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Infection-Related And Lifestyle-Related Cancer Burden In Kampala, Uganda: Projection Of The Future Cancer Incidence Up To 2030, Judith Asasira, Sanghee Lee, Thi Xuan Mai Tran, Collins Mpamani, Henry Wabinga, So-Youn Jung, Yoon Jung Chang, Yikyung Park, Hyunsoon Cho Mar 2022

Infection-Related And Lifestyle-Related Cancer Burden In Kampala, Uganda: Projection Of The Future Cancer Incidence Up To 2030, Judith Asasira, Sanghee Lee, Thi Xuan Mai Tran, Collins Mpamani, Henry Wabinga, So-Youn Jung, Yoon Jung Chang, Yikyung Park, Hyunsoon Cho

Open Access Publications

OBJECTIVES: In Uganda, infection-related cancers have made the greatest contribution to cancer burden in the past; however, burden from lifestyle-related cancers has increased recently. Using the Kampala Cancer Registry data, we projected incidence of top five cancers, namely, Kaposi sarcoma (KS), cervical, breast and prostate cancer, and non-Hodgkin's lymphoma (NHL) in Uganda.

DESIGN: Trend analysis of cancer registry data.

SETTING: Kampala Cancer Registry, Uganda.

MAIN OUTCOME MEASURE: Cancer incidence data from 2001 to 2015 were used and projected to 2030. Population data were obtained from the Uganda Bureau of Statistics. Age-standardised incidence rates (ASRs) and their trends over the observed …


Cd4/Cd8 Double-Negative Mycosis Fungoides With Large Cell Transformation And Involvement Of The Lungs And Leptomeninges, Kelly M Wilmas, Alexander B Aria, Laura N Landis, Sri Krishna Chaitanya, Victor G Prieto, Madeleine Duvic Mar 2022

Cd4/Cd8 Double-Negative Mycosis Fungoides With Large Cell Transformation And Involvement Of The Lungs And Leptomeninges, Kelly M Wilmas, Alexander B Aria, Laura N Landis, Sri Krishna Chaitanya, Victor G Prieto, Madeleine Duvic

Open Access Publications

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, classically has an indolent clinical course, with lesions slowly progressing from patch to plaque to tumor stage. In some cases, the late stages of disease involve extra-cutaneous dissemination to lymph nodes or viscera. Although this "Alibert-Bazin" type is the prototypic MF, there are several variants and subtypes of MF that may have different clinical implications for treatment and prognosis. We describe a woman whose disease course involved a variety of histopathologic and immunophenotypic variants including folliculotropic MF, granulomatous MF with loss of CD8, and then finally CD4/CD8 double-negative MF with large …


Principles And Applications Of Crispr Toolkit In Virus Manipulation, Diagnosis, And Virus-Host Interactions, Saleh Jamehdor, Sara Pajouhanfar, Sadaf Saba, Georges Uzan, Ali Teimoori, Sina Naserian Mar 2022

Principles And Applications Of Crispr Toolkit In Virus Manipulation, Diagnosis, And Virus-Host Interactions, Saleh Jamehdor, Sara Pajouhanfar, Sadaf Saba, Georges Uzan, Ali Teimoori, Sina Naserian

Open Access Publications

Viruses are one of the most important concerns for human health, and overcoming viral infections is a worldwide challenge. However, researchers have been trying to manipulate viral genomes to overcome various disorders, including cancer, for vaccine development purposes. CRISPR (clustered regularly interspaced short palindromic repeats) is becoming one of the most functional and widely used tools for RNA and DNA manipulation in multiple organisms. This approach has provided an unprecedented opportunity for creating simple, inexpensive, specific, targeted, accurate, and practical manipulations of viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus-1 (HIV-1), and vaccinia virus. Furthermore, …


Air Exchanges, Climate Change, And Severe Acute Respiratory Coronavirus Virus 2 (Sars-Cov-2): Results From A Survey Of The Society Of Healthcare Epidemiology Of America Research Network (Srn), Jason P. Burnham, Fred Betz, Roger Lautz, Ehsan Mousavi, Richard A. Martinello, Forbes Mcgain, Jodi D. Sherman Mar 2022

