Medicine and Health Sciences Commons^™

Exome Sequencing Revealed Pde11a As A Novel Candidate Gene For Early-Onset Alzheimer's Disease, Wei Qin, Aihong Zhou, Xiumei Zuo, Longfei Jia, Fangyu Li, Qi Wang, Ying Li, Yiping Wei, Hongmei Jin, Carlos Cruchaga, Bruno A Benitez, Jianping Jia

2020-Current year OA Pubs

To identify novel risk genes and better understand the molecular pathway underlying Alzheimer's disease (AD), whole-exome sequencing was performed in 215 early-onset AD (EOAD) patients and 255 unrelated healthy controls of Han Chinese ethnicity. Subsequent validation, computational annotation and in vitro functional studies were performed to evaluate the role of candidate variants in EOAD. We identified two rare missense variants in the phosphodiesterase 11A (PDE11A) gene in individuals with EOAD. Both variants are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation and are classified as pathogenic. Furthermore, we found significantly decreased protein levels of …

Novel Autosegmentation Spatial Similarity Metrics Capture The Time Required To Correct Segmentations Better Than Traditional Metrics In A Thoracic Cavity Segmentation Workflow, Kendall J Kiser, Arko Barman, Sonja Stieb, Clifton D Fuller, Luca Giancardo

2020-Current year OA Pubs

Automated segmentation templates can save clinicians time compared to de novo segmentation but may still take substantial time to review and correct. It has not been thoroughly investigated which automated segmentation-corrected segmentation similarity metrics best predict clinician correction time. Bilateral thoracic cavity volumes in 329 CT scans were segmented by a UNet-inspired deep learning segmentation tool and subsequently corrected by a fourth-year medical student. Eight spatial similarity metrics were calculated between the automated and corrected segmentations and associated with correction times using Spearman's rank correlation coefficients. Nine clinical variables were also associated with metrics and correction times using Spearman's rank …

Semi-Supervised Peak Calling With Span And Jbr Genome Browser, Oleg Shpynov, Aleksei Dievskii, Roman Chernyatchik, Petr Tsurinov, Maxim N Artyomov

2020-Current year OA Pubs

UNLABELLED: The widespread application of ChIP-seq led to a growing need for consistent analysis of multiple epigenetics profiles, for instance, in human studies where multiple replicates are a common element of design. Such multisamples experimental designs introduced analytical and computational challenges. For example, when peak calling is done independently for each sample, small differences in signal strength/quality lead to a very different number of peaks for individual samples, making group-level analysis difficult. On the other side, when samples are pooled together for joint analysis, individual-level statistical differences are averaged out. Recently we have demonstrated that a semi-supervised peak calling approach …

Electronic Clinical Decision Support For Children With Minor Head Trauma And Intracranial Injuries: A Sociotechnical Analysis, Jacob K Greenberg, Ayodamola Otun, Azzah Nasraddin, Ross C Brownson, Nathan Kuppermann, David D Limbrick, Po-Yin Yen, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Current management of children with minor head trauma (MHT) and intracranial injuries is not evidence-based and may place some children at risk of harm. Evidence-based electronic clinical decision support (CDS) for management of these children may improve patient safety and decrease resource use. To guide these efforts, we evaluated the sociotechnical environment impacting the implementation of electronic CDS, including workflow and communication, institutional culture, and hardware and software infrastructure, among other factors.

METHODS: Between March and May, 2020 semi-structured qualitative focus group interviews were conducted to identify sociotechnical influences on CDS implementation. Physicians from neurosurgery, emergency medicine, critical care, …

One-Year Urinary And Sexual Outcome Trajectories Among Prostate Cancer Patients Treated By Radical Prostatectomy: A Prospective Study, Lin Yang, Jung Ae Lee, Emily Heer, Claire Pernar, Graham A Colditz, Ratna Pakpahan, Kellie R Imm, Eric H Kim, Robert L Grubb 3rd, Kathleen Y Wolin, Adam S Kibel, Siobhan Sutcliffe

2020-Current year OA Pubs

BACKGROUND: To examine one-year trajectories of urinary and sexual outcomes, and correlates of these trajectories, among prostate cancer patients treated by radical prostatectomy (RP).

METHODS: Study participants were recruited from 2011 to 2014 at two US institutions. Self-reported urinary and sexual outcomes were measured at baseline before surgery, and 5 weeks, 6 months and 12 months after surgery, using the modified Expanded Prostate Cancer Index Composite-50 (EPIC-50). Changes in EPIC-50 scores from baseline were categorized as improved (beyond baseline), maintained, or impaired (below baseline), using previously-reported minimum clinically important differences.

