Medicine and Health Sciences Commons^™

Society For Immunotherapy Of Cancer (Sitc) Consensus Definitions For Resistance To Combinations Of Immune Checkpoint Inhibitors With Chemotherapy, Naiyer Rizvi, Foluso O. Ademuyiwa, Z Alexander Cao, Helen X. Chen, Robert L. Ferris, Sarah B. Goldberg, Matthew D. Hellmann, Ranee Mehra, Ina Rhee, Jong Chul Park, Harriet Kluger, Hussein Tawbi, Ryan J. Sullivan

2020-Current year OA Pubs

Although immunotherapy can offer profound clinical benefit for patients with a variety of difficult-to-treat cancers, many tumors either do not respond to upfront treatment with immune checkpoint inhibitors (ICIs) or progressive/recurrent disease occurs after an interval of initial control. Improved response rates have been demonstrated with the addition of ICIs to cytotoxic therapies, leading to approvals from the US Food and Drug Administration and regulatory agencies in other countries for ICI-chemotherapy combinations in a number of solid tumor indications, including breast, head and neck, gastric, and lung cancer. Designing trials for patients with tumors that do not respond or stop …

Clinical Pattern Of Tolvaptan-Associated Liver Injury In Trial Participants With Autosomal Dominant Polycystic Kidney Disease (Adpkd): An Analysis Of Pivotal Clinical Trials, David H Alpers, James H Lewis, Christine M Hunt, James W Freston, Vicente E Torres, Hui Li, Wenchyi Wang, Molly E Hoke, Sharin E Roth, Lucas Westcott-Baker, Alvin Estilo

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Tolvaptan is associated with risk of drug-induced liver injury when used to treat autosomal dominant polycystic kidney disease (ADPKD). After this risk was described based on the clinical trials TEMPO 3:4 and TEMPO 4:4, additional data from the REPRISE trial and a long-term extension of TEMPO 4:4, REPRISE, and other tolvaptan trials in ADPKD have become available. To further characterize the hepatic safety profile of tolvaptan, an analysis of the expanded dataset was conducted.

STUDY DESIGN: Analysis of safety data from prospective clinical trials of tolvaptan.

SETTING & PARTICIPANTS: Multicenter clinical trials including more than 2,900 tolvaptan-treated …

Impact Of The Covid-19 Pandemic On Breast, Colorectal, Lung, And Prostate Cancer Stage At Diagnosis According To Race, Jennifer Berrian, Ying Liu, Nkiruka Ezenwajiaku, Alvaro Moreno-Aspitia, Sara J Holton, Adetunji T Toriola, Graham A Colditz, Ashley J Housten, Lannis Hall, Mark A Fiala, Foluso O Ademuyiwa

2020-Current year OA Pubs

PURPOSE: To determine if the COVID-19 pandemic has further exacerbated racial disparities in late-stage presentation of breast, colorectal, lung, and prostate cancers.

METHODS: We conducted a registry-based retrospective study of patients with newly reported diagnoses of breast, colorectal, lung, and prostate cancers between March 2019-June 2019 (pre-COVID-19) and March 2020-June 2020 (early-COVID-19). We compared the volume of new diagnoses and stage at presentation according to race between both periods.

RESULTS: During the study period, a total of 3528 patients had newly diagnosed cancer; 3304 of which had known disease stages and were included in the formal analyses. 467 (14.1%) were …

Apolipoprotein M Attenuates Anthracycline Cardiotoxicity And Lysosomal Injury, Zhen Guo, Carla Valenzuela Ripoll, Antonino Picataggi, David R Rawnsley, Mualla Ozcan, Ezhilarasi Chendamarai, Amanda Girardi, Terrence Riehl, Hosannah Evie, Ahmed Diab, Attila Kovacs, Krzysztof Hyrc, Xiucui Ma, Lauren N Pedersen, Carmen Bergom, Nathan O Stitziel, Michael P Rettig, John F Dipersio, Abhinav Diwan, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.

