Medicine and Health Sciences Commons^™

Multicenter Validation Of An Rna-Based Assay To Predict Anti-Pd-1 Disease Control In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma: The Predapt Study, Kevin C Flanagan, Jessica Ley, Douglas Adkins, Eric J Duncavage, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors.

METHODS: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from …

Distinct Escherichia Coli Transcriptional Profiles In The Guts Of Recurrent Uti Sufferers Revealed By Pangenome Hybrid Selection, Mark G Young, Jesús Bazan Villicana, Philippe Azimzadeh, Andrew Kau, Karen W Dodson, Henry L Schreiber 4th, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Low-abundance members of microbial communities are difficult to study in their native habitats, including Escherichia coli, a minor but common inhabitant of the gastrointestinal tract, and key opportunistic pathogen of the urinary tract. While multi-omic analyses have detailed interactions between uropathogenic Escherichia coli (UPEC) and the bladder mediating urinary tract infection (UTI), little is known about UPEC in its pre-infection reservoir, the gastrointestinal tract, partly due to its low relative abundance (<1%). To sensitively explore the genomes and transcriptomes of diverse gut E. coli, we develop E. coli PanSelect, which uses probes designed to specifically capture E. coli's broad pangenome. We demonstrate its ability to enrich diverse E. coli by orders of magnitude, in a mock community and in human stool from a study investigating recurrent UTI (rUTI). Comparisons of transcriptomes between gut E. coli of women with and without history of rUTI suggest rUTI gut E. coli are responding to increased oxygen and nitrate, suggestive of mucosal inflammation, which may have implications for recurrent disease. E. coli PanSelect is well suited for investigations of in vivo E. coli biology in other low-abundance environments, and the framework described here has broad applicability to other diverse, low-abundance organisms.

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

Efficacy, Safety, And Quality Of Life 4 Years After Valoctocogene Roxaparvovec Gene Transfer For Severe Hemophilia A In The Phase 3 Gener8-1 Trial, Andrew D Leavitt, Elaine Majerus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.

OBJECTIVES: Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.

METHODS: In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10

RESULTS: Median follow-up was 214.3 weeks; 2 participants discontinued since the previous data cutoff. Declines from baseline in mean treated annualized bleed rate (-82.6%;

CONCLUSION: Valoctocogene roxaparvovec provides persistent FVIII expression, hemostatic control, and health-related quality of life improvements with …

Fusobacterium Nucleatum Abundance Is Associated With Cachexia In Colorectal Cancer Patients: The Colocare Study, Mmadili N Ilozumba, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% …

Effect Of Surgical Fixation Timing On In-Hospital Mortality And Morbidity Of Distal Femur Fractures, Joseph T Gutbrod, Dustin Stwalley, Anna N Miller

2020-Current year OA Pubs

INTRODUCTION: The literature lacks a large-scale study investigating the effect of surgical fixation timing on early mortality and morbidity outcomes in distal femur fractures. The aims of this study were to determine the effect of fixation timing on in-hospital mortality and morbidity outcomes for operatively treated distal femur fractures retrospectively using large database data.

METHODS: This study is a retrospective analysis using data from the National Trauma Data Bank. Patients were stratified into a fragility cohort (age ≥ 60, ISS < 16) and polytrauma cohort (age < 60, ISS ≥16), with both cohorts analyzed separately. Within each cohort, patients were split into three fixation timing groups: within 24 h, between 24 and 48 h, and greater than 48 h from presentation to the hospital. Fixation-timing groups were compared based on the primary outcome of in-hospital mortality rate. Secondary outcomes included hospital length of stay (LOS), ICU length of stay (ICU LOS), days on a ventilator, and complications.

RESULTS: The fragility and polytrauma cohorts included 22,045 and 5,905 patients, respectively. The in-hospital mortality rate was 1.23 % in …

The Known And Unknown Reality Of Knee Dislocations: A Systematic Review, Zachary D Randall, Matthew J Strok, Jacob W Mazzola, Ravi Agrawal, Lauren H Yaeger, Marschall B Berkes

2020-Current year OA Pubs

BACKGROUND: Knee dislocations (KD) are limb threatening injuries known to cause significant dysfunction and disability. This review aims to summarize KD knowledge and uncover areas where more research is needed.

METHODS: The published literature was queried according to PRISMA guidelines. Studies eligible for inclusion were clinical studies of knee dislocations. Studies published before 1990, or that focused on patellofemoral dislocation were excluded.

