in US dollars per person per year (USD PPPY) were calculated from the health-system perspective. To compare costs of cCMVi cases and controls, direct medical costs were estimated using a generalized linear model with a log link function and γ distribution after adjustment for patient characteristics.A total of 351 cCMVi cases and 11,733 control infants with continuous follow-up during their first year of life (Y1) were included in the study. In Y1, cases were more likely to have a hospital admission (8.5% cases vs 4.5% control; P0.001) and higher numbers of pediatrician visits (median, 18 vs 15), audiology visits and tests, and cranial ultrasounds (all, P0.05). Longitudinally, incremental costs associated with cases were highest in Y1 (1686.7 USD PPPY; cost ratio = 2.6; P0.001) and remained elevated through Y4.cCMVi was associated with substantial increases in HCRU and economic burden during early childhood, and particularly during the first year of life.

Miniaturized, multicolored light-emitting device arrays are promising for applications in sensing, imaging, computing, and more, but the range of emission colors achievable by a conventional light-emitting diode is limited by material or device constraints. In this work, we demonstrate a highly multicolored light-emitting array with 49 different, individually addressable colors on a single chip. The array consists of pulsed-driven metal-oxide-semiconductor capacitors, which generate electroluminescence from microdispensed materials spanning a diverse range of colors and spectral shapes, enabling facile generation of arbitrary light spectra across a broad wavelength range (400 to 1400 nm). When combined with compressive reconstruction algorithms, these arrays can be used to perform spectroscopic measurements in a compact manner without diffractive optics. As an example, we demonstrate microscale spectral imaging of samples using a multiplexed electroluminescent array in conjunction with a monochrome camera.

Purpose:BRAFV600E mutations are associated with poor clinical prognosis in colorectal cancer (CRC). Although selective BRAF inhibitors are effective for treatment of melanoma, comparable efforts in CRC have been disappointing. Here, we investigated potential mechanisms underlying this resistance to BRAF inhibitors in BRAFV600E CRC.Experimental Design: We examined phosphoinositide 3-kinase (PI3K)/mTOR signaling in BRAFV600E CRC cell lines after BRAF inhibition and cell viability and apoptosis after combined BRAF and PI3K/mTOR inhibition. We assessed the efficacy of in vivo combination treatment using a novel genetically engineered mouse model (GEMM) for BRAFV600E CRC.Results: Western blot analysis revealed sustained PI3K/mTOR signaling upon BRAF inhibition. Our BRAFV600E GEMM presented with sessile serrated adenomas/polyps, as seen in humans. Combination treatment in vivo resulted in induction of apoptosis and tumor regression.Conclusions: We have established a novel GEMM to interrogate BRAFV600E CRC biology and identify more efficacious treatment strategies. Combination BRAF and PI3K/mTOR inhibitor treatment should be explored in clinical trials. Clin Cancer Res; 19(10); 2688–98. ©2013 AACR.

Supplementary Figure 1 PDF file 118K, Development a GEMM for BRAFV600E CRC

Supplementary Figure 2 PDF file 152K, APC tumors do not recapitulate the sessile serrated CRC pathway

Supplementary Figure Legends PDF file 89K, Supplementary Figure Legends for Supplementary Figure 1 and Supplementary Figure 2

Introduction: Latinx and Asian American communities in the U.S. face unique yet similar structural barriers to maintaining adequate diet quality, contributing to an increased burden of diabetes and non-alcoholic fatty liver disease in these groups. These inequities have been exacerbated in recent years due to overt anti-immigrant and anti-Asian sentiment during the COVID-19 pandemic, invoking fear and cultural shame for these groups, and amplifying challenges towards accessing food and economic stability. Hypothesis: Herein we describe a community-centered, multi-level approach aligned with the National Institute of Minority Health and Health Disparities Framework. We hypothesize our study will result in increased fruit and vegetable intake (self-report, measured via skin carotenoids), social cohesion and ethnic pride at the individual level and improved socioeconomic outcomes at the neighborhood level. Methods: Working collaboratively with 8 community-based and farm partners, the goal of the Building Access to Food through Systems and Solidarity (BASIS) Study is to improve diet and economic stability in Sunset Park—a neighborhood of Mexican and Chinese American families in Brooklyn, NY. This neighborhood has been hard-hit during the COVID-19 pandemic and lagged in economic recovery, and its residents are disconnected from government support. BASIS addresses food access, nutrition education, policy change, and hands-on learning (e.g., gardening, cooking) incorporating culturally appropriate values, foods, and taste preferences throughout each of these activities. Results: To date, we have held four group model-building workshops with partners to identify common priorities/goals towards improving nutrition in immigrant communities; co-developed Mexican and Chinese American-specific nutrition education materials; held eight virtual and in-person sessions with community members (n=291); conducted qualitative interviews (n=19) and quantitative data collection (n=175) amongst community residents to inform program development; and implemented a subsidized, community-supported agriculture pilot program for 20 weeks in 2022 (n=38). BASIS resources have been well-received by community members, with high engagement (90% attend weekly produce box pick-up events) and acceptance (100% indicated they would recommend the program to others). Conclusions: Planned evaluation will include mixed methods and administrative data analyses for assessment of multi-level outcomes. BASIS will expand to more participants (n=150), and will include additional program components (e.g., food policy assessment; workforce development; small business owner education). BASIS presents a powerful model to improve diet in immigrant communities applying systems thinking and community-centered best practices, lessons which may be gleaned for other immigrant communities.

