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Full-Text Articles in Entire DC Network
Mucosal Immunization With Chad-Sars-Cov-2-S Prevents Sequential Transmission Of Sars-Cov-2 To Unvaccinated Hamsters, Tamarand L Darling, Houda H Harastani, Astha Joshi, Traci L Bricker, Nadia Soudani, Kuljeet Seehra, Ahmed O Hassan, Michael S Diamond, Adrianus C M Boon
Mucosal Immunization With Chad-Sars-Cov-2-S Prevents Sequential Transmission Of Sars-Cov-2 To Unvaccinated Hamsters, Tamarand L Darling, Houda H Harastani, Astha Joshi, Traci L Bricker, Nadia Soudani, Kuljeet Seehra, Ahmed O Hassan, Michael S Diamond, Adrianus C M Boon
2020-Current year OA Pubs
COVID-19 vaccines have successfully reduced severe disease and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nonetheless, COVID-19 vaccines are variably effective in preventing transmission and symptomatic SARS-CoV-2 infection. Here, we evaluated the impact of mucosal or intramuscular vaccine immunization on airborne infection and transmission of SARS-CoV-2 in Syrian hamsters. Immunization of the primary contact hamsters with a mucosal chimpanzee adenoviral-vectored vaccine (ChAd-CoV-2-S), but not intramuscular messenger RNA (mRNA) vaccine, reduced infectious virus titers ~100-fold and 100,000-fold in the upper and lower respiratory tract of the primary contact hamster following SARS-CoV-2 exposure. This reduction in virus titer in …
Dihydrothiazolo Ring-Fused 2-Pyridone Antimicrobial Compounds Streptococcus Pyogenes Skin And Soft Tissue Infection, Zongsen Zou, Pardeep Singh, Jerome S Pinkner, Chloe L P Obernuefemann, Wei Xu, Taylor M Nye, Karen W Dodson, Fredrik Almqvist, Scott J Hultgren, Michael G Caparon
Dihydrothiazolo Ring-Fused 2-Pyridone Antimicrobial Compounds Streptococcus Pyogenes Skin And Soft Tissue Infection, Zongsen Zou, Pardeep Singh, Jerome S Pinkner, Chloe L P Obernuefemann, Wei Xu, Taylor M Nye, Karen W Dodson, Fredrik Almqvist, Scott J Hultgren, Michael G Caparon
2020-Current year OA Pubs
We have developed GmPcides from a peptidomimetic dihydrothiazolo ring-fused 2-pyridone scaffold that has antimicrobial activities against a broad spectrum of Gram-positive pathogens. Here, we examine the treatment efficacy of GmPcides using skin and soft tissue infection (SSTI) and biofilm formation models by
Adeno-Associated Virus Vector Delivery To The Brain: Technology Advancements And Clinical Applications, Dezhuang Ye, Chinwendu Chukwu, Yaoheng Yang, Zhongtao Hu, Hong Chen
Adeno-Associated Virus Vector Delivery To The Brain: Technology Advancements And Clinical Applications, Dezhuang Ye, Chinwendu Chukwu, Yaoheng Yang, Zhongtao Hu, Hong Chen
2020-Current year OA Pubs
Adeno-associated virus (AAV) vectors have emerged as a promising tool in the development of gene therapies for various neurological diseases, including Alzheimer's disease and Parkinson's disease. However, the blood-brain barrier (BBB) poses a significant challenge to successfully delivering AAV vectors to the brain. Strategies that can overcome the BBB to improve the AAV delivery efficiency to the brain are essential to successful brain-targeted gene therapy. This review provides an overview of existing strategies employed for AAV delivery to the brain, including direct intraparenchymal injection, intra-cerebral spinal fluid injection, intranasal delivery, and intravenous injection of BBB-permeable AAVs. Focused ultrasound has emerged …
Local Complement Activation And Modulation In Mucosal Immunity, Devesha H Kulkarni, Marick Starick, Rafael Aponte Alburquerque, Hrishikesh S Kulkarni
Local Complement Activation And Modulation In Mucosal Immunity, Devesha H Kulkarni, Marick Starick, Rafael Aponte Alburquerque, Hrishikesh S Kulkarni
2020-Current year OA Pubs
The complement system is an evolutionarily conserved arm of innate immunity, which forms one of the first lines of host response to pathogens and assists in the clearance of debris. A deficiency in key activators/amplifiers of the cascade results in recurrent infection, whereas a deficiency in regulating the cascade predisposes to accelerated organ failure, as observed in colitis and transplant rejection. Given that there are over 60 proteins in this system, it has become an attractive target for immunotherapeutics, many of which are United States Food and Drug Administration-approved or in multiple phase 2/3 clinical trials. Moreover, there have been …
Activated Sputum Eosinophils Associated With Exacerbations In Children On Mepolizumab, Gabriella E Wilson, Michelle Gill, Et Al.