Aim18p And Aim46p Are Chalcone Isomerase Domain-Containing Mitochondrial Hemoproteins In Saccharomyces Cerevisiae, Jonathan M Schmitz, John F Wolters, Nathan H Murray, Rachel M Guerra, Craig A Bingman, Chris Todd Hittinger, David J Pagliarini

2020-Current year OA Pubs

Chalcone isomerases (CHIs) have well-established roles in the biosynthesis of plant flavonoid metabolites. Saccharomyces cerevisiae possesses two predicted CHI-like proteins, Aim18p (encoded by YHR198C) and Aim46p (YHR199C), but it lacks other enzymes of the flavonoid pathway, suggesting that Aim18p and Aim46p employ the CHI fold for distinct purposes. Here, we demonstrate using proteinase K protection assays, sodium carbonate extractions, and crystallography that Aim18p and Aim46p reside on the mitochondrial inner membrane and adopt CHI folds, but they lack select active site residues and possess an extra fungal-specific loop. Consistent with these differences, Aim18p and Aim46p lack CHI activity and also …

Clinical Outcomes After Reverse Shoulder Arthroplasty In Patients 60 Years Old And Younger; Medium-Term Results, Aaron M Chamberlain, Alexander W Aleem, Julianne A Sefko, Karen Steger-May, Jay D Keener

2020-Current year OA Pubs

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has been well-described as a surgical solution to manage rotator cuff tear arthropathy in elderly, low demand paitents. As experience has increased along with improvements in technique and implant design, RTSA has become increasingly used to manage more varied pathologic conditions of the shoulder in younger, more active patients. This study evaluates outcomes in a consecutive series of patients aged 60 years old and younger after undergoing RTSA.

METHODS: There were 94 shoulders in 89 patients enrolled. Mean age of the cohort was 54.8 (range 18-60 years). Surgical indications included rotator cuff tear arthropathy, …

Computational Modeling Of The N-Back Task In The Abcd Study: Associations Of Drift Diffusion Model Parameters To Polygenic Scores Of Mental Disorders And Cardiometabolic Diseases, Mads L Pedersen, Dag Alnæs, Dennis Van Der Meer, Sara Fernandez-Cabello, Pierre Berthet, Andreas Dahl, Rikka Kjelkenes, Emanuel Schwarz, Wesley K Thompson, Deanna M Barch, Ole A Andreassen, Lars T Westlye

2020-Current year OA Pubs

BACKGROUND: Cognitive dysfunction is common in mental disorders and represents a potential risk factor in childhood. The nature and extent of associations between childhood cognitive function and polygenic risk for mental disorders is unclear. We applied computational modeling to gain insight into mechanistic processes underlying decision making and working memory in childhood and their associations with polygenic risk scores (PRSs) for mental disorders and comorbid cardiometabolic diseases.

METHODS: We used the drift diffusion model to infer latent computational processes underlying decision making and working memory during the n-back task in 3707 children ages 9 to 10 years from the Adolescent …

Definitive Treatment And Risk Of Death Among Men Diagnosed With Metastatic Prostate Cancer At The Veterans Health Administration, Bettina F Drake, Saira Khan, Mei Wang, Veronica Hicks, Kate Nichols, Meghan Taylor, Eric H Kim, Su-Hsin Chang

2020-Current year OA Pubs

PURPOSE: To assess the potential survival benefit associated with receipt of definitive treatment (radical prostatectomy or radiation), compared to non-definitive treatment (hormonal therapy or chemotherapy) among men with metastatic prostate cancer.

METHODS: A cohort of men diagnosed with metastatic (T4/M1/N1 or T4/M1) prostate cancer from 1999 to 2013 in the Veterans Health Administration were identified and followed to December 28, 2014. All-cause and prostate cancer-specific mortality were evaluated at 10 years for the T4/M1/N1 cohort and 8 years for the T4/M1/ cohort. The association of definitive treatment (radical prostatectomy or radiation), compared to non-definitive (hormonal therapy or chemotherapy) with both …

A Trpv4-Dependent Neuroimmune Axis In The Spinal Cord Promotes Neuropathic Pain, Xueming Hu, Lixia Du, Shenbin Liu, Zhou Lan, Kaikai Zang, Jing Feng, Yonghui Zhao, Xingliang Yang, Zili Xie, Peter L. Wang, Aaron M. Ver Heul, Lvyi Chen, Vijay K. Samineni, Yan-Qing Wang, Kory J. Lavine, Robert W. Gereau, Gregory F. Wu, Hongzhen Hu

