Digital Commons Network^™

Pathobiology Of Aortic Aneurysms And Dissections: Synthesis Of Recent Investigations And Evolving Insights, L Maximilian Buja, Bihong Zhao, Deborah Vela, Ana Segura, Navneet Narula

Faculty, Staff and Student Publications

The pathobiology of aortic disease is linked to aortic region: atherosclerosis for abdominal aorta, primary medial degeneration or aortitis for ascending thoracic aorta, and all causes for descending thoracic aorta and thoracoabdominal lesions. The pathogenesis of aortic dissection involves damage of the outer media from impaired perfusion from dysfunctional vasa vasorum, formation of discrete foci of disrupted vascular smooth muscle cell-elastic fiber extension-contractile units, and imbalance of radial sheer stress across the aortic wall, thereby creating an intimal tear and linear dissection. Thoracic aortic aneurysms develop from the chronic progression of medial degeneration coupled with the weakening of the remodeled …

Neuroimaging-Based Variability In Subtyping Biomarkers For Psychiatric Heterogeneity, Zhenfu Wen, Mira Z Hammoud, Carole E Siegel, Eugene M Laska, Duna Abu-Amara, Amit Etkin, Mohammed R Milad, Charles R Marmar

Faculty, Staff and Student Publications

Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total n = 566) that included controls (n = 268) and cases (n = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The …

Genome-Wide Association Meta-Analyses Of Drug-Resistant Epilepsy, Costin Leu, Andreja Avbersek, Remi Stevelink, Helena Martins Custodio, Siwei Chen, Doug Speed, Caitlin A Bennett, Lina Jonsson, Unnur Unnsteinsdóttir, Andrea L Jorgensen, Gianpiero L Cavalleri, Norman Delanty, John J Craig, Chantal Depondt, Michael R Johnson, Bobby P C Koeleman, Emadeldin Hassanin, Maryam Erfanian Omidvar, Roland Krause, Holger Lerche, Anthony G Marson, Terence J O'Brien, Josemir W Sander, Graeme J Sills, Pasquale Striano, Federico Zara, Hreinn Stefansson, Kari Stefansson, Patrick May, Benjamin M Neale, Dennis Lal, Samuel F Berkovic, Epi25 Collaborative, Epipgx Consortium, Sanjay M Sisodiya

Faculty, Staff and Student Publications

Background: Epilepsy is one of the most common neurological disorders, affecting over 50 million people worldwide. One-third of people with epilepsy do not respond to currently available anti-seizure medications, constituting one of the most important problems in epilepsy. Little is known about the molecular pathology of drug resistance in epilepsy, in particular, possible underlying genetic factors are largely unknown.

Methods: We performed a genome-wide association study (GWAS) in two epilepsy cohorts of European ancestry, comparing drug-resistant (N = 4208) to drug-responsive individuals (N = 2618) followed by meta-analyses across the studies. Next, we performed subanalyses split into two broad subtypes: …

Dosimetric Predictors Of Toxicity For Brainstem Metastases And Avms Treated With Stereotactic Radiosurgery: An International, Multi-Institutional Analysis, Raj Singh, Samantha Dayawansa, Duy Pham, Georgios Mantziaris, Selcuk Peker, Yavuz Samanci, Ali Haluk Duzkalir, David Mathieu, Anne-Marie Langlois, Molly L Egnot, Ronald E Warnick, Herwin Speckter, Erwin Lazo, Laura Mendez, Angel I Blanco, Mark J Amsbaugh, Collin Liu, Andrea Becerril-Gaitan, Yoshua Esquenazi, Ching-Jen Chen, Peter Zaki, Yun Liang, Rodney Wegner, Manjul Tripathi, Zhishuo Wei, Shivani A Jajoo, Ajay Niranjan, L Dade Lunsford, Joshua D Palmer, Jason P Sheehan

Faculty, Staff and Student Publications

Background: There are limited data on dosimetric predictors of radiation-induced changes (RICs) for brainstem metastases or arteriovenous malformations (AVMs) following single-fraction stereotactic radiosurgery (SRS).

Methods: We examined a multi-institutional cohort of patients with brainstem metastases or AVMs treated with SRS. We evaluated predictors of RICs graded per CTCAE(Common Terminology Criteria for Adverse Events), including D5%, D95%, D0.03 cc, and D0.5 cc (brainstem minus lesion). Univariate logistic regressions were initially performed with independent variables trending towards significance included on multivariate logistic regression.