RESULTS: Of the 426 eligible participants who completed the baseline …

Tofacitinib, An Oral Janus Kinase Inhibitor: Analysis Of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across The Ulcerative Colitis Clinical Program, Gary R Lichtenstein, Gerhard Rogler, Matthew A Ciorba, Chinyu Su, Gary Chan, Ronald D Pedersen, Nervin Lawendy, Daniel Quirk, Chudy I Nduaka, Andrew J Thorpe, Julian Panés

2020-Current year OA Pubs

BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we performed an integrated analysis of malignancy events from the tofacitinib phase 3 UC clinical development program (excluding nonmelanoma skin cancer [NMSC]).

METHODS: Data (up to May 2019) were pooled from two phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension (OLE) study, and analyzed as 3 cohorts: induction (N = 1139), maintenance (N = 592), and overall (induction, maintenance, and ongoing OLE study; N = 1124). Proportions and incidence rates (IRs; unique patients with events …

Stroma-Targeting Strategies In Pancreatic Cancer: Past Lessons, Challenges And Prospects, Faran Polani, Patrick M Grierson, Kian-Huat Lim

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is projected to emerge as the second leading cause of cancer-related death after 2030. Extreme treatment resistance is perhaps the most significant factor that underlies the poor prognosis of PDAC. To date, combination chemotherapy remains the mainstay of treatment for most PDAC patients. Compared to other cancer types, treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and shorter-lived. Aside from typically harboring genetic alterations that to date remain un-druggable and are drivers of treatment resistance, PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting …

Increased Complement Activation Is A Distinctive Feature Of Severe Sars-Cov-2 Infection, Lina Ma, Sanjaya K. Sahu, Marlene Cano, Vasanthan Kuppuswamy, Jamal Bajwa, Ja’Nia Mcphatter, Tingting Lei, Aaron Day, Daniel Reynolds, Xiaobo Wu, Rebecca Schriefer, Adriana M. Rauseo, Charles W. Goss, Jane A. O’Halloran, Rachel M. Presti, Alfred H. Kim, Andrew E. Gelman, Philip A. Mudd, John P. Atkinson, Hrishikesh S. Kulkarni, Et Al.

2020-Current year OA Pubs

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers: Washington University School of Medicine (n=134) and Yale School of Medicine …

Presepsin As A Diagnostic And Prognostic Biomarker In Sepsis, Dimitrios Velissaris, Nicholas Zareifopoulos, Vasileios Karamouzos, Evangelos Karanikolas, Charalampos Pierrakos, Ioanna Koniari, Menelaos Karanikolas

2020-Current year OA Pubs

Sepsis is a condition characterized by high morbidity and mortality which is commonly encountered in an emergency and critical care setting. Despite a substantial body of research, the ideal biomarker for the diagnosis and prognostic stratification of septic patients remains unknown. This review aimed to summarize the publications referring to the validity of the biomarker presepsin when used for the detection, monitoring and prognosis in patients suffering with sepsis. This work is a narrative review based on a PubMed/Medline search conducted in order to identify all relevant publications referring to the use of presepsin in sepsis. Search was not limited …

Cancer-Associated Mutations Reveal A Novel Role For Epcam As An Inhibitor Of Cathepsin-L And Tumor Cell Invasion, Narendra V Sankpal, Taylor C Brown, Timothy P Fleming, John M Herndon, Anusha A Amaravati, Allison N Loynd, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors.

METHODS: The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of …

Implementation And Sustainability Factors Of Two Early-Stage Breast Cancer Conversation Aids In Diverse Practices, Danielle Schubbe, Mary C Politi, Julie Margenthaler, Courtney Goodwin, Et Al

2020-Current year OA Pubs

BACKGROUND: Conversation aids can facilitate shared decision-making and improve patient-centered outcomes. However, few examples exist of sustained use of conversation aids in routine care due to numerous barriers at clinical and organizational levels. We explored factors that will promote the sustained use of two early-stage breast cancer conversation aids. We examined differences in opinions between the two conversation aids and across socioeconomic strata.

