Digital Commons Network^™

Adding Metastasis-Directed Therapy To Standard-Of-Care Systemic Therapy For Oligometastatic Breast Cancer (Extend): A Multicenter, Randomized Phase 2 Trial, Jay P Reddy, Alexander D Sherry, Bryan Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Lorenzo Cohen, Benjamin D Smith, David Ramirez, Simona F Shaitelman, Stephen G Chun, Marina Medina-Rosales, Mediget Teshome, Abenaa Brewster, Carlos H Barcenas, Alexandre Reuben, Amol J Ghia, Ethan B Ludmir, Daniel Weed, Shalin J Shah, Melissa P Mitchell, Wendy A Woodward, Daniel R Gomez, Chad Tang

Faculty, Staff and Student Publications

PURPOSE: Prior evidence suggests a progression-free survival (PFS) benefit from adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy for patients with some oligometastatic solid tumors. Randomized trials testing this hypothesis in breast cancer have yet to be published. We sought to determine whether adding MDT to SOC systemic therapy improves PFS in oligometastatic breast cancer.

METHODS AND MATERIALS: External Beam Radiation to Eliminate Nominal Metastatic Disease is a multicenter phase 2 randomized basket trial testing the addition of MDT to SOC systemic therapy in patients with ≤5 metastases (NCT03599765). Patients were randomly assigned 1:1 to MDT (definitive local treatment …

Extensive Epigenomic Dysregulation Is A Hallmark Of Homologous Recombination Deficiency In Triple-Negative Breast Cancer, Youdinghuan Chen, Lucas A Salas, Jonathan D Marotti, Nicole P Jenkins, Chao Cheng, Todd W Miller, Arminja N Kettenbach, Brock C Christensen

Faculty, Staff and Students Publications

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with substantial disease heterogeneity, limited treatment options, and dismal clinical outcomes. Some TNBCs display homologous recombination deficiency (HRD), a phenotype with elevated genomic burden and worse prognosis if left untreated but chemotherapeutic sensitivity. While the molecular landscape of TNBC is distinct from other breast cancer subtypes, the TNBC-specific link between HRD and epigenome-wide methylation has not been established. This study reports two independent cohorts of TNBC tumors (n = 32 and n = 58) with HRD and epigenomic landscapes measured by the Multiplex Ligation-dependent Probe Amplification assay and the …

Matrix Metalloproteinases Accelerate Pericellular Matrix Breakdown And Disrupt Mechanotransduction In Osteoarthritis, Jule Nieuwstraten, Rosa Riester, Ulf Krister Hofmann, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

The pericellular matrix (PCM) is a specialized, narrow matrix surrounding each chondrocyte in articular cartilage, together constituting the chondron - the fundamental metabolic and functional unit of cartilage. The PCM plays a vital role in mediating biomechanical and biochemical signals essential for chondrocyte function. In osteoarthritis (OA), a chronic joint disorder characterized by progressive cartilage degradation, the PCM is one of the earliest sites of catabolic degradation, primarily driven by matrix metalloproteinases (MMPs). This study aims to investigate the functional relationship between PCM degradation and chondrocyte mechanosignaling, with an emphasis on MMP-driven changes in mechanotransduction in osteoarthritic cartilage. Human chondrons …

Investigation Of Dynamic Regulation Of Tfeb Nuclear Shuttling By Microfluidics And Quantitative Modelling, Iacopo Ruolo, Sara Napolitano, Lorena Postiglione, Gennaro Napolitano, Andrea Ballabio, Diego Di Bernardo

Duncan NRI Faculty and Staff Publications

Transcription Factor EB (TFEB) controls lysosomal biogenesis and autophagy in response to nutritional status and other stress factors. Although its regulation by nuclear translocation is known to involve a complex network of well-studied regulatory processes, the precise contribution of each of these mechanisms is unclear. Using microfluidics technology and real-time imaging coupled with mathematical modelling, we explored the dynamic regulation of TFEB under different conditions. We found that TFEB nuclear translocation upon nutrient deprivation happens in two phases: a fast one characterised by a transient boost in TFEB dephosphorylation dependent on transient calcium release mediated by mucolipin 1 (MCOLN1) followed …

