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Western Honduras Copán Population–Based Cancer Registry: Initial Estimates and a Model for Rural Central America
(American Society of Clinical Oncology, 2021) Norwood, Dalton Argean; Montalvan-Sanchez, Eleazar Enrique; Corral, Juan E.; Estévez-Ordoñez, Dagoberto; Paredes, Andrea A.; Domínguez, Lucia B.; Rodríguez, Aida A.; Bravo, Luis E.; Morgan, Douglas R.; Domínguez, Ricardo L.; Medicine, School of Medicine
Purpose: Population-based cancer registries (PBCRs) are critical for national cancer control planning, yet few low- and middle-income countries (LMICs) have quality PBCRs. The Central America Four region represents the principal LMIC region in the Western hemisphere. We describe the establishment of a PBCR in rural Western Honduras with first estimates for the 2013-2017 period.
Methods: The Western Honduras PBCR was established through a collaboration of academic institutions and the Honduras Ministry of Health for collection of incident cancer data from public and private health services. Data were recorded using the Research Electronic Data Capture (REDCap) web-based platform with data monitoring and quality checks. Crude and age-standardized rates (ASRs) were calculated at the regional level, following WHO methodology.
Results: The web-based platform for data collection, available ancillary data services (eg, endoscopy), and technical support from international centers (United States and Colombia) were instrumental for quality control. Crude cancer incidence rates were 112.2, 69.8, and 154.6 per 100,000 habitants overall, males, and females, respectively (excluding nonmelanoma skin cancer). The adjusted ASRs were 84.2, 49.6, and 118.9 per 100,000 overall habitants, males, and females, respectively. The most common sites among men were stomach (ASR 26.0, 52.4%), colorectal (ASR 5.11, 10.15%), and prostate (ASR 2.7, 5.4%). The most common sites in women were cervix (ASR 34.2, 36.7%), breast (ASR 11.2, 12.3%), and stomach (ASR 10.8, 11.7%).
Conclusion: The Copán-PBCR represents a successful model to develop cancer monitoring in rural LMICs. Innovations included the use of the REDCap platform and leverage of Health Ministry resources. This provides the first PBCR data for Honduras and the Central America Four and confirms that infection-driven cancers, such as gastric and cervical, should be priority targets for cancer control initiatives.
γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans
(Public Library of Science, 2021-12-06) Chu, Timothy H.; Khairallah, Camille; Shieh, Jason; Cho, Rhea; Qiu, Zhijuan; Zhang, Yue; Eskiocak, Onur; Thanassi, David G.; Kaplan, Mark H.; Beyaz, Semir; Yang, Vincent W.; Bliska, James B.; Sheridan, Brian S.; Microbiology and Immunology, School of Medicine
Yersinia pseudotuberculosis is a foodborne pathogen that subverts immune function by translocation of Yersinia outer protein (Yop) effectors into host cells. As adaptive γδ T cells protect the intestinal mucosa from pathogen invasion, we assessed whether Y. pseudotuberculosis subverts these cells in mice and humans. Tracking Yop translocation revealed that the preferential delivery of Yop effectors directly into murine Vγ4 and human Vδ2+ T cells inhibited anti-microbial IFNγ production. Subversion was mediated by the adhesin YadA, injectisome component YopB, and translocated YopJ effector. A broad anti-pathogen gene signature and STAT4 phosphorylation levels were inhibited by translocated YopJ. Thus, Y. pseudotuberculosis attachment and translocation of YopJ directly into adaptive γδ T cells is a major mechanism of immune subversion in mice and humans. This study uncovered a conserved Y. pseudotuberculosis pathway that subverts adaptive γδ T cell function to promote pathogenicity.
Correction: γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans
(Public Library of Science, 2022-05-25) Chu, Timothy H.; Khairallah, Camille; Shieh, Jason; Cho, Rhea; Qiu, Zhijuan; Zhang, Yue; Eskiocak, Onur; Thanassi, David G.; Kaplan, Mark H.; Beyaz, Semir; Yang, Vincent W.; Bliska, James B.; Sheridan, Brian S.; Microbiology and Immunology, School of Medicine
This corrects the article "γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans" in volume 17, e1010103.
Special Section on Inclusive Digital Health: Notable Papers on Addressing Bias, Equity, and Literacy to Strengthen Health Systems
(Thieme, 2022-12-04) Dixon, Brian E.; Holmes, John H.; Epidemiology, Richard M. Fairbanks School of Public Health
Objective: To summarize significant research contributions on addressing bias, equity, and literacy in health delivery systems published in 2021.