Results: A total of 124 brainstem lesions treated with SRS were analyzed (21 AVMs and 103 metastases). The median …

Targeting Discrepancies In Linear Growth Measurements In The Neonatal Intensive Care Unit Through Nursing Interventions: A Quality Improvement Initiative, Gail Snyder, Rebekah Wilkinson, Raina Evans, Meagan Owen, Akram Yazdani, Covi Tibe, Catherine Perez, Lindsay F Holzapfel

Faculty, Staff and Student Publications

Objective: Accurate length measurements are essential for infants to identify growth deficiencies and adjust nutrition accordingly. The gold standard for length measurement in infants is using a length board with two people to obtain an accurate clinical assessment. We aimed to improve the number of measurements with the desired minimal difference, defined as a discrepancy ≤1 cm between nurse and audit measurements, in our center. Our secondary aim was to increase and maintain the number of length boards available.

Methods: This quality improvement (QI) study used a before-and-after intervention comparison design in a single-level IV neonatal intensive care unit between …

First Step To Environmentally Sustainable Endoscopy Practice: A Prospective Study Of Minimizing Multiple Device Use During Screening Colonoscopy At A Large Tertiary Center, Prateek S Harne, Vaishali Harne, Asad Rehman, Nirav Thosani, Madhav Desai

Faculty, Staff and Student Publications

The healthcare sector generates 8% of greenhouse gas emissions in the USA, of which gastrointestinal (GI) endoscopy is the third largest contributor. Single-use tools are a major contributor to modifiable waste generation during GI endoscopy. Through a quality improvement initiative, we aimed to reduce endoscopy waste by urging gastroenterologists to be mindful of tools used during polypectomies by avoiding using multiple tools.We discussed green endoscopy initiatives in monthly journal club and business meetings. Over 14 weeks, 210 patients were included in the pre-intervention group and 112 in the post-intervention group.At baseline, 34% of colonoscopies required no intervention, 32% required one …

Endobronchial Ultrasound Transbronchial Needle Aspiration In The Diagnosis Of Visceral Leishmaniasis In A Patient With Human Immunodeficiency Virus Infection, Mohammad A Amjad, Y H Zhang, Rosa M Estrada-Y-Martin, Sujith V Cherian

Faculty, Staff and Student Publications

No abstract provided.

Tumour Size Is Associated With Growth Rates Of >0.5 Cm/Year And Delayed Intervention In Small Renal Masses In Patients On Active Surveillance, Maximilian Pallauf, Michael Rezaee, Roy Elias, Tina Wlajnitz, Sean A Fletcher, Joseph Cheaib, Khalid Alkhatib, Peter Chang, Andrew A Wagner, James M Mckiernan, Mohamad E Allaf, Phillip M Pierorazio, Nirmish Singla

Faculty, Staff and Student Publications

Objective: To evaluate the association between tumour size and the growth rate (GR) of small renal masses (SRMs) in patients managed by active surveillance (AS).

Materials and methods: We queried the prospective, multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry for patients on AS with an imaging interval of ≥6 months, identifying 456 patients. We tracked tumour size over time; a GR >0.5 cm/year was defined as a GR event. We used multivariable recurrent events and time-to-event Cox regression modelling to evaluate the association between tumour size and GR events (primary outcome) and tumour size and delayed …

Randomized Controlled Trial Of "Bounce Back Now," A Mobile App To Reduce Post-Disaster Symptoms Of Posttraumatic Stress, Depressed Mood, And Sleep Disturbance, Kenneth J Ruggiero, Arthur Andrews, Tatiana M Davidson, Yulia Gavrilova, Brian E Bunnell, Jennifer Dahne, Matthew Price, Zoe M F Brier, Gregory Cohen, Dean Kilpatrick, Ron Acierno, Sandro Galea

Faculty, Staff and Student Publications

Objective: There is tremendous public health interest in cost-efficient, scalable interventions to improve post-disaster mental health. The authors examined the efficacy of Bounce Back Now (BBN), a mobile application, versus an enhanced usual care app (EUC).

