Digital Commons Network^™

Vitamin B6 Predicts Poor Outcomes In Geographically Distinct Populations With Primary Sclerosing Cholangitis, Peder R Braadland, Ahmad H Ali, Philip Puchas, Brian D Juran, Elizabeth J Atkinson, Erik M Schlicht, Jackie K Bianchi, Bryan M Mccauley, Sara K V Tjønnfjord, Hólmfríður Helgadottir, Per M Ueland, Arve Ulvik, Peter Sauer, Trine Folseraas, Tom H Karlsen, Mette Vesterhus, Michael T Dill, Konstantinos N Lazaridis, Johannes R Hov

Faculty, Staff and Students Publications

Background & aims: Primary sclerosing cholangitis (PSC) has a variable disease course, complicating patient counseling and the timing of liver transplantation. Vitamin B6 deficiency predicts reduced liver transplantation-free survival in Scandinavian PSC cohorts. Here, we aimed to validate this observation in US and German PSC cohorts and to expand our analyses to include hepatic decompensation as a clinical outcome.

Methods: Serum active vitamin B6 (pyridoxal 5'-phosphate [PLP]) was analyzed using liquid chromatography-tandem mass spectrometry in retrospective cohorts of people with PSC from Norway (n = 315), the USA (n = 756), and Germany (n = 149). Cox proportional hazards and …

Long-Term Outcomes In Seronegative Rheumatoid Arthritis, Bradly A Kimbrough, Roslin Jose George, Cynthia S Crowson, Sara J Achenbach, Elizabeth J Atkinson, Vanessa L Kronzer, John M Davis, Elena Myasoedova

Faculty, Staff and Students Publications

Objective: The purpose of this study was to determine the cumulative incidence of diagnosis switching, drug-free remission, and initiation of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in individuals with seronegative rheumatoid arthritis (RA).

Methods: Adult residents of Olmsted County, Minnesota, with incident seronegative (rheumatoid factor negative/anti-cyclic citrullinated peptide antibody negative) RA meeting the 1987 and/or 2010 American College of Rheumatology classification criteria were included. Data were collected from January 1, 2005, to December 31, 2023, through manual chart review. Drug-free remission was defined as a period of at least six months where the individual was no longer …

Colocalization Of Eqtls With Type 2 Diabetes And Glycemic Traits Using Whole-Genome Sequences In Diverse Populations From The Nhlbi Trans-Omics In Precision Medicine (Topmed) Program, Ningyuan Wang, Daniel A Dicorpo, Yixin Zhang, Erica Kleinbrink, Donna K Arnett, John Barnard, John Blangero, Donald W Bowden, April P Carson, Yii-Der Ida Chen, Mina K Chung, Joanne E Curran, Dawood Darbar, Ravindranath Duggirala, Patrick T Ellinor, Diane Fatkin, Myriam Fornage, Nancy Heard-Costa, Jiang He, Lifang Hou, Sharon L R Kardia, Charles Kooperberg, Ruth J F Loos, David D Mcmanus, Braxton D Mitchell, Ryan L Minster, Kari E North, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Dan Roden, Jerome I Rotter, Moore B Shoemaker, Jonathan D Smith, David R Van Wagoner, Francois Aguet, Kristin Ardlie, Joshua C Bis, Jennifer A Brody, Brian E Cade, Clary B Clish, Paul S De Vries, James S Floyd, Barry I Freedman, Stacey Gabriel, Robert E Gerzsten, Mark O Goodarzi, Charles Gu, Xiuqing Guo, Namrata Gupta, Susan R Heckbert, Sarah Hsu, Yi-Jen Hung, Rita R Kalyani, Tanika N Kelly, Gregory L Kinney, Changwei Li, Simin Liu, Yongmei Liu, Donald M Lloyd-Jones, Joann E Manson, Rasika A Mathias, Josep M Mercader, Alanna C Morrison, Take Naseri, Suna Onengut, Nicholette D Palmer, Patricia A Peyser, Qibin Qi, Sridharan Raghavan, Alex P Reiner, Mary R Rooney, Magdalena Sevilla-Gonzalez, Chloe Sarnowski, Joshua D Smith, Jennifer A Smith, Nicole L Spartano, Usman Tahir, Kent D Taylor, Deirdre K Tobias, Russel P Tracy, Satupa'itea Viali, Heming Wang, Alexis C Wood, Lisa R Yanek, Wei Zhao, Yinan Zheng, Josée Dupuis, Ching-Ti Liu, Robert Sladek, Jennifer Wessel, James B Meigs, Alisa K Manning, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium

Faculty, Staff and Students Publications

Large-scale multiancestry genome-wide association studies have identified hundreds of loci associated with type 2 diabetes (T2D) and glycemic traits, yet imputed genotyping arrays limit the detection of low-frequency and rare variants. Whole-genome sequencing (WGS) offers a more complete view of genetic variation, especially across diverse populations. We analyzed high-coverage (38×) WGS data from 21,913 T2D case subjects, 61,036 control subjects, and up to 50,011 individuals with no diabetes with fasting glucose, fasting insulin, and HbA1c from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Program. We performed single-variant association testing, conditional analysis, fine-mapping, and Bayesian colocalization to …

Proteomic Signatures Of 3-Year Progression From Impaired Fasting Glucose To Diabetes: The Atherosclerosis Risk In Communities (Aric) Study, Mary R Rooney, Justin B Echouffo Tcheugui, Jingsha Chen, Keenan A Walker, Christie M Ballantyne, Eric Boerwinkle, Tanika N Kelly, Chiadi E Ndumele, James S Pankow, Morgan E Grams, Wendy S Post, Peter J Ganz, Alexis C Wood, Jerome I Rotter, Elizabeth Selvin, Josef Coresh

Faculty, Staff and Students Publications

Objective: To identify proteomic signatures underlying 3-year progression from impaired fasting glucose (IFG) to diabetes.

Research design and methods: We examined IFG progression in the Atherosclerosis Risk in Communities (ARIC) study from visit 2 (1990-1992) to visit 3 (1993-1995). We tested associations of 4,955 plasma proteins (SomaScan version 4.0) with ∼3-year progression from IFG (FG 100-125 mg/dL without diabetes) to diabetes (diagnosis, medication, or FG ≥126 mg/dL) using logistic regression models adjusted for demographics, cardiometabolic risk factors, and baseline glucose with Bonferroni correction (P < 10-5). We explored biological pathways enriched among the top proteins and calculated improvements in prediction (ΔAUC and net reclassification using 3-year risk thresholds of 6% and 15% in 80% training and 20% internal validation subsamples). We validated results in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.

Results: There were 3,786 ARIC participants with IFG (mean [SD] age 57 [6] years, 52% female, …

Fuimos Olvidados Y Descuidados [Forgotten And Neglected]: Lessons Learned And Findings From On-Farm Covid-19 Education And Vaccine Clinics For Agricultural Workers And Their Multigenerational Families In Texas, Anabel Rodriguez, David I Douphrate, Ana L Pineda Reyes, Susana Zavala, Lus Chavez, Sofia Nicole Lopez, Andrea V Cabrera Cruz, Annie J Keeney, Nora Hernandez, Brenda Berumen-Flucker, Eva M Shipp, Matthew W Nonnenmann, Shannon P Guillot-Wright, Bethany Boggess Alcauter, G Lopez Ixta, Paula M Cuccaro, Higinio Fernandez-Sanchez, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

Background: Despite being deemed essential non-healthcare workers, agricultural workers were excluded from COVID-19 vaccine prioritization in Texas. This professional practice report describes the multifaceted worker health and safety approaches to protecting agricultural workers and their families during the COVID-19 pandemic.

Methods: Between March 2020 and January 2025, several outreach, education, and training grants from various funding agencies were leveraged to deliver training, personal protective equipment, vaccines, and economic relief to agricultural workers in partnership with community-based organizations, industry, local public health departments, and academic institutions.

