Medicine and Health Sciences Commons^™

Care Levels For Fetal Therapy Centers, Ahmet A Baschat, Barbara B Warner, Et Al

2020-Current year OA Pubs

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels …

A Multi-Institutional Study Evaluating And Describing Atypical Parathyroid Tumors Discovered After Parathyroidectomy, Alice L Tang, Benjamin Aunins, Katherine Chang, James C Wang, Matthew Hagen, Lan Jiang, Cortney Y Lee, Reese W Randle, Jeffery J Houlton, David Sloan, David L Steward

2020-Current year OA Pubs

Objective: To describe common intraoperative and pathologic findings of atypical parathyroid tumors (APTs) and evaluate clinical outcomes in patients undergoing parathyroidectomy.

Methods: In this multi-institutional retrospective case series, data were collected from patients who underwent parathyroidectomy from 2000 to 2018 from three tertiary care institutions. APTs were defined according to the AJCC eighth edition guidelines and retrospective chart review was performed to evaluate the incidence of recurrent laryngeal nerve injury, recurrence of disease, and disease-specific mortality.

Results: Twenty-eight patients were identified with a histopathologic diagnosis of atypical tumor. Mean age was 56 years (range, 23-83) and 68% (19/28) were female. …

Rationale Of Using The Dual Chemokine Receptor Ccr2/Ccr5 Inhibitor Cenicriviroc For The Treatment Of Covid-19, Daniel Clark Files, Frank Tacke, Alexandra O'Sullivan, Patrick Dorr, William G. Ferguson, William G. Powderly

2020-Current year OA Pubs

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may have the potential to reduce respiratory and cardiovascular organ failures related to COVID-19. Inhibiting the CCR2 and CCR5 pathways could attenuate or prevent inflammation or fibrosis in both early and …

Distinct Developmental And Degenerative Functions Of Sarm1 Require Nad+ Hydrolase Activity, E. J. Brace, Kow Essuman, Xianrong Mao, John Palucki, Yo Sasaki, Jeff Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

SARM1 is the founding member of the TIR-domain family of NAD+ hydrolases and the central executioner of pathological axon degeneration. SARM1-dependent degeneration requires NAD+ hydrolysis. Prior to the discovery that SARM1 is an enzyme, SARM1 was studied as a TIR-domain adaptor protein with non-degenerative signaling roles in innate immunity and invertebrate neurodevelopment, including at the Drosophila neuromuscular junction (NMJ). Here we explore whether the NADase activity of SARM1 also contributes to developmental signaling. We developed transgenic Drosophila lines that express SARM1 variants with normal, deficient, and enhanced NADase activity and tested their function in NMJ development. We find that NMJ …

Antibiotic-Resistant Organisms Establish Reservoirs In New Hospital Built Environments And Are Related To Patient Blood Infection Isolates, Kimberley V Sukhum, Erin P Newcomer, Candice Cass, Meghan A Wallace, Caitlin Johnson, Jeremy Fine, Steven Sax, Margaret H Barlet, Carey-Ann D Burnham, Gautam Dantas, Jennie H Kwon

2020-Current year OA Pubs

Background: Healthcare-associated infections due to antibiotic-resistant organisms pose an acute and rising threat to critically ill and immunocompromised patients. To evaluate reservoirs of antibiotic-resistant organisms as a source of transmission to patients, we interrogated isolates from environmental surfaces, patient feces, and patient blood infections from an established and a newly built intensive care unit.

Methods: We used selective culture to recover 829 antibiotic-resistant organisms from 1594 environmental and 72 patient fecal samples, in addition to 81 isolates from blood cultures. We conducted antibiotic susceptibility testing and short- and long-read whole genome sequencing on recovered isolates.

Results: Antibiotic-resistant organism burden is …

Age-Dependent White Matter Disruptions After Military Traumatic Brain Injury: Multivariate Analysis Results From Enigma Brain Injury, Heather C Bouchard, Paul M Thompson, Aristeidis Sotiras, Et Al.