METHODS: We nested this study within a randomized controlled trial that demonstrated the effectiveness of two early-stage breast cancer surgery conversation aids, one text-based and one picture-based. These conversation aids facilitated more shared decision-making and improved the …

Long-Term Mortality After Histoplasma Infection In People With Hiv, Joseph Cherabie, Patrick Mazi, Adriana M Rauseo, Chapelle Ayres, Lindsey Larson, Sasinuch Rutjanawech, Jane O'Halloran, Rachel Presti, William G Powderly, Andrej Spec

2020-Current year OA Pubs

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death < 90 days), late mortality (death ≥ 90 days), and long-term survivors. Patients diagnosed during or after 2008 were considered part of the modern antiretroviral therapy (ART) era. Insurance type (private vs. public) was a surrogate indicator of socioeconomic status. Out of 54 PWH infected with histoplasmosis, overall mortality was 37%; 14.8% early mortality and 22.2% late mortality. There was no statistically significant difference in survival based on the availability of modern ART (

Model Organisms Contribute To Diagnosis And Discovery In The Undiagnosed Diseases Network: Current State And A Future Vision, Dustin Baldridge, Michael F Wangler, Angela N Bowman, Shinya Yamamoto, Undiagnosed Diseases Network, Tim Schedl, Stephen C Pak, John H Postlethwait, Jimann Shin, Lilianna Solnica-Krezel, Hugo J Bellen, Monte Westerfield

2020-Current year OA Pubs

Decreased sequencing costs have led to an explosion of genetic and genomic data. These data have revealed thousands of candidate human disease variants. Establishing which variants cause phenotypes and diseases, however, has remained challenging. Significant progress has been made, including advances by the National Institutes of Health (NIH)-funded Undiagnosed Diseases Network (UDN). However, 6000-13,000 additional disease genes remain to be identified. The continued discovery of rare diseases and their genetic underpinnings provides benefits to affected patients, of whom there are more than 400 million worldwide, and also advances understanding the mechanisms of more common diseases. Platforms employing model organisms enable …

Neurological Diseases And Covid-19: Prospective Analyses Using The Uk Biobank, Nicola Veronese, Lee Smith, Mario Barbagallo, Gianluigi Giannelli, Maria Gabriella Caruso, Anna Maria Cisternino, Maria Notarnicola, Chao Cao, Thomas Waldhoer, Lin Yang

2020-Current year OA Pubs

COVID-19 (Coronavirus disease-19) may present with neurological signs, but whether people already affected by neurological conditions are at a higher risk of contracting COVID-19 is still not known. We, therefore, aimed to investigate the association of previously diagnosed neurological conditions with COVID-19. 502,536 community-dwelling UK Biobank participants (54.4% male, mean age 56.6 ± 10.3 years) were included. Among these, 57,463 participants had a diagnosis of neurological conditions (11.43%) and a total of 1326 COVID-19-positive cases were identified (0.26%). Neurological conditions were identified through medical history and linkage to data on hospital admissions (ICD-10 code G00-G99). COVID-19 presence was diagnosed using …

A Neuroskeletal Atlas: Spatial Mapping And Contextualization Of Axon Subtypes Innervating The Long Bones Of C3h And B6 Mice, Madelyn R Lorenz, Jennifer M Brazill, Alec T Beeve, Ivana Shen, Erica L Scheller

2020-Current year OA Pubs

Nerves in bone play well-established roles in pain and vasoregulation and have been associated with progression of skeletal disorders, including osteoporosis, fracture, arthritis, and tumor metastasis. However, isolation of the region-specific mechanisms underlying these relationships is limited by our lack of quantitative methods for neuroskeletal analysis and precise maps of skeletal innervation. To overcome these limitations, we developed an optimized workflow for imaging and quantitative analysis of axons in and around the bone, including validation of Baf53b-Cre in concert with R26R-tdTomato (Ai9) as a robust pan-neuronal reporter system for use in musculoskeletal tissues. In addition, we created comprehensive maps of …

Patient-Reported Outcomes From A Randomized, Active-Controlled, Open-Label, Phase 3 Trial Of Burosumab Versus Conventional Therapy In Children With X-Linked Hypophosphatemia, Raja Padidela, Michael P Whyte, Et Al.

2020-Current year OA Pubs

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue …

The Prove Study: Us Real-World Experience With Chlormethine/Mechlorethamine Gel In Combination With Other Therapies For Patients With Mycosis Fungoides Cutaneous T-Cell Lymphoma, Ellen J Kim, Joan Guitart, Christiane Querfeld, Michael Girardi, Amy Musiek, Oleg E Akilov, James T Angello, William L Bailey, Larisa J Geskin

2020-Current year OA Pubs

BACKGROUND: Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking.

OBJECTIVE: Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting.

METHODS: This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary …

The Impact Of Covid-19 On The Well-Being And Cognition Of Older Adults Living In The United States And Latin America, Ganesh M Babulal, Ana Baena, Jorge Llibre-Guerra, Et Al

2020-Current year OA Pubs

BACKGROUND: In the COVID-19 pandemic, older adults from vulnerable ethnoracial groups are at high risk of infection, hospitalization, and death. We aimed to explore the pandemic's impact on the well-being and cognition of older adults living in the United States (US), Argentina, Chile, Mexico, and Peru.