Findings: Timely funding efforts led to the distribution of 1,000 PPE kits, with more than …

Leveraging Administrative Health Data To Capture Rare Adverse Drug Reactions: Identifying Pediatric Patients With Trimethoprim-Sulfamethoxazole Acute Respiratory Distress Syndrome., Keith Feldman, Jenna Miller, Katherine Doane, Laura Loftis, James W. Antoon, Kevin J. Downes, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

Rare adverse drug reactions (ADRs) are underrecognized and underreported in the electronic medical record (EMR). These events often require clinical review, making systematic identification challenging. The study aim was to develop an approach to prioritize identification and validation of a rare ADR to trimethoprim-sulfamethoxazole causing acute respiratory distress syndrome (TMP-SMX ARDS) across medical institutions. We developed a clinical phenotype based on 2 local TMP-SMX ARDS cases mapped to standardized elements of a national comparative healthcare database (PHIS). We validated identification of TMP-SMX ARDS at scale across medical institutions. A set of scoring criteria was created to prioritize cases and generate …

A Cooking Skills Intervention For Long-Term Weight Loss In Young Adults With Intellectual Disabilities: Rationale And Design For A Randomized Trial., Lauren T. Ptomey, Jessica C. Danon, Delwyn Catley, Richard A. Washburn, Amy Bodde, Francisco J. Diaz, Brian C. Helsel, Anna M. Rice, Joseph R. Sherman, Madison Koester, Walker S. Mckinney Ph.D., Joseph E. Donnelly

Manuscripts, Articles, Book Chapters and Other Papers

Young adults with intellectual disability (ID) are an underserved population with a high prevalence of obesity, obesity-related health conditions, and reduced ability to complete instrumental and basic activities of daily living (I/ADLs). After leaving the structured environment of public school, many young adults with ID spend more time at home or in day programs, begin living more independently, or enter the workforce. These transitions may increase reliance on fast or processed foods and reduce opportunities for physical activity, contributing to accelerated weight gain. Previous research has demonstrated clinically meaningful short- and long-term weight loss (18-24 months) in adults with mild-to-moderate …

Cyp2c19 C.681g>A Is Not In Complete Linkage Disequilibrium With C.332-23a>G: Implications For Pharmacogenetic Testing., Amy J Turner, Erin C. Boone, Cyrine E Haidar, Wenjian Yang, Ashley D Derezinski, Andrew Haddad, Philip E. Empey, Ulrich Broeckel, Andrea Gaedigk

Manuscripts, Articles, Book Chapters and Other Papers

CYP2C19 plays an important role in the metabolism of many medications, including the antiplatelet agent clopidogrel, the antifungal agent voriconazole, selective serotonin reuptake inhibitors, select tricyclic antidepressants, and proton pump inhibitors. The Clinical Pharmacogenetics Implementation Consortium has published several guidelines emphasizing the importance of CYP2C19 genotype-guided therapy to optimize patient outcomes. Formerly, the no function CYP2C19*2 allele was defined by three variants, c.332-23A>G (splice defect), c.681G>A (splice defect), and c.991A>G (p.I331V). The discovery of two new haplotypes, one containing only a single variant, c.681G>A, and another with only c.681G>A and c.991A>G, challenged the assumption …

Are We Winning At Twinning? Persistent Cni Use In Identical Kidney Transplants., Nicholas S. Herrera, Shivani Wadnerkar, Diane M. Cibrik

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Calcineurin inhibitors (CNIs) revolutionized kidney transplantation by reducing acute rejection rates. Identical twin kidney transplantation is the only setting in which the allograft is immunologically indistinguishable from self, yet CNI use persists. We characterized CNI utilization across end-stage kidney disease etiologies and examined whether CNI exposure was associated with reduced rejection or improved death-censored graft survival (DCGS).

