Digital Commons Network^™

Inclusion Of Premenopausal Women In Breast Cancer Clinical Trials, Kelsey L Corrigan, Ramez Kouzy, Joseph Abi Jaoude, Roshal R Patel, Rachel M Layman, Sharon H Giordano, Wendy A Woodward, Benjamin D Smith, Simona F Shaitelman, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.

METHODS: Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.

RESULTS: Of 170 breast …

Obstetric And Neonatal Outcomes 1 Or More Years After A Diagnosis Of Breast Cancer, Kirsten Jorgensen, Roni Nitecki, Hazel B Nichols, Shuangshuang Fu, Chi-Fang Wu, Alexander Melamed, Paula Brady, Mariana Chavez Mac Gregor, Mark A Clapp, Sharon Giordano, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis.

METHODS: We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December …

A Cross-National Comparison Of The Linkages Between Family Structure Histories And Early Adolescent Substance Use, Haley Stritzel, Michael Green, Robert Crosnoe

Faculty, Staff and Student Publications

Family structure can influence adolescent health with cascading implications into adulthood. Life course theory emphasizes how this phenomenon is dynamic across time, contextualized in policy systems, and grounded in processes of selection and socialization. This study used data from the U.S. (National Longitudinal Survey of Youth 1979 Child and Young Adults, n = 6,236) and U.K. (Millennium Cohort Study, n = 11,095) to examine associations between a single mother family structure between ages 0-14 and early adolescent substance use at age 14 across time and place, using inverse probability of treatment weighting to explore how results varied by selection into …

Conceptualization Of Surrogate Decision-Making Among Spokespersons For Chronically Ill Patients, Lauren J Van Scoy, Michael J Green, Theresa Smith, Erika Vandyke, Andrew J Foy, Laurie Badzek, Benjamin H Levi

Faculty, Staff and Student Publications

IMPORTANCE: The value of advance care planning (ACP) has been the subject of recent debate because of mixed findings. This may be, in part, because trials presume that researchers and patient spokespersons share the same understanding of the role of a surrogate decision-maker. We explored how patient surrogates conceptualized and defined surrogate decision-making vs patient advocacy. Understanding how surrogates perceive their role in decision-making is important to avoid misinterpreting the effectiveness of ACP interventions.

OBJECTIVE: To understand how patient spokespersons distinguish surrogate decision-making from patient advocacy.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative thematic analysis of a subsample of participants from …

Distinct Germline Genetic Susceptibility Profiles Identified For Common Non-Hodgkin Lymphoma Subtypes, Sonja I Berndt, Joseph Vijai, Yolanda Benavente, Nicola J Camp, Alexandra Nieters, Zhaoming Wang, Karin E Smedby, Geffen Kleinstern, Henrik Hjalgrim, Caroline Besson, Christine F Skibola, Lindsay M Morton, Angela R Brooks-Wilson, Lauren R Teras, Charles Breeze, Joshua Arias, Hans-Olov Adami, Demetrius Albanes, Kenneth C Anderson, Stephen M Ansell, Bryan Bassig, Nikolaus Becker, Parveen Bhatti, Brenda M Birmann, Paolo Boffetta, Paige M Bracci, Paul Brennan, Elizabeth E Brown, Laurie Burdett, Lisa A Cannon-Albright, Ellen T Chang, Brian C H Chiu, Charles C Chung, Jacqueline Clavel, Pierluigi Cocco, Graham Colditz, Lucia Conde, David V Conti, David G Cox, Karen Curtin, Delphine Casabonne, Immaculata De Vivo, Arjan Diepstra, W Ryan Diver, Ahmet Dogan, Christopher K Edlund, Lenka Foretova, Joseph F Fraumeni, Attilio Gabbas, Hervé Ghesquières, Graham G Giles, Sally Glaser, Martha Glenn, Bengt Glimelius, Jian Gu, Thomas M Habermann, Christopher A Haiman, Corinne Haioun, Jonathan N Hofmann, Theodore R Holford, Elizabeth A Holly, Amy Hutchinson, Aalin Izhar, Rebecca D Jackson, Ruth F Jarrett, Rudolph Kaaks, Eleanor Kane, Laurence N Kolonel, Yinfei Kong, Peter Kraft, Anne Kricker, Annette Lake, Qing Lan, Charles Lawrence, Dalin Li, Mark Liebow, Brian K Link, Corrado Magnani, Marc Maynadie, James Mckay, Mads Melbye, Lucia Miligi, Roger L Milne, Thierry J Molina, Alain Monnereau, Rebecca Montalvan, Kari E North, Anne J Novak, Kenan Onel, Mark P Purdue, Kristin A Rand, Elio Riboli, Jacques Riby, Eve Roman, Gilles Salles, Douglas W Sborov, Richard K Severson, Tait D Shanafelt, Martyn T Smith, Alexandra Smith, Kevin W Song, Lei Song, Melissa C Southey, John J Spinelli, Anthony Staines, Deborah Stephens, Heather J Sutherland, Kaitlyn Tkachuk, Carrie A Thompson, Hervé Tilly, Lesley F Tinker, Ruth C Travis, Jenny Turner, Celine M Vachon, Claire M Vajdic, Anke Van Den Berg, David J Van Den Berg, Roel C H Vermeulen, Paolo Vineis, Sophia S Wang, Elisabete Weiderpass, George J Weiner, Stephanie Weinstein, Nicole Wong Doo, Yuanqing Ye, Meredith Yeager, Kai Yu, Anne Zeleniuch-Jacquotte, Yawei Zhang, Tongzhang Zheng, Elad Ziv, Joshua Sampson, Nilanjan Chatterjee, Kenneth Offit, Wendy Cozen, Xifeng Wu, James R Cerhan, Stephen J Chanock, Susan L Slager, Nathaniel Rothman