METHODS: 1,608 (646 White, 852 Latino, 77 Black, 33 Asian; 72% female) individuals from the US and four Latin American countries aged ≥ 55 years completed an online survey regarding well-being and cognition during the pandemic between May and September 2020. Outcome variables (pandemic impact, discrimination, loneliness, purpose of life, subjective cognitive concerns) were …

Gardnerella Vaginalis Promotes Group B Streptococcus Vaginal Colonization, Enabling Ascending Uteroplacental Infection In Pregnant Mice, Nicole M Gilbert, Lynne R Foster, Bin Cao, Yin Yin, Indira U Mysorekar, Amanda L Lewis

2020-Current year OA Pubs

BACKGROUND: Group B Streptococcus is a common vaginal bacterium and the leading cause of invasive fetoplacental infections. Group B Streptococcus in the vagina can invade through the cervix to cause ascending uteroplacental infections or can be transmitted to the neonate during vaginal delivery. Some studies have found that women with a "dysbiotic" polymicrobial or Lactobacillus-depleted vaginal microbiota are more likely to harbor group B Streptococcus. Gardnerella vaginalis is often the most abundant bacteria in the vaginas of women with dysbiosis, while being detected at lower levels in most other women, and has been linked with several adverse pregnancy outcomes. Mouse …

Association Of Physician Group Practice Participation In Bundled Payments With Patient Selection, Costs, And Outcomes For Joint Replacement, Karen E Joynt Maddox, E John Orav, Jie Zheng, Arnold M Epstein

2020-Current year OA Pubs

IMPORTANCE: Medicare's Bundled Payments for Care Improvement (BPCI) program, which ran from 2013 to 2018, was an important experiment in physician-focused alternative payment models. However, little is known about whether the program was associated with better quality or outcomes or lower costs.

OBJECTIVE: To determine whether participation in BPCI among physician group practices was associated with advantageous or deleterious changes in costs or patient outcomes.

DESIGN SETTING AND PARTICIPANTS: This cross-sectional study used 2013 to 2017 Medicare files and difference-in-differences (DID) models to compare the change over time in Medicare payments, patient selection, and clinical outcomes between 91 orthopedic groups …

Should Weight-Bearing Activity Be Reduced During Healing Of Plantar Diabetic Foot Ulcers, Even When Using Appropriate Offloading Devices?, Gustav Jarl, Jaap J Van Netten, Peter A Lazzarini, Ryan T Crews, Bijan Najafi, Michael J Mueller

2020-Current year OA Pubs

Physical activity is an essential part of general health and diabetes management. However, recommending weight-bearing physical activity for people with plantar diabetic foot ulcers is controversial, even when gold standard offloading devices are used, as it is commonly thought to delay healing. We aimed to narratively review relevant studies investigating the relationship between plantar diabetic foot ulcer healing and weight-bearing activity, plantar pressure and device adherence. We defined relevant studies as those from two systematic reviews, along with those identified since using a similar updated Pubmed search strategy. We identified six studies. One study found that more daily steps were …

Endoscopic Retrieval Of A Proximally Migrated Biliary Stent Using Extracorporeal Shockwave Lithotripsy, Electrohydraulic Lithotripsy, And Cholangioscopy With Minisnare, Michael J Weaver, Vladimir M Kushnir

2020-Current year OA Pubs

Video 1ERCP was notable for a proximally migrated biliary stent. Cholangiogram demonstrated multiple filling defects consistent with choledocholithiasis surrounding the proximally migrated biliary stent. Retrieval of the stent was successful using cholangioscopy-directed electrohydraulic lithotripsy, extracorporeal shockwave lithotripsy, mechanical lithotripsy, and minisnare over the course of 2 ERCPs. Complete duct clearance of stones was accomplished with balloon sweeps.

The Poly(Adp-Ribosyl)Ation Of Brd4 Mediated By Parp1 Promoted Pathological Cardiac Hypertrophy, Zhenzhen Li, Zhen Guo, Rui Lan, Sidong Cai, Zhirong Lin, Jingyan Li, Junjian Wang, Zhuoming Li, Peiqing Liu

2020-Current year OA Pubs

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced …

Bacterial Sepsis Increases Hippocampal Fibrillar Amyloid Plaque Load And Neuroinflammation In A Mouse Model Of Alzheimer's Disease, Jacob M Basak, Aura Ferreiro, Lucy S Cohen, Patrick W Sheehan, Collin J Nadarajah, Michael F Kanan, Kimberley V Sukhum, Gautam Dantas, Erik S Musiek