Methods: A population-based trial was conducted with a diverse sample of 1,357 adults affected by Hurricane Harvey, Irma, Maria, Florence, or Michael in 2017 and 2018. Participants were eligible if they were ≥18 years of age, had access to an Internet-accessible device, were English speaking, and lived in a hurricane-affected area. BBN is designed to address symptoms of posttraumatic stress, depression, and sleep disturbance …

Adherence To Life’S Essential 8 Is Associated With Delayed White Matter Aging, Li Feng, Zhenyao Ye, Yezhi Pan, Rozalina G Mccoy, Braxton D Mitchell, Peter Kochunov, Paul M Thompson, Jie Chen, Menglu Liang, Thu T Nguyen, Edmond Shenassa, Yan Li, Travis Canida, Hongjie Ke, Hwiyoung Lee, Song Liu, L Elliot Hong, Chixiang Chen, David K Y Lei, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

Background: The American Heart Association introduced Life's Essential 8 (LE8) to promote cardiovascular health and longevity. However, its impact on brain ageing and interactions with genetic risk factors of dementia, such as APOE4, remains unclear. This study investigates the relationship between LE8 and white matter brain ageing and evaluates the moderating effects of the APOE4 allele.

Methods: This cross-sectional study utilized data from the UK Biobank, including genetic, neuroimaging, and health-related data from touchscreen questionnaires, physical examinations, and biological samples. Participants were non-pregnant whites with LE8 variables, diffusion tensor imaging (DTI) data, and APOE4 genetic information available, excluding those with …

Race And Clinical Outcomes In Hormone Receptor-Positive, Her2-Negative, Node-Positive Breast Cancer In The Randomized Rxponder Trial, Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky

Faculty, Staff and Student Publications

Background: The phase III RxPONDER trial has affected treatment for node-positive (1-3), hormone receptor-positive, HER2-negative breast cancer with a 21-gene recurrence score (RS) less than 26. We investigated how these findings apply to different racial and ethnic groups within the trial.

Methods: The trial randomly assigned women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS), with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathological characteristics, RS, and treatment.

Results: A total of 4048 …

Predicting Thoracic Aortic Dissection In A Diverse Biobank Using A Polygenic Risk Score, John Depaolo, Siavash Zamirpour, Sarah Abramowitz, Gina Biagetti, Renae Judy, Cameron Beeche, Jeffrey Duda, James Gee, Walter R Witschey, Julio A Chirinos, Nicholas J Goel, Nimesh Desai, Wilson Y Szeto, Dongchuan Guo, Dianna M Milewicz, Michael G Levin, James P Pirruccello, Scott M Damrauer

Faculty, Staff and Student Publications

Background: Thoracic aortic dissection is a life-threatening condition that often occurs in the presence of aortic dilation. However, currently there are limited clinical risk factors beyond aortic diameter (AoD) used to determine individual-level dissection risk.

Objectives: The purpose of this study was to determine whether common variant genetics can be used to improve identification of individuals most at risk for dissection.

Methods: A genome-wide association study (GWAS)-by-subtraction was performed to characterize the diameter-independent genetics of thoracic aortic dissection by subtracting a GWAS of AoD from a GWAS of thoracic aortic aneurysm and dissection. A polygenic risk score (PRS) was calculated …

Blood Pressure Misclassification Among Stroke Survivors Followed In A Comprehensive Stroke Prevention Clinic, M Carter Denny, Maha Almohamad, Emmanuel Ebirim, Adriana Morell, Munachi Okpala, Kevin O Hwang, Sean Savitz, Anjail Sharrief

Faculty, Staff and Student Publications

Background: Hypertension is the most important modifiable risk factor for secondary stroke prevention; however, blood pressure (BP) remains uncontrolled for at least 50 % of stroke survivors following an incident stroke. Accurate in-clinic assessment of BP is important for appropriate medication titration. We evaluated misclassification of clinic BP control in a racially diverse stroke clinic population using two BP measurement methods.