METHODS: We performed a retrospective cohort study using scientific registry of transplant recipients data (January 2000-August 2025). Among 255 adult identical twin kidney transplant recipients, discharge regimens were categorized by CNI use; Firth penalized Cox regression was the primary method for 10-year …

Quantitative Imaging Of Pyruvate Metabolism In A Patient With Anaplastic Thyroid Cancer, James A Bankson, Joshua S Niedzielski, Collin J Harlan, Yunyun Chen, Christopher M Walker, Philip L Lorenzi, Lin Tan, Vikas Kundra, Matthew E Merritt, Mukundan Ragavan, Dawid Schellingerhout, Renjie He, Yao Ding, Sahana Datar, Qing Wang, Christine B Peterson, Clifton D Fuller, Vlad C Sandulache, Stephen Y Lai

Faculty, Staff and Students Publications

Purpose: Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate.

Methods: A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. …

De Novo Complex Genomic Rearrangement Spanning 2q31.1 In A Proband With Congenital Malformations: Genotype-Phenotype Correlation And Development Of A Cgr Detection Pipeline, Katherine Helle, Jesse D Bengtsson, Mira Gandhi, Christopher M Grochowski, Ming Yin Lun, Neha Sudhir, Shalini N Jhangiani, Fritz J Sedlazeck, Seema R Lalani, Neil A Hanchard, Claudia M B Carvalho

Faculty, Staff and Students Publications

The 2q31 region is commonly associated with pathogenic alleles of the HOXD cluster leading to various clinical phenotypes related to skeletal development. We present a proband with tetralogy of Fallot and multiple congenital anomalies. Genomic variant screening including an in-house CGR detection pipeline pairing genome sequencing (GS) structural variant calls with read-depth data revealed a de novo complex genomic rearrangement (CGR) spanning 2.7 Mb across 2q31 characterized by a series of duplications and triplications including the HOXD gene cluster. The genomic structure was assembled by applying combined methodologies including short-read and long-read GS, and optical genome mapping (OGM). This in-house …

Indications, Techniques, And Safety Of Cryotherapy And Cryobiopsy Via Flexible Bronchoscopy In Pediatric Patients, Alex J Katz, Haley Haskett, Kubra M Bozkanat, Aoife Corcoran, Lauren M C Grant, Antoinette Wannes Daou, Sin Tran, Esra Caylan, Alfin Vicencio, Dan T Benscoter, Cherie A Torres-Silva, Sara M Zak, Gregory Burg, Lisa R Young, Pelton Phinizy, Shailendra Das, Richard Paul Boesch, Erik B Hysinger, Joseph Piccione

Faculty, Staff and Students Publications

Rationale: Cryotherapy and its diagnostic analogue, cryobiopsy, are emerging techniques via bronchoscopy with a wide range of clinical applications. While the use of cryotherapy and cryobiopsy has been established in adult pulmonary medicine, pediatric data describing the indications, procedural specifics, outcomes, and complications are limited.

Objective: To describe the indications, procedural specifics, outcomes, and complications of cryotherapy and cryobiopsy use in pediatric bronchoscopy.

Methods: A multicenter retrospective observational study was conducted at 5 pediatric hospitals in the United States. Patients aged 0 to 21 years who underwent cryotherapy or cryobiopsy via bronchoscopy between January 2017 and January 2025 were included. …

Rates Of, Reasons For, And Reactions To Discontinuation Of Glp-1 Receptor Agonists: A Narrative Review, Henry D Heisey, L Parker Gregg, Christopher D Verrico, Dennis T Villareal, Terri L Fletcher

Faculty, Staff and Students Publications

GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual …

The Crisis Of Adolescent Firearm Reinjury: A 14-Year Retrospective Cohort Analysis, Kristen L Mueller, Daphne Lew, Nicholas Szoko, Zoe M Miller, Taylor Kaser, Benjamin P Cooper, Christopher Behr, Lindsay Clukies, Joseph Finney, Marguerite W Spruce, Lindsay M Kranker, Michael A Mancini, Melissa Kroll, Erin G Dawson, Matt Vogel, Rachel M Ancona, Vicki Moran, Melik Coffey, Kateri-Chapman Kramer, Doug J E Schuerer, Elvin Geng, Megan L Ranney, Randi E Foraker

Faculty, Staff and Students Publications

Background: Firearm injuries are the leading cause of death among US adolescents. Adolescents are among the highest risk, and those with nonfatal injuries experience high rates of reinjury. Identifying factors that predict firearm reinjury among adolescents may support tailored prevention strategies. This study sought to identify factors associated with firearm reinjury among adolescents who presented with acute nonfatal firearm injury in the St. Louis, Missouri region.