Faculty, Staff and Student Publications

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9,505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P<5 >× 10−8) for subsets of NHL subtypes, …

Tilsotolimod Exploits The Tlr9 Pathway To Promote Antigen Presentation And Type 1 Ifn Signaling In Solid Tumors: A Multicenter International Phase I/Ii Trial (Illuminate-101), Hani Babiker, Erkut Borazanci, Vivek Subbiah, Sanjiv Agarwala, Alain Algazi, Jacob Schachter, Michael Lotem, Corinne Maurice-Dror, Daniel Hendler, Shah Rahimian, Hans Minderman, Cara Haymaker, Daruka Mahadevan, Chantale Bernatchez, Ravi Murthy, Rolf Hultsch, Nadia Kaplan, Gregory Woodhead, Charles Hennemeyer, Srinivas Chunduru, Peter M Anderson, Adi Diab, Igor Puzanov

Faculty, Staff and Student Publications

PURPOSE: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors.

PATIENTS AND METHODS: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the …

Mathematical Modeling Of Cancer Immunotherapy For Personalized Clinical Translation, Joseph D Butner, Prashant Dogra, Caroline Chung, Renata Pasqualini, Wadih Arap, John Lowengrub, Vittorio Cristini, Zhihui Wang

Faculty, Staff and Student Publications

Encouraging advances are being made in cancer immunotherapy modeling, especially in the key areas of developing personalized treatment strategies based on individual patient parameters, predicting treatment outcomes and optimizing immunotherapy synergy when used in combination with other treatment approaches. Here we present a focused review of the most recent mathematical modeling work on cancer immunotherapy with a focus on clinical translatability. It can be seen that this field is transitioning from pure basic science to applications that can make impactful differences in patients' lives. We discuss how researchers are integrating experimental and clinical data to fully inform models so that …

Further Evidence That Arih1 Rare Variants Predispose To Thoracic Aortic Disease, Maura L Boerio, Nicole M Engelhardt, Sanmati Cuddapah, Jessica I Gold, Isabella C Marin, Amélie Pinard, Dongchuan Guo, Siddharth K Prakash, Dianna M Milewicz

Faculty, Staff and Student Publications

No abstract provided.