Observations: We followed ischemic stroke, intracerebral hemorrhage, and transient ischemic attack patients after hospital discharge in a comprehensive stroke clinic. Casual BP was obtained using a standard office automated machine, attended by a medical assistant. BP was also measured …

Justification, Margin Values, And Analysis Populations For Oncologic Noninferiority And Equivalence Trials: A Meta-Epidemiological Study, Troy J Kleber, Alexander D Sherry, Andrew J Arifin, Gabrielle S Kupferman, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Esther J Beck, Avital M Miller, Adina H Passy, Zachary R Mccaw, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Background: Noninferiority and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint is contained within an acceptable margin compared with standard of care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used.

Methods: A meta-epidemiological study was performed of phase 3 randomized noninferiority and equivalence oncologic trials registered at ClinicalTrials.gov. Data were extracted from each trial's registration page and primary manuscript.

Results: We identified 65 noninferiority and 10 equivalence trials that collectively enrolled 61 632 patients. Of these, 61 (81%) …

Enhancing The Safety And Efficacy Of Cell Therapy With Programmed Sense-And-Respond Function, Andrew J Walters, Xiaoyu Yang, Scott D Olson, Caleb J Bashor

Faculty, Staff and Student Publications

No abstract provided.

Development Of A Treatment Decision Aid For Patients With Dysplastic Nevi Who Are Candidates For Re-Excision, Jaclyn N Roland-Mcgowan, Steven Caleb Freeman, Wenelia Baghoomian, Bryan T Carroll, Caroline Choi Kim, Clara Curiel-Lewandrowski, Emily Y Chu, Erin L Foster, Kelly Carter Nelson, Kevin P White, Michael E Ming, Rebecca I Hartman, Sancy A Leachman, Stephanie Mengden-Koon, Suephy C Chen, Susan M Swetter, Victor G Prieto, Elizabeth Berry, Wesley Y Yu

Faculty, Staff and Student Publications

No abstract provided.

Imaging In Pelvic Exenteration-A Multidisciplinary Practice Guide From The Esgar-Sar-Esur-Pelvex Collaborative Group, Stephanie Nougaret, Doenja M J Lambregts, Geerard L Beets, Regina G H Beets-Tan, Lennart Blomqvist, David Burling, Quentin Denost, Maria A Gambacorta, Benedetta Gui, Ann Klopp, Yulia Lakhman, Kate E Maturen, Riccardo Manfredi, Iva Petkovska, Luca Russo, Atul B Shinagare, James A Stephenson, Damian Tolan, Aradhana M Venkatesan, Aaron J Quyn, Rosemarie Forstner

Faculty, Staff and Student Publications

Pelvic exenteration (PE) is a radical surgical approach designed for the curative treatment of advanced pelvic malignancies, requiring en-bloc resection of multiple pelvic organs. While the procedure is radical, it has shown promise in enhancing long-term survival and is now comparable in surgical mortality to elective resections for primary pelvic cancers. Imaging plays a crucial role in preoperative planning, with MRI, CT, and PET/CT being pivotal in assessing the extent of cancer and formulating a surgical roadmap. This paper presents clinical practice guidelines for imaging in the context of PE, developed jointly by ESGAR, SAR, ESUR, and the PelvEx Collaborative. …

Donor Age Matters For Haploidentical Hct Patients Even After Adjusting For Hla Factors: A Machine Learning Approach, Rohtesh S Mehta, Rodney Sparapani, Tao Wang, Stephen Spellman, Stephanie J Lee, Effie W Petersdorf

Faculty, Staff and Student Publications

No abstract provided.

Cafe: Improved Federated Data Imputation By Leveraging Missing Data Heterogeneity, Sitao Min, Hafiz Asif, Xinyue Wang, Jaideep Vaidya

Faculty, Staff and Student Publications

Federated learning (FL), a decentralized machine learning approach, offers great performance while alleviating autonomy and confidentiality concerns. Despite FL's popularity, how to deal with missing values in a federated manner is not well understood. In this work, we initiate a study of federated imputation of missing values, particularly in complex scenarios, where missing data heterogeneity exists and the state-of-the-art (SOTA) approaches for federated imputation suffer from significant loss in imputation quality. We propose Cafe, a personalized FL approach for missing data imputation. Cafe is inspired from the observation that heterogeneity can induce differences in observable and missing data distribution across …

The Association Of Discrimination, Inflammation, And Coping Style On Self-Rated Health Among South Asian Individuals In The Masala Study, Raji Pillai, Sahiti Myneni, Constance M Johnson, Nilay S Shah, Alka M Kanaya, Jennifer E S Beauchamp

Faculty, Staff and Student Publications

Objectives: South Asian individuals (SAs) may have heightened levels of inflammatory markers, such as C reactive protein (CRP), Tumor Necrosis Factor-α (TNF-α), leptin, and resistin, and decreased levels of anti-inflammatory adiponectin, contributing to higher cardiovascular disease (CVD) incidence. Social determinants of health, like discrimination, are also associated with risks for CVD in SAs. This study examined the associations between discrimination and inflammation and whether coping styles moderated the association between discrimination and self-rated health (SRH) among SAs in the United States.