Superior Preclinical Efficacy Of Co-Treatment With Brg1/Brm And Flt3 Inhibitor Against Aml Cells With Flt3 Mutations, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K Reville, Lauren B Flores, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Kapil N Bhalla

Faculty, Staff and Student Publications

Although treatment with standard frontline therapies, including a FLT3 inhibitor (FLT3i) reduces AML burden and achieves clinical remissions, most patients with AML with FLT3 mutation relapse due to therapy-resistant stem/progenitor cells. The core ATPases, BRG1 (SMARCA4) and BRM (SMARCA2) of the canonical (c) BAF (BRG1/BRM-associated factor) complex is a dependency in AML cells, including those harboring FLT3 mutations. We have previously reported that treatment with FHD-286, a BRG1/BRM ATPases inhibitor, induces differentiation and loss of viability of AML stem/progenitor cells. Findings of present studies demonstrate that treatment with FHD-286 induces lethality in AML cells, regardless of sensitivity or resistance to …

Apc/C-Mediated Ubiquitylation Of Extranucleosomal Histone Complexes Lacking Canonical Degrons, Aleksandra Skrajna, Kyle M Lapak, Anh Nguyen, Dennis Goldfarb, Et Al.

2020-Current year OA Pubs

Non-degradative histone ubiquitylation plays a myriad of well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of degradative histone ubiquitylation on genomic processes has remained elusive. Recently, the APC/C has been shown to ubiquitylate histones to regulate gene expression in pluripotent cells, but the molecular mechanism is unclear. Here we show that despite directly binding to the nucleosome through subunit APC3, the APC/C is unable to ubiquitylate nucleosomal histones. In contrast, extranucleosomal H2A/H2B and H3/H4 complexes are broadly ubiquitylated by the APC/C in an unexpected manner. Using a combination of cryo-electron …

Precision Phenotyping For Curating Research Cohorts Of Patients With Unexplained Post-Acute Sequelae Of Covid-19, Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews …

Should Proximal Fixation Be At C2 Or C3-C4? An Application Of The Operative Value Index For Elective Posterior Cervical Decompression And Fusion, Advith Sarikonda, D. Mitchell Self, Danyal Quraishi, Ashmal Sami, Emily L. Isch, Steven Glener, Joshua Heller, Srinivas Prasad, Ashwini Sharan, Jack Jallo, Alex R. Vaccaro, James Harrop, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: There is clinical equipoise regarding the ideal upper instrumented vertebrae (UIV) for elective posterior cervical decompression and fusion (PCDF). Instrumentation may be performed at the axial C2 level, or at the subaxial C3/C4 vertebrae. To our knowledge, a true "value" (outcomes per dollar spent) comparison axial versus subaxial UIV for PCDF has never been performed.

METHODS: We retrospectively identified 275 long-segment (≥3-levels fused) PCDFs with available Neck Disability Index (NDI) scores at baseline and at 3 months postoperatively. C2 UIV (n = 67) was compared to C3/C4 UIV (n = 208). Time-driven activity-based costing was applied to identify the …

Body Composition And Its Outcomes And Management In Multiple Sclerosis: Narrative Review, Ariel Kidwell-Chandler, Justin Jackson, Brenda Jeng, Stephanie L Silveira, Lara A Pilutti, Paul R Hibbing, Robert W Motl

Faculty, Staff and Student Publications

Background: There is emerging interest in obesity and its prevalence, outcomes, and management in people with multiple sclerosis (MS). Body mass index (BMI) is the traditional marker of obesity in MS, whereas body composition, inclusive of specific body tissue compartments (e.g., fat, bone, and muscle), is often overlooked despite its relevance.