Methods: We conducted a multicenter observational cohort study of youth aged 15 to 17 years presenting to 2 adult and 2 pediatric trauma centers from 2010 through 2023. We collected data on firearm-injured patient …

Clingen Variant Curation Interface Workshops: Training Variant Scientists On An International Platform, Deborah I Ritter, Mark Mandell, Christine Preston, Marina Distefano, Sahia M Bryant, Nadia Carstens, Rolanda S Julius, Aimé Lumaka, Madhuri Hegde, Joanne Ngeow, Joannella Morales, Matt W Wright, Heidi L Rehm, Sharon E Plon

Faculty, Staff and Students Publications

Purpose: The Clinical Genome Resource (ClinGen) is creating a central resource of clinically relevant genetic knowledge to improve genomic medicine. Dissemination and use of the ClinGen Resource is essential to ensure broad community uptake. We report on experiences and sustained use of ClinGen tools through engaging international genetics groups based in India, Africa, and Singapore in variant classification training workshops using the ClinGen Variant Curation Interface (VCI).

Methods: We developed pre- and postworkshop questionnaires and analyzed ClinGen tool use following the workshops. We evaluated organizational aspects and costs of creating a dedicated ClinGen VCI instance for each workshop.

Results: The …

Increased Risk Of Sarcomas In Children With Congenital Anomalies: Findings From The Genetic Overlap Between Anomalies And Cancer In Kids (Goback) Registry Linkage Study, Russ Wolters, Ji Yun Tark, Tiffany M Chambers, Tania A Desrosiers, Michael E Scheurer, Charles Shumate, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Jean Paul Tanner, Russell S Kirby, Jason L Salemi, Yao Yu, Chad D Huff, Sharon E Plon, Philip J Lupo, Jeremy M Schraw

Faculty, Staff and Students Publications

Background: Pediatric sarcomas are a heterogeneous group of tumors that contribute disproportionately to cancer mortality in children. Although congenital anomalies are among the strongest known risk factors for childhood cancer, the risk of specific sarcoma subtypes among affected individuals has not yet been thoroughly evaluated.

Procedure: We obtained data on maternal and perinatal characteristics, congenital anomalies, and pediatric sarcoma diagnoses for all live births in nine states. We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of sarcoma (overall and by subtype) among children with non-syndromic congenital anomalies. We considered all non-syndromic …

Cost-Effectiveness Of Hes V2.0 And Galad For Hepatocellular Carcinoma Surveillance In Patients With Cirrhosis, Mert Sahinkoc, Gizem S Nemutlu, Hashem B El-Serag, Mary Linton B Peters, Ali Hajjar, Anthony E Samir, Leigh Anne Dageforde, Fasiha Kanwal, Jagpreet Chhatwal

Faculty, Staff and Students Publications

Background: Ultrasound-based surveillance for HCC is limited by suboptimal sensitivity and low adherence. Blood-based biomarkers are potential alternatives for routine HCC surveillance. We aimed to define optimal sensitivity, specificity, and cost parameters under which blood-based biomarkers could serve as cost-effective alternatives in patients with cirrhosis.