Air Exchanges, Climate Change, And Severe Acute Respiratory Coronavirus Virus 2 (Sars-Cov-2): Results From A Survey Of The Society Of Healthcare Epidemiology Of America Research Network (Srn), Jason P. Burnham, Fred Betz, Roger Lautz, Ehsan Mousavi, Richard A. Martinello, Forbes Mcgain, Jodi D. Sherman

Open Access Publications

No abstract provided.


Feasibility And Efficacy Of Telehealth-Based Resistance Exercise Training In Adolescents With Cystic Fibrosis And Glucose Intolerance, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados Mar 2022

Feasibility And Efficacy Of Telehealth-Based Resistance Exercise Training In Adolescents With Cystic Fibrosis And Glucose Intolerance, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados

Open Access Publications

The aims of this study were to (1) determine the feasibility of a home-based resistance exercise training (RET) program in patients with cystic fibrosis and impaired glucose tolerance using virtual personal training and (2) observe the effects completion of the RET program had on glucose metabolism, pulmonary function, body composition, and physical fitness. The feasibility of the program was defined as 80% compliance. Ten participants (15.80 ± 2.20 yr, 25.1 ± 7.4 kg/m


Exploiting Radiation Induction Of Antigens In Cancer: Targeted Drug Delivery, Vaishali Kapoor, Abhay K Singh, Calvin D Lewis, Sapna Deore, Dennis E Hallahan Mar 2022

Exploiting Radiation Induction Of Antigens In Cancer: Targeted Drug Delivery, Vaishali Kapoor, Abhay K Singh, Calvin D Lewis, Sapna Deore, Dennis E Hallahan

Open Access Publications

Therapeutic antibodies used to treat cancer are effective in patients with advanced-stage disease. For example, antibodies that activate T-lymphocytes improve survival in many cancer subtypes. In addition, antibody-drug conjugates effectively target cytotoxic agents that are specific to cancer. This review discusses radiation-inducible antigens, which are stress-regulated proteins that are over-expressed in cancer. These inducible cell surface proteins become accessible to antibody binding during the cellular response to genotoxic stress. The lead antigens are induced in all histologic subtypes and nearly all advanced-stage cancers, but show little to no expression in normal tissues. Inducible antigens are exploited by using therapeutic antibodies …


Pftaire Kinase L63 Interactor 1a (Pif1a Protein) Is Required For Actin Cone Movement During Spermatid Individualization In Drosophila Melanogaster, Harrison D Pravder, Dorota Grabowska, Kaushik Roychoudhury, Betty Zhang, Deborah Frank, Przemysław Zakrzewski, Marta Lenartowska, Kathryn G Miller Mar 2022

Pftaire Kinase L63 Interactor 1a (Pif1a Protein) Is Required For Actin Cone Movement During Spermatid Individualization In Drosophila Melanogaster, Harrison D Pravder, Dorota Grabowska, Kaushik Roychoudhury, Betty Zhang, Deborah Frank, Przemysław Zakrzewski, Marta Lenartowska, Kathryn G Miller

Open Access Publications

A useful model for determining the mechanisms by which actin and actin binding proteins control cellular architecture is the


Clinical Severity Of, And Effectiveness Of Mrna Vaccines Against, Covid-19 From Omicron, Delta, And Alpha Sars-Cov-2 Variants In The United States: Prospective Observational Study, Adam S Lauring, Hilary M Babcock, Jennie H Kwon, Et Al Mar 2022

Clinical Severity Of, And Effectiveness Of Mrna Vaccines Against, Covid-19 From Omicron, Delta, And Alpha Sars-Cov-2 Variants In The United States: Prospective Observational Study, Adam S Lauring, Hilary M Babcock, Jennie H Kwon, Et Al

Open Access Publications

OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant.

DESIGN: Case-control study.