Activated Sputum Eosinophils Associated With Exacerbations In Children On Mepolizumab, Gabriella E Wilson, Michelle Gill, Et Al.
2020-Current year OA Pubs
BACKGROUND: MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations.
OBJECTIVE: We aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma.
METHODS: Sputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. …
Head And Neck Squamous Cell Carcinomas Of Unknown Primary: Can Ancillary Studies Help Identify More Primary Tumor Sites?, Troy Hutchens, Wade Thorstad, Xiaowei Wang, Yuanxiang Li, Eric J Duncavage, Lulu Sun, Rebecca D Chernock
Head And Neck Squamous Cell Carcinomas Of Unknown Primary: Can Ancillary Studies Help Identify More Primary Tumor Sites?, Troy Hutchens, Wade Thorstad, Xiaowei Wang, Yuanxiang Li, Eric J Duncavage, Lulu Sun, Rebecca D Chernock
2020-Current year OA Pubs
A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as …
Geometric Accuracy Of Low-Dose Ct Scans For Use In Shoulder Musculoskeletal Research Applications, Rebekah L Lawrence, Lydia Nicholson, Erin C S Lee, Kelby Napier, Benjamin Zmistowski, Michael J Rainbow
Geometric Accuracy Of Low-Dose Ct Scans For Use In Shoulder Musculoskeletal Research Applications, Rebekah L Lawrence, Lydia Nicholson, Erin C S Lee, Kelby Napier, Benjamin Zmistowski, Michael J Rainbow
2020-Current year OA Pubs
Computed tomography (CT) imaging is frequently employed in a variety of musculoskeletal research applications. Although research studies often use imaging protocols developed for clinical applications, lower dose protocols are likely possible when the goal is to reconstruct 3D bone models. Our purpose was to describe the dose-accuracy trade-off between incrementally lower-dose CT scans and the geometric reconstruction accuracy of the humerus, scapula, and clavicle. Six shoulder specimens were acquired and scanned using 5 helical CT protocols: 1) 120 kVp, 450 mA (full-dose); 2) 120 kVp, 120 mA; 3) 120 kVp, 100 mA; 4) 100 kVp, 100 mA; 5) 80 kVp, …
Predicting Post-Surgical Functional Status In High-Grade Glioma With Resting State Fmri And Machine Learning, Patrick H Luckett, Michael O Olufawo, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt
Predicting Post-Surgical Functional Status In High-Grade Glioma With Resting State Fmri And Machine Learning, Patrick H Luckett, Michael O Olufawo, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt
2020-Current year OA Pubs
PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care.
METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of …
Nlrp1 Inflammasome Promotes Senescence And Senescence-Associated Secretory Phenotype, Inés Muela-Zarzuela, Juan Miguel Suarez-Rivero, Andrea Gallardo-Orihuela, Chun Wang, Kumi Izawa, Marta De Gregorio-Procopio, Isabelle Couillin, Bernhard Ryffel, Jiro Kitaura, Alberto Sanz, Thomas Von Zglinicki, Gabriel Mbalaviele, Mario D Cordero
Nlrp1 Inflammasome Promotes Senescence And Senescence-Associated Secretory Phenotype, Inés Muela-Zarzuela, Juan Miguel Suarez-Rivero, Andrea Gallardo-Orihuela, Chun Wang, Kumi Izawa, Marta De Gregorio-Procopio, Isabelle Couillin, Bernhard Ryffel, Jiro Kitaura, Alberto Sanz, Thomas Von Zglinicki, Gabriel Mbalaviele, Mario D Cordero
2020-Current year OA Pubs
BACKGROUND: Senescence is a cellular aging-related process triggered by different stresses and characterized by the secretion of various inflammatory factors referred to as senescence-associated secretory phenotype (SASP), some of which are produced by the NLRP3 inflammasome. Here, we present evidence that the NLRP1 inflammasome is a DNA damage sensor and a key mediator of senescence.