RESULTS: A total of 132 studies involving 43,869 knee dislocations were analyzed. The majority of patients were young adult males, with high-velocity trauma, particularly motor vehicle accidents, being the most common cause. Substance use and alcohol involvement were …

Influence Of Physical Activity Measurement On The Association Between Life's Essential 8 And Incident Cardiovascular Disease In Older Women, Eric T Hyde, Steve Nguyen, Michael J Lamonte, Chongzhi Di, John Bellettiere, Lesley F Tinker, Randi E Foraker, Hilary A Tindle, Marcia L Stefanick, Andrea Z Lacroix

2020-Current year OA Pubs

OBJECTIVE: The American Heart Association's Life's Essential 8 (LE8) metric includes self-reported physical activity as one of the metrics for assessing cardiovascular health. Self-reported physical activity is prone to misclassification, whereas accelerometer measures are less biased. We examined associations of LE8 and incident cardiovascular disease (CVD) using self-reported and accelerometer-measured physical activity.

METHODS: Participants in the Women's Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health Study (n = 4,243; mean age = 79 ± 7 years) with no CVD history completed the WHI physical activity questionnaire and the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire prior to …

Evidence Of Human Bourbon Virus Infections, North Carolina, Usa, Diana L Zychowski, Gayan Bamunuarachchi, Scott P Commins, Ross M Boyce, Adrianus C M Boon

2020-Current year OA Pubs

Bourbon virus is a tickborne virus that can cause human disease. Cases have been reported in Kansas, Oklahoma, and Missouri, USA. We identified Bourbon virus-specific neutralizing antibodies in patients from North Carolina. Bourbon virus infections are likely more common than previously thought, highlighting the need for improved diagnostics and surveillance.

Transmembrane Protein 53 Craniotubular Dysplasia (Omim # 619727): The Skeletal Disease And Consequent Blindness Of This New Disorder, Michael P Whyte, Robert S Weinstein, Paul H Phillips, William H Mcalister, Raghuhr H Ramakrishnaiah, G Bradley Schaefer, Rongsheng Cai, Michele R Hutchison, Shenghui Duan, Gary S Gottesman, Steven Mumm

2020-Current year OA Pubs

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad …

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab For Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results And Correlative Analyses From Atempt, Paolo Tarantino, Ron Bose, Et Al.

2020-Current year OA Pubs

PURPOSE: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

METHODS: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. …

Clinical Validation Of A Cell-Free Dna Fragmentome Assay For Augmentation Of Lung Cancer Early Detection, Peter J Mazzone, David Gierada, Et Al.

2020-Current year OA Pubs

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out …

Distinct Patterns Of Smooth Muscle Phenotypic Modulation In Thoracic And Abdominal Aortic Aneurysms, Chien-Jung Lin, Campbell Keating, Robyn Roth, Yasar Caliskan, Mustafa Nazzal, Vernat Exil, Richard Dipaolo, Divya Ratan Verma, Kishore Harjai, Mohamed Zayed, Chieh-Yu Lin, Robert P Mecham, Ajay K Jain

2020-Current year OA Pubs

Thoracic and abdominal aortic aneurysms (TAAs and AAAs, respectively) share morphological features but have distinct clinical and hereditary characteristics. Studies using bulk RNA comparisons revealed distinct patterns of gene expression in human TAA and AAA tissues. However, given the summative nature of bulk RNA studies, these findings represent the totality of gene expression without regards to the differences in cellular composition. Single-cell RNA sequencing provides an opportunity to interrogate cell-type-specific transcriptomes. Single cell RNA sequencing datasets from mouse TAA (GSE153534) and AAA (GSE164678 and GSE152583) with respective controls were obtained from the Gene Expression Omnibus. Bioinformatic analysis was performed with …

Il-10r Inhibition Reprograms Tumor-Associated Macrophages And Reverses Drug Resistance In Multiple Myeloma, Jennifer Sun, Monica Shokeen, Barbara Muz, Kinan Alhallak, Chaelee Park, Berit Lubben, Yixuan Chen, Ola Adebayo, Hannah Bash, Sarah Kelley, Mark Fiala, Diane E Bender, Ravi Vij, Abdel Kareem Azab, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In …

Multiomic Profiling Identifies Predictors Of Survival In African American Patients With Acute Myeloid Leukemia, Andrew Stiff, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger …

Limitations And Potential Of Κor Biased Agonists For Pain And Itch Management, Amal El Daibani, Manish K Madasu, Ream Al-Hasani, Tao Che

2020-Current year OA Pubs

The concept of ligand bias is based on the premise that different agonists can elicit distinct responses by selectively activating the same receptor. These responses often determine whether an agonist has therapeutic or undesirable effects. Therefore, it would be highly advantageous to have agonists that specifically trigger the therapeutic response. The last two decades have seen a growing trend towards the consideration of ligand bias in the development of ligands to target the κ-opioid receptor (κOR). Most of these ligands selectively favor G-protein signaling over β-arrestin signaling to potentially provide effective pain and itch relief without adverse side effects associated …