SETTING: 21 hospitals across the United States.

PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 …


Evolutionary Genomic Relationships And Coupling In Mk-Styx And Styx Pseudophosphatases, Yi Qi, Di Kuang, Kylan Kelley, William J Buchser, Shantá D Hinton Mar 2022

Evolutionary Genomic Relationships And Coupling In Mk-Styx And Styx Pseudophosphatases, Yi Qi, Di Kuang, Kylan Kelley, William J Buchser, Shantá D Hinton

Open Access Publications

The dual specificity phosphatase (DUSP) family has catalytically inactive members, called pseudophosphatases. They have mutations in their catalytic motifs that render them enzymatically inactive. This study analyzes the significance of two pseudophosphatases, MK-STYX [MAPK (mitogen-activated protein kinase phosphoserine/threonine/tyrosine-binding protein]) and STYX (serine/threonine/tyrosine-interacting protein), throughout their evolution and provides measurements and comparison of their evolutionary conservation. Phylogenetic trees were constructed to show any deviation from various species evolutionary paths. Data was collected on a large set of proteins that have either one of the two domains of MK-STYX, the DUSP domain or the cdc-25 homology (CH2) /rhodanese-like domain. The distance between …


Dose-Finding Study Of Ibrutinib And Venetoclax In Relapsed Or Refractory Mantle Cell Lymphoma, Craig A Portell, Nolan A Wages, Brad S Kahl, Lihua E Budde, Robert W Chen, Jonathon B Cohen, Nikole E Varhegyi, Gina R Petroni, Michael E Williams Mar 2022

Dose-Finding Study Of Ibrutinib And Venetoclax In Relapsed Or Refractory Mantle Cell Lymphoma, Craig A Portell, Nolan A Wages, Brad S Kahl, Lihua E Budde, Robert W Chen, Jonathon B Cohen, Nikole E Varhegyi, Gina R Petroni, Michael E Williams

Open Access Publications

Relapsed Mantle cell lymphoma (MCL) is often treated with Bruton's tyrosine kinase inhibitors (BTKi); however, post-BTKi relapse can be challenging. Adding venetoclax (VEN) to ibrutinib (IBR) has shown synergy in preclinical MCL models. Prior MCL studies of the combination show promising efficacy but have conducted limited dose finding. We sought to identify the optimal dosing combination, based on efficacy and toxicity, utilizing a continual reassessment method of 6 combinations of IBR (280 mg, 420 mg, and 560 mg by mouth daily) and VEN (max dose of 200 mg and 400 mg by mouth daily). Eligible participants were not previously exposed …


Structure Of The Wilson Disease Copper Transporter Atp7b, Ryan M Bitter, Secheol Oh, Zengqin Deng, Suhaila Rahman, Richard K Hite, Peng Yuan Mar 2022

Structure Of The Wilson Disease Copper Transporter Atp7b, Ryan M Bitter, Secheol Oh, Zengqin Deng, Suhaila Rahman, Richard K Hite, Peng Yuan

Open Access Publications

ATP7A and ATP7B, two homologous copper-transporting P1B-type ATPases, play crucial roles in cellular copper homeostasis, and mutations cause Menkes and Wilson diseases, respectively. ATP7A/B contains a P-type ATPase core consisting of a membrane transport domain and three cytoplasmic domains, the A, P, and N domains, and a unique amino terminus comprising six consecutive metal-binding domains. Here, we present a cryo-electron microscopy structure of frog ATP7B in a copper-free state. Interacting with both the A and P domains, the metal-binding domains are poised to exert copper-dependent regulation of ATP hydrolysis coupled to transmembrane copper transport. A ring of negatively charged residues …


Renin-Angiotensin Blockade Reduces Readmission For Acute Chest Syndrome In Sickle Cell Disease, Nneoma Wamkpah, Anuj Shrestha, Gary Salzman, Stephen Simon, Sahil Suman, Alan Poisner, Agostino Molteni Mar 2022