Background In the U.S., HIV transmission persists largely through sexual transmission in gender and sexual minorities. Transactional sex (TS) is a known risk factor for HIV transmission, yet risk behaviors and engagement in HIV treatment and other medical services among transgender (TG) individuals who have TS are poorly understood. Methods PATCH is a natural history study of TG individuals in Washington, DC. Participants complete laboratory testing and surveys, including assessment of TS – defined as previous year sex in exchange for drugs, money or shelter. Fisher’s exact test was used for statistical analysis. Results Of 54 participants assigned male at birth (AMAB), 21(39%) endorsed TS, the majority of whom were female (81%), Black (95%), median age 35, and HIV+ (76%; Table 1). Of those with HIV, 12 (75%) were prescribed ART, though only 8 (50%) had HIV VL < 200. The majority of TG people with TS had sex weekly or more (75%), with > 5 partners/year (62%) and used their penis (80%) and anus (90%) during TS. A minority consistently used condoms in receptive anal sex (29%), penetrative anal sex (25%), penetrative vaginal sex (17%), and chem sex (8%). While 95% had ever taken gender affirming hormone therapy (GAHT), 62% were not prescribed GAHT at screening, of whom, 54% were interested in seeing a provider for GAHT. When compared to non-TS participants, TG individuals with TS were more likely to have chem sex (p< 0.01), use drugs daily or more (p=0.04), use amphetamines (p< 0.01) and cocaine (p< 0.01), and less likely to have GAHT prescribed by a provider (p=0.03). HIV+ patients with TS were less likely to have HIV VL< 200 (p=0.02). Table 1:Participant Characteristics and Associations with Transactional Sex Conclusion This cohort of AMAB TG individuals with TS had high rates of viremic HIV, and multiple risk factors for HIV transmission, including frequent condomless sex with multiple partners. Additionally, those with TS were more likely to have high risk drug use, indicating that novel strategies to decrease risk associated with chem sex, particularly stimulant use, should be prioritized. Further, nearly all TG participants with TS had taken GAHT, yet were less likely to get GAHT from a provider. As many had interest in seeing a provider for GAHT, co-locating GAHT with HIV treatment and prevention services could help providers engage this population and address HIV-related risks. Disclosures Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant Sarah Kattakuzhy, MD, Gilead: Grant/Research Support Elana S. Rosenthal, MD, Gilead: Grant/Research Support|Merck: Grant/Research Support.

