Digital Commons Network^™

Dna Methylation-Derived Immune Cell Proportions And Cancer Risk In Black Participants, Christopher S Semancik, Naisi Zhao, Devin C Koestler, Eric Boerwinkle, Jan Bressler, Rachel J Buchsbaum, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities Study. During a mean of 17.5 years of follow-up, 668 incident cancers were diagnosed in 2,467 Black participants. Cox proportional hazards regression was used to examine immune cell subtype proportions and overall cancer incidence and site-specific incidence (lung, breast, and …

Contemporary Epidemiology Of Hepatocellular Carcinoma: Understanding Risk Factors And Surveillance Strategies, Fouad Jaber, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The contemporary epidemiology of hepatocellular carcinoma (HCC) shows a shift in the main etiological risk factors from less common but highly virulent (eg, hepatitis C and B) to more common but weak risk factors (eg, alcohol and metabolic syndrome). Therefore, we are in a seemingly paradoxical state of declining overall incidence rates of HCC-related to improved prevention and treatment of viral hepatitis but burgeoning number of people at an elevated risk of HCC. Several geographic regions have reported an increase in HCC attributable to alcoholic liver disease and metabolic dysfunction associated with steatotic liver disease (MASLD). The importance of risk …

Return To Eden: God’S Design For Human Sexuality In The Song Of Songs, Richard M. Davidson

Faculty Publications

No abstract provided.

Healthy From The Start: Co-Designing Sleep, Nutrition And Physical Activity Resources For Young Shiftworkers—Novel Implementation And Evaluation, Alexandra E. Shriane, Sally A. Ferguson, Gabrielle Rigney, Charlotte C. Gupta, Tracy Kolbe-Alexander, Madeline Sprajcer, Cassie Hilditch, Robert Stanton, Matthew J.W. Thomas, Jessica L. Paterson, Jamie Marino, Grace E. Vincent

Faculty Research, Scholarly, and Creative Activity

Introduction: The increasing prevalence of shiftwork among young adults poses significant health risks, primarily due to its disruptive effects on sleep, nutrition and physical activity. Addressing these risks necessitates the development of tailored, evidence-based resources to support these key health behaviours. Participatory research approaches, engaging those with relevant lived experience (i.e., co-design) are a novel and effective approach in developing these resources. As such, the aim of the present study was to explore whether sleep, nutrition and physical activity resources for young shiftworkers could be developed using participatory, co-design approaches and how co-designers would rate both the approaches used and …

Structural Basis For Adhesin Secretion By The Outer-Membrane Usher In Type 1 Pili, Ryan M Bitter, Maxwell I Zimmerman, Brock T Summers, Jerome S Pinkner, Karen W Dodson, Scott J Hultgren, Peng Yuan

2020-Current year OA Pubs

Gram-negative bacteria produce chaperone-usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Early Detection Of Malignant And Premalignant Peripheral Nerve Tumors Using Cell-Free Dna Fragmentomics, R Taylor Sundby, Paul A Jones, Divya Srihari, Amy E Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, John S A Chrisinger, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.

EXPERIMENTAL DESIGN: cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: …

Adherence To Hygiene Protocols And Doxycycline Therapy In Ameliorating Lymphatic Filariasis Morbidity In An Endemic Area Post-Interruption Of Disease Transmission In Ghana, Linda Batsa Debrah, Philip J Budge, Et Al.

2020-Current year OA Pubs

Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018-2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1-3 from two districts in the Upper East Region of Ghana. In addition to regular …

A Retrospective Assessment Of Guideline Adherence And Treatment Outcomes From Clostridioides Difficile Infection Following The Idsa 2021 Clinical Guideline Update: Clostridioides Difficile Infection, Erik R Dubberke, Qinghua Li, Engels N Obi, Vladimir Turzhitsky, Fakhar Siddiqui, Brian H Nathanson

2020-Current year OA Pubs

BACKGROUND: The 2021 update to the Infectious Diseases Society of America

METHODS: This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections.

RESULTS: A total of …

Sequential Early-Life Viral Infections Modulate The Microbiota And Adaptive Immune Responses To Systemic And Mucosal Vaccination, Yuhao Li, Jerome M. Molleston, Crystal Lovato, Jasmine Wright, Isabel Erickson, Duyen Bui, Andrew H. Kim, Harshad Ingle, Somya Aggarwal, Lila S Nolan, Ahmed O. Hassan, Lynne Foster, Michael S. Diamond, Megan T. Baldridge

2020-Current year OA Pubs

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, …

Body Mass Index And Postacute Sequelae Of Sars-Cov-2 Infection In Children And Young Adults, Ting Zhou, Chongliang Luo, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Obesity is associated with increased severity of COVID-19. Whether obesity is associated with an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among pediatric populations, independent of its association with acute infection severity, is unclear.