Renin-Angiotensin Blockade Reduces Readmission For Acute Chest Syndrome In Sickle Cell Disease, Nneoma Wamkpah, Anuj Shrestha, Gary Salzman, Stephen Simon, Sahil Suman, Alan Poisner, Agostino Molteni

Open Access Publications

Rationale Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Current treatment is supportive-supplemental oxygen, transfusions, and antibiotics. Prevention of ACS may reduce morbidity and mortality in patients with SCD. Acute chest syndrome appears similar to pulmonary fat embolism (PFE), a complication of severe skeletal trauma or orthopedic procedures from pulmonary micro-vessel blockage by bone marrow fat. Vascular obstruction and bone marrow necrosis occur in PFE and ACS. Pulmonary fat embolism rat models have shown that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) mitigate damage in PFE. These medications could work similarly in …


Oncology Trainee Perceptions Of The Prior Authorization Process: A National Survey, Hyun Kim, Amar Srivastava, Prashant Gabani, Elizabeth Kim, Hohyun Lee, Katrina S Pedersen Mar 2022

Oncology Trainee Perceptions Of The Prior Authorization Process: A National Survey, Hyun Kim, Amar Srivastava, Prashant Gabani, Elizabeth Kim, Hohyun Lee, Katrina S Pedersen

Open Access Publications

Purpose: The medical trainee perspective regarding the prior authorization process has not been previously assessed. Here we evaluate the perceptions of radiation and medical oncology trainees regarding the prior authorization process and its effect on their training and patient care.

Methods and Materials: A 12-question, nonincentivized, electronic national survey of radiation and medical oncology trainees at all Accreditation Council for Graduate Medical Education accredited oncology programs was conducted. Participation, perspectives, and experiences with the prior authorization process were assessed by Likert scale, free response, and multiple response selection.

Results: Between January and March of 2019, the survey was distributed to …


Use Of Statins For The Prevention Of Cardiovascular Disease In 41 Low-Income And Middle-Income Countries: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Maja E Marcus, Mark D Huffman, Et Al Mar 2022

Use Of Statins For The Prevention Of Cardiovascular Disease In 41 Low-Income And Middle-Income Countries: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Maja E Marcus, Mark D Huffman, Et Al

Open Access Publications

BACKGROUND: In the prevention of cardiovascular disease, a WHO target is that at least 50% of eligible people use statins. Robust evidence is needed to monitor progress towards this target in low-income and middle-income countries (LMICs), where most cardiovascular disease deaths occur. The objectives of this study were to benchmark statin use in LMICs and to investigate country-level and individual-level characteristics associated with statin use.

METHODS: We did a cross-sectional analysis of pooled, individual-level data from nationally representative health surveys done in 41 LMICs between 2013 and 2019. Our sample consisted of non-pregnant adults aged 40-69 years. We prioritised WHO …


Fk506-Binding Protein-Like And Fk506-Binding Protein 8 Regulate Dual Leucine Zipper Kinase Degradation And Neuronal Responses To Axon Injury, Bohm Lee, Yeonsoo Oh, Eunhye Cho, Aaron Diantonio, Valeria Cavalli, Jung Eun Shin, Hae Woong Choi, Yongcheol Cho Mar 2022

Fk506-Binding Protein-Like And Fk506-Binding Protein 8 Regulate Dual Leucine Zipper Kinase Degradation And Neuronal Responses To Axon Injury, Bohm Lee, Yeonsoo Oh, Eunhye Cho, Aaron Diantonio, Valeria Cavalli, Jung Eun Shin, Hae Woong Choi, Yongcheol Cho

Open Access Publications

The dual leucine zipper kinase (DLK) is a key regulator of axon regeneration and degeneration in response to neuronal injury; however, regulatory mechanisms of the DLK function via its interacting proteins are largely unknown. To better understand the molecular mechanism of DLK function, we performed yeast two-hybrid screening analysis and identified FK506-binding protein-like (FKBPL, also known as WAF-1/CIP1 stabilizing protein 39) as a DLK-binding protein. FKBPL binds to the kinase domain of DLK and inhibits its kinase activity. In addition, FKBPL induces DLK protein degradation through ubiquitin-dependent pathways. We further assessed other members in the FKBP protein family and found …