2020-Current year OA Pubs

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional …

Pdxnet Portal: Patient-Derived Xenograft Model, Data, Workflow And Tool Discovery, Soner Koc, Ramaswamy Govindan, Li Ding, Shunqiang Li, Et Al.

2020-Current year OA Pubs

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples …

Phase I Trial Of Atm Inhibitor M3541 In Combination With Palliative Radiotherapy In Patients With Solid Tumors, Saiama N Waqar, Clifford Robinson, Anthony J Olszanski, Alexander Spira, Melissa Hackmaster, Luisa Lucas, Laura Sponton, Hulin Jin, Ursula Hering, Damien Cronier, Marianna Grinberg, Annick Seithel-Keuth, Ivan Diaz-Padilla, Jordan Berlin

2020-Current year OA Pubs

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.

METHODS: This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50-300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic …

Challenges And New Opportunities For Detecting Endogenous Opioid Peptides In Reward, Sineadh M Conway, Marwa O Mikati, Ream Al-Hasani

2020-Current year OA Pubs

The endogenous opioid peptide system, comprised of enkephalins, endorphins, dynorphins, and nociceptin, is a highly complex neurobiological system. Opioid peptides are derived from four precursor molecules and undergo several processing events yielding over 20 unique opioid peptides. This diversity together with low

Joint Eanm/Snmmi/Anzsnm Practice Guidelines/Procedure Standards On Recommended Use Of [18f]Fdg Pet/Ct Imaging During Immunomodulatory Treatments In Patients With Solid Tumors Version 1.0, E Lopci, R J Hicks, A Dimitrakopoulou-Strauss, L Dercle, A Iravani, R D Seban, C Sachpekidis, O Humbert, O Gheysens, A W J M Glaudemans, W Weber, R L Wahl, A M Scott, N Pandit-Taskar, N Aide

2020-Current year OA Pubs

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [

METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard.

CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [

PREAMBLE: The European Association of Nuclear Medicine (EANM) is a …

Noninvasive Testing And Surrogate Markers In Invasive Fungal Diseases, George R Thompson, Andrej Spec, Et Al.

2020-Current year OA Pubs

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these …

Management Of Diarrhea In Patients With Her2-Positive Breast Cancer Treated With Neratinib: A Case Series And Summary Of The Literature, Megan L Kruse, Irene M Kang, Nusayba A Bagegni, W Todd Howell, Halle C F Moore, Cynthia H Bedell, Christopher T Stokoe

2020-Current year OA Pubs

INTRODUCTION: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2-positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast …

22q11.2 Deletion Syndrome - A Series Of Patients With Midline Skull Base Defects, Spencer S. Souza, Lia Jacobson, Dylan Chan, Anna Meyer, Jarod L. Roland, Kimberly Luu

2020-Current year OA Pubs

No abstract provided.

Rate Of Infarct-Edema Growth On Ct Predicts Need For Surgical Intervention And Clinical Outcome In Patients With Cerebellar Infarction, Yan Wang, Michael M Binkley, Min Qiao, Amanda Pardon, Salah Keyrouz, Rajat Dhar, Andria L Ford

2020-Current year OA Pubs

BACKGROUND: Up to 20% of patients with cerebellar infarcts will develop malignant edema and deteriorate clinically. Radiologic measures, such as initial infarct size, aid in identifying individuals at risk. Studies of anterior circulation stroke suggest that mapping early edema formation improves the ability to predict deterioration; however, the kinetics of edema in the posterior fossa have not been well characterized. We hypothesized that faster edema growth within the first hours after acute cerebellar stroke would be an indicator for individuals requiring surgical intervention and those with worse neurological outcomes.

METHODS: Consecutive patients admitted to the neurological intensive care unit with …

Genomic And Transcriptomic Somatic Alterations Of Hepatocellular Carcinoma In Non-Cirrhotic Livers, Zachary L Skidmore, Jason Kunisaki, Yiing Lin, Kelsy C Cotto, Erica K Barnell, Jasreet Hundal, Kilannin Krysiak, Vincent Magrini, Lee Trani, Jason R Walker, Robert Fulton, Elizabeth M Brunt, Christopher A Miller, Richard K Wilson, Elaine R Mardis, Malachi Griffith, William Chapman, Obi L Griffith

2020-Current year OA Pubs

No abstract provided.