Methods: We developed a microsimulation model of the natural history of HCC in individuals with compensated cirrhosis. We compared the cost-effectiveness of biannual surveillance using 2 blood-based biomarkers-HES V2.0 and GALAD-versus ultrasound-based surveillance across a range of sensitivity, specificity, test costs, and adherence levels. Outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios …

Diabetter Together: Outcomes Of A Randomized Controlled Trial Evaluating A Peer Mentor Behavioral Intervention For Young Adults With Type 1 Diabetes During The Transfer From Pediatric To Adult Care, Marisa E Hilliard, Charles G Minard, Samantha A Carreon, Wendy L Levy, Sarah K Lyons, Randi Streisand, Tricia S Tang, Siripoom V Mckay, Sridevi Devaraj, Barbara J Anderson

Faculty, Staff and Students Publications

Objective: Transition between pediatric and adult health care is complex, with high risk for loss to follow-up and suboptimal health outcomes for young adults with type 1 diabetes. This trial evaluated the efficacy of DiaBetter Together, a 12-month strengths-based behavioral intervention delivered by trained peer mentors. The intervention aimed to help young adults navigate the transfer process to promote optimal glycemic outcomes, shorten time to adult care follow-up, and improve psychosocial outcomes.

Research design and methods: Using a single-site randomized clinical trial design, we compared the 12-month intervention to usual care among n = 100 young adults aged 17-25 years …

Deep Learning-Based Comparison Of Knee Minimum Joint Space Width In Patients With Rheumatoid Arthritis And Osteoarthritis Before Total Knee Arthroplasty, Miguel M Girod, Monty Khela, Sami Saniei, Kellen L Mulford, Cassondra A Hulshizer, Elizabeth J Atkinson, Cody C Wyles, John M Davis, Gavin A Mckenzie, Cynthia S Crowson

Faculty, Staff and Students Publications

Objective: Although both osteoarthritis (OA) and rheumatoid arthritis (RA) can necessitate total knee arthroplasty (TKA), their mechanisms and radiographic patterns of joint space narrowing (JSN) differ. Deep learning (DL) enables compartment-specific measurement of minimum joint space width (mJSW). This study compared JSN patterns between patients with RA and OA undergoing TKA and evaluated the associations between mJSW and RA disease activity.

Methods: In this retrospective study, 409 patients with RA undergoing TKA (2000-2021) were age- and sex-matched with OA patients. A validated DL model quantified medial and lateral mJSW from anteroposterior knee radiographs at 2 timepoints: early (> 2 years …

Select Plasma Oxylipins As Potential Biomarkers Of Effective Indomethacin Treatment Response In Preterm Infants With Patent Ductus Arteriosus., Khanh C K Nguyen, Cindy H T Yeung, Allison Scott, Thomas J. Velenosi, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Patent ductus arteriosus (PDA) is one of the most common heart conditions in preterm infants, and indomethacin treatment is used for PDA closure. However, its efficacy varies among patients. This pilot study aimed to identify novel metabolic biomarkers to predict effective indomethacin response in infants with PDA.

METHODS: Preterm infants with PDA <  34 weeks gestational age were recruited and treated with indomethacin. Plasma and urine samples were collected before and 2-7 days after initial treatment. Longitudinal targeted oxylipin and untargeted metabolomics analysis were performed on plasma and urine samples.

RESULTS: Among 17 infants, 12 were responders and 5 non-responders to indomethacin treatment. Before the treatment, four plasma oxylipins: 12,13-DiHOME, 9,10-DiHOME, 15,16-DiHODE, and 9,10-DiHODE were significantly higher in responders compared to non-responders (P <  0.05). Following treatment, these oxylipins decreased in responders but remained stable in non-responders. Urinary 12,13-DiHOME showed an opposite trend, with lower baseline concentrations in the responders.

CONCLUSIONS: Pre-treatment plasma levels of four oxylipins were associated with effective PDA response to …

Comment On: Managing Sickle Cell Disease And Related Complications In Pregnancy: Results Of An International Delphi Panel, Deva Sharma, Ilknur Pamuk, Kenneth I. Ataga, Alexandra Benachi, Selim Büyükkurt, Sophie Lanzkron, Hakan Ozdogu, Shivan Pancham, Lydia H. Pecker, Susan E. Robinson, Safak Yilmaz Baran

Cardeza Foundation for Hematologic Research

Consensus-based recommendations on managing sickle cell disease in pregnancy were recently published in a hematology journal. As this topic is also of great interest to obstetricians and gynecologists, we summarize some of these recommendations, while highlighting the challenges of providing evidence-based medical care to pregnant individuals with sickle cell disease.