Defective Synaptic Plasticity In A Model Of Coffin-Lowry Syndrome Is Rescued By Simultaneously Targeting Pka And Mapk Pathways, Rong-Yu Liu, Yili Zhang, Paul Smolen, Leonard J Cleary, John H Byrne

Faculty, Staff and Student Publications

Empirical and computational methods were combined to examine whether individual or dual-drug treatments can restore the deficit in long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse observed in a cellular model of Coffin–Lowry syndrome (CLS). The model was produced by pharmacological inhibition of p90 ribosomal S6 kinase (RSK) activity. In this model, coapplication of an activator of the mitogen-activated protein kinase (MAPK) isoform ERK and an activator of protein kinase A (PKA) resulted in enhanced phosphorylation of RSK and enhanced LTF to a greater extent than either drug alone and also greater than their additive effects, which is termed …

Dysregulation Of Complement System In Neuropsychiatric Disorders: A Mini Review, Danny Perez Sierra, Ashutosh Tripathi, Anilkumar Pillai

Faculty, Staff and Student Publications

Complement system is one of the most important defense mechanisms of the innate immune system. In addition to their roles in immune regulation, complement proteins are also involved in neurodevelopment and adult brain plasticity. Complement dysregulation has been shown in neurodevelopmental disorders including schizophrenia and autism spectrum disorder as well as in mood disorders. A number of clinical as well as genetic studies suggest the role of complement proteins in the cortical thinning and excessive synaptic pruning frequently associated with schizophrenia. The changes in complement proteins are also associated with the pathophysiology of autism spectrum disorder, major depressive disorder and …

Which Children Are Frequently Victimized In Us Elementary Schools? Population-Based Estimates, Paul L Morgan, Adrienne D Woods, Yangyang Wang, George Farkas, Yoonkyung Oh, Marianne M Hillemeier, Cynthia Mitchell

Faculty, Staff and Student Publications

We analyzed a population-based cohort of 11,780 U.S. kindergarten children to identify risk and protective factors predictive of frequent verbal, social, reputational, and/or physical bullying victimization during the upper elementary grades. We also stratified the analyses by biological sex. Both girls and boys displaying kindergarten externalizing problem behaviors were at consistently higher risk of frequent victimization during 3rd-5th grade (for the combined sample of boys and girls, verbal odds ratio [OR] = 1.82, social OR = 1.60, reputational OR = 1.85, physical OR = 1.67, total OR = 1.93). Hispanic children relative to non-Hispanic White children and those from higher …

Delayed-Interval Delivery In Multiple Gestation Pregnancies: Neonatal Mortality, Morbidity, And Development, Nicolas J Bouey, Shampa Saha, Deanne E Wilson-Costello, Matthew A Rysavy, Michele Walsh, Myra H Wyckoff, Anna Maria Hibbs

Faculty, Staff and Student Publications

OBJECTIVE: Delayed-interval delivery (DID) is the delivery of the first fetus in a multiple gestation pregnancy without prompt delivery of the remaining fetus(es). We aimed to assess infant outcomes of DID.

STUDY DESIGN: We performed a retrospective cohort study of infants born 22-28 weeks' gestation or weighing 401-1500 g. DID was defined as a passage of >24 h between the birth of firstborn and retained infants. Rates of mortality, morbidity, and developmental outcomes were compared within DID multiples, to other multiples not born by DID, and all infants in the Generic Database and follow-up datasets (excluding DID-born).

RESULTS: DID-born multiples …

Reproducing Statistics Performed In Published Randomized Controlled Trials, Naila H Dhanani, Oscar A Olavarria, Cynthia S Bell, Julie L Holihan, Mike K Liang

Faculty, Staff and Student Publications

INTRODUCTION: Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs.

METHODS: PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. …

Etiology And Pathophysiology Of Hypoparathyroidism: A Narrative Review, Janice L Pasieka, Kelly Wentworth, Caitlin T Yeo, Serge Cremers, David Dempster, Seiji Fukumoto, Ravinder Goswami, Pascal Houillier, Michael A Levine, Jesse D Pasternak, Nancy D Perrier, Antonio Sitges-Serra, Dolores M Shoback

Faculty, Staff and Student Publications

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness …

Extensive Accumulation Of Misfolded Protein Aggregates During Natural Aging And Senescence, Karina Cuanalo-Contreras, Jonathan Schulz, Abhisek Mukherjee, Kyung-Won Park, Enrique Armijo, Claudio Soto

Faculty, Staff and Student Publications

Accumulation of misfolded protein aggregates is a hallmark event in many age-related protein misfolding disorders, including some of the most prevalent and insidious neurodegenerative diseases. Misfolded protein aggregates produce progressive cell damage, organ dysfunction, and clinical changes, which are common also in natural aging. Thus, we hypothesized that aging is associated to the widespread and progressive misfolding and aggregation of many proteins in various tissues. In this study, we analyzed whether proteins misfold, aggregate, and accumulate during normal aging in three different biological systems, namely senescent cells,

Non-Traumatic Open Globe Injuries: Presenting Characteristics And Visual Outcomes, Andrew W Gross, James Z Fan, Margaret L Pfeiffer, Alice Z Chuang, Karina Richani, Eric L Crowell

Faculty, Staff and Student Publications

Purpose: To describe clinical characteristics and visual outcomes of non-traumatic open globe injuries.

Setting: A level 1 trauma centre in a large urban medical centre.

Design: Retrospective study.

Methods: Charts of non-traumatic open globe patients admitted to MHH-TMC from 1/2010 to 3/2015 were reviewed for demographics, cause, clinical characteristics, visual acuity (VA) and enucleation.

Results: Thirty eyes were included: 15 (50%) were males with a mean age of 47 (±28) years. All presented with zone 1 injury. Twenty-five (83%) had a perforated corneal ulcer. Presenting VA was count fingers (n = 3, 10%) to NLP (n = 6, 20%). Twenty-four …

Evaluation Of Murine Host Sex As A Biological Variable In Transplanted Human Intestinal Organoid Development, Eoin P Mcneill, Vikas S Gupta, David J Sequeira, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Background: Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.

Aims: We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.

Methods: HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8-9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR …

Using Single Molecule Molecular Inversion Probes As A Cost-Effective, High-Throughput Sequencing Approach To Target All Genes And Loci Associated With Macular Diseases, Rebekkah J Hitti-Malin, Claire-Marie Dhaenens, Daan M Panneman, Zelia Corradi, Mubeen Khan, Anneke I Den Hollander, G Jane Farrar, Christian Gilissen, Alexander Hoischen, Maartje Van De Vorst, Femke Bults, Erica G M Boonen, Patrick Saunders, Susanne Roosing, Frans P M Cremers

Faculty, Staff and Student Publications

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 …

A Cluster-Randomized Controlled Trial Of Automated Internet Weight-Loss Programs In Primary Care: Role Of Automated Provider Feedback, Deborah F Tate, Jennifer L Kraschnewski, Caitlin Martinez, Molly Diamond, Susan Veldheer, Kevin O Hwang, Erik B Lehman, Chengwu Yang, Christopher N Sciamanna

Faculty, Staff and Student Publications

OBJECTIVE: Despite the high prevalence of obesity and associated health risks in the United States adult population, few primary care providers (PCPs) have time and training to provide weight-management counseling to their patients. This study aims to compare the effect of referral to a comprehensive automated digital weight-loss program, with or without provider email feedback, with usual care on weight loss in patients with overweight or obesity.

METHODS: A total of 550 adults (mean [SD], 51.4 [11.2] years, BMI = 35.1 [5.5] kg/m

RESULTS: Weight changes (mean [SE]) at 12 months were -0.92 (0.46), -3.68 (0.46), and -3.58 (0.48) kg …

Association Of Patient Belief About Success Of Antibiotics For Appendicitis And Outcomes: A Secondary Analysis Of The Coda Randomized Clinical Trial, Writing Group For The Coda Collaborative, Irene Y Zhang, Emily C Voldal, Giana H Davidson, Joshua M Liao, Callie M Thompson, Wesley H Self, Lillian S Kao, Jill Cherry-Bukowiec, Krishnan Raghavendran, Amy H Kaji, Daniel A Deugarte, Eva Gonzalez, Katherine A Mandell, Kristen Ohe, Nicole Siparsky, Thea P Price, David C Evans, Jesse Victory, William Chiang, Alan Jones, Matthew E Kutcher, Hailie Ciomperlik, Mike K Liang, Heather L Evans, Brett A Faine, Miriam Neufeld, Sabrina E Sanchez, Anusha Krishnadasan, Bryan A Comstock, Patrick J Heagerty, Sarah O Lawrence, Sarah E Monsell, Erin E C Fannon, Larry G Kessler, David A Talan, David R Flum

Faculty, Staff and Student Publications

IMPORTANCE: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials.