Design: Secondary analysis of data obtained from 1164 SAs (mean age = 57 years, SD = 9.4, 48% women) …

Association Of Delayed Asthma Diagnosis With Asthma Exacerbations In Children, Chung-Il Wi, Euijung Ryu, Katherine S King, Jung Hyun Kwon, Joshua T Bublitz, Miguel Park, Sergio E Chiarella, Jason D Greenwood, Thanai Pongdee, Lynnea Myers, Björn Nordlund, Sunghwan Sohn, Elham Sagheb, Bhavani Singh Agnikula Kshatriya, Dave Watson, Hongfang Liu, Beverley J Sheares, Carla M Davis, Wade Schulz, Young J Juhn

Faculty, Staff and Student Publications

Background: There is a significant delay between symptom onset and diagnosis of childhood asthma, but the impact of this delay on asthma outcomes has not been well understood.

Objectives: We sought to study the association of delayed diagnosis of asthma with asthma exacerbations (AEs) in children.

Methods: Using the Mayo Clinic birth cohort, we identified children with a diagnosis of asthma from electronic health records. We defined onset date as the date when subjects first met predetermined asthma criteria ascertained by an electronic health records-based natural language processing algorithm. Delay in diagnosis (DD) was defined as first diagnosis >30 days …

Igtp: Learning Interpretable Cellular Embedding For Inferring Biological Mechanisms Underlying Single-Cell Transcriptomics, Kang-Lin Hsieh, Kai Zhang, Yan Chu, Lishan Yu, Xiaoyang Li, Nuo Hu, Isha Kawosa, Patrick G Pilié, Pratip K Bhattacharya, Degui Zhi, Xiaoqian Jiang, Zhongming Zhao, Yulin Dai

Faculty, Staff and Student Publications

Deep-learning models like Variational AutoEncoder have enabled low dimensional cellular embedding representation for large-scale single-cell transcriptomes and shown great flexibility in downstream tasks. However, biologically meaningful latent space is usually missing if no specific structure is designed. Here, we engineered a novel interpretable generative transcriptional program (iGTP) framework that could model the importance of transcriptional program (TP) space and protein-protein interactions (PPI) between different biological states. We demonstrated the performance of iGTP in a diverse biological context using gene ontology, canonical pathway, and different PPI curation. iGTP not only elucidated the ground truth of cellular responses but also surpassed other …

Pharmacotherapy And Non-Invasive Neuromodulation For Neuropathic Pain: A Systematic Review And Meta-Analysis, Nadia Soliman, Xavier Moisset, Michael C Ferraro, Daniel Ciampi De Andrade, Ralf Baron, Joletta Belton, David L H Bennett, Margarita Calvo, Patrick Dougherty, Ian Gilron, Aki J Hietaharju, Koichi Hosomi, Peter R Kamerman, Harriet Kemp, Elena K Enax-Krumova, Ewan Mcnicol, Theodore J Price, Srinivasa N Raja, Andrew S C Rice, Blair H Smith, Fiona Talkington, Andrea Truini, Jan Vollert, Nadine Attal, Nanna B Finnerup, Simon Haroutounian

Faculty, Staff and Student Publications

Background: There remains a substantial unmet need for effective and safe treatments for neuropathic pain. The Neuropathic Pain Special Interest Group aimed to update treatment recommendations, published in 2015, on the basis of new evidence from randomised controlled trials, emerging neuromodulation techniques, and advances in evidence synthesis.

