Medicine and Health Sciences Commons^™

Community Research Fellows Training Program: Evaluation Of A Covid-19-Precipitated Virtual Adaptation, Nicole Ackermann, Sarah Humble, Jacquelyn V Coats, Carlette Lewis Rhone, Craig Schmid, Vetta Sanders Thompson, Kia L Davis

2020-Current year OA Pubs

Community engagement is important for promoting health equity. However, effective community engagement requires trust, collaboration, and the opportunity for all stakeholders to share in decision-making. Community-based training in public health research can build trust and increase community comfort with shared decision-making in academic and community partnerships. The Community Research Fellows Training (CRFT) Program is a community-based training program that promotes the role of underserved populations in research by enhancing participant knowledge and understanding of public health research and other relevant topics in health. This paper describes the process of modifying the original 15-week in-person training program to a 12-week online, …

Outcomes In Participants With Ventilated Nosocomial Pneumonia And Organ Failure Treated With Ceftolozane/Tazobactam Versus Meropenem: A Subset Analysis Of The Phase 3, Randomized, Controlled Aspect-Np Trial, Ignacio Martin-Loeches, Andrew F Shorr, Richard G Wunderink, Marin H Kollef, Jean-François Timsit, Brian Yu, Jennifer A Huntington, Erin Jensen, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: The pivotal ASPECT-NP trial showed ceftolozane/tazobactam was non-inferior to meropenem for the treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we evaluated treatment outcomes by degree of respiratory or cardiovascular dysfunction.

METHODS: This was a subset analysis of data from ASPECT-NP, a randomized, double-blind, non-inferiority trial (ClinicalTrials.gov NCT02070757). Adults with vHABP/VABP were randomized 1:1 to 3 g ceftolozane/tazobactam or 1 g meropenem every 8 h for 8-14 days. Outcomes in participants with a baseline respiratory component of the Sequential Organ Failure Assessment (SOFA) score (R-SOFA) ≥ 2 (indicative of severe respiratory failure), cardiovascular component of the SOFA score (CV-SOFA) …

Phase Ib Study Of Telisotuzumab Vedotin In Combination With Erlotinib In Patients With C-Met Protein-Expressing Non-Small-Cell Lung Cancer, D Ross Camidge, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

PURPOSE: Overexpression of c-Met protein and epidermal growth factor receptor (

PATIENTS AND METHODS: This study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age ≥ 18 years) with c-Met+ NSCLC. Later enrollment required presence of an

RESULTS: As of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months …

The Mechanism Of Enantioselective Neurosteroid Actions On Gaba, Hiroki Tateiwa, Satyanarayana M Chintala, Ziwei Chen, Lei Wang, Fatima Amtashar, John Bracamontes, Allison L Germann, Spencer R Pierce, Douglas F Covey, Gustav Akk, Alex S Evers

2020-Current year OA Pubs

The neurosteroid allopregnanolone (ALLO) and pregnanolone (PREG), are equally effective positive allosteric modulators (PAMs) of GABA

Chikungunya Virus And Its Envelope Protein E2 Induce Hyperalgesia In Mice: Inhibition By Anti-E2 Monoclonal Antibodies And By Targeting Trpv1, Carina Z Segato-Vendrameto, Felipe A Pinho-Ribeiro, Et Al.

2020-Current year OA Pubs

Chikungunya virus is an arthropod-borne infectious agent that causes Chikungunya fever disease. About 90% of the infected patients experience intense polyarthralgia, affecting mainly the extremities but also the large joints such as the knees. Chronic disease symptoms persist for months, even after clearance of the virus from the blood. Envelope proteins stimulate the immune response against the Chikungunya virus, becoming an important therapeutic target. We inactivated the Chikungunya virus (iCHIKV) and produced recombinant E2 (rE2) protein and three different types of anti-rE2 monoclonal antibodies. Using these tools, we observed that iCHIKV and rE2 protein induced mechanical hyperalgesia (electronic aesthesiometer test) …

Retinoid X Receptor Promotes Hematopoietic Stem Cell Fitness And Quiescence And Preserves Hematopoietic Homeostasis, María Piedad Menéndez-Gutiérrez, Jesús Porcuna, Ramesh Nayak, Ana Paredes, Haixia Niu, Vanessa Núñez, Aditi Paranjpe, Manuel J Gómez, Anukana Bhattacharjee, Daniel J Schnell, Fátima Sánchez-Cabo, John S Welch, Nathan Salomonis, Jose A Cancelas, Mercedes Ricote

2020-Current year OA Pubs

Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRβ induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRβ maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRβ-deficient HSCs include premature acquisition of an …

Incidence, Attributable Mortality, And Healthcare And Out-Of-Pocket Costs Of Clostridioides Difficile Infection In Us Medicare Advantage Enrollees, Holly Yu, Tamuno Alfred, Jennifer L Nguyen, Jingying Zhou, Margaret A Olsen

2020-Current year OA Pubs

BACKGROUND: US attributable Clostridioides difficile infection (CDI) mortality and cost data are primarily from Medicare fee-for-service populations, and little is known about Medicare Advantage Enrollees (MAEs). This study evaluated CDI incidence among MAEs from 2012 to 2019 and determined attributable mortality and costs by comparing MAEs with and without CDI occurring in 2018.

METHODS: This retrospective cohort study assessed CDI incidence and associated mortality and costs for eligible MAEs ≥65 years of age using the de-identified Optum Clinformatics Data Mart database (Optum; Eden Prairie, Minnesota, USA). Outcomes included mortality, healthcare utilization, and costs, which were assessed via a propensity score-matched …

Protection Of Messenger Rna Vaccines Against Hospitalized Coronavirus Disease 2019 In Adults Over The First Year Following Authorization In The United States, Mark W Tenforde, Hilary M Babcock, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization.

METHODS: Case-control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states 11 March-15 December 2021, including COVID-19 case patients and reverse transcriptase-polymerase chain reaction-negative controls. We included adults who were unvaccinated or vaccinated with 2 doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing …

Bintrafusp Alfa: A Bifunctional Fusion Protein Targeting Pd-L1 And Tgf-Β, In Patients With Pretreated Colorectal Cancer: Results From A Phase I Trial, Alexander Spira, Michael S Wertheim, Edward J Kim, Benjamin Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia L Rich, Genevieve Jehl, Andreas Machl, Rena Ito, James L Gulley, Scott Kopetz

2020-Current year OA Pubs

Colorectal cancer (CRC) is a heterogeneous and complex disease with limited treatment options. Targeting transforming growth factor β (TGF-β) and programmed death ligand 1 pathways may enhance antitumor efficacy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death ligand 1. We report results from an expansion cohort of a phase I study (NCT02517398) in patients with heavily pretreated advanced CRC treated with bintrafusp alfa. As of May 15, 2020, 32 patients with advanced CRC had received bintrafusp alfa …

The Impact Of Universal Glove And Gown Use On Clostridioides Difficile Acquisition: A Cluster-Randomized Trial, Daniel J Morgan, Erik R Dubberke, Tiffany Hink, Gwen Paszkiewicz, Carey-Ann D Burnham, Lisa Pineles, Larry Magder, J Kristie Johnson, Surbhi Leekha, Anthony D Harris

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infections in the United States. It is unknown whether universal gown and glove use in intensive care units (ICUs) decreases acquisition of C. difficile.

METHODS: This was a secondary analysis of a cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from 4 January 2012 to 4 October 2012. After a baseline period, ICUs were randomized to standard practice for glove and gown use versus the intervention of all healthcare workers being required to wear gloves and gowns for all patient contact and when entering any patient …

Body Mass Index And Molecular Subtypes Of Colorectal Cancer, Neil Murphy, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease.

METHODS: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables.

RESULTS: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = …

Structures Of Human Gastrin-Releasing Peptide Receptors Bound To Antagonist And Agonist For Cancer And Itch Therapy, Shuman Peng, Yuting Zhan, Dongqi Zhang, Lu Ren, Anqi Chen, Zhou-Feng Chen, Haitao Zhang

2020-Current year OA Pubs

Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog …

Prognostic Significance Of Early Platelet Dynamics In Staphylococcus Aureus Bacteremia, Rachid Douglas-Louis, Mimi Lou, Brian Lee, Emi Minejima, Juliane Bubeck-Wardenburg, Annie Wong-Beringer

2020-Current year OA Pubs

BACKGROUND: Platelets are recognized as key immune effectors, but they are targets of bacterial virulence factors. In the present study, we aimed to examine the relationship between early platelet dynamics and the outcome of Staphylococcus aureus bacteremia (SAB).

METHOD: Electronic medical records of adult patients hospitalized for SAB between July 2012 and November 2020 were retrospectively reviewed for relevant demographic, laboratory, and clinical data. The outcome endpoints were mortality and microbial persistence.

RESULTS: Among the 811 patients evaluated, 29% experienced thrombocytopenia on Day 1. Platelet count nadir occurred on Days 2-3 following SAB onset, and Day 4 was a determining …

Fifty Years Of Global Cardiovascular Research In Africa: A Scientometric Analysis, 1971 To 2021, Jean Jacques Noubiap, Dominic Millenaar, Dike Ojji, Q Eileen Wafford, Christian Ukena, Michael Böhm, Karen Sliwa, Mark D Huffman, Felix Mahfoud

2020-Current year OA Pubs

Background To analyze the quantity and impact of cardiovascular research done in Africa or coauthored by researchers based in Africa, their determinants, and the patterns of research collaboration. Methods and Results We retrieved data from Web of Science and additional sources. We analyzed temporal trends from 1971 to 2021 and geographical distribution, research impact using country-level h-index, international research cooperation, and associations of research quantity and quality using linear regression. The annual volume of cardiovascular research from Africa has increased from 4 publications in 1971 to 3867 in 2020 and currently represents ~3% of the global cardiovascular research output. Authors …

Evaluation Of Apparent Diffusion Coefficient Repeatability And Reproducibility For Preclinical Mris Using Standardized Procedures And A Diffusion-Weighted Imaging Phantom, Dariya Malyarenko, Ghoncheh Amouzandeh, Stephen Pickup, Rong Zhou, Henry Charles Manning, Seth T Gammon, Kooresh I Shoghi, James D Quirk, Renuka Sriram, Peder Larson, Michael T Lewis, Robia G Pautler, Paul E Kinahan, Mark Muzi, Thomas L Chenevert

2020-Current year OA Pubs

Relevant to co-clinical trials, the goal of this work was to assess repeatability, reproducibility, and bias of the apparent diffusion coefficient (ADC) for preclinical MRIs using standardized procedures for comparison to performance of clinical MRIs. A temperature-controlled phantom provided an absolute reference standard to measure spatial uniformity of these performance metrics. Seven institutions participated in the study, wherein diffusion-weighted imaging (DWI) data were acquired over multiple days on 10 preclinical scanners, from 3 vendors, at 6 field strengths. Centralized versus site-based analysis was compared to illustrate incremental variance due to processing workflow. At magnet isocenter, short-term (intra-exam) and long-term (multiday) …

Widespread Contribution Of Transposable Elements To The Rewiring Of Mammalian 3d Genomes, Mayank N K Choudhary, Kara Quaid, Xiaoyun Xing, Heather Schmidt, Ting Wang

2020-Current year OA Pubs

Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders, and RNA-DNA interactions. These play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We …

The P97-Ubxd8 Complex Regulates Er-Mitochondria Contact Sites By Altering Membrane Lipid Saturation And Composition, Rakesh Ganji, Joao A Paulo, Yuecheng Xi, Ian Kline, Jiang Zhu, Christoph S Clemen, Conrad C Weihl, John G Purdy, Steve P Gygi, Malavika Raman

2020-Current year OA Pubs

The intimate association between the endoplasmic reticulum (ER) and mitochondrial membranes at ER-Mitochondria contact sites (ERMCS) is a platform for critical cellular processes, particularly lipid synthesis. How contacts are remodeled and the impact of altered contacts on lipid metabolism remains poorly understood. We show that the p97 AAA-ATPase and its adaptor ubiquitin-X domain adaptor 8 (UBXD8) regulate ERMCS. The p97-UBXD8 complex localizes to contacts and its loss increases contacts in a manner that is dependent on p97 catalytic activity. Quantitative proteomics and lipidomics of ERMCS demonstrates alterations in proteins regulating lipid metabolism and a significant change in membrane lipid saturation …

Improving Communication In Intensive Care Unit To Ward Transitions: Protocol For Multisite National Implementation Of The Icu-Pause Handoff Tool, Elle Mizuki Fukui, Patrick G Lyons, Emily Harris, Emma K Mccune, Juan C Rojas, Lekshmi Santhosh

2020-Current year OA Pubs

BACKGROUND: The intensive care unit (ICU)-ward transfer poses a particularly high-risk period for patients. The period after transfer has been associated with adverse events and additional work for care teams related to miscommunication or omission of information. Standardized handoff processes have been found to reduce communication errors and adverse patient events in other clinical environments but are understudied at the ICU-ward interface. We previously developed an electronic ICU-ward transfer tool, ICU-PAUSE, which embeds the key elements and diagnostic reasoning to facilitate a safe transfer of care at ICU discharge.

OBJECTIVE: The aim of this study is to evaluate the implementation …

Antitumour Activity Of Neratinib In Patients With Her2-Mutant Advanced Biliary Tract Cancers, James J Harding, Haeseong Park, Et Al.

2020-Current year OA Pubs

HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs). Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has activity in HER2-mutant tumours. SUMMIT is an open-label, single-arm, multi-cohort, phase 2, 'basket' trial of neratinib in patients with solid tumours harbouring oncogenic HER2 somatic mutations (ClinicalTrials.gov: NCT01953926). The primary objective of the BTC cohort, which is now complete, is first objective response rate (ORR) to neratinib 240 mg orally daily. Secondary objectives include confirmed ORR, clinical benefit rate, progression-free survival, duration of response, overall survival, safety and tolerability. Genomic analyses were exploratory. …

Ion Channel Regulation Of Gut Immunity, Jing Feng, Zili Xie, Hongzhen Hu

2020-Current year OA Pubs

Mounting evidence indicates that gastrointestinal (GI) homeostasis hinges on communications among many cellular networks including the intestinal epithelium, the immune system, and both intrinsic and extrinsic nerves innervating the gut. The GI tract, especially the colon, is the home base for gut microbiome which dynamically regulates immune function. The gut's immune system also provides an effective defense against harmful pathogens entering the GI tract while maintaining immune homeostasis to avoid exaggerated immune reaction to innocuous food and commensal antigens which are important causes of inflammatory disorders such as coeliac disease and inflammatory bowel diseases (IBD). Various ion channels have been …

Preclinical Efficacy Of A Parp-1 Targeted Auger-Emitting Radionuclide In Prostate Cancer, Sreeja Sreekumar, Dong Zhou, Cedric Mpoy, Elsa Schenk, Jalen Scott, Jeffrey M Arbeit, Jinbin Xu, Buck E Rogers

2020-Current year OA Pubs

There is an unmet need for better therapeutic strategies for advanced prostate cancer. Poly (ADP-ribose) polymerase-1 (PARP-1) is a chromatin-binding DNA repair enzyme overexpressed in prostate cancer. This study evaluates whether PARP-1, on account of its proximity to the cell's DNA, would be a good target for delivering high-linear energy transfer Auger radiation to induce lethal DNA damage in prostate cancer cells. We analyzed the correlation between PARP-1 expression and Gleason score in a prostate cancer tissue microarray. A radio-brominated Auger emitting inhibitor ([

Netprophet 3: A Machine Learning Framework For Transcription Factor Network Mapping And Multi-Omics Integration, Dhoha Abid, Michael R Brent

2020-Current year OA Pubs

MOTIVATION: Many methods have been proposed for mapping the targets of transcription factors (TFs) from gene expression data. It is known that combining outputs from multiple methods can improve performance. To date, outputs have been combined by using either simplistic formulae, such as geometric mean, or carefully hand-tuned formulae that may not generalize well to new inputs. Finally, the evaluation of accuracy has been challenging due to the lack of genome-scale, ground-truth networks.

RESULTS: We developed NetProphet3, which combines scores from multiple analyses automatically, using a tree boosting algorithm trained on TF binding location data. We also developed three independent, …

The Efficacy Of A Posterior Approach To Surgical Correction For Neglected Idiopathic Scoliosis: A Comparative Analysis According To Health-Related Quality Of Life, Pulmonary Function, Back Pain And Sexual Function, Pawel Grabala, Ilkka J Helenius, Jacob M Buchowski, Suken A Shah

2020-Current year OA Pubs

BACKGROUND: This study aimed to evaluate the treatment outcomes of severe idiopathic scoliosis (IS) and hypothesized that surgical treatment would have a superior impact on the health-related quality of life (HRQoL), pulmonary function (PF), back pain, and sexual function.

METHODS: We retrospectively reviewed 195 consecutive patients with IS classified into severe (SG) and moderate groups (MG) with a minimum follow-up of two years.

RESULTS: The mean preoperative curve was 131° and 60° in the SG and MG, respectively. The mean preoperative flexibility in the bending films averaged between 22% in the SG and 41% in the MG. After definitive surgery, …

Ssris Differentially Modulate The Effects Of Pro-Inflammatory Stimulation On Hippocampal Plasticity And Memory Via Sigma 1 Receptors And Neurosteroids, Yukitoshi Izumi, Angela M Reiersen, Eric J Lenze, Steven J Mennerick, Charles F Zorumski

2020-Current year OA Pubs

Certain selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory effects in preclinical models, and recent clinical studies suggest that fluvoxamine can prevent deterioration in patients with COVID-19, possibly through activating sigma 1 receptors (S1Rs). Here we examined potential mechanisms contributing to these effects of fluvoxamine and other SSRIs using a well-characterized model of pro-inflammatory stress in rat hippocampal slices. When hippocampal slices are exposed acutely to lipopolysaccharide (LPS), a strong pro-inflammatory stimulus, basal synaptic transmission in the CA1 region remains intact, but induction of long-term potentiation (LTP), a form of synaptic plasticity thought to contribute to learning and memory, is completely …

Microbes, Histology, Blood Analysis, Enterotoxins, And Cytokines: Findings From The Aserf Systemic Symptoms In Women-Biospecimen Analysis Study: Part 3, Patricia Mcguire, Caroline Glicksman, Roger Wixtrom, C James Sung, Robert Hamilton, Marisa Lawrence, Melinda Haws, Sarah Ferenz, Marshall Kadin

2020-Current year OA Pubs

BACKGROUND: There has been an increasing need to acquire rigorous scientific data to answer the concerns of physicians, patients, and the FDA regarding the self-reported illness identified as breast implant illness (BII). There are no diagnostic tests or specific laboratory values to explain the reported systemic symptoms described by these patients.

OBJECTIVES: The aim of this study was to determine if there are quantifiable laboratory findings that can be identified in blood, capsule tissue pathology, or microbes that differentiate women with systemic symptoms they attribute to their implants from 2 control groups.

METHODS: A prospective blinded study enrolled 150 subjects …

Presence Of Trans-Fatty Acids Containing Ingredients In Pre-Packaged Foods And The Availability Of Reported Trans-Fat Levels In Kenya And Nigeria, Liping Huang, Adedayo E Ojo, Judith Kimiywe, Alex Kibet, Boni M Ale, Clementina E Okoro, Jimmy Louie, Fraser Taylor, Mark D Huffman, Dike B Ojji, Jason H Y Wu, Matti Marklund

2020-Current year OA Pubs

In most African countries, the prevalence of industrially produced

The Ntpase Activity Of The Double Fyve Domain-Containing Protein 1 Regulates Lipid Droplet Metabolism., Victoria A. Ismail, Teri Naismith, David J. Kast

2020-Current year OA Pubs

Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks and therefore play a central role in cellular metabolism. However, the molecular factors and underlying mechanisms that regulate the growth and degradation of LDs are poorly understood. It has emerged that proteins that establish contacts between LDs and the endoplasmic reticulum play a critical role in regulating LD metabolism. Recently, the autophagy-related protein, double FYVE domain-containing protein 1 (DFCP1/ZFYVE1) was shown to reside at the interface of the endoplasmic reticulum and LDs, however, little is known about the …

Primary Central Nervous System Germ Cell Tumors In Children And Young Adults: A Review Of Controversies In Diagnostic And Treatment Approach, Kee Kiat Yeo, Sumanth Nagabushan, Girish Dhall, Mohamed S Abdelbaki

2020-Current year OA Pubs

Primary central nervous system (CNS) germ cell tumors (GCT) are a rare heterogenous group of cancers, arising most commonly in the second decade of life. Through several clinical trials conducted around the world by various groups, the treatment approach for CNS GCT has advanced substantially with generally improved overall outcomes. In recent years, the goal of clinical trials has been focused on reduction of the radiotherapy burden and minimization of long-term toxicity. This review summarizes the current diagnostic and treatment regimens for CNS GCT, examines the controversies associated with these approaches, gaps in contemporary knowledge, and underscores the challenges we …

Machine Learning Approximations To Predict Epigenetic Age Acceleration In Stroke Patients, Isabel Fernández-Pérez, Joan Jiménez-Balado, Uxue Lazcano, Eva Giralt-Steinhauer, Lucía Rey Álvarez, Elisa Cuadrado-Godia, Ana Rodríguez-Campello, Adrià Macias-Gómez, Antoni Suárez-Pérez, Anna Revert-Barberá, Isabel Estragués-Gázquez, Carolina Soriano-Tarraga, Jaume Roquer, Angel Ois, Jordi Jiménez-Conde

2020-Current year OA Pubs

Age acceleration (Age-A) is a useful tool that is able to predict a broad range of health outcomes. It is necessary to determine DNA methylation levels to estimate it, and it is known that Age-A is influenced by environmental, lifestyle, and vascular risk factors (VRF). The aim of this study is to estimate the contribution of these easily measurable factors to Age-A in patients with cerebrovascular disease (CVD), using different machine learning (ML) approximations, and try to find a more accessible model able to predict Age-A. We studied a CVD cohort of 952 patients with information about VRF, lifestyle habits, …

Navigating Care For Rare Diseases: Caregiver And Patient Advice For Families And Clinicians Managing Care For Vascular Malformations, Anna M Kerr, Christine Bereitschaft, Kayla M Duty, Bryan A Sisk

2020-Current year OA Pubs

OBJECTIVE: Families affected by rare diseases face many challenges finding adequate care and often report poor communication with clinicians. In the current study, we explore patient and caregiver advice for families and clinicians in the context of complex vascular malformations (VMs), a condition that is frequently misunderstood and misdiagnosed.

METHODS: We performed semi-structured interviews with 21 adult patients with complex VMs and 24 caregivers of children with VMs. We analyzed the transcripts using thematic analysis.

RESULTS: Participants advised patients and caregivers to advocate for care, address mental and emotional well-being, seek social support, and promote self-management and self-care. Participants advised …