OBJECTIVE: To quantify the association of body mass index (BMI) status before SARS-CoV-2 infection with pediatric PASC risk, controlling for acute infection severity.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study occurred at 26 US children's hospitals from March 2020 to May 2023 with a minimum follow-up of 179 days. Eligible participants included children and young adults aged 5 to 20 years with …

Dominantly Inherited Muscle Disorders: Understanding Their Complexity And Exploring Therapeutic Approaches, Andrew R Findlay

2020-Current year OA Pubs

Treatments for disabling and life-threatening hereditary muscle disorders are finally close to becoming a reality. Research has thus far focused primarily on recessive forms of muscle disease. The gene replacement strategies that are commonly employed for recessive, loss-of-function disorders are not readily translatable to most dominant myopathies owing to the presence of a normal chromosome in each nucleus, hindering the development of novel treatments for these dominant disorders. This is largely due to their complex, heterogeneous disease mechanisms that require unique therapeutic approaches. However, as viral and RNA interference-based therapies enter clinical use, key tools are now in place to …

Network-Level Enrichment Provides A Framework For Biological Interpretation Of Machine Learning Results, Jiaqi Li, Ari Segel, Xinyang Feng, Jiaxin Cindy Tu, Andy Eck, Kelsey T King, Babatunde Adeyemo, Nicole R Karcher, Likai Chen, Adam T Eggebrecht, Muriah D Wheelock

2020-Current year OA Pubs

Machine learning algorithms are increasingly being utilized to identify brain connectivity biomarkers linked to behavioral and clinical outcomes. However, research often prioritizes prediction accuracy at the expense of biological interpretability, and inconsistent implementation of ML methods may hinder model accuracy. To address this, our paper introduces a network-level enrichment approach, which integrates brain system organization in the context of connectome-wide statistical analysis to reveal network-level links between brain connectivity and behavior. To demonstrate the efficacy of this approach, we used linear support vector regression (LSVR) models to examine the relationship between resting-state functional connectivity networks and chronological age. We compared …

Postprostatectomy Radiotherapy Timing And Long-Term Health-Related Quality Of Life, Sagar A Patel, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The association between radiotherapy (RT) timing after radical prostatectomy and long-term patient-reported health-related quality of life (HRQOL) in men with prostate cancer is unknown.

OBJECTIVE: To measure long-term HRQOL in men with prostate cancer up to 15 years after prostatectomy with or without RT and examine whether early vs late postprostatectomy RT is associated with differences in sexual, urinary, and bowel HRQOL.

DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, longitudinal cohort analysis using HRQOL data from the PROST-QA (2003-2006) and RP2 consortium (2010-2013) studies was conducted. Men with localized prostate cancer undergoing radical prostatectomy were included. Data were analyzed …

Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province

2020-Current year OA Pubs

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genome-wide association study (GWAS) p-values in 4182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of …

Htlv-1 Infected T Cells Cause Bone Loss Via Small Extracellular Vesicles, Nitin Kumar Pokhrel, Haniya Habib, Shamreethaa Seeniraj, Ancy Joseph, Daniel Rauch, Linda Cox, Robert Sprung, Petra Erdmann Gilmore, Qiang Zhang, Robert Reid Townsend, Lee Ratner, Katherine N Weilbaecher, Deborah J Veis, Et Al.

2020-Current year OA Pubs

Adult T cell leukaemia (ATL), caused by infection with human T- lymphotropic virus type 1 (HTLV-1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient-derived ATL cells (ATL-PDX) and HTLV-1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow-replacing ATL-PDX, despite the fact that few HTLV/T cells persisted in the bone. To study the direct effect of HTLV/T and ATL-PDX on osteoclasts, supernatants were added to murine and human osteoclast …

A Quadriocellar Hedychridium Caeruleum (Hymenoptera: Chrysididae) From Manitoba, Canada, Kira Peters, Jason Gibbs

The Great Lakes Entomologist

A specimen of Hedychridium caeruleum (Norton) with four ocelli was discovered in Manitoba, Canada. The supernumerary ocellus is located to the right of the ocellar triangle, which otherwise appears normal. This is the first report of an ocellar or ocular teratology within Chrysididae, adding to the small body of literature currently available on supernumerary ocelli within Hymenoptera. This is the first published record of H. caeruleum in Canada.