Covid-19 Outcomes And Vaccination In People With Relapsing Multiple Sclerosis Treated With Ofatumumab, Anne H Cross, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients.

METHODS: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated.

RESULTS: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) …

Accuracy Of Chest Computed Tomography In Distinguishing Cystic Pleuropulmonary Blastoma From Benign Congenital Lung Malformations In Children, Abigail J Engwall-Gill, Jacqueline M Saito, Rebecca L Hulett Bowling, Et Al.

2020-Current year OA Pubs

Importance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.

Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.

Design, Setting, and Participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed …

Gene-Lifestyle Interactions In The Genomics Of Human Complex Traits, Vincent Laville, Yun J Sung, Karen Schwander, Mary F Feitosa, Aldi T Kraja, Mike Province, C Charles Gu, D C Rao, Et Al

2020-Current year OA Pubs

The role and biological significance of gene-environment interactions in human traits and diseases remain poorly understood. To address these questions, the CHARGE Gene-Lifestyle Interactions Working Group conducted series of genome-wide interaction studies (GWIS) involving up to 610,475 individuals across four ancestries for three lipids and four blood pressure traits, while accounting for interaction effects with drinking and smoking exposures. Here we used GWIS summary statistics from these studies to decipher potential differences in genetic associations and G×E interactions across phenotype-exposure-ancestry combinations, and to derive insights on the potential mechanistic underlying G×E through in-silico functional analyses. Our analyses show first that …

Whole-Exome Sequencing Reveals Damaging Gene Variants Associated With Hypoalphalipoproteinemia, Weilai Dong, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4-36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those …

Assessment Of The Impact Of The Covid-19 Pandemic On Health Services Use, Kimberly J Johnson, Charles W Goss, Jeannette Jackson Thompson, Anne M Trolard, Brett B Maricque, Victoria Anwuri, Rachel Cohen, Kate Donaldson, Elvin Geng

2020-Current year OA Pubs

OBJECTIVES: The coronavirus disease of 2019 (COVID-19) pandemic declared by the World Health Organization on March 11, 2020 impacted healthcare services with provider and patient cancellations, delays, and patient avoidance or delay of emergency department or urgent care. Limited data exist on the population proportion affected by delayed healthcare, which is important for future healthcare planning efforts. Our objective was to evaluate the impact of the COVID-19 pandemic on healthcare service cancellations or delays and delays/avoidance of emergency/urgent care overall and by population characteristics.

STUDY DESIGN: This was a cross-sectional study.

METHODS: Our sample (n = 2314) was assembled through …

Association Of The Receptor For Activated C-Kinase 1 With Ribosomes In Plasmodium Falciparum, Jessey Erath, Sergej Djuranovic

2020-Current year OA Pubs

The receptor for activated C-kinase 1 (RACK1), a highly conserved eukaryotic protein, is known to have many varying biological roles and functions. Previous work has established RACK1 as a ribosomal protein, with defined regions important for ribosome binding in eukaryotic cells. In Plasmodium falciparum, RACK1 has been shown to be required for parasite growth, however, conflicting evidence has been presented about RACK1 ribosome binding and its role in mRNA translation. Given the importance of RACK1 as a regulatory component of mRNA translation and ribosome quality control, the case could be made in parasites that RACK1 either binds or does not …

Toll-Like Receptor And Cytokine Expression Throughout The Bone Marrow Differs Between Patients With Low- And High-Risk Myelodysplastic Syndromes, Luana Chiquetto Paracatu, Darlene A Monlish, Zev J Greenberg, Daniel A C Fisher, Matthew J Walter, Stephen T Oh, Laura G Schuettpelz

2020-Current year OA Pubs

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders, the pathogenesis of which involves enhanced immune signaling that promotes or selects for mutant hematopoietic stem and progenitor cells (HSPCs). In particular, toll-like receptor (TLR) expression and signaling are enhanced in MDS, and their inhibition is an attractive therapeutic strategy. Although prior studies have reported increased expression of TLR2 and its binding partners TLR1 and TLR6 in the CD34

Escape-Noncapture Bigeminy, Lisa M. Roelle, George F. Van Hare

2020-Current year OA Pubs

No abstract provided.