Background In the United States, HIV is highly prevalent among transgender individuals, but factors contributing to viremia in this population are poorly understood. We aimed to assess factors associated with HIV viremia among transgender people living with HIV (PLWH). Methods PATCH is a longitudinal natural history study of transgender individuals in Washington, DC. Participants complete laboratory assessments, as well as surveys assessing demographics, behaviors, and mental health. Patients whose HIV viral load was >200 copies/mL at screening were considered viremic. Fisher’s exact test was used for statistical analysis. Results Of 62 enrolled participants, 35(56%) were HIV+, the majority of whom were prescribed antiretroviral therapy (31, 89%) and had an undetectable viral load (25, 71%). Of PLWH, 35(100%) were assigned male at birth, 34(97%) were Black, and the median age was 37 years. PLWH were predominately stably housed (24, 69%), with 9(26%) reporting daily drug use or more, and 16(46%) reporting transactional sex within a year. When comparing PLWH who were viremic versus those virally suppressed, viremic PLWH were less likely to be prescribed antiretroviral therapy (60% vs 100%, p=0.004), and more likely to have unstable housing (60% vs 25%, p=0.04), use drugs daily or more in the last month (60% vs 12%, p=0.007), and engage in transactional sex in the last 12 months (80% vs 32%, p=0.02). HIV viral suppression was not significantly associated with number of sexual partners within the last 12 months or always using condoms during any type of sex (p >0.05). Conclusion In this cohort of transgender PLWH, we found moderate rates of HIV viremia associated with chaotic life factors such as daily drug use, unstable housing, and engaging in transactional sex. In addition, we found low rates of consistent condom use despite multiple sexual partners, regardless of viral load. Comprehensive care programs that improve access to ART, address substance use disorders and facilitate housing may serve to improve treatment outcomes and reduce risk of HIV transmission in this population. Disclosures Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support.

The dried roots and rhizomes of

Purpose: To determine the evolution of abdominal aortic aneurysm (AAA) diameter in the presence of persisting type 2 endoleaks (pEL2) following endovascular abdominal aortic aneurysm repair (EVAR). Materials and Methods: This is a retrospective, single-center, case-control study. All patients with pEL2 (pEL2 group, persisting for > 12 months) between 2004 and 2018 were identified and compared with a 1:1 age- and gender-matched control with no endoleak (control group). Primary outcome measures were freedom from AAA expansion and freedom from AAA shrinkage over time. AAA diameter measurements were performed on computed tomography angiography (CTA). Secondary outcome measures were survival, AAA-related mortality, reinterventions for pEL2, incidence of secondary type 1 endoleaks (EL1), and infrarenal aortic branch vessel anatomy. Results: A total of 773 patients were treated with EVAR for AAA between 2004 and 2018. Of them, 286 patients demonstrated type 2 endoleaks (EL2) in postoperative CTA or intraoperative angiography (37%). Forty-five of 286 EL2 (15.7%) were pEL2 (pEL2 group). Freedom from AAA expansion in the pEL2 group was 100%, 96.7%, 85.2%, and 54.3% after 1, 2, 3, and 4 years, respectively, compared with 100% after 1, 2, 3, and 4 years in the control group (pConclusion: pEL2 are associated with AAA expansion during midterm FU. Further studies are warranted to evaluate the association of AAA expansion due to pEL2 with clinical outcomes to allow recommendations with regard to treatment indications.

Pleural mesothelioma (PM) comprises three major histologic types: epithelioid, sarcomatoid, and a mixture of the two types termed biphasic. We and others have investigated whole transcriptome profiles of bulk PM samples, identifying a molecular gradient with features of epithelial-mesenchymal transition, which is related to, but not redundant with, histology. To date bulk studies of heterogeneity across PM tumors have not explained how biphasic tumors contain sarcomatoid (mesenchymal) and epithelioid (epithelial) components. We hypothesized that sarcomatoid and epithelioid components arose from distinct tumor clones. We performed integrated bulk and single-cell RNA-sequencing and pathologic analyses of 93 samples from 39 patients’ surgical resections including 3 negative-control pleura cases with non-PM pathology. Single-cell sequencing analysis was performed using the Seq-Well S3 platform. Tumor clones were identified using inferCNV in R. Copy number and somatic variants were identified in adjacent bulk samples of each PM case with optical genome mapping and exome sequencing, respectively. We generated libraries from 19 epithelioid, 3 sarcomatoid, and 13 biphasic cases resulting in an average of 6,657 single cells per case (n=266,262 total cells; UMIs ≥ 300 & features ≥ 80). Among the 32,383 high quality malignant cells, we characterized epithelioid and sarcomatoid programs independent of non-malignant cells in the microenvironment. We observed malignant cells expressing both programs at low levels, termed uncommitted. Uncommitted cells were not outliers in terms of UMIs detected, genes expressed, or mitochondrial transcript content, and were detected in 96.4% of PM cases with at least 50 high quality tumor cells. Most (72.7%) uncommitted cells were isolated from biphasic tumors. Additionally, we observed that individual tumor clones from biphasic tumors exhibited all three cell phenotypes. In one biphasic tumor, five of six clones comprised cells from all three types, where these clones were well-represented across multiple sites with epithelioid content ranging from 10% to 40%. In conclusion, our integrated analysis of multi-site pleural mesothelioma samples suggests that a single tumor clone may be capable of generating all molecular subtypes. Further work aims to identify candidate drivers of this plasticity, to relate single-cell transcriptomic phenotype to histology and to further characterize uncommitted cells. We will also assess the prognostic implications of uncommitted cells content in a wider cohort. Citation Format: David T. Severson, Samuel Freyaldenhoven, Benjamin Wadowski, Travis Hughes, Yin P. Hung, Roderick V. Jensen, William G. Richards, Corinne E. Gustafson, Kimberly Vermilya, Simona Innocenti, Julianne S. Barlow, Matthew B. Cougar, Jamie Anderson, Vivian Wang, Mary N. Dao, Alex K. Shalek, Assunta De Rienzo, Raphael Bueno. Uncommitted cells and phenotypic plasticity elucidate the complexity of the epithelial-mesenchymal molecular gradient of pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 95.