Jagged1/Notch3 Activation Promotes Aortic Hypermuscularization And Stenosis In Elastin Deficiency, Jui M. Dave, Robert Mecham, Et Al Mar 2022

Jagged1/Notch3 Activation Promotes Aortic Hypermuscularization And Stenosis In Elastin Deficiency, Jui M. Dave, Robert Mecham, Et Al

Open Access Publications

Obstructive arterial diseases, including supravalvular aortic stenosis (SVAS), atherosclerosis, and restenosis, share 2 important features: an abnormal or disrupted elastic lamellae structure and excessive smooth muscle cells (SMCs). However, the relationship between these pathological features is poorly delineated. SVAS is caused by heterozygous loss-of-function, hypomorphic, or deletion mutations in the elastin gene (ELN), and SVAS patients and elastin-mutant mice display increased arterial wall cellularity and luminal obstructions. Pharmacological treatments for SVAS are lacking, as the underlying pathobiology is inadequately defined. Herein, using human aortic vascular cells, mouse models, and aortic samples and SMCs derived from induced pluripotent stem cells of …


Traf2, An Innate Immune Sensor, Reciprocally Regulates Mitophagy And Inflammation To Maintain Cardiac Myocyte Homeostasis, Xiucui Ma, David R Rawnsley, Attila Kovacs, Moydul Islam, John T Murphy, Chen Zhao, Minu Kumari, Layla Foroughi, Haiyan Liu, Kevin Qi, Aaradhya Diwan, Krzysztof Hyrc, Sarah Evans, Takashi Satoh, Brent A French, Kenneth B Margulies, Ali Javaheri, Babak Razani, Douglas L Mann, Kartik Mani, Abhinav Diwan Mar 2022

Traf2, An Innate Immune Sensor, Reciprocally Regulates Mitophagy And Inflammation To Maintain Cardiac Myocyte Homeostasis, Xiucui Ma, David R Rawnsley, Attila Kovacs, Moydul Islam, John T Murphy, Chen Zhao, Minu Kumari, Layla Foroughi, Haiyan Liu, Kevin Qi, Aaradhya Diwan, Krzysztof Hyrc, Sarah Evans, Takashi Satoh, Brent A French, Kenneth B Margulies, Ali Javaheri, Babak Razani, Douglas L Mann, Kartik Mani, Abhinav Diwan

Open Access Publications

Mitochondria are essential for cardiac myocyte function, but damaged mitochondria trigger cardiac myocyte death. Although mitophagy, a lysosomal degradative pathway to remove damaged mitochondria, is robustly active in cardiac myocytes in the unstressed heart, its mechanisms and physiological role remain poorly defined. We discovered a critical role for TRAF2, an innate immunity effector protein with E3 ubiquitin ligase activity, in facilitating physiological cardiac myocyte mitophagy in the adult heart, to prevent inflammation and cell death, and maintain myocardial homeostasis.


Safety And Efficacy Of Pembrolizumab In Combination With Acalabrutinib In Advanced Head And Neck Squamous Cell Carcinoma: Phase 2 Proof-Of-Concept Study, Matthew H Taylor, Courtney B Betts, Lauren Maloney, Eric Nadler, Alain Algazi, Michael J Guarino, John Nemunaitis, Antonio Jimeno, Priti Patel, Veerendra Munugalavadla, Lin Tao, Douglas Adkins, Jerome H Goldschmidt, Ezra E W Cohen, Lisa M Coussens Mar 2022

Safety And Efficacy Of Pembrolizumab In Combination With Acalabrutinib In Advanced Head And Neck Squamous Cell Carcinoma: Phase 2 Proof-Of-Concept Study, Matthew H Taylor, Courtney B Betts, Lauren Maloney, Eric Nadler, Alain Algazi, Michael J Guarino, John Nemunaitis, Antonio Jimeno, Priti Patel, Veerendra Munugalavadla, Lin Tao, Douglas Adkins, Jerome H Goldschmidt, Ezra E W Cohen, Lisa M Coussens

Open Access Publications

PURPOSE: Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton's tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8+ T cell responses, resulting in enhanced antitumor activity. This phase 2, multicenter, open-label, randomized study evaluated pembrolizumab (anti-PD-1 monoclonal antibody) plus acalabrutinib (BTK inhibitor) in recurrent or metastatic HNSCC.