2020-Current year OA Pubs

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest …

Aberrant Right Gastric Vein Mimicking Hepatic Spread Of Prostate Cancer On Psma-Pet/Ct, Genevieve C Muñoz, Tyler J Fraum

2020-Current year OA Pubs

Hepatic vasculature can exhibit a wide variety of variants, some of which may resemble pathologic findings. In this case, a 53-year-old man presenting for staging of biochemically recurrent prostatic adenocarcinoma was found to have focally increased prostate-specific membrane antigen (PSMA) tracer uptake on positron emission tomography (PET) imaging in hepatic segment IV. This finding was initially concerning for hepatic metastasis of the patient's primary prostate adenocarcinoma. However, the area of radiotracer uptake was not associated with a discrete lesion on CT, and the geographic morphology of the uptake raised the possibility of a vascular etiology. Magnetic resonance imaging (MRI) of …

Reduction Of Surgical Site Infection After Trauma Laparotomy Through Use Of A Specific Protocol For Antibiotic Prophylaxis, John E Mazuski, William J Symons, Stephen Jarman, Bryan Sato, William Carroll, Grant V Bochicchio, John P Kirby, Douglas J Schuerer

2020-Current year OA Pubs

No abstract provided.

Design Of Serena-6, A Phase Iii Switching Trial Of Camizestrant In Esr1-Mutant Breast Cancer During First-Line Treatment, Nicholas Turner, Cynthia Huang-Bartlett, Kevin Kalinsky, Massimo Cristofanilli, Giampaolo Bianchini, Stephen Chia, Hiroji Iwata, Wolfgang Janni, Cynthia X Ma, Erica L Mayer, Yeon Hee Park, Steven Fox, Xiaochun Liu, Sasha Mcclain, Francois-Clement Bidard

2020-Current year OA Pubs

No abstract provided.

Genomic Patterns Of Malignant Peripheral Nerve Sheath Tumor (Mpnst) Evolution Correlate With Clinical Outcome And Are Detectable In Cell-Free Dna, Isidro Cortes-Ciriano, Dana C Borcherding, Jeffrey J Szymanski, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

UNLABELLED: Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling …

Recent Advances In Serum Biomarkers For Risk Stratification And Patient Management In Cardio-Oncology, Pouya Joolharzadeh, Mario Rodriguez, Raja Zaghlol, Lauren N Pedersen, Jesus Jimenez, Carmen Bergom, Joshua D Mitchell

2020-Current year OA Pubs

PURPOSE OF REVIEW: Following significant advancements in cancer therapeutics and survival, the risk of cancer therapy-related cardiotoxicity (CTRC) is increasingly recognized. With ongoing efforts to reduce cardiovascular morbidity and mortality in cancer patients and survivors, cardiac biomarkers have been studied for both risk stratification and monitoring during and after therapy to detect subclinical disease. This article will review the utility for biomarker use throughout the cancer care continuum.

RECENT FINDINGS: A recent meta-analysis shows utility for troponin in monitoring patients at risk for CTRC during cancer therapy. The role for natriuretic peptides is less clear but may be useful in …

Determinants Of Mortality For Ventilated Hospital-Acquired Pneumonia And Ventilator-Associated Pneumonia, Hayley Motowski, Daniel Ilges, Nicholas Hampton, Marin H. Kollef, Scott T. Micek

2020-Current year OA Pubs

UNLABELLED: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection, accounting for 22% of all nosocomial infections. The available studies to date have not attempted to assess whether confounding factors may account for the observed difference in mortality for the two forms of nosocomial pneumonia associated with mechanical ventilation, namely ventilated HAP (vHAP) and ventilator-associated pneumonia (VAP).

OBJECTIVES: To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia.