2020-Current year OA Pubs

BACKGROUND: Sepsis, a leading cause for intensive care unit admissions, causes both an acute encephalopathy and chronic brain dysfunction in survivors. A history of sepsis is also a risk factor for future development of dementia symptoms. Similar neuropathologic changes are associated with the cognitive decline of sepsis and Alzheimer's disease (AD), including neuroinflammation, neuronal death, and synaptic loss. Amyloid plaque pathology is the earliest pathological hallmark of AD, appearing 10 to 20 years prior to cognitive decline, and is present in 30% of people over 65. As sepsis is also more common in older adults, we hypothesized that sepsis might …

Long-Term Outcomes Of Operatively Treated Medial Epicondyle Fractures In Pediatric And Adolescent Patients, Ronak M Patel, Yash Tarkunde, Lindley B Wall, Gregory Schimizzi, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Medial epicondyle fractures are among the most common pediatric elbow injuries. The management of these fractures continues to be debated. To better understand patient results with operative fixation, we reviewed the outcomes of operatively treated medial epicondyle fractures.

METHODS: A retrospective review was performed to identify all patients less than 18 years of age at the time of injury who were treated surgically for medial epicondyle fractures. Outcomes were assessed based on the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity and Pain Interference domains, Visual Analog Scale for pain, subjective range of motion, ulnar nerve function, and requirement …

A Systematic Review Of Higher-Risk Myelodysplastic Syndromes Clinical Trials To Determine The Benchmark Of Azacitidine And Explore Alternative Endpoints For Overall Survival, Jacqueline S Garcia, Ronan T Swords, Gail J Roboz, Meagan A Jacoby, Guillermo Garcia-Manero, Wan-Jen Hong, Xiaoqing Yang, Ying Zhou, Uwe Platzbecker, David P Steensma, Johannes E Wolff, Pierre Fenaux

2020-Current year OA Pubs

The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional regimens. However, outcomes differ largely between studies, making it challenging to determine the contribution of novel therapies added to azacitidine. Further, a discrepancy is seen between complete (CR) or partial (PR) response rates and OS improvement with azacitidine, making it challenging to rely on earlier endpoints than OS. We conducted a systematic literature search and study-level systematic review of 237 clinical studies to better understand outcomes for HR-MDS patients treated with azacitidine. Pooled marrow CR was 9% (N = 2654; 95% …

A Blood-Based Diagnostic Test Incorporating Plasma Aβ42/40 Ratio, Apoe Proteotype, And Age Accurately Identifies Brain Amyloid Status: Findings From A Multi Cohort Validity Analysis, Tim West, Kristopher M Kirmess, Matthew R Meyer, Mary S Holubasch, Stephanie S Knapik, Yan Hu, John H Contois, Erin N Jackson, Scott E Harpstrite, Randall J Bateman, David M Holtzman, Philip B Verghese, Ilana Fogelman, Joel B Braunstein, Kevin E Yarasheski

2020-Current year OA Pubs

BACKGROUND: The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status.

METHODS: We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic …

Ancestry Specific Associations Of A Genetic Risk Score, Dietary Patterns And Metabolic Syndrome: A Longitudinal Aric Study, Dale S Hardy, Susan B Racette, Jane T Garvin, Hirut T Gebrekristos, Tesfaye B Mersha

2020-Current year OA Pubs

BACKGROUND: Associations have been observed among genetic variants, dietary patterns, and metabolic syndrome (MetS). A gap in knowledge is whether a genetic risk score (GRS) and dietary patterns interact to increase MetS risk among African Americans. We investigated whether MetS risk was influenced by interaction between a GRS and dietary patterns among Whites and African Americans. A secondary aim examined if molecular genetic clusterings differed by racial ancestry.

METHODS: We used longitudinal data over 4-visits (1987-1998) that included 10,681 participants aged 45-64y at baseline from the Atherosclerosis Risk in Communities study (8451 Whites and 2230 African Americans). We constructed a …

The Effect Of Convalescent Plasma Therapy On Mortality Among Patients With Covid-19: Systematic Review And Meta-Analysis, Stephen A Klassen, Brenda J Grossman, Jeffrey P Henderson, Et Al

2020-Current year OA Pubs

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments. Additional analyses showed that early transfusion (within 3 days of hospital admission) of …

The Efficacy And Safety Of Enzalutamide With Trastuzumab In Patients With Her2+ And Androgen Receptor-Positive Metastatic Or Locally Advanced Breast Cancer, Andrew Wardley, Ron Bose, Et Al

2020-Current year OA Pubs

PURPOSE: Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab.

METHODS: Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 …