PATIENTS AND METHODS: Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety …


Segmental Colitis Associated With Diverticulosis Masquerading As Polyploid-Appearing Mucosa In The Rectosigmoid Area On Endoscopy And As Focal Thickening On Imaging, Eugene C. Nwankwo Jr, Gebran Khneizer, Gregory Sayuk, Jill Elwing, Necat Havlioglu, Michael Presti Mar 2022

Segmental Colitis Associated With Diverticulosis Masquerading As Polyploid-Appearing Mucosa In The Rectosigmoid Area On Endoscopy And As Focal Thickening On Imaging, Eugene C. Nwankwo Jr, Gebran Khneizer, Gregory Sayuk, Jill Elwing, Necat Havlioglu, Michael Presti

Open Access Publications

Segmental colitis associated with diverticulosis (SCAD) is an inflammatory disease affecting segments of the large bowel with diverticular disease. SCAD presents several challenges in diagnoses and treatment because it often mimics a range of disorders including inflammatory bowel disease and malignancy. Here, we present the case of a 72-year-old man with lower abdominal pain and bloody stools whose initial abdominal workup showed nonspecific large bowel thickening and concerns for malignancy. Ultimately, the patient was diagnosed with mild SCAD and treated conservatively with a resolution of symptoms. He had no symptoms at the three-month and 1-year follow-ups. This case highlights the …


Preferences And Priorities For Relapsed Multiple Myeloma Treatments Among Patients And Caregivers In The United States, Daniel Auclair, Carol Mansfield, Mark A Fiala, Ajai Chari, Craig E Cole, Jonathan L Kaufman, Gregory J Orloff, David S Siegel, Jeffrey A Zonder, Brennan Mange, Jennifer Yesil, Mehul Dalal, Joseph R Mikhael Mar 2022

Preferences And Priorities For Relapsed Multiple Myeloma Treatments Among Patients And Caregivers In The United States, Daniel Auclair, Carol Mansfield, Mark A Fiala, Ajai Chari, Craig E Cole, Jonathan L Kaufman, Gregory J Orloff, David S Siegel, Jeffrey A Zonder, Brennan Mange, Jennifer Yesil, Mehul Dalal, Joseph R Mikhael

Open Access Publications

Introduction/Background: This study aimed to describe patient and caregiver preferences for treatments of relapsed or refractory multiple myeloma (MM).

Materials and Methods: A survey including discrete-choice experiment (DCE) and best-worst scaling (BWS) exercises was conducted among US patients with relapsed or refractory MM and their caregivers. The DCE included six attributes with varying levels including progression-free survival (PFS), toxicity, and mode and frequency of administration. In addition, the impact of treatment cost was assessed using a fixed-choice question. The BWS exercise included 18 items (modes and frequency of administration, additional treatment convenience, and toxicity items). The survey was administered online …


Obstructive Hydrocephalus And Intracerebral Mass Secondary To Epicoccum Nigrum, Taylor L Charron, Michelle A Gill, Laura M Filkins, Veena Rajaram, Christian A Wysocki, Brett A Whittemore Mar 2022

Obstructive Hydrocephalus And Intracerebral Mass Secondary To Epicoccum Nigrum, Taylor L Charron, Michelle A Gill, Laura M Filkins, Veena Rajaram, Christian A Wysocki, Brett A Whittemore