Objective: This narrative review (a) underscored the use and utility of dual-energy X-ray absorptiometry (DEXA) as an accurate and reliable measure of body composition; (b) thematically analyzed and synthesized the current evidence regarding body composition (using DEXA); and (c) determined gaps to be addressed in future research. Methods: …

Tunneling Nanotube-Like Structures Regulate Distant Cellular Interactions During Heart Formation, Lianjie Miao, Yangyang Lu, Anika Nusrat, Guizhen Fan, Shaohua Zhang, Luqi Zhao, Chia-Ling Wu, Hongyan Guo, Trang Le Nu Huyen, Yi Zheng, Zhen-Chuan Fan, Weinian Shou, Robert J Schwartz, Yu Liu, Ashok Kumar, Haixin Sui, Irina I Serysheva, Alan R Burns, Leo Q Wan, Bin Zhou, Sylvia M Evans, Mingfu Wu

Faculty, Staff and Student Publications

In the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube-like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and …

Preoperative Brain Volume Loss Is Associated With Postoperative Delirium In Advanced Heart Failure Patients Supported By Left Ventricular Assist Device, Iván Murrieta-Álvarez, Jacob P Scioscia, José M Benítez-Salazar, Jason Uwaeze, Zicheng Xu, Guangyao Zheng, Shiyi Li, Vladimir Braverman, Carl P Walther, Alexis E Shafii, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Delirium is a common neurological complication in patients with advanced heart failure (ADHF) following left ventricular assist device (LVAD) implantation, significantly impacting recovery. This study aimed to analyze non-contrast computed tomography (CT) scans of the brain in ADHF patients undergoing LVAD implantation to determine the association between pre-existing brain atrophy and postoperative delirium. A study involving 166 ADHF patients was conducted from March 2020 to July 2023. Non-contrast CT scans were analyzed using advanced quantitative neuroimaging techniques before implantation. The primary marker assessed was the lateral ventricle fraction (LVF), with secondary markers including cortical gray matter fraction (cGMF), white matter …

Exploration Of Working Memory Retrieval Stage For Mild Cognitive Impairment: Time-Varying Causality Analysis Of Electroencephalogram Based On Dynamic Brain Networks, Yi Jiang, Zhiwei Guo, Xiaobo Zhou, Ning Jiang, Jiayuan He

Faculty, Staff and Student Publications

Background: Mild Cognitive Impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and Alzheimer's disease (AD). Its management is crucial for it helps intervene and slow the progression of cognitive decline to AD. However, the understanding of the MCI mechanism is not completely clear. As working memory (WM) damage is a common symptom of MCI, this study focused on the core stage of WM, i.e., the memory retrieval stage, to investigate information processing and the causality relationships among brain regions based on electroencephalogram (EEG) signals.

Method: 21 MCI and 20 normal cognitive control (NC) participants …

Youtube User Traffic To Paired Epilepsy Education Videos In English And Spanish: Comparative Study., Luna Kimahri Varela, Stephanie Horton, Ahmed Abdelmoity, Jean-Baptist Lepichon, Mark A. Hoffman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Effectively managing epilepsy in children necessitates the active engagement of parents, a factor that is reliant on their understanding of this neurological disorder. Widely available, high-quality, patient-focused, bilingual videos describing topics important for managing epilepsy are limited. YouTube Analytics is a helpful resource for gaining insights into how users of differing backgrounds consume video content.

OBJECTIVE: This study analyzes traffic to paired educational videos of English and Spanish versions of the same content. By examining the use patterns and preferences of individuals seeking information in different languages, we gained valuable insights into how language influences the use of clinical …

New Recommendations For Reversal Of High-Dose Methotrexate Cytotoxicity With Folinic Acid., Jesper Heldrup, Archie Bleyer, Laura Ramsey, Lauren Schaff, Brooke Bernhardt, Stefan Schwartz, Etienne Chatelut, Miriam Hwang, Carolina Ten, Martin Guscott, Scott Howard

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Folinic acid (FA) rescue protocols to counter the adverse effects of high-dose methotrexate (HDMTX) vary widely, and the risk of over-rescue and potential adverse effects of excessive FA (e.g., hypercalcemia) are under-recognized issues when providing augmented rescue in cases of delayed methotrexate elimination (DME). This opinion summary defines over-rescue, describes its potential adverse impacts, highlights the risk of hypercalcemia associated with excessive FA dosing in patients with acute kidney injury (AKI) from HDMTX, and provides recommendations to improve safety and efficacy of FA rescue in patients receiving HDMTX.

METHODS: A multidisciplinary panel of experts with clinical experience in HDMTX …

Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

Faculty, Staff and Student Publications

Background: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings.

Methods: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

Efficacy And Safety Of Venetoclax Plus Azacitidine For Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes, Jacqueline S Garcia, Uwe Platzbecker, Olatoyosi Odenike, Shaun Fleming, Chun Yew Fong, Uma Borate, Meagan A Jacoby, Daniel Nowak, Maria R Baer, Pierre Peterlin, Brenda Chyla, Huipei Wang, Grace Ku, David Hoffman, Jalaja Potluri, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). …

Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings.

METHODS: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through …

Differences In Plasma Metabolome Between Non-Hispanic White And Non-Hispanic Black Women, Ghazaleh Pourali, Liang Li, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: To understand potential racial differences in disease susceptibility and develop targeted prevention strategies, it is essential to establish biological differences between racial groups in healthy individuals. However, knowledge about how race impacts metabolites is limited. We therefore performed a cross-sectional study using comprehensive metabolomics analysis to investigate racial differences in metabolites among 506 non-Hispanic White (NHW) women and 163 non-Hispanic Black (NHB) women.

METHODS: We performed untargeted plasma metabolomic profiling using Metabolon's platform (Durham, NC®) and identified 1074 metabolites in 9 super-pathways. We used multivariable linear regression models, adjusted for confounders, to identify associations between race and metabolites. We …

Structure-Guided Design Of Partial Agonists At An Opioid Receptor, Balazs R Varga, Sarah M Bernhard, Amal El Daibani, Jhoan Aguilar, Kevin Appourchaux, Alexa Kouvelis, Amynah Pradhan, Susruta Majumdar, Tao Che, Et Al.

2020-Current year OA Pubs

Chronic pain and opioid overdose deaths highlight the need for non-addictive analgesics with novel mechanisms. The δ opioid receptor (δOR) is a promising target, as it lacks the respiratory depression associated with µ opioid receptor (µOR) agonists. However, early δOR full agonists caused seizures, limiting their clinical use. Partial δOR agonists may offer more controlled receptor activation than full agonists, but their development has been hindered by uncertainty regarding the molecular mechanism of partial agonism. Here we show that C6-Quino, a bitopic ligand developed through structure-based design, acts as a selective δOR partial agonist. Functional studies reveal that C6-Quino shows …

Worldwide Innovative Network (Win) Consortium In Personalized Cancer Medicine: Bringing Next-Generation Precision Oncology To Patients., Wafik S El-Deiry, Catherine Bresson, Fanny Wunder, Benedito A Carneiro, Don S Dizon, Jeremy L Warner, Stephanie L Graff, Christopher G Azzoli, Eric T Wong, Liang Cheng, Sendurai A Mani, Howard P Safran, Casey Williams, Tobias Meissner, Benjamin Solomon, Eitan Rubin, Angel Porgador, Guy Berchem, Pierre Saintigny, Amir Onn, Jair Bar, Raanan Berger, Manon Gantenbein, Zhen Chen, Cristiano De Pádua Souza, Rui Manuel Vieira Reis, Marina Sekacheva, Andrés Cervantes, William L Dahut, Christina M Annunziata, Kerri Gober, Khaled M Musallam, Humaid O Al-Shamsi, Ibrahim Abu-Gheida, Ramon Salazar, Sewanti Limaye, Adel T Aref, Roger R Reddel, Mohammed Ussama Al Homsi, Abdul Rouf, Said Dermime, Jassim Al Suwaidi, Catalin Vlad, Rares Buiga, Amal Al Omari, Hikmat Abdel-Razeq, Luis F Oñate-Ocaña, Finn Cilius Nielsen, Leah C. Graham, Jens Rueter, Anthony M Joshua, Eugenia Girda, Steven Libutti, Gregory Riedlinger, Mohammed E Salem, Carol J Farhangfar, Ruben A Mesa, Bishoy M Faltas, Olivier Elemento, C S Pramesh, Manju Sengar, Satoru Aoyama, Sadakatsu Ikeda, Ioana Berindan-Neagoe, Himabindu Gaddipati, Mandar Kulkarni, Elisabeth Auzias, Maria Gerogianni, Nicolas Wolikow, Simon Istolainen, Pessie Schlafrig, Naftali Z Frankel, Amanda R Ferraro, Jim Palma, Alejandro Piris Gimenez, Alberto Hernando-Calvo, Enriqueta Felip, Apostolia M Tsimberidou, Roy S Herbst, Josep Tabernero, Richard L Schilsky, Jia Liu, Yves Lussier, Jacques Raynaud, Gerald Batist, Shai Magidi, Razelle Kurzrock

Faculty Research 2025

The human genome project ushered in a genomic medicine era that was largely unimaginable three decades ago. Discoveries of druggable cancer drivers enabled biomarker-driven gene- and immune-targeted therapy and transformed cancer treatment. Minimizing treatment not expected to benefit, and toxicity-including financial and time-are important goals of modern oncology. The Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine founded by Drs. John Mendelsohn and Thomas Tursz provided a vision for innovation, collaboration and global impact in precision oncology. Through pursuit of transcriptomic signatures, artificial intelligence (AI) algorithms, global precision cancer medicine clinical trials and input from an international Molecular Tumor …

Respiratory Muscle Training Reduces Painful Swallowing And Opioid Use During Radiation Therapy For Head And Neck Cancer: A Matched Pair Analysis, Andrew D. Ray, Chi-Chen Hong, Nicolas F. Schlecht, Han Yu, Kristopher Attwood, Kent L. Nastiuk, Bryan A. Spinelli, Ann Marie Flores, Hillary Jacobson, Julia Fulfaro, M. Jeffrey Mador, Austin J. Iovoli, Mark K. Farrugia, Anurag K. Singh

Department of Physical Therapy Faculty Papers

BACKGROUND: Patients with head and neck cancer (HNC) receiving radiation therapy (RT) are at increased risk for symptoms of oral mucositis (OM), opioid use, and declines in physical function, outcomes that contribute to increased morbidity and mortality. The study objective was to determine the effects of respiratory muscle training (RMT) on OM and opioid use, as well as functional performance in patients with HNC receiving RT with or without concurrent chemotherapy (CCRT).

METHODS: Patients aged ≥ 18 years of age with stage I to IV HNC being treated with RT or CCRT receiving a home-based respiratory muscle training (RMT) (n …

Associations Of Sociodemographic, Clinical Factors And Hla-B Alleles With Enthesitis And Peripheral Arthritis In Patients With Ankylosing Spondylitis, Benjamin Sornrung Naovarat, Lianne Gensler, Michael Ward, Mark Hwang, Amirali Tahanan, Mohammad Hossein Rahbar, Mariko Ishimori, Minjae Lee, Matthew A Brown, Michael H Weisman, John D Reveille

Faculty, Staff and Student Publications

Objectives: Factors associated with peripheral arthritis and enthesitis, especially Achilles tendonitis and plantar fasciitis, were examined in a longitudinal cohort of 1075 patients with ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis).

Methods: Patients were derived from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort. Disease activity and functional indices, as well as physical examination and medications used, were measured at every study visit. Univariable and multivariable analyses of the association of peripheral arthritis and enthesitis with clinical, sociodemographic factors were performed. Human leucocyte antigen (HLA)-B alleles were analysed by single-stranded conformational polymorphism analysis.

Results: Those with peripheral …

The Dnase Trex1 Is A Substrate Of The Intramembrane Protease Spp With Implications For Disease Pathogenesis, Onur Kerem Tever, Torben Mentrup, Ivan Kingyue Chinn, Hitoshi Ishikuma, Regina Fluhrer, Marc Schmitz, Rebekka Wehner, Rayk Behrendt, Javier Chinen, Bernd Schröder

Faculty, Staff and Students Publications

Signal peptide peptidase (SPP) is an ER-resident aspartyl intramembrane protease cleaving proteins within type II-oriented transmembrane segments. Here, we identified the tail-anchored protein Three prime repair exonuclease 1 (TREX1) as a novel substrate of SPP. Based on its DNase activity, TREX1 removes cytosolic DNA acting as a negative regulator of the DNA-sensing cGAS/STING pathway. TREX1 loss-of-function variants cause Aicardi-Goutières syndrome (AGS), a type I interferonopathy. Cleavage of ER-bound TREX1 by SPP releases a cleavage product into the cytosol. Proteolysis depends on sequence determinants within the transmembrane segment and is modulated by different disease-associated TREX1 variants. The AGS-causing T303P variant greatly …

Electrostatic Effects On Tau Nanocondensates, Phoebe S Tsoi, Lathan Lucas, Derek Rhoades, Josephine C Ferreon, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Biomolecular condensates (BMCs) are membrane-less protein compartments with physiological and pathological relevance. The formation of BMCs is driven by a process known as liquid-liquid phase separation (LLPS), a field that has largely focused on the study of micron-sized condensates. However, there have been recent studies showing that proteins that undergo LLPS also form nanometer-sized condensates. These nanometer-sized condensates, or nanocondensates, are distinct from microcondensates and potentially exhibit more relevance in cell biology. The field of nanocondensate research is in its infancy, with limited biophysical studies of these structures. Here, we studied condensate formation and dissolution of wild-type and disease-linked (hyperphosphorylated …

The Role Of Electrophysiologic Study In Device Selection For Leadless Atrial Pacing, Joshua R Hirsch, Jordan M Gales, Irakli Giorgberidze, Hamid Afshar

The Texas Heart Institute Journal

The AVEIR DR (Abbott Medical) was the first dual-chamber leadless pacing system approved by the US Food and Drug Administration. Many patients with sinus node dysfunction have physiologically normal atrioventricular conduction, so an atrial-only pacing system may be appropriate for them. Three patients with symptomatic sinus node dysfunction underwent device implantation with electrophysiologic study, including incremental atrial pacing until loss of 1:1 atrioventricular conduction (atrioventricular Wenckebach cycle length) and His-ventricular interval measurement. If the atrioventricular Wenckebach cycle length was no more than 400 milliseconds and the His-ventricular interval measurement was no more than 55 milliseconds, single-chamber atrial implantation was deemed …

Comprehensive Cross-Sectional And Longitudinal Comparisons Of Plasma Glial Fibrillary Acidic Protein And Neurofilament Light Across Ftd Spectrum Disorders, Udit Sheth, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker.

METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and …

Factors Influencing Cyanoacrylate Tissue Adhesive Outcomes For Corneal Thinning And Perforation, Anjali Om, Anjali Badami, Yuqing Wang, Xiangqin Cui, Soroosh Behshad, Joung Kim, Praneetha Thulasi

2020-Current year OA Pubs

No abstract provided.

Innate Immune Sensing Of Rotavirus By Intestinal Epithelial Cells Leads To Diarrhea, Gaopeng Hou, Juhee Son, Maria Florencia Gomez Castro, Takahiro Kawagishi, Avan Antia, Qiru Zeng, Anna L Deveaux, Hinissan P Kohio, Megan T Baldridge, Siyuan Ding, Et Al.

2020-Current year OA Pubs

Diarrhea is the predominant symptom of acute gastroenteritis resulting from enteric infections and a leading cause of death in infants and young children. However, the role of the host response in diarrhea pathogenesis is unclear. Using rotavirus and neonatal mice as a model, we found that oral inoculation of UV-inactivated replication-defective rotavirus consistently induced watery diarrhea by robust activation of cytosolic double-stranded RNA sensing pathways and type III interferon (IFN-λ) secretion. Diarrhea was significantly diminished in mice lacking the IFN-λ receptor. Mechanistically, IFN-λ signaling downregulates the expression of Dra, a chloride and bicarbonate exchanger, which contributes to reduced water absorption. …

Late Adverse Event Reporting From Medical Device Manufacturers To The Us Food And Drug Administration: Cross Sectional Study, Alexander O Everhart, Pinar Karaca-Mandic, Rita F Redberg, Joseph S Ross, Sanket S Dhruva

2020-Current year OA Pubs

OBJECTIVE: To describe the extent of late adverse event reporting by manufacturers to the US Food and Drug Administration's (FDA) Manufacturer And User Facility Device Experience (MAUDE) database as well as the distribution of late reporting among manufacturers and associations with device characteristics.

DESIGN: Cross sectional study.

SETTING: The FDA MAUDE database, a central postmarket safety surveillance tool for US medical devices, from 1 September 2019 to 31 December 2022.

PARTICIPANTS: Medical device manufacturers that submitted initial adverse event reports to the FDA between 1 September 2019 and 31 December 2022.

MAIN OUTCOME MEASURES: Time in days between date manufacturer …