DESIGN SETTING AND PARTICIPANTS: Single-center retrospective cohort study conducted at Barnes-Jewish Hospital, St. Louis, MO, between 2016 and 2019. Adult patients with a pneumonia discharge diagnosis were …

Metabolically Healthy Obesity Is Not A Myth, Sarah S Farabi, Gordon I Smith, Jun Yoshino, Samuel Klein

2020-Current year OA Pubs

People with obesity who do not have the metabolic syndrome or components of the metabolic syndrome have been characterized as having metabolically healthy obesity (MHO). However, the existence of MHO has been questioned because people with MHO are at greater risk of developing diabetes and fatal cardiovascular disease than people who are lean and healthy. Here we report findings from a 25-year-old woman with rigorously defined MHO (normal oral glucose tolerance, insulin sensitivity [assessed using the hyperinsulinemic-euglycemic clamp procedure], plasma triglyceride, and intrahepatic triglyceride content) evaluated at baseline (body mass index, 37.7 kg/m

The Impact On Central Line-Associated Bloodstream Infection Rates Following The Introduction Of A Closed System Transfer Device In Oncology Wards, Josephine Fox, Ashley Rumsey, Rebecca Rojek, Kathleen Rensing, Heather Gasama, Lydia Grimes-Jenkins, Helen Wood, Erik R Dubberke, David K Warren

2020-Current year OA Pubs

Prevention of hazardous drug exposure is essential in averting unnecessary health risks to health care workers (HCW). To address the risk to HCWs when handling hazardous drugs, engineering controls can be utilized to reduce the exposure. A closed system transfer device (CSTD) was introduced for hazardous drugs administration in 6 oncology wards; this new CSTD was associated with a significant increase in CLABSI rates.

A Cross-Sectional Study Of Tampering In Xtampza Er, An Abuse-Deterrent Formulation Of An Extended-Release Opioid, In A Treatment Center Population, Jennifer Jewell, Joshua Black, Matthew Ellis, Heather Olsen, Janetta Iwanicki, Richard Dart

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVE: While the current landscape of opioid use disorder (OUD) is complicated by the increase in use of non-prescription opioids, prescription opioids continue to be frequently used in non-medical ways. In response to this abuse, pharmaceutical companies have developed abuse deterrent formulations (ADFs) for extended-release (ER) opioids. To test the effectiveness of Xtampza ER ADF (oxycodone myristate) at reducing tampering, its rate of tampering in a treatment-center population was compared to immediate release (IR) single entity (SE) oxycodone, other ER oxycodone opioids, and ER oxymorphone.

METHODS: Data were collected between the third quarter of 2018 and the third …

Lifestyle Intervention In Ovarian Cancer Enhanced Survival (Lives) Study (Nrg/Gog0225): Recruitment, Retention And Baseline Characteristics Of A Randomized Trial Of Diet And Physical Activity In Ovarian Cancer Survivors, Cynthia A Thomson, Matthew Powell, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The Lifestyle Intervention for oVarian cancer Enhanced Survival (LIVES) is a national study of a combined diet and physical activity intervention for stage II-IV ovarian cancer survival, an under-represented cancer in lifestyle behavioral intervention research. Here, we present the data on recruitment, retention, and baseline demographic, clinical and lifestyle behavior characteristics of the LIVES study participants.

METHODS: The LIVES study (NRG Oncology/GOG 0225) is a Phase III diet plus physical activity intervention trial testing the hypothesis that ovarian cancer survivors in the lifestyle intervention will demonstrate better progression-free survival than those in the control condition. Study interventions were delivered …

Tnk2/Ack1-Mediated Phosphorylation Of Atp5f1a (Atp Synthase F1 Subunit Alpha) Selectively Augments Survival Of Prostate Cancer While Engendering Mitochondrial Vulnerability, Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P. Mahajan

2020-Current year OA Pubs

The challenge of rapid macromolecular synthesis enforces the energy-hungry cancer cell mitochondria to switch their metabolic phenotypes, accomplished by activation of oncogenic tyrosine kinases. Precisely how kinase activity is directly exploited by cancer cell mitochondria to meet high-energy demand, remains to be deciphered. Here we show that a non-receptor tyrosine kinase, TNK2/ACK1 (tyrosine kinase non receptor 2), phosphorylated ATP5F1A (ATP synthase F1 subunit alpha) at Tyr243 and Tyr246 (Tyr200 and 203 in the mature protein, respectively) that not only increased the stability of complex V, but also increased mitochondrial energy output in cancer cells. Further, phospho-ATP5F1A (p-Y-ATP5F1A) prevented its binding …

Prospective Associations Between Accelerometry-Derived Physical Activity And Sedentary Behaviors And Mortality Among Cancer Survivors, Elizabeth A Salerno, Pedro F Saint-Maurice, Fei Wan, Lindsay L Peterson, Yikyung Park, Yin Cao, Ryan P Duncan, Richard P Troiano, Charles E Matthews

2020-Current year OA Pubs

BACKGROUND: Survival benefits of self-reported recreational physical activity (PA) during cancer survivorship are well-documented in common cancer types, yet there are limited data on the associations between accelerometer-derived PA of all domains, sedentary behavior, and mortality in large, diverse cohorts of cancer survivors.

METHODS: Participants included adults who reported a cancer diagnosis in the National Health and Nutrition Examination Survey and wore an accelerometer for up to 7 days in 2003-2006. Participants were followed for subsequent mortality through 2015. We examined the association of light PA, moderate to vigorous PA, total PA, and sedentary behavior, with all-cause mortality. Cox proportional …

A Pilot Study Of Same-Day Mri-Only Simulation And Treatment With Mr-Guided Adaptive Palliative Radiotherapy (Map-Rt), Joshua P Schiff, Borna Maraghechi, Re-I Chin, Alex Price, Eric Laugeman, Souman Rudra, Casey Hatscher, Matthew B Spraker, Shahed N Badiyan, Lauren E Henke, Olga Green, Hyun Kim

2020-Current year OA Pubs

We conducted a prospective pilot study evaluating the feasibility of same day MRI-only simulation and treatment with MRI-guided adaptive palliative radiotherapy (MAP-RT) for urgent palliative indications (NCT#03824366). All (16/16) patients were able to complete 99% of their first on-table attempted fractions, and no grades 3-5 toxicities occurred.

Surgical Results Of The Lung Cancer Mutation Consortium 3 Trial: A Phase Ii Multicenter Single-Arm Study To Investigate The Efficacy And Safety Of Atezolizumab As Neoadjuvant Therapy In Patients With Stages Ib-Select Iiib Resectable Non-Small Cell Lung Cancer, Valerie W Rusch, G Alexander Patterson, Salama N Waqar, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.

METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was …

Resolution Of Hepatic Fibrosis After Zfn-Mediated Gene Editing In The Piz Mouse Model Of Human Α1-Antitrypsin Deficiency, Yanfeng Li, Chandan Guha, Patrik Asp, Xia Wang, Tatyana L. Tchaikovskya, Kenneth Kim, Matthew Mendel, Gregory J. Cost, David H. Perlmutter, Namita Roy-Chowdhury, Ira J. Fox, Anthony Conway, Jayanta Roy-Chowdhury

2020-Current year OA Pubs

BACKGROUND: α1-antitrypsin deficiency is most commonly caused by a mutation in exon-7 of SERPINA1 (SA1-ATZ), resulting in hepatocellular accumulation of a misfolded variant (ATZ). Human SA1-ATZ-transgenic (PiZ) mice exhibit hepatocellular ATZ accumulation and liver fibrosis. We hypothesized that disrupting the SA1-ATZ transgene in PiZ mice by in vivo genome editing would confer a proliferative advantage to the genome-edited hepatocytes, enabling them to repopulate the liver.

METHODS: To create a targeted DNA break in exon-7 of the SA1-ATZ transgene, we generated 2 recombinant adeno-associated viruses (rAAV) expressing a zinc-finger nuclease pair (rAAV-ZFN), and another rAAV for gene correction by targeted insertion …

A New Mouse Model Of Elastin Haploinsufficiency Highlights The Importance Of Elastin To Vascular Development And Blood Pressure Regulation, Bridget M Brengle, Michelle Lin, Robyn A Roth, Kara D Jones, Jessica E Wagenseil, Robert P Mecham, Carmen M Halabi