Methods: For this systematic review and meta-analysis, we searched Embase, PubMed, the International Clinical Trials Registry, and ClinicalTrials.gov from data inception for neuromodulation trials and from Jan 1, 2013, for pharmacological interventions until Feb 12, 2024. We included double-blind, randomised, placebo-controlled trials that evaluated pharmacological and neuromodulation treatments administered for at least 3 …

What Rankings, Ratings, And Utilities Do Breast Cancer Patients Place On Tissue- And Implant-Based Breast Reconstruction?, Haoqi Wang, Nsikak M Jackson, Danmeng Huang, Rachel E Alexander, Mary Catherine Bordes, Jun Liu, Tzuan A Chen, Fatima Merchant, Summer E Hanson, Mark Schaverien, Mia K Markey, Gregory P Reece, Scott B Cantor, Aubri S Hoffman

Faculty, Staff and Student Publications

Background: Utility analysis is well-established for comparing treatment options but challenging to assess with patients in clinical care. Preference assessment may be more feasible, but it is not yet known whether it correlates with utilities. The aims of this study were to (1) assess women's rankings, ratings, and utilities for tissue-based, implant-based, and no reconstruction after total mastectomy; and (2) explore assessment methods and correlations with clinical and psychosocial factors.

Methods: Forty patients considering or undergoing breast reconstruction completed 3 assessments-card ranking, visual analog scale, and standard gamble-and psychosocial questionnaires. Each woman rated 9 health states with case-matched images: 4 …

Identification Of Frailty Clusters Using Cross-Sectional Frailty And Frailty Trajectory: Cohort Of Heart Failure Veterans, Javad Razjouyan, Saeed Tofighi, Ariela R Orkaby, Biykem Bozkurt, Amir Sharafkhaneh, Molly J Horstman, Parag Goyal, Christopher I Amos, Orna Intrator, Aanand D Naik

Faculty, Staff and Student Publications

BACKGROUND: Frailty is a syndrome associated with increased vulnerability and diminished physiological reserves. Three-quarters (78%) of heart failure (HF) patients are frail. Traditional frailty indices (FIs) assess cross-sectional deficits, while frailty trajectories (FTs) measure changes over time.

OBJECTIVES: This study aims to examine the interaction between FI and FT to enhance risk stratification in hospitalized adults with HF.

METHODS: This retrospective cohort study utilized data from the Veterans Health Administration, including 143,687 veterans aged >50 admitted for HF from 2005 to 2019. FT measurements were derived from FI calculations for each of the 3 years before index hospitalization. Unsupervised clustering …

Maternal Dysbiosis Produces Long-Lasting Behavioral Changes In Offspring, Jacob Hudobenko, Claudia M Di Gesù, Patrick R Mooz, Joseph Petrosino, Nagireddy Putluri, Bhanu P Ganesh, Kristen Rebeles, Frank W Blixt, Venugopal R Venna, Louise D Mccullough

Faculty, Staff and Student Publications

Advanced maternal age (AMA) is defined as a pregnancy in a woman older than 35 years of age. AMA increases the risk for both maternal and neonatal complications, including miscarriage and stillbirth. AMA has also been linked to neurodevelopmental and neuropsychiatric disorders in the offspring. Recent studies have found that age-associated compositional shifts in the gut microbiota contribute to altered microbial metabolism and enhanced inflammation in the host. We investigated the specific contribution of the maternal microbiome on pregnancy outcomes and offspring behavior by recolonizing young female mice with aged female microbiome prior to pregnancy. We discovered that pre-pregnancy colonization …

Interplay Between Skeletal Muscle Catabolism And Remodeling Of Arteriovenous Fistula By Yes-Associated Protein 1 (Yap1) Signaling, Yongdong Wu, Tae Hoon Lee, Owen H Cheng, Eric K Peden, Qingtian Li, Jun Wang, Fengzhang Huang, Marites P Melancon, David Sheikh-Hamad, Tao Wang, Luan Truong, William E Mitch, Ming Liang, Jizhong Cheng

Faculty, Staff and Student Publications

Key Points:

1. Atrophied muscle–derived myostatin stimulated mesenchymal stem cell differentiation and adverse arteriovenous (AV) fistula remodeling through yes-associated protein 1 (YAP1) activation.

2. Treatment with myostatin peptibody inhibited muscle wasting and blocked mesenchymal stem cell activation and AV fistula fibrosis.

3. A light-sensitive drug-release strategy was engineered for the periadventitial delivery of verteporfin to improve AV fistula patency.