Current Best Practices And Future Opportunities For Reproducible Findings Using Large-Scale Neuroimaging In Psychiatry, Neda Jahanshad, Petra Lenzini, Janine Bijsterbosch

2020-Current year OA Pubs

Research into the brain basis of psychopathology is challenging due to the heterogeneity of psychiatric disorders, extensive comorbidities, underdiagnosis or overdiagnosis, multifaceted interactions with genetics and life experiences, and the highly multivariate nature of neural correlates. Therefore, increasingly larger datasets that measure more variables in larger cohorts are needed to gain insights. In this review, we present current "best practice" approaches for using existing databases, collecting and sharing new repositories for big data analyses, and future directions for big data in neuroimaging and psychiatry with an emphasis on contributing to collaborative efforts and the challenges of multi-study data analysis.

Extrapolative Validity Evidence Of The Anastomosis Objective Structured Assessment Of Technical Skill (A-Osats) For Robotic Ileocolic Anastomosis, Tiffany K Brocke, Cory Fox, Julie M Clanahan, Coen L Klos, William C Chapman Jr, Paul E Wise, Michael M Awad, Kerri A Ohman

2020-Current year OA Pubs

OBJECTIVE: To collect validity evidence for the use of the Anastomosis Objective Structured Assessment of Technical Skills (A-OSATS) instrument, which has been developed to evaluate performance of a minimally invasive side-to-side bowel anastomosis with hand-sewn common enterotomy.

DESIGN: Residents performed a robotic ileocolic anastomosis simulation on an ex vivo porcine model. Faculty scored each resident with the A-OSATS and performed a provocative leak test on the completed anastomoses. Residents were reassessed on the sewing sub-score 1 month later. Data were compared with parametric and nonparametric analysis.

SETTING: Single academic general surgery residency PARTICIPANTS: PGY-4 and -5 general surgery residents (n …

Iglon5 Frequency In Idiopathic Rem Sleep Behavior Disorder: A Multicenter Study, Ronald Postuma, Jennifer Mcleland, Albert A. Davis, Yo-El S. Ju, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma …

Clinical Trials For Lennox-Gastaut Syndrome: Challenges And Priorities, Juliet K Knowles, Aaron E L Warren, Ismail S Mohamed, Carl E Stafstrom, Hyun Yong Koh, Debopam Samanta, Renée A Shellhaas, Gita Gupta, Tracy Dixon-Salazar, Linh Tran, Sonal Bhatia, Jane M Mccabe, Anup D Patel, Zachary M Grinspan

2020-Current year OA Pubs

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy that is typically refractory to treatment. We surveyed the current landscape of LGS treatment, aiming to identify challenges to the development of efficacious therapies, and to articulate corresponding priorities toward clinical trials that improve outcomes.

METHODS: The LGS Special Interest Group of the Pediatric Epilepsy Research Consortium integrated evidence from the literature and expert opinion, into a narrative review.

RESULTS: We provide an overview of approved and emerging medical, dietary, surgical and neuromodulation approaches for LGS. We note that quality of care could be improved by standardizing LGS treatment based on …

A Finite Element Model For Biomechanical Characterization Of Ex Vivo Peripheral Nerve Dysfunction During Stretch, Nicholas C Vasas, Adam M Forrest, Nathaniel A Meyers, Michael B Christensen, Jenny L Pierce, Sidney M Kaufmann, Kimberly B Lanaghen, Randal C Paniello, Julie M Barkmeier-Kraemer, Jonathan P Vande Geest

2020-Current year OA Pubs

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague-Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive …

Impact Of Self-Reported Race On Villalta Scale Postthrombotic Syndrome Scores And Correlation With Venous Disease-Specific Quality Of Life: An Exploratory Analysis Of The Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis Trial, James Shih, Chu-Shu Gu, Suresh Vedantham, John Kaufman, Susan R Kahn

2020-Current year OA Pubs

BACKGROUND: The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.

OBJECTIVES: Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.

METHODS: Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for …

Evaluation Of Combat Harmonization For Reducing Across-Tracer Differences In Regional Amyloid Pet Analyses, Braden Yang, Tom Earnest, Sayantan Kumar, Deydeep Kothapalli, Tammie Benzinger, Brian Gordon, Aristeidis Sotiras

2020-Current year OA Pubs

Differences in amyloid positron emission tomography (PET) radiotracer pharmacokinetics and binding properties lead to discrepancies in amyloid-β uptake estimates. Harmonization of tracer-specific biases is crucial for optimal performance of downstream tasks. Here, we investigated the efficacy of ComBat, a data-driven harmonization model, for reducing tracer-specific biases in regional amyloid PET measurements from [

Attention-Based Cnn-Bilstm For Sleep State Classification Of Spatiotemporal Wide-Field Calcium Imaging Data, Xiaohui Zhang, Eric C Landsness, Hanyang Miao, Wei Chen, Michelle J Tang, Lindsey M Brier, Joseph P Culver, Jin-Moo Lee, Mark A Anastasio

2020-Current year OA Pubs

BACKGROUND: Wide-field calcium imaging (WFCI) with genetically encoded calcium indicators allows for spatiotemporal recordings of neuronal activity in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming, invasive and often suffers from low inter- and intra-rater reliability. Therefore, an automated sleep state classification method that operates on spatiotemporal WFCI data is desired.