Coronavirus-19 misinformation poses a unique challenge for public health communication efforts. In rural communities, COVID-19 misinformation is not well studied. We investigate patients' ability to discriminate COVID-19 fact from fiction from their news sources, as well as general COVID-19 knowledge, perceptions, public health practices, and their primary news sources in 258 adult patients at a primary health clinic in rural Michigan. Most of the population surveyed was able to correctly differentiate reliable COVID-19 public health information from fabricated information. However, only 55.4% of participants reported that they would be somewhat or extremely likely to get a COVID-19 vaccine. The most reported news source was mainstream broadcast television channels such as CBS and ABC. Our data support those older participants are better informed and more likely to practice safe public health practices than younger participants. Based on our data, we offer strategies for public health campaigns in rural communities, such as targeted interventions towards younger people and utilizing local television stations and community institutions to disseminate public health communications and health promotions. Public health interventions beyond education should be considered to mitigate the gap between COVID-19 knowledge and prevention behaviors. Future studies should investigate the role of health care providers in COVID-19 communication with patients, understanding hesitations toward COVID-19 vaccination, and communication strategies to best increase COVID-19 vaccine uptake in rural communities.

Human papillomavirus (HPV) infection, which poses significant disease burden, is decreasing following implementation of vaccination programs. Synthesized evidence on HPV vaccine real-world benefit was published in 2016. However, long-term impact of vaccination, and how vaccination programs influence infection rates and disease outcomes, requires further examination. We systematically reviewed observational studies on HPV vaccination within MEDLINE, EMBASE, and Google Scholar from 2016 to 2020, involving 14 years of follow-up data. We identified 138 peer-reviewed publications reporting HPV vaccine impact or effectiveness. Outcomes of interest included rates of infection at different anatomical sites and incidence of several HPV-related disease endpoints. The expansion of HPV vaccination programs worldwide has led to a reduction in genital infection and significant decreases in incidence of HPV-related disease outcomes. Therefore, the WHO has set goals for the elimination of cervical cancer as a public health concern. To track progress toward this requires an understanding of the effectiveness of different vaccination initiatives. However, the impact on males, and potential benefit of gender-neutral vaccination programs have not been fully explored. To present an accurate commentary on the current outlook of vaccination and to help shape policy therefore requires a systematic review of available data.

One's personal physician, national and state or local public health officials, and the broader medical profession play important roles in encouraging vaccine uptake for COVID-19. However, the relationship between trust in these experts and vaccine hesitancy has been underexplored, particularly among racial/minority groups where historic medical mistrust may reduce uptake. Using an April 2021 online sample of US adults (n = 3041) that explored vaccine hesitancy, regression models estimate levels of trust in each of these types of experts and between trust in each of these experts and the odds of being COVID-19 vaccine takers vs refusers or hesitaters. Interaction terms assess how levels of trust in the medical profession by race/ethnicity are associated with vaccine hesitancy. Trust in each expert is positively associated with trust in other experts, except for trust in the medical profession. Only trust in one's own doctor was associated with trust in the medical profession, as measured by factor scores derived from a validated scale. Lower levels of trust in experts were significantly associated with being either a hesitater or a refuser compared to being a taker. Black respondents had higher odds of being either a hesitater or a refuser compared to white respondents but the interaction with trust was insignificant. For Hispanic respondents only, the odds of being a hesitater declined significantly when trust in the medical profession rose. Mistrust in the medical profession, one's doctor and national experts contributes to vaccine hesitancy. Mobilizing personal physicians to speak to their own patients may help.