Background: Arteriovenous (AV) fistulas are the preferred access for dialysis but have a high incidence of failure. The aim of this study was to understand the crosstalk between skeletal muscle catabolism and AV fistula maturation failure.

Methods: Skeletal muscle metabolism and AV fistula maturation …

Overlapping Clinical Phenotypes In Patients With Primary Ciliary Dyskinesia Or Activated Phosphoinositide 3-Kinase Delta Syndrome, Adam J Shapiro, Eveline Y Wu, Deborah J Morris-Rosendahl, Kenneth N Olivier, Sharon D Dell, Scott D Sagel, Cullen M Dutmer, Ricardo A Mosquera, Markus Rose, Michael G O'Connor, Chi A Ma, Gulbu Uzel, Timothy J Vece, Maimoona A Zariwala, Michael R Knowles, Margaret W Leigh, Stephanie D Davis, Thomas W Ferkol

Faculty, Staff and Student Publications

Primary ciliary dyskinesia and activated phosphoinositide 3-kinase delta syndrome type 1 present similarly, with recurrent respiratory infections and reduced nasal nitric oxide levels. When diagnostic confirmation of primary ciliary dyskinesia with genetic testing and/or ciliary electron microscopy is inconclusive, activated phosphoinositide 3-kinase delta syndrome type 1 and other inborn errors of immunity must be investigated.

Precision Proteogenomics Reveals Pan-Cancer Impact Of Germline Variants, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Kathleen J Imbach, Karl R Clauser, Myvizhi Esai Selvan, Isabel Mendizabal, Yifat Geffen, Yo Akiyama, Myranda Maynard, Tomer M Yaron, Yize Li, Song Cao, Erik P Storrs, Olivia S Gonda, Adrian Gaite-Reguero, Akshay Govindan, Emily A Kawaler, Matthew A Wyczalkowski, Robert J Klein, Berk Turhan, Karsten Krug, D R Mani, Felipe Da Veiga Leprevost, Alexey I Nesvizhskii, Steven A Carr, David Fenyö, Michael A Gillette, Antonio Colaprico, Antonio Iavarone, Ana I Robles, Kuan-Lin Huang, Chandan Kumar-Sinha, François Aguet, Alexander J Lazar, Lewis C Cantley, Urko M Marigorta, Zeynep H Gümüş, Matthew H Bailey, Gad Getz, Eduard Porta-Pardo, Li Ding

Faculty, Staff and Student Publications

We investigate the impact of germline variants on cancer patients' proteomes, encompassing 1,064 individuals across 10 cancer types. We introduced an approach, "precision peptidomics," mapping 337,469 coding germline variants onto peptides from patients' mass spectrometry data, revealing their potential impact on post-translational modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases. We identified rare pathogenic and common germline variants in cancer genes potentially affecting proteomic features, including variants altering protein abundance and structure and variants in kinases (ERBB2 and MAP2K2) impacting phosphorylation. Precision peptidome analysis predicted destabilizing events in signal-regulatory protein alpha (SIRPA) and glial …

Development Of A Reference Standard To Assign Bacterial Versus Viral Infection Etiology Using An All-Inclusive Methodology For Comparison Of Novel Diagnostic Tool Performance, Coburn Allen, J Kate Deanehan, Yaniv Dotan, Matthew A Eisenberg, Andrew M Fine, Jonathan Isenberg, Ann Kane, Dani Kirshner, Todd W Lyons, Yasmin Maor, Ami Neuberger, Daniel G Ostermayer, Sharona Paz, Oded Scheuerman, Shachaf Shiber, Victoria A Statler, Michal Stein, Renata Yakubov, Shirly Yanai, Roy Navon, Lior Kellerman, Tanya M Gottlieb, Eran Eden

Faculty, Staff and Student Publications

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included. Adjudicators, blinded to C-reactive protein, procalcitonin, and MeMed BV (MMBV), labeled each case (bacterial/viral/non-infectious/indeterminate). Initial adjudication involved 3 adjudicators. Reference standard cohorts were defined: Microbiologically confirmed (3/3 adjudicators concur with high confidence and a concordant microbiological finding), unanimous (3/3 adjudicators concur with high confidence), suspected (3/3 adjudicators concur with …