2020-Current year OA Pubs

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disease resulting from elastin (ELN) haploinsufficiency. Individuals with SVAS typically develop a thickened arterial media with an increased number of elastic lamellae and smooth muscle cell (SMC) layers and stenosis superior to the aortic valve. A mouse model of SVAS (Eln

Molecular Phenotyping Of Single Pancreatic Islet Leader Beta Cells By "Flash-Seq", Pauline Chabosseau, Fiona Yong, Luis F Delgadillo-Silva, Eun Young Lee, Rana Melhem, Shiying Li, Nidhi Gandhi, Jules Wastin, Livia Lopez Noriega, Isabelle Leclerc, Yusuf Ali, Jing W Hughes, Robert Sladek, Aida Martinez-Sanchez, Guy A Rutter

2020-Current year OA Pubs

AIMS: Spatially-organized increases in cytosolic Ca

MAIN METHODS: High speed confocal Ca

KEY FINDINGS: Distinct Ca

SIGNIFICANCE: The existence of both a discrete transcriptome and unique localisation implies a role for these features in defining the specialized function of leaders. These data also raise the possibility that localised signalling between delta and leader cells contributes to the initiation and propagation of islet Ca

Clinical Application Of A Template-Guided Automated Planning Routine, Matthew C Schmidt, Christopher D Abraham, Jiayi Huang, Clifford G Robinson, Geoffrey Hugo, Nels C Knutson, Baozhou Sun, Chipo Raranje, Erno Sajo, Piotr Zygmanski, Marian Jandel, Peter Szentivanyi, Jessica Hilliard, Jessica Hamilton, Francisco J Reynoso

2020-Current year OA Pubs

PURPOSE: Determine the dosimetric quality and the planning time reduction when utilizing a template-based automated planning application.

METHODS: A software application integrated through the treatment planning system application programing interface, QuickPlan, was developed to facilitate automated planning using configurable templates for contouring, knowledge-based planning structure matching, field design, and algorithm settings. Validations are performed at various levels of the planning procedure and assist in the evaluation of readiness of the CT image, structure set, and plan layout for automated planning. QuickPlan is evaluated dosimetrically against 22 hippocampal-avoidance whole brain radiotherapy patients. The required times to treatment plan generation are compared …

Targeted Deletion Of Fgf9 In Tendon Disrupts Mineralization Of The Developing Enthesis, Elahe Ganji, Connor Leek, William Duncan, Debabrata Patra, David M Ornitz, Megan L Killian

2020-Current year OA Pubs

The enthesis is a transitional tissue between tendon and bone that matures postnatally. The development and maturation of the enthesis involve cellular processes likened to an arrested growth plate. In this study, we explored the role of fibroblast growth factor 9 (Fgf9), a known regulator of chondrogenesis and vascularization during bone development, on the structure and function of the postnatal enthesis. First, we confirmed spatial expression of Fgf9 in the tendon and enthesis using in situ hybridization. We then used Cre-lox recombinase to conditionally knockout Fgf9 in mouse tendon and enthesis (Scx-Cre) and characterized enthesis morphology as well as mechanical …

Frequent First-Trimester Pregnancy Loss In Rhesus Macaques Infected With African-Lineage Zika Virus, Jenna R. Rosinski, Kevin K. Noguchi, Et Al.

2020-Current year OA Pubs

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest …

Selective Dorsal Rhizotomy For Treatment Of Spasticity After Hemispherectomy In Children: A Case Report, Ts Park, Susan Joh, Matthew D. Smyth, Nicole L. Meyer, Deanna M. Walter

2020-Current year OA Pubs

Performing a hemispherotomy or hemispherectomy is known to treat medically intractable epilepsy successfully, yet contralateral hemiparesis and increased muscle tone follow the epilepsy surgery. Spasticity and coexisting dystonia presumably cause the increased muscle tone in the lower extremity on the opposite side of epilepsy surgery. However, the extent of the role of spasticity and dystonia in high muscle tone is unknown. A selective dorsal rhizotomy is performed to reduce spasticity. If a selective dorsal rhizotomy is performed in the affected patient and muscle tone is reduced, the high muscle tone is not due to dystonia. Two children, who previously underwent …