Open Access Publications

Here we report a case of a 14-week-old girl with a history of intrauterine drug exposure and hypoxic ischemic encephalopathy secondary to cardiac arrest requiring prolonged resuscitation at birth presented with irritability and a bulging anterior fontanelle. After neurosurgical resection, pathologic examination showed fungal hyphae, and


Commissioning A Secondary Dose Calculation Software For A 0.35 T Mr-Linac, Alex T Price, Nels C Knutson, Taeho Kim, Olga L Green Mar 2022

Commissioning A Secondary Dose Calculation Software For A 0.35 T Mr-Linac, Alex T Price, Nels C Knutson, Taeho Kim, Olga L Green

Open Access Publications

Secondary external dose calculations for a 0.35 T magnetic resonance image-guided radiation therapy (MRgRT) are needed within the radiation oncology community to follow safety standards set forth within the field. We evaluate the commercially available software, RadCalc, in its ability to accurately perform monitor unit dose calculations within a magnetic field. We also evaluate the potential effects of a 0.35 T magnetic field upon point dose calculations. Monitor unit calculations were evaluated with (wMag) and without (noMag) a magnetic field considerations in RadCalc for the ViewRay MRIdian. The magnetic field is indirectly accounted for by using asymmetric profiles for calculation. …


Partial Ablation Of Postsynaptic Dopamine D2 Receptors In The Central Nucleus Of The Amygdala Increases Risk Avoidance In Exploratory Tasks, Eric Casey, María Elena Avale, Alexxai Kravitz, Marcelo Rubinstein Mar 2022

Partial Ablation Of Postsynaptic Dopamine D2 Receptors In The Central Nucleus Of The Amygdala Increases Risk Avoidance In Exploratory Tasks, Eric Casey, María Elena Avale, Alexxai Kravitz, Marcelo Rubinstein

Open Access Publications

The central nucleus of the amygdala (CeA) is involved in the expression of fear and has been implicated in several anxiety disorders. This structure is densely innervated by DAergic projections that impinge on amygdalar neurons expressing various dopamine (DA) receptor subtypes, including D2 receptors (D2Rs). Although various pharmacological approaches have assessed the role of D2Rs in the CeA, the actual participation of postsynaptic D2Rs in the CeA to defensive behaviors remains unclear. Here, we investigated the distribution of D2Rs in the CeA and their role in modifying neuronal activity and fear related behaviors in mice. First, using the mouse reporter …


Translational Randomized Phase Ii Trial Of Cabozantinib In Combination With Nivolumab In Advanced, Recurrent, Or Metastatic Endometrial Cancer, Stephanie Lheureux, Carolyn Mccourt, Et Al Mar 2022

Translational Randomized Phase Ii Trial Of Cabozantinib In Combination With Nivolumab In Advanced, Recurrent, Or Metastatic Endometrial Cancer, Stephanie Lheureux, Carolyn Mccourt, Et Al

Open Access Publications

BACKGROUND: Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling.

PATIENTS AND METHODS: In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was …


Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke Mar 2022

Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke

Open Access Publications

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women's Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through …


Transcriptomic Profile Investigations Highlight A Putative Role For Nudt16 In Sepsis, Susie Shih Yin Huang, Darawan Rinchai, Mohammed Toufiq, Basirudeen Syed Ahamed Kabeer, Jessica Roelands, Wouter Hendrickx, Sabri Boughorbel, Davide Bedognetti, Nicholas Van Panhuys, Damien Chaussabel, Mathieu Garand Mar 2022

Transcriptomic Profile Investigations Highlight A Putative Role For Nudt16 In Sepsis, Susie Shih Yin Huang, Darawan Rinchai, Mohammed Toufiq, Basirudeen Syed Ahamed Kabeer, Jessica Roelands, Wouter Hendrickx, Sabri Boughorbel, Davide Bedognetti, Nicholas Van Panhuys, Damien Chaussabel, Mathieu Garand