NEW METHOD: A hybrid network architecture consisting of a convolutional neural network (CNN) to extract spatial features of image frames and …

Assessment Of Lesion Insertion Tool In Pelvis Pet/Mr Data With Applications To Attenuation Correction Method Development, Yutaka Natsuaki, Andrew Leynes, Kristen Wangerin, Mahdjoub Hamdi, Abhejit Rajagopal, Paul E Kinahan, Richard Laforest, Peder E Z Larson, Thomas A Hope, Sara St James

2020-Current year OA Pubs

BACKGROUND: In modern positron emission tomography (PET) with multi-modality imaging (e.g., PET/CT and PET/MR), the attenuation correction (AC) is the single largest correction factor for image reconstruction. One way to assess AC methods and other reconstruction parameters is to utilize software-based simulation tools, such as a lesion insertion tool. Extensive validation of these simulation tools is required to ensure results of the study are clinically meaningful.

PURPOSE: To evaluate different PET AC methods using a synthetic lesion insertion tool that simulates lesions in a patient cohort that has both PET/MR and PET/CT images. To further demonstrate how lesion insertion tool …

Impact Of Artificial Intelligence-Based Autosegmentation Of Organs At Risk In Low- And Middle-Income Countries, Solomon Kibudde, Awusi Kavuma, Yao Hao, Tianyu Zhao, Hiram Gay, Jacaranda Van Rheenen, Pavan Mukesh Jhaveri, Minjmaa Minjgee, Enkhsetseg Vanchinbazar, Urdenekhuu Nansalmaa, Baozhou Sun

2020-Current year OA Pubs

PURPOSE: Radiation therapy (RT) processes require significant human resources and expertise, creating a barrier to rapid RT deployment in low- and middle-income countries (LMICs). Accurate segmentation of tumor targets and organs at risk (OARs) is crucial for optimal RT. This study assessed the impact of artificial intelligence (AI)-based autosegmentation of OARs in 2 LMICs.

METHODS AND MATERIALS: Ten patients, comprising 5 head and neck (HN) cancer patients and 5 prostate cancer patients, were randomly selected. Planning computed tomography images were subjected to autosegmentation using an Food and Drug Administration-approved AI software tool and manual segmentation by experienced radiation oncologists from …

Assessing Radiology And Radiation Therapy Needs For Cancer Care In Low-And-Middle-Income Countries: Insight From A Global Survey Of Departmental And Institutional Leaders, Stephanie A Parker, Yao Hao, Et Al.

2020-Current year OA Pubs

PURPOSE: The global cancer burden and mortality rates are increasing, with significant disparities in access to care in low- and middle-income countries (LMICs). This study aimed to identify radiology and radiation therapy needs in LMICs from the perspective of departmental and institutional leaders.

METHODS AND MATERIALS: A survey was developed and conducted by the American Association of Physicists in Medicine Global Needs Assessment Committee and the American Association of Physicists in Medicine International Council. The survey, organized into 5 sections (Introduction, Infrastructure Needs, Education Needs, Research Needs, and General Information), was open to respondents from March 1, to August 16, …

Relationship Between Mri Brain-Age Heterogeneity, Cognition, Genetics And Alzheimer's Disease Neuropathology, Mathilde Antoniades, Pamela Lamontagne, Tammie Benzinger, Daniel S Marcus, John C Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

METHODS: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age …

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel In Relapsed Or Refractory Large B-Cell Lymphoma, Frederick L Locke, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort …

Pdgf-Bb Overexpression In P53 Null Oligodendrocyte Progenitors Increases H3k27me3 And Induces Transcriptional Changes Which Favor Proliferation, Dennis Huang, Angeliki Mela, Natarajan V Bhanu, Benjamin A Garcia, Peter Canoll, Patrizia Casaccia

2020-Current year OA Pubs

Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs with Trp53 deletion and PDGF-BB overexpression (BB-p53n) and those carrying only p53 deletion (p53n). In culture, the BB-p53n OPCs display growth characteristics more similar to glioma cells than p53n OPCs. When injected in mouse brains, BB-p53n OPC form tumors, while the p53n OPCs do not. Unbiased histone proteomics and transcriptomic analysis on these OPC populations identified higher levels of the histone H3K27me3 mark and lower levels of the histone H4K20me3. …