OBJECTIVE: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive …

Continued Treatment With Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: Data From Senscis-On, Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Martina Gahlemann, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland, Senscis-On Trial Investigators

Faculty, Staff and Student Publications

Objectives: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) versus placebo, with adverse events that were manageable for most patients. An open-label extension trial, SENSCIS-ON, is assessing safety and FVC decline during longer term nintedanib treatment.

Methods: Patients who completed the SENSCIS trial or a drug-drug interaction (DDI) study of nintedanib and oral contraceptive on treatment were eligible to enter SENSCIS-ON. Adverse events and changes in FVC over 52 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib …

A Phase Ii Randomized Double Blinded Trial Evaluating The Efficacy Of Curcumin With Pre-Operative Chemoradiation For Rectal Cancer, Jillian R Gunther, Awalpreet S Chadha, Sushovan Guha, Gottumukkala S Raju, Dipen M Maru, Mark F Munsell, Yan Jiang, Peiying Yang, Edd Felix, Marilyn Clemons, Geena George Mathew, Pankaj K Singh, John M Skibber, Miguel A Rodriguez-Bigas, George J Chang, Cathy Eng, Marc E Delclos, Christopher H Crane, Prajnan Das, Sunil Krishnan

Faculty, Staff and Student Publications

Background

In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods

From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. …

An Optimized Cell-Based Assay To Assess Influenza Virus Replication By Measuring Neuraminidase Activity And Its Applications For Virological Surveillance, Mira C Patel, Daniel Flanigan, Chenchen Feng, Anton Chesnokov, Ha T Nguyen, Anwar Abd Elal, John Steel, Rebecca J Kondor, David E Wentworth, Larisa V Gubareva, Vasiliy P Mishin

Faculty, Staff and Student Publications

Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of …

Predictors For Outcomes Of Noninvasive, Individualized Transcranial Magnetic Neuromodulation In Multiple Sclerosis Women With Neurogenic Voiding Dysfunction, Yongchang Jang, Khue Tran, Zhaoyue Shi, Karmonik Christof, Darshil Choksi, Betsy H Salazar, John A Lincoln, Rose Khavari

Faculty, Staff and Student Publications

Purpose:

Multiple sclerosis (MS) is a multifocal demyelinating disease that affects the central nervous system (CNS) and commonly leads to neurogenic lower urinary tract dysfunction (NLUTD). Proper storage and release of urine relies on synchronized activity of the LUT, which is meticulously regulated by supraspinal circuits, making it vulnerable to diseases such as MS. NLUTD, characterized by voiding dysfunction (VD), storage issues, or a combination of both is a common occurrence in MS. Unfortunately, there are limited treatment options for NLUTD, making the search for alternative treatments such as transcranial rotating permanent magnet stimulation (TRPMS) of utmost importance. To assess …

A Pilot Survey: Retention In Pain Medicine Among Fellowship Trained Anesthesiologists, Sarang S Koushik, Kelly Leap, Kenneth Seier, Kay See Tan, Naum Shaparin, Alan D Kaye, Omar Viswanath, Grant H Chen

Faculty, Staff and Student Publications

BACKGROUND: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine.

OBJECTIVES/STUDY DESIGN: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists.