Open Access Publications

Sepsis is an aberrant systemic inflammatory response mediated by the acute activation of the innate immune system. Neutrophils are important contributors to the innate immune response that controls the infection, but harbour the risk of collateral tissue damage such as thrombosis and organ dysfunction. A better understanding of the modulations of cellular processes in neutrophils and other blood cells during sepsis is needed and can be initiated via transcriptomic profile investigations. To that point, the growing repertoire of publicly accessible transcriptomic datasets serves as a valuable resource for discovering and/or assessing the robustness of biomarkers. We employed systematic literature mining, …


Sars-Cov-2 Omicron Virus Causes Attenuated Disease In Mice And Hamsters, Peter J Halfmann, Shun Iida, Kiyoko Iwatsuki-Horimoto, Tadashi Maemura, Maki Kiso, Suzanne M Scheaffer, Tamarand L Darling, Astha Joshi, Baoling Ying, James Brett Case, Zhenlu Chong, Bradley Whitener, Zhenlu Chong, Larissa B Thackray, Adrianus C M Boon, Michael S Diamond, Et Al Mar 2022

Sars-Cov-2 Omicron Virus Causes Attenuated Disease In Mice And Hamsters, Peter J Halfmann, Shun Iida, Kiyoko Iwatsuki-Horimoto, Tadashi Maemura, Maki Kiso, Suzanne M Scheaffer, Tamarand L Darling, Astha Joshi, Baoling Ying, James Brett Case, Zhenlu Chong, Bradley Whitener, Zhenlu Chong, Larissa B Thackray, Adrianus C M Boon, Michael S Diamond, Et Al

Open Access Publications

The recent emergence of B.1.1.529, the Omicron variant


Long-Term Cardiovascular Outcomes Of Covid-19, Yan Xie, Evan Xu, Benjamin Bowe, Ziyad Al-Aly Mar 2022

Long-Term Cardiovascular Outcomes Of Covid-19, Yan Xie, Evan Xu, Benjamin Bowe, Ziyad Al-Aly

Open Access Publications

The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning …


Evaluation Of Hiv Treatment Outcomes With Reduced Frequency Of Clinical Encounters And Antiretroviral Treatment Refills: A Systematic Review And Meta-Analysis, Noelle Le Tourneau, Ashley Germann, Ryan R. Thompson, Nathan Ford, Sheree Schwartz, Laura Beres, Aaloke Mody, Stefan Baral, Elvin H. Geng, Ingrid Eshun-Wilson Mar 2022

Evaluation Of Hiv Treatment Outcomes With Reduced Frequency Of Clinical Encounters And Antiretroviral Treatment Refills: A Systematic Review And Meta-Analysis, Noelle Le Tourneau, Ashley Germann, Ryan R. Thompson, Nathan Ford, Sheree Schwartz, Laura Beres, Aaloke Mody, Stefan Baral, Elvin H. Geng, Ingrid Eshun-Wilson

Open Access Publications

BACKGROUND: Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral treatment (ART) to reduce the burden of seeking care and to decongest health facilities. The overall effect of reduced visit frequency on HIV treatment outcomes is however unknown. We conducted a systematic review and meta-analysis to evaluate the effect of implementation strategies that reduce the frequency of clinical appointments and ART refills for PLWH established on ART.

METHODS AND FINDINGS: We searched databases​ between 1 January 2010 and 9 November 2021 to identify randomized controlled …


Sirt1 Selectively Exerts The Metabolic Protective Effects Of Hepatocyte Nicotinamide Phosphoribosyltransferase, Cassandra B Higgins, Allyson L Mayer, Yiming Zhang, Michael Franczyk, Samuel Ballentine, Jun Yoshino, Brian J Debosch Feb 2022

Sirt1 Selectively Exerts The Metabolic Protective Effects Of Hepatocyte Nicotinamide Phosphoribosyltransferase, Cassandra B Higgins, Allyson L Mayer, Yiming Zhang, Michael Franczyk, Samuel Ballentine, Jun Yoshino, Brian J Debosch

Open Access Publications

Calorie restriction abates aging and cardiometabolic disease by activating metabolic signaling pathways, including nicotinamide adenine dinucleotide (NAD