Under Pressure: Negative Urgency And Disordered Eating In The Context Of Parental Differential Support, Hamide Gozu, Jenna K. Rieder

College of Humanities and Sciences Faculty Papers

Disordered eating behaviors are prevalent in emerging adulthood and may be shaped by family dynamics. This study examined associations among maternal and paternal differential support, weight-shape concerns, and binge eating and compensatory behaviors in emerging adulthood, while testing the moderating role of negative urgency. Participants were 517 emerging adults from across the United States (ages 18-29; M = 22.60, SD = 3.81; 76% female). Participants reported on parental differential support, weight-shape concerns, eating behaviors, and negative urgency. Using moderated-mediation analyses, we found that weight-shape concerns mediated associations between differential support and eating behaviors. Unequal maternal support and paternal favoritism showed …

Ophthoevidence Report: Comparative Effects Of Prophylactic Strategies For Post-Intravitreal Injection Endophthalmitis: Protocol For A Systematic Review And Network Meta-Analysis, Maryam Ghadimi, Dena Zeraatkar, João Pedro Lima, Jinhui Ma, Sunir J. Garg, Peter Kaiser, David Steel, Tien Yin Wong, Sobha Sivaprasad, Charles Wykoff, Varun Chaudhary

Wills Eye Hospital Papers

BACKGROUND: Endophthalmitis is a rare but serious complication of intravitreal injections (IVI). To mitigate the risk of post-injection endophthalmitis (PIE), retinal specialists use different strategies, combining various prophylactic measures. However, existing systematic reviews have evaluated the effects of these measures in isolation, which does not consider their concurrent use in practice. A trustworthy systematic review with network meta-analysis (NMA) by providing a framework for simultaneous comparisons of different prophylactic combinations is essential to guide decision-making.

OBJECTIVES: To present a protocol for addressing the comparative effects of different strategies for the prevention of PIE.

METHODS: We will search Medline, EMBASE, Cochrane …

Notch Signaling Regulates The Secretion Of Pro-Metastatic Factors In Extracellular Vesicles In Liposarcoma, Menchus Quan, Yi-Kai Liu, Ying Zhao, Madeline Kay, Kai Sun, Timothy P Gavin, Raphael E Pollock, W Andy Tao, Shihuan Kuang

The Brown Foundation: Institute of Molecular Medicine

Notch signaling is an emerging regulator of liposarcoma (LPS), but its role in mediating communication with the tumor microenvironment (TME) is unclear. Here, we investigate how Notch activation (NICD overexpression) alters the proteomes of LPS-derived extracellular vesicles (EVs). We used quantitative mass spectrometry to profile the EV proteome in multiple contexts: cultured LPS cells, LPS tumor, circulating EVs of LPS-bearing mice, and human LPS samples. We found that Notch signaling increases the secretion of EV proteins that favor tumor progression and metastasis but suppresses immune responses in murine LPS cells. Overlapping murine and human LPS data identifies 18 proteins that …

From Chromosomes To Precision Therapy: Clinical Cytogenetics And Cytogenomics In The Era Of Genomic Medicine, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Acalabrutinib Monotherapy As A First-Line Treatment For Cll: 3 Years Follow-Up Of The Real-World Epic Study: 3-Year Follow-Up Of The Real-World Epic Study, Toby A. Eyre, Nicolás Martínez-Calle, Shankara Paneesha, Mohsen Norouzi, David L Tucker, Harriet Sarah Walter, Alison Boden, Mari Kilner, Neil Phillips, Piers Em Patten, Nimish Shah, Meghna Ruparelia, Sharon Oddy, Tan Tsawayo, Francesco Forconi, Helen Wardle, Tobore Gbemre, Chris Gregory, Lucy B. M. Cook, David J Allsup, Anna Morris, Christopher J C Knechtli, Jenni Davies, Joy Galani, Helen Marr, Claire Hutchinson, Stella Williams, Joe Hickey, Hannah Harding, Sukhjit Hunjan