Methods: An extensive search using PubMed and Scopus was conducted to identify peer-reviewed articles published in 2021 that examined ways that informatics methods, approaches, and tools could address bias, equity, and literacy in health systems and care delivery processes. The selection process comprised three steps: (1) 15 candidate best papers were first selected by the two section editors; (2) external reviewers from internationally renowned research teams reviewed each candidate best paper; and (3) the final selection of three best papers was conducted by the editorial committee of the Yearbook.
Results: Selected best papers represent studies that characterized significant challenges facing biomedical informatics with respect to equity and practices that support equity and literacy in the design of health information systems. Selected papers represent the full spectrum of this year’s yearbook theme. In general, papers identified in the search fell into one of the following categories: (1) descriptive accounts of algorithmic bias in medical software or machine learning approaches; (2) enabling health information systems to appropriately encode for gender identity and sex; (3) approaches to support health literacy among individuals who interact with information systems and mobile applications; and (4) approaches to engage diverse populations in the use of health information systems and the biomedical informatics workforce
Conclusions: Although the selected papers are notable, our collective efforts as a biomedical informatics community to address equity, literacy, and bias remain nascent. More work is needed to ensure health information systems are just in their use of advanced computing approaches and all persons have equal access to health care and informatics tools.
Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels
(Springer, 2022-12-27) Murray, Melissa E.; Moloney, Christina M.; Kouri, Naomi; Syrjanen, Jeremy A.; Matchett, Billie J.; Rothberg, Darren M.; Tranovich, Jessica F.; Hicks Sirmans, Tiffany N.; Wiste, Heather J.; Boon, Baayla D. C.; Nguyen, Aivi T.; Reichard, R. Ross; Dickson, Dennis W.; Lowe, Val J.; Dage, Jeffrey L.; Petersen, Ronald C.; Jack, Clifford R., Jr.; Knopman , David S.; Vemuri, Prashanthi; Graff-Radford, Jonathan; Mielke, Michelle M.; Neurology, School of Medicine
Background
Advances in ultrasensitive detection of phosphorylated tau (p-tau) in plasma has enabled the use of blood tests to measure Alzheimer’s disease (AD) biomarker changes. Examination of postmortem brains of participants with antemortem plasma p-tau levels remains critical to understanding comorbid and AD-specific contribution to these biomarker changes.
Methods
We analyzed 35 population-based Mayo Clinic Study of Aging participants with plasma p-tau at threonine 181 and threonine 217 (p-tau181, p-tau217) available within 3 years of death. Autopsied participants included cognitively unimpaired, mild cognitive impairment, AD dementia, and non-AD neurodegenerative disorders. Global neuropathologic scales of tau, amyloid-β, TDP-43, and cerebrovascular disease were examined. Regional digital pathology measures of tau (phosphorylated threonine 181 and 217 [pT181, pT217]) and amyloid-β (6F/3D) were quantified in hippocampus and parietal cortex. Neurotransmitter hubs reported to influence development of tangles (nucleus basalis of Meynert) and amyloid-β plaques (locus coeruleus) were evaluated.
Results
The strongest regional associations were with parietal cortex for tau burden (p-tau181 R = 0.55, p = 0.003; p-tau217 R = 0.66, p < 0.001) and amyloid-β burden (p-tau181 R = 0.59, p < 0.001; p-tau217 R = 0.71, p < 0.001). Linear regression analysis of global neuropathologic scales explained 31% of variability in plasma p-tau181 (Adj. R2 = 0.31) and 59% in plasma p-tau217 (Adj. R2 = 0.59). Neither TDP-43 nor cerebrovascular disease global scales independently contributed to variability. Global scales of tau pathology (β-coefficient = 0.060, p = 0.016) and amyloid-β pathology (β-coefficient = 0.080, p < 0.001) independently predicted plasma p-tau217 when modeled together with co-pathologies, but only amyloid-β (β-coefficient = 0.33, p = 0.021) significantly predicted plasma p-tau181. While nucleus basalis of Meynert neuron count/mm2 was not associated with plasma p-tau levels, a lower locus coeruleus neuron count/mm2 was associated with higher plasma p-tau181 (R = -0.50, p = 0.007) and higher plasma p-tau217 (R = -0.55, p = 0.002). Cognitive scores (Adj. R2 = 0.25–0.32) were predicted by the global tau scale, but not by the global amyloid-β scale or plasma p-tau when modeled simultaneously.
Conclusions
Higher soluble plasma p-tau levels may be the result of an intersection between insoluble deposits of amyloid-β and tau accumulation in brain, and may be associated with locus coeruleus degeneration.