New Records Of Two Adventive Bee Species In Indiana (Hymenoptera: Colletidae; Megachilidae), Hannah G. Kernen, Robert P. Jean, Brock A. Harpur, Jacob Buck, Jennifer Noseworthy

The Great Lakes Entomologist

Here we report the first records of Pseudoanthidium nanum (Mocsáry) (Hymenoptera: Megachilidae) and Hylaeus hyalinatus Smith (Hymenoptera: Colletidae) for the state of Indiana. P. nanum was first detected in Gary, Lake County during August, 2023, and multiple specimens of H. hyalinatus were collected from 2021 to 2023 in Marion, Grant County. These records fill gaps in the Midwestern ranges of both species.

Confirmation Of Avian Dispersal Of A Seed Chalcid Wasp In North America And A New Host Record For Megastigmus Aculeatus (Hymenoptera: Megastigmidae), Julie A. Craves

The Great Lakes Entomologist

Dispersal of chalcid wasp larvae inhabiting the seeds of angiosperms by wild birds in North America has never been verified. I describe adult Megastigmus aculeatus Swederus that successfully emerged from seeds extracted from the droppings of six species of native North American non-captive birds. Rosa setigera is also confirmed as a host for this wasp for the first time.

Laboratory Rearing Methods For The Soybean Tentiform Leafminer (Lepidoptera: Gracillariidae), A New Pest Of Soybean, James Menger, Arthur Ribeiro, Fabio Fuhr, Robert L. Koch

The Great Lakes Entomologist

Soybean tentiform leafminer (STL), Macrosaccus morrisella (Fitch) (Lepidoptera: Gracillariidae), is a leaf-mining microlepidopteran native to North America that was recently discovered feeding on soybean, Glycine max (L.) Merr., in Canada and the United States. A laboratory rearing system for STL was developed on live soybean plants. The methods for continuous rearing or cyclic (i.e., generational) production of insects are described herein. All rearing was performed in a walk-in environmental chamber at 25°C (±2°C), with ~70% relative humidity and a photoperiod of 16:8 (L:D). Adults of STL were allowed to oviposit on clean soybean plants in an oviposition cage. Soybean plants …

Ambrosia Beetle (Coleoptera: Curculionidae: Scolytinae) Responses To Ice Storm Damage In Mesic, Mixed Deciduous Forests In Southeast Ohio, United States, Christopher J. Hayes, Richard M. Turcotte

The Great Lakes Entomologist

In the eastern United States abiotic forest disturbances are common and cause extensive tree damage. Freshly broken trees and tree branches attract bark and ambrosia beetles that utilize inner bark and xylem of damaged branches and trees to fill requisite habitat needs. An ice storm in February 2003 on the Wayne National Forest presented an opportunity to study the local ambrosia beetle species and their reaction to this storm event. Ethanol baited Lindgren traps were deployed from 2003-2006 starting in the summer after the storm. Eight native and introduced Scolytinae ambrosia beetle species were trapped in large numbers (>500 …

Impact Of Debarking And Bark Grinding On Survival Of Ips Calligraphus (Coleoptera: Curculionidae: Scolytinae), Robert A. Haack, Toby Petrice, John Foltz, Hui Ye

The Great Lakes Entomologist

Chipping and debarking of infested woody material such as branches and logs are common sanitation methods used to kill bark- and wood-infesting insects. The sixspined ips, Ips calligraphus (Germar), is a native North American bark beetle (Coleoptera: Curculionidae: Scolytinae) that infests several pine (Pinus) species. We evaluated I. calligraphus mortality after debarking and grinding, using 12 recently cut longleaf pine (Pinus palustris Mill.) logs that had undergone natural colonization for three weeks in Florida. Initial bark beetle densities were estimated from samples collected the day before debarking. Similar amounts of bark were collected at three steps in …

Phenology And Host Choice Among Common Yet Little Understood Wood Borers (Coleoptera: Bostrichidae) In A Midwestern Savanna, Noah I. Finney, Derek W. Rosenberger

The Great Lakes Entomologist

Horned powder-post beetles (Coleoptera: Bostrichidae) are a geographically widespread family of wood-boring beetles. While members of this family represent important grain pests, are often intercepted in ports, and may play an important role in ecosystem processes, little work has investigated bostrichid life history in their native ranges. This gap limits our ability to assess ecosystem services and invasiveness. Three native species, Amphicerus bicaudatus (Say), Scobicia bidentata (Horn), and Xylobiops basilaris (Say), are commonly found in savannas in Northern Illinois. Although little is currently known about the life history of S. bidentata, A. bicaudatus and X. basilaris can be minor pests …