Protein Proximity Networks And Functional Evaluation Of The Casein Kinase 1 Gamma Family Reveal Unique Roles For Ck1Γ3 In Wnt Signaling, Megan J. Agajanian, Frances M. Potjewyd, Brittany M. Bowman, Smaranda Solomon, Kyle M. Lapak, Dhaval P. Bhatt, Jeffery L. Smith, Dennis Goldfarb, Alison D. Axtman, Michael B. Major

2020-Current year OA Pubs

Aberrant activation or suppression of WNT/β-catenin signaling contributes to cancer initiation and progression, neurodegeneration, and bone disease. However, despite great need and more than 40 years of research, targeted therapies for the WNT pathway have yet to be fully realized. Kinases are considered exceptionally druggable and occupy key nodes within the WNT signaling network, but several pathway-relevant kinases remain understudied and "dark." Here, we studied the function of the casein kinase 1γ (CSNK1γ) subfamily of human kinases and their roles in WNT signaling. miniTurbo-based proximity biotinylation and mass spectrometry analysis of CSNK1γ1, CSNK1γ2, and CSNK1γ3 revealed numerous components of the …

An Examination Of The Sex-Specific Nature Of Nutrition Assessment Within The Nutrition Care Process: Considerations For Nutrition And Dietetics Practitioners Working With Transgender And Gender Diverse Clients, Whitney Linsenmeyer, Sarah Garwood, Jennifer Waters

2020-Current year OA Pubs

No abstract provided.

Joint Eanm, Snmmi And Iaea Enabling Guide: How To Set Up A Theranostics Centre, Ken Herrmann, Richard L Wahl, Et Al.

2020-Current year OA Pubs

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of …

Assessing Researchers' Capabilities, Opportunities, And Motivation To Conduct Equity-Oriented Dissemination And Implementation Research, An Exploratory Cross-Sectional Study, Ana A Baumann, Eva N Woodward, Rajinder Sonia Singh, Prajakta Adsul, Rachel C Shelton

2020-Current year OA Pubs

BACKGROUND: A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants' perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research.

METHODS: We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the …

Determination Of The Electronic Portal Imaging Device Pixel-Sensitivity-Map For Quality Assurance Applications. Part 2: Photon Beam Dependence, Michael Paul Barnes, Baozhou Sun, Brad Michael Oborn, Bishnu Lamichhane, Stuart Szwec, Matthew Schmidt, Bin Cai, Frederick Menk, Peter Greer

2020-Current year OA Pubs

PURPOSE: The EPID PSM is a useful EPID calibration method for QA applications. The dependence of the EPID PSM on the photon beam used to acquire it has been investigated in this study for the four available PSM methods. The aim is to inform upon the viability of applying a single PSM for all available photon beams to simplify PSM implementation and maintenance.

METHODS: Four methods of PSM determination were each measured once in a single session on a single TrueBeam ® STx linac using 6 MV, 10 MV, 6 MV Flattening-Filter-Free (FFF), and 10 MV FFF photon beams. The …

Association Of Molecular Senescence Markers In Late-Life Depression With Clinical Characteristics And Treatment Outcome, Breno S Diniz, Benoit H Mulsant, Charles F Reynolds, Daniel M Blumberger, Jordan F Karp, Meryl A Butters, Ana Paula Mendes-Silva, Erica L Vieira, George Tseng, Eric J Lenze

2020-Current year OA Pubs

Importance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population.

Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted …

Intracorporeal And Extracorporeal Anastomosis For Robotic-Assisted And Laparoscopic Right Colectomy: Short-Term Outcomes Of A Multi-Center Prospective Trial, Robert K Cleary, Matthew Silviera, Et Al.

2020-Current year OA Pubs

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy.

METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates.

RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic …