Medicine and Health Sciences Commons^™

Glua3 Subunits Are Required For Appropriate Assembly Of Ampar Glua2 And Glua4 Subunits On Cochlear Afferent Synapses And For Presynaptic Ribbon Modiolar-Pillar Morphology, Mark A Rutherford, Atri Bhattacharyya, Maolei Xiao, Hou-Ming Cai, Indra Pal, Maria Eulalia Rubio

2020-Current year OA Pubs

Cochlear sound encoding depends on α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), but reliance on specific pore-forming subunits is unknown. With 5-week-old male C57BL/6J

Quantification Of Patient-Specific Coronary Material Properties And Their Correlations With Plaque Morphological Characteristics: An In Vivo Ivus Study, Liang Wang, Akiko Maehara, Xiaoguo Zhang, Rui Lv, Yangyang Qu, Xiaoya Guo, Jian Zhu, Zheyang Wu, Kristen L Billiar, Jie Zheng, Lijuan Chen, Genshan Ma, Gary S Mintz, Dalin Tang

2020-Current year OA Pubs

BACKGROUND: A method using in vivo Cine IVUS and VH-IVUS data has been proposed to quantify material properties of coronary plaques. However, correlations between plaque morphological characteristics and mechanical properties have not been studied in vivo.

METHOD: In vivo Cine IVUS and VH-IVUS data were acquired at 32 plaque cross-sections from 19 patients. Six morphological factors were extracted for each plaque. These samples were categorized into healthy vessel, fibrous plaque, lipid-rich plaque and calcified plaque for comparisons. Three-dimensional thin-slice models were constructed using VH-IVUS data to quantify in vivo plaque material properties following a finite element updating approach by matching …

Outcomes Of The 2019 Hydrocephalus Association Workshop, "Driving Common Pathways: Extending Insights From Posthemorrhagic Hydrocephalus", Jason K Karimy, Jessie C Newville, Cameron Sadegh, Jill A Morris, Edwin S Monuki, David D Limbrick, James P Mcallister Ii, Jenna E Koschnitzky, Maria K Lehtinen, Lauren L Jantzie

2020-Current year OA Pubs

The Hydrocephalus Association (HA) workshop, Driving Common Pathways: Extending Insights from Posthemorrhagic Hydrocephalus, was held on November 4 and 5, 2019 at Washington University in St. Louis. The workshop brought together a diverse group of basic, translational, and clinical scientists conducting research on multiple hydrocephalus etiologies with select outside researchers. The main goals of the workshop were to explore areas of potential overlap between hydrocephalus etiologies and identify drug targets that could positively impact various forms of hydrocephalus. This report details the major themes of the workshop and the research presented on three cell types that are targets for new …

Endogenous Retrovirus Rna Expression Differences Between Race, Stage And Hpv Status Offer Improved Prognostication Among Women With Cervical Cancer, Jill Alldredge, Vinay Kumar, James Nguyen, Brooke E Sanders, Karina Gomez, Kay Jayachandran, Jin Zhang, Julie Schwarz, Farah Rahmatpanah

2020-Current year OA Pubs

Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the human genome. Using publicly available RNA-seq data from 63 cervical cancer patients, we investigated the expression of ERVs in cervical cancers. Four aspects of cervical cancer were investigated: patient ancestral background, tumor HPV type, tumor stage and patient survival. Between the racial subgroups, 74 ERVs were significantly differentially expressed, with Black Americans having 30 upregulated and 44 downregulated (including MER21C, HERV9-int, and HERVH-int) ERVs when compared to White Americans. We found that 3313 ERVs were differentially expressed between HPV subgroups, including MER41A, HERVH-int and HERVK9. There …

Long-Term Hematologic Improvement In A Patient With Cytopenic Myelofibrosis Treated With Pacritinib, Abdulraheem Yacoub, Ruben A Mesa, Stephen T Oh

2020-Current year OA Pubs

No abstract provided.

Whole-Exome Sequence Analysis Of Anthropometric Traits Illustrates Challenges In Identifying Effects Of Rare Genetic Variants, Kristin L Young, Ping An, Petra Lenzini, Michael Province, Et Al.

2020-Current year OA Pubs

Anthropometric traits, measuring body size and shape, are highly heritable and significant clinical risk factors for cardiometabolic disorders. These traits have been extensively studied in genome-wide association studies (GWASs), with hundreds of genome-wide significant loci identified. We performed a whole-exome sequence analysis of the genetics of height, body mass index (BMI) and waist/hip ratio (WHR). We meta-analyzed single-variant and gene-based associations of whole-exome sequence variation with height, BMI, and WHR in up to 22,004 individuals, and we assessed replication of our findings in up to 16,418 individuals from 10 independent cohorts from Trans-Omics for Precision Medicine (TOPMed). We identified four …

Students Stress Patterns In A Kenyan Socio-Cultural And Economic Context: Toward A Public Health Intervention, Victoria N Mutiso, David M Ndetei, Esther N Muia, Christine Musyimi, Monicah Masake, Tom L Osborn, Andre Sourander, John R Weisz, Daniel Mamah

2020-Current year OA Pubs

This study aimed at determining the prevalence of stress, different types of stress, their severity and their determinants in Kenyan university, college and high school students. The following tools were administered to 9741 students: (1) Researcher-designed socio-demographic tool, (2) Psychiatric Diagnostic Screening Questionnaire (PDSQ) for psychiatric disorders, (3) WERC Stress Screen for stress, (4) Washington Early Recognition Center Affectivity and Psychosis (WERCAP) screen for psychosis and affectivity, (5) Wealth Index Questionnaire for economic indicators. Descriptive analysis for the prevalence of different types of stress and inferential analysis for stress and independent variables were done. Significant variables (p < 0.05) were fitted into generalized linear model to determine independent predictors. The mean age of the respondents was 21.4 years (range 16-43). Money issues were the commonest stressors while alcohol and drug use were the least. The independent predictors of stress were females, college students and use of gas stove. In conclusion, up to 30% of the students suffer from mild to severe stress. The students experience a wide range of stressors. The most important stressors include money and finances, family related problems and concerns about their future. Our findings suggest a public health approach to create stress awareness in students.

Combining Ivus + Oct Data, Biomechanical Models And Machine Learning Method For Accurate Coronary Plaque Morphology Quantification And Cap Thickness And Stress/Strain Index Predictions, Rui Lv, Liang Wang, Akiko Maehara, Mitsuaki Matsumura, Xiaoya Guo, Habib Samady, Don P Giddens, Jie Zheng, Gary S Mintz, Dalin Tang

2020-Current year OA Pubs

Assessment and prediction of vulnerable plaque progression and rupture risk are of utmost importance for diagnosis, management and treatment of cardiovascular diseases and possible prevention of acute cardiovascular events such as heart attack and stroke. However, accurate assessment of plaque vulnerability assessment and prediction of its future changes require accurate plaque cap thickness, tissue component and structure quantifications and mechanical stress/strain calculations. Multi-modality intravascular ultrasound (IVUS), optical coherence tomography (OCT) and angiography image data with follow-up were acquired from ten patients to obtain accurate and reliable plaque morphology for model construction. Three-dimensional thin-slice finite element models were constructed for 228 …

Childhood Adversities And Risk Of Posttraumatic Stress Disorder And Major Depression Following A Motor Vehicle Collision In Adulthood, H N Ziobrowski, S L House, D M Barch, Et Al.

2020-Current year OA Pubs

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions.

METHODS: Data came from

RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month …

Dry Eye Disease In Mice Activates Adaptive Corneal Epithelial Regeneration Distinct From Constitutive Renewal In Homeostasis, Joseph B Lin, Xiaolei Shen, Charles W Pfeifer, Fion Shiau, Andrea Santeford, Philip A Ruzycki, Brian S Clark, Qin Liu, Andrew J W Huang, Rajendra S Apte

2020-Current year OA Pubs

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only …

Gene Regulatory Network Reconfiguration In Direct Lineage Reprogramming, Kenji Kamimoto, Mohd Tayyab Adil, Kunal Jindal, Christy M Hoffmann, Wenjun Kong, Xue Yang, Samantha A Morris

2020-Current year OA Pubs

In direct lineage conversion, transcription factor (TF) overexpression reconfigures gene regulatory networks (GRNs) to reprogram cell identity. We previously developed CellOracle, a computational method to infer GRNs from single-cell transcriptome and epigenome data. Using inferred GRNs, CellOracle simulates gene expression changes in response to TF perturbation, enabling in silico interrogation of network reconfiguration. Here, we combine CellOracle analysis with lineage tracing of fibroblast to induced endoderm progenitor (iEP) conversion, a prototypical direct reprogramming paradigm. By linking early network state to reprogramming outcome, we reveal distinct network configurations underlying successful and failed fate conversion. Via in silico simulation of TF perturbation, …

Discussing Cost And Value In Patient Decision Aids And Shared Decision Making: A Call To Action, Mary C. Politi, Ashley J. Housten, Rachel C. Forcino, Jesse Jansen, Glyn Elwyn

2020-Current year OA Pubs

Direct and indirect costs of care influence patients' health choices and the ability to implement those choices. Despite the significant impact of care costs on patients' health and daily lives, patient decision aid (PtDA) and shared decision-making (SDM) guidelines almost never mention a discussion of costs of treatment options as part of minimum standards or quality criteria. Given the growing study of the impact of costs in health decisions and the rising costs of care more broadly, in fall 2021 we organized a symposium at the Society for Medical Decision Making's annual meeting. The focus was on the role of …

Postibrutinib Relapse Outcomes For Patients With Marginal Zone Lymphoma, Narendranath Epperla, Lauren Shea, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

No abstract provided.

Gene-Folic Acid Interactions And Risk Of Conotruncal Heart Defects: Results From The National Birth Defects Prevention Study, Daniel M Webber, Ming Li, Stewart L Macleod, Xinyu Tang, Joseph W Levy, Mohammad A Karim, Stephen W Erickson, Charlotte A Hobbs, The National Birth Defects Prevention Study

2020-Current year OA Pubs

Conotruncal heart defects (CTDs) are heart malformations that affect the cardiac outflow tract and typically cause significant morbidity and mortality. Evidence from epidemiological studies suggests that maternal folate intake is associated with a reduced risk of heart defects, including CTD. However, it is unclear if folate-related gene variants and maternal folate intake have an interactive effect on the risk of CTDs. In this study, we performed targeted sequencing of folate-related genes on DNA from 436 case families with CTDs who are enrolled in the National Birth Defects Prevention Study and then tested for common and rare variants associated with CTD. …

Fungal Assisted Valorisation Of Polymeric Lignin: Mechanism, Enzymes And Perspectives, Kavya Dashora, Meghana Gattupalli, Gyan Datta Tripathi, Zoya Javed, Shweta Singh, Maria Tuohy, Prakash Kumar Sarangi, Deepti Diwan, Harikesh B. Singh, Vijai Kumar Gupta

2020-Current year OA Pubs

No abstract provided.

Relations Of Current And Past Cancer With Severe Outcomes Among 104,590 Hospitalized Covid-19 Patients: The Covid Ehr Cohort At The University Of Wisconsin, Margaret B Nolan, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics.

METHODS: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined.

RESULTS: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current …

A Cdh3-Β-Catenin-Laminin Signaling Axis In A Subset Of Breast Tumor Leader Cells Control Leader Cell Polarization And Directional Collective Migration, Priscilla Y Hwang, Jairaj Mathur, Yanyang Cao, Jose Almeida, Jiayu Ye, Vasilios Morikis, Daphne Cornish, Maria Clarke, Sheila A Stewart, Amit Pathak, Gregory D Longmore

2020-Current year OA Pubs

Carcinoma dissemination can occur when heterogeneous tumor and tumor-stromal cell clusters migrate together via collective migration. Cells at the front lead and direct collective migration, yet how these leader cells form and direct migration are not fully appreciated. From live videos of primary mouse and human breast tumor organoids in a 3D microfluidic system mimicking native breast tumor microenvironment, we developed 3D computational models, which hypothesize that leader cells need to generate high protrusive forces and overcome extracellular matrix (ECM) resistance at the leading edge. From single-cell sequencing analyses, we find that leader cells are heterogeneous and identify and isolate …

Histopathologic And Proteogenomic Heterogeneity Reveals Features Of Clear Cell Renal Cell Carcinoma Aggressiveness, Yize Li, Yige Wu, Rita Jiu-Hsien Lu, Siqi Chen, Yanyan Zhao, Wagma Caravan, Nataly Naser Al Deen, Matthew A Wyczalkowski, Michael C Wendl, Melissa A Reimers, Russell Pachynski, Brian A Van Tine, Feng Chen, Li Ding, Et Al.

2020-Current year OA Pubs

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 …

Docosahexaenoic Acid Stability In Ready-To-Use Therapeutic Food, Genevieve James, Kevin Stephenson, Meghan Callaghan-Gillespie, Mohamed Tabita Kamara, Hui Gyu Park, J Thomas Brenna, Mark J Manary

2020-Current year OA Pubs

Ready-to-use therapeutic food (RUTF) is used to treat young children diagnosed with severe acute malnutrition. RUTF with low and balanced linoleic and alpha-linolenic acid, plus omega-3 docosahexaenoic acid (DHA), supports long-term cognitive recovery. DHA is prone to degradation due to peroxidation, possibly exacerbated by the iron inherently in RUTF. Our goals were to prepare benchtop and manufacturing scale of RUTF formulations that include DHA and measure its retention. Twenty-seven RUTF formulas with base ingredients, including oats, high oleic or commodity peanuts, and encapsulated or oil-based DHA at various levels were prepared at benchtop scale, followed by seven months of climate-controlled …

Discovery And Characterization Of A New Class Of O-Linking Oligosaccharyltransferases From The Moraxellaceae Family, Cory J Knoot, Paeton L Wantuch, Lloyd S Robinson, David A Rosen, Nichollas E Scott, Christian M Harding

2020-Current year OA Pubs

Bacterial protein glycosylation is commonly mediated by oligosaccharyltransferases (OTases) that transfer oligosaccharides en bloc from preassembled lipid-linked precursors to acceptor proteins. Natively, O-linking OTases usually transfer a single repeat unit of the O-antigen or capsular polysaccharide to the side chains of serine or threonine on acceptor proteins. Three major families of bacterial O-linking OTases have been described: PglL, PglS, and TfpO. TfpO is limited to transferring short oligosaccharides both in its native context and when heterologously expressed in glycoengineered Escherichia coli. On the other hand, PglL and PglS can transfer long-chain polysaccharides when expressed in glycoengineered E. coli. Herein, we …

Silencing Mir-146a-5p Protects Against Injury-Induced Osteoarthritis In Mice, Haocheng Qin, Cuicui Wang, Yonghua He, Aiwu Lu, Tiandao Li, Bo Zhang, Jie Shen

2020-Current year OA Pubs

Osteoarthritis (OA), the most prevalent joint disease and the leading cause of disability, remains an incurable disease largely because the etiology and pathogenesis underlying this degenerative process are poorly understood. Low-grade inflammation within joints is a well-established factor that disturbs joint homeostasis and leads to an imbalance between anabolic and catabolic processes in articular cartilage; however, the complexity of the network between inflammatory factors that often involves positive and negative feedback loops makes current anti-cytokine therapy ineffective. MicroRNAs (miRNAs) have emerged as key regulators to control inflammation, and aberrant miRNAs expression has recently been linked to OA pathophysiology. In the …

Use Of Serial Smartphone-Based Assessments To Characterize Diverse Neuropsychiatric Symptom Trajectories In A Large Trauma Survivor Cohort, Francesca L Beaudoin, Stacey L House, Deanna M Barch, Et Al.

2020-Current year OA Pubs

The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along …

Multimodal Brain Age Estimates Relate To Alzheimer Disease Biomarkers And Cognition In Early Stages: A Cross-Sectional Observational Study, Peter R Millar, Brian A Gordon, Patrick H Luckett, Tammie L S Benzinger, Carlos Cruchaga, Anne M Fagan, Jason J Hassenstab, Richard J Perrin, Suzanne E Schindler, Randall J Bateman, John C Morris, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Estimates of 'brain-predicted age' quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD) but has not been well explored in presymptomatic AD. Prior studies have typically modeled BAG with structural MRI, but more recently other modalities, including functional connectivity (FC) and multimodal MRI, have been explored.

METHODS: We trained three models to predict age from FC, structural (S), or multimodal MRI (S+FC) in 390 amyloid-negative cognitively normal (CN/A-) participants (18-89 years old). In independent samples of 144 CN/A-, 154 CN/A+, …

Excretory/Secretory Proteome Of Females And Males Of The Hookworm Ancylostoma Ceylanicum, Samuel C Uzoechi, Bruce A Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K Bracken, Paul J Brindley, R Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

2020-Current year OA Pubs

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm's excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm

Protocol For The Phase 2 Edelife Trial Investigating The Efficacy And Safety Of Intra-Amniotic Er004 Administration To Male Subjects With X-Linked Hypohidrotic Ectodermal Dysplasia, Holm Schneider, Smail Hadj-Rabia, Florian Faschingbauer, Christine Bodemer, Dorothy K Grange, Mary E Norton, Riccardo Cavalli, Gianluca Tadini, Holger Stepan, Angus Clarke, Encarna Guillén-Navarro, Sigrun Maier-Wohlfart, Athmane Bouroubi, Florence Porte

2020-Current year OA Pubs

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (

Civicdb 2022: Evolution Of An Open-Access Cancer Variant Interpretation Knowledgebase, Kilannin Krysiak, Arpad M Danos, Jason Saliba, Joshua F Mcmichael, Adam C Coffman, Susanna Kiwala, Erica K Barnell, Lana Sheta, Lynzey Kujan, Shahil Pema, Nicholas C Spies, Kaitlin A Clark, Ajay C Venigalla, Avila Suda, Benjamin J Ainscough, Haolin Shen, Alex R Marr, My H Hoang, Kartik Singhal, Mariam Khanfar, Brian V Li, Katie M Campbell, Kelsy C Cotto, Zachary L Skidmore, Jason R Walker, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination …

Methylc-Analyzer: A Comprehensive Downstream Pipeline For The Analysis Of Genome-Wide Dna Methylation, Rita Jui-Hsien Lu, Pei-Yu Lin, Ming-Ren Yen, Bing-Heng Wu, Pao-Yang Chen

2020-Current year OA Pubs

DNA methylation is a crucial epigenetic modification involved in multiple biological processes and diseases. Current approaches for measuring genome-wide DNA methylation via bisulfite sequencing (BS-seq) include whole-genome bisulfite sequencing (WGBS), reduced representation bisulfite sequencing (RRBS), and enzymatic methyl-seq (EM-seq). The computational analysis tools available for BS-seq data include customized aligners for mapping bisulfite-converted reads and computational pipelines for downstream data analysis. Current post-alignment methylation tools are specialized for the interpretation of CG methylation, which is known to dominate mammalian genomes, however, non-CG methylation (CHG and CHH, where H refers to A, C, or T) is commonly observed in plants and …

A Phase Ii Study Of Palbociclib Plus Letrozole Plus Trastuzumab As Neoadjuvant Treatment For Clinical Stages Ii And Iii Er+ Her2+ Breast Cancer (Paltan), Foluso O Ademuyiwa, Jingqin Luo, Yu Tao, Jeremy Hoog, Marie L Laury, Tracy Summa, Trish Hammerschmidt, Zhanfang Guo, Ashley Frith, Katherine Weilbaecher, Mateusz Opyrchal, Rebecca Aft, Katherine Clifton, Rama Suresh, Nusayba Bagegni, Ian S Hagemann, Michael D Iglesia, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Patients with ER+/HER2+ breast cancer (BC) are less likely to achieve pathological complete response (pCR) after chemotherapy with dual HER2 blockade than ER-/HER2+ BC. Endocrine therapy plus trastuzumab is effective in advanced ER+/HER2+ BC. Inhibition of CDK4/6 and HER2 results in synergistic cell proliferation reduction. We combined palbociclib, letrozole, and trastuzumab (PLT) as a chemotherapy-sparing regimen. We evaluated neoadjuvant PLT in early ER+/HER2+ BC. Primary endpoint was pCR after 16 weeks. Research biopsies were performed for whole exome and RNA sequencing, PAM50 subtyping, and Ki67 assessment for complete cell cycle arrest (CCCA: Ki67 ≤ 2.7%). After 26 patients, accrual stopped …

Conformational Plasticity Of Nak2k And Trek2 Potassium Channel Selectivity Filters, Marcos Matamoros, Xue Wen Ng, Joshua B Brettmann, David W Piston, Colin G Nichols

2020-Current year OA Pubs

The K

Historic Clinical Trial External Control Arm Provides Actionable Gen-1 Efficacy Estimate Before A Randomized Trial, Xiang Yin, Ruthanna Davi, Elizabeth B Lamont, Premal H Thaker, William H Bradley, Charles A Leath 3rd, Kathleen M Moore, Khursheed Anwer, Lauren Musso, Nicholas Borys

2020-Current year OA Pubs

PURPOSE: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients' end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy.

METHODS: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to …