METHODS: Senescence was induced in fibroblasts in vitro and in mice. Cellular senescence was assessed by Western blot analysis of several proteins, including p16, p21, p53, and SASP factors, released in the culture media or serum. Inflammasome components, including NLRP1, NLRP3 and GSDMD were knocked …
Poly-Basic Peptides And Polymers As New Drug Candidates Against Plasmodium Falciparum, Roshan Sivakumar, Katherine Floyd, Jessey Erath, Alex Jacoby, Jenny Kim Kim, Peter O Bayguinov, James A J Fitzpatrick, Dennis Goldfarb, Marko Jovanovic, Abhai Tripathi, Sergej Djuranovic, Slavica Pavlovic-Djuranovic
Poly-Basic Peptides And Polymers As New Drug Candidates Against Plasmodium Falciparum, Roshan Sivakumar, Katherine Floyd, Jessey Erath, Alex Jacoby, Jenny Kim Kim, Peter O Bayguinov, James A J Fitzpatrick, Dennis Goldfarb, Marko Jovanovic, Abhai Tripathi, Sergej Djuranovic, Slavica Pavlovic-Djuranovic
2020-Current year OA Pubs
BACKGROUND: Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite's growing resistance to existing therapies. In this study, a common characteristic of the P. falciparum proteome-stretches of poly-lysine residues, such as those found in proteins related to adhesion and pathogenicity-is investigated for its potential to treat infected erythrocytes.
METHODS: This study utilizes in vitro culturing of intra-erythrocytic P. falciparum to assess the …
A Training Protocol Compliance Of 13% Was Observed In A Research Study Of Clinical Research Professionals, Erin D Solomon, Jessica Mozersky, Meredith V Parsons, Kari Baldwin, Melody Goodman, James M Dubois
A Training Protocol Compliance Of 13% Was Observed In A Research Study Of Clinical Research Professionals, Erin D Solomon, Jessica Mozersky, Meredith V Parsons, Kari Baldwin, Melody Goodman, James M Dubois
2020-Current year OA Pubs
OBJECTIVE: We attempted to conduct a randomized controlled trial of three different informed consent training formats to evaluate their effectiveness. We recruited 503 clinical research professionals, who received $50 for participation. Incidental findings showed unexpectedly low rates of compliance with completing the study training protocols, resulting in insufficient statistical power to test our original hypotheses. In this report, we conducted a secondary analysis of the data in which we characterize and evaluate the observed low compliance. This involved using literature on average reading times, speed-reading times, and video play speeds to calculate the timeframes required to complete the three training …
Treatment Patterns In Women With Postmenopausal Osteoporosis Using Abaloparatide: A Real-World Observational Study, Deborah T Gold, Tammy Beckett, Chad Deal, Andrew L James, Mahshid Mohseni, Abigail Mcmillan, Tom Bailey, Leny Pearman, John Caminis, Yamei Wang, Setareh A Williams, Jacqueline M Kernaghan
Treatment Patterns In Women With Postmenopausal Osteoporosis Using Abaloparatide: A Real-World Observational Study, Deborah T Gold, Tammy Beckett, Chad Deal, Andrew L James, Mahshid Mohseni, Abigail Mcmillan, Tom Bailey, Leny Pearman, John Caminis, Yamei Wang, Setareh A Williams, Jacqueline M Kernaghan
2020-Current year OA Pubs
UNLABELLED: Review of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed.
PURPOSE: Abaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history.
METHODS: Data for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six …
Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al.
Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al.
2020-Current year OA Pubs
BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with …
Potential Clinical Applications Of Advanced Genomic Analysis In Cerebral Palsy, Sara A Lewis, Andrew Ruttenberg, Tuğçe Iyiyol, Nahyun Kong, Sheng Chih Jin, Michael C Kruer
Potential Clinical Applications Of Advanced Genomic Analysis In Cerebral Palsy, Sara A Lewis, Andrew Ruttenberg, Tuğçe