Changes In Ground Beetle (Coleoptera: Carabidae) Species Assemblages After Removal Of Red Pine (Pinus Resinosa) Overstory On Dry Sand Prairie Sites In Michigan, Robert A. Haack, Toby Petrice, Robert L. Davidson, Robert E. Acciavatti

The Great Lakes Entomologist

Ground beetle (Coleoptera: Carabidae) species assemblages were studied at sites on the Huron-Manistee National Forests in Newaygo County, Michigan. The goal was to monitor changes in carabid diversity on areas where mature red pine (Pinus resinosa Sol. ex Aiton) was removed during the 1996-1997 winter and compare with carabid diversity at nearby natural dry sand prairie sites, natural oak-pine barrens, and uncut red pine stands. The red pine had been planted on dry sand prairie sites during 1940-1950. Sampling with pitfall traps occurred during May-August in both 1996 and 1997, but only July-August in 1999. Overall, 16,259 carabid specimens …

Tgle Vol. 57 Nos. 1 & 2 Cover Pages

The Great Lakes Entomologist

TGLE Vol. 57 Nos. 1 & 2 Cover Pages

Effectiveness Of A Fast- Vs. Slow-Velocity Training On Load-Velocity Characteristics In Older Adults: A Pilot Study, Blake Murphy, Kelley Hammond, Leland Barker, Mae Grahek, Mikayla Grocki, Jake A. Siedlik, Mitchel Magrini

International Journal of Exercise Science

Resistance training at fast velocities is suggested to be more effective for improving muscular strength and movement speed compared slow, heavy training. This study aimed to examine the effects of a fast-velocity (FVRT) compared to a slow-velocity (SVRT) resistance training program on maximal strength, maximal movement speed, and load-velocity characteristics in older adults. Nineteen community-dwelling older adults were randomly assigned to either the FVRT or SVRT group and completed a twice weekly, progressive resistance training protocol for 8-weeks. Both groups were instructed to move the weight “as fast as possible” and received movement velocity biofeedback. Absolute (1RM_ABS) and …

Diagnostic Overshadowing: A Delayed Diagnosis Of Autism Spectrum Disorder In A Deaf Child, Quynh-Chi Dang, Michael Hoffman, Rachel St. John

Journal of Early Hearing Detection and Intervention

Diagnostic overshadowing occurs when a patient with a pre-existing diagnosis presents with symptoms that are attributed to the diagnosis, but actually reflect a separate issue. This diagnostic overshadowing can lead to delays in diagnosis, as well as disparities in health care and outcomes. The following case will provide an example in which diagnostic overshadowing contributed to the delay of an autism diagnosis in a child who is deaf. With at least 40 to 50% of children who are deaf or hard of hearing having at least one co-existing medical/developmental condition, and the current prevalence of autism at 1 in 36 …

Utopian Genderscapes, Michelle C. Smith

Rhetoric

No abstract provided.

Intrinsic And Environmental Drivers Of Pairwise Cohesion In Wild Canis Social Groups, John F. Benson

School of Natural Resources: Faculty Publications

Animals within social groups respond to costs and benefits of sociality by adjusting the proportion of time they spend in close proximity to other individuals in the group (cohesion). Variation in cohesion between individuals, in turn, shapes important group-level processes such as subgroup formation and fission–fusion dynamics. Although critical to animal sociality, a comprehensive understanding of the factors influencing cohesion remains a gap in our knowledge of cooperative behavior in animals. We tracked 574 individuals from six species within the genus Canis in 15 countries on four continents with GPS telemetry to estimate the time that pairs of individuals within …

Dynamic Localization Of Endoplasmic Reticulum During Tetrahymena Conjugation, Guerrier Sabrice, Michael Patterson, Kaitlin Crofton, Michael Tucker, Shyhiem Walker

Faculty Publications

Changes in lipid composition at membrane fusion sites in mating Tetrahymena are thought to involve the endoplasmic reticulum (ER), but its localization to these sites has not been observed. Here we show ER distribution during Tetrahymena mating using TtRET1-GFP and GFP-KDEL. We find that both markers localize to perinuclear membranes and tubular structures that connect perinuclear membrane to plasma membrane at fusion sites. Interestingly, both markers disappear from parental macronuclei after emergence of zygotic macronuclei. These similarities in localization of established ER marker, GFP-KDEL, and TtRET1-GFP reveal TtRET1-GFP as a useful new live cell marker for the ER in Tetrahymena.