METHODS: In this study, all 114 pain …

Unilateral ‘Crazy-Paving’ Pattern: An Exceptional Presentation Of Squamous Cell Carcinoma Of The Lung, Sumeera Banday, Shamim U Khan, Sabina Khan, Surinderpal S Anand, Ashok Shah

Faculty, Staff and Student Publications

The 'crazy-paving' pattern on high resolution computed tomography (HRCT) is a distinct imaging appearance that is still considered to be a radiological hallmark of pulmonary alveolar proteinosis. However, since its first description about three decades ago, more than 40 different clinical entities presenting as 'crazy-paving' patterns have been documented. This rather remarkable but uncommon imaging appearance is now considered to be a non-specific manifestation. A 62-year-old male referred for evaluation of productive cough, breathlessness and fever presented with 'crazy-paving' pattern on HRCT. Endobronchial biopsy done on presentation was consistent with the diagnosis of squamous cell carcinoma. This report highlights this …

Chemoradiation Therapy Alters The Pd-L1 Score In Locoregional Recurrent Squamous Cell Carcinomas Of The Head And Neck, Brian J Park, Austin K Mattox, Daniel Clayburgh, Mihir Patel, R Bryan Bell, Bevan Yueh, Rom Leidner, Hong Xiao, Marcus Couey, Shiting Li, Tingting Qin, Maureen A Sartor, Belinda Cairns, Tracy Macdonough, Kyle Halliwill, Daniel Deschler, Derrick T Lin, William C Faquin, Peter M Sadow, Sara I Pai

Faculty, Staff and Student Publications

PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did …

Association Of Initial Sars-Cov-2 Test Positivity With Patient-Reported Well-Being 3 Months After A Symptomatic Illness, Lauren E Wisk, Michael A Gottlieb, Erica S Spatz, Huihui Yu, Ralph C Wang, Benjamin H Slovis, Sharon Saydah, Ian D Plumb, Kelli N O'Laughlin, Juan Carlos C Montoy, Samuel A Mcdonald, Zhenqiu Lin, Jin-Mann S Lin, Katherine Koo, Ahamed H Idris, Ryan M Huebinger, Mandy J Hill, Nicole L Gentile, Anna Marie Chang, Jill Anderson, Bala Hota, Arjun K Venkatesh, Robert A Weinstein, Joann G Elmore, Graham Nichol, Inspire Group

Faculty, Staff and Student Publications

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.

OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive …

Freedom As Prevention: Mechanisms Of Autonomy Support For Promoting Hiv Pre-Exposure Prophylaxis Use And Condom Use Among Black Msm In 3 Us Cities—Hptn 073, Laron E Nelson, Donte T Boyd, Geetha Beauchamp, Lynda Emel, Leo Wilton, Darren Whitfield, S Raquel Ramos, Wale Ajiboye, Mandy J Hill, Donaldson F Conserve, Portia Thomas, Lisa Hightow-Weidman, Steve Shoptaw, Manya Magnus, Kenneth H Mayer, Estelle Piwowar-Manning, Sheldon D Fields, Darrell P Wheeler, Hptn 073 Study Team

Faculty, Staff and Student Publications

Healthcare providers who use controlling or coercive strategies may compel short-term enactment of HIV and sexually transmitted infection prevention behaviors but may inadvertently undermine their client's motivation to maintain those behaviors in the absence of external pressure. Autonomous motivation refers to the self-emanating and self-determined drive for engaging in health behaviors. It is associated with long-term maintenance of health behaviors. We used structural equation modeling to investigate whether autonomy support was associated with increased odds of therapeutic serum levels of pre-exposure prophylaxis, through a pathway that satisfies basic psychological needs for autonomous self-regulation and competence regarding pre-exposure prophylaxis use. We …

Remodeling Of The Plasma Membrane By Surface-Bound Protein Monomers And Oligomers: The Critical Role Of Intrinsically Disordered Regions, Mussie K Araya, Yong Zhou, Alemayehu A Gorfe

Faculty, Staff and Student Publications

The plasma membrane (PM) of cells is a dynamic structure whose morphology and composition is in constant flux. PM morphologic changes are particularly relevant for the assembly and disassembly of signaling platforms involving surface-bound signaling proteins, as well as for many other mechanochemical processes that occur at the PM surface. Surface-bound membrane proteins (SBMP) require efficient association with the PM for their function, which is often achieved by the coordinated interactions of intrinsically disordered regions (IDRs) and globular domains with membrane lipids. This review focuses on the role of IDR-containing SBMPs in remodeling the composition and curvature of the PM. …