Peninsula Medical School

Clinical trials indicate that acalabrutinib, a second-generation Bruton tyrosine kinase inhibitor, is safe and effective for treating patients with chronic lymphocytic leukemia (CLL), but real-world evidence on its clinical effectiveness is limited. This ongoing multicenter retrospective chart review included UK adults with previously untreated CLL who received acalabrutinib monotherapy as part of a UK-wide early access program. These patients received their first dose of acalabrutinib between 1 April 2020 and 1 April 2021. Data from 282 patients (male patients, n = 156 [55%]) collected from 29 sites across the United Kingdom revealed a median age of 73.9 years (interquartile range …

Effects Of Non-Surgical Periodontal Therapy On Dental Plaque Microbiome, Qingguo Wang, Bing-Yan Wang, Derek Wilus, Hua Xie

Faculty, Staff and Student Publications

Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3–4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced probing …

Neural-Immune-Cardiovascular Axis: From Mechanistic Crosstalk To Therapeutic Targets In Cardiovascular Disease, Junkang Cheng, Shuang Gao, Haowei Zhang, Wei Gao, Zeyuan Mei, Xiaoling Liu, Jocelyn Gao, Chenghu Guo, Guipeng An

Student Papers, Posters & Projects

The neural-immune-cardiovascular axis represents an emerging and highly integrated physiological and pathophysiological concept, describing a complex bidirectional communication network between the nervous, immune, and vascular systems. This review systematically examines the pivotal role of this axis in maintaining cardiovascular homeostasis and in the pathogenesis of cardiovascular diseases. We first provide an overview of the fundamental signaling pathways between the components of this axis. Subsequently, we delve into the specific crosstalk mechanisms within the axis in the context of major cardiovascular conditions, including atherosclerosis, hypertension, and heart failure. A central focus is placed on critically evaluating the potential therapeutic targets and …

Barriers To Recommendation Of Integrative Oncology Modalities In Supportive Care: A Mascc/Sio Survey, Alexandre Chan, Dalia Kagramanov, Reem Nasr, Chioma Asuzu, Ting Bao, Yin Ting Cheung, Jung Hye Kwon, Judith Lacey, Richard T. Lee, Maryam Lustberg, Beatrice M. Ohaeri, Santosh Rao, Enrique Soto-Perez-De-Celis, Claudia M. Witt, Ana M. Lopez

Kimmel Cancer Center Faculty Papers

PURPOSE: Integrative oncology (IO) modalities aim to improve the quality of life of persons with cancer, including strategies to manage treatment and disease-related symptoms. As evidence increases to include IO in supportive care, interest grows globally. Understanding barriers to IO recommendation is key to facilitating its uptake.

METHODS: Members of the Multinational Association of Supportive Care in Cancer (MASCC) and the Society for Integrative Oncology (SIO) were invited to complete an online survey in Fall 2023 assessing barriers to IO recommendation on a 5-point scale. Descriptive statistics assessed demographic data and general counts of scaled agreement, while logistic regression analysis …

Cervical Cancer Screening Coverage And Associated Factors Among Women Aged 25-59 In Eswatini: Insights From The 2021 Population-Based Hiv Impact Assessment (Phia), Abenezer Melaku Tafese, Bikiltu Dirbaba, Meseker Fentie, Charnita Zeigler-Johnson

College of Population Health Faculty Papers

BACKGROUND: Cervical cancer is the most common cancer and the leading cause of cancer mortality among women in Eswatini, which reported the highest cervical cancer incidence and mortality rates globally in 2022. However, recent nationally representative published data on cervical cancer screening coverage in Eswatini remain limited. This study aimed to estimate cervical cancer screening coverage and identify factors associated with screening uptake among women aged 25-59 years in Eswatini.

METHOD: Data were drawn from the 2021 Eswatini Population-based HIV Impact Assessment (PHIA), a nationally representative cross-sectional household survey. Survey-weighted bivariable and multivariable logistic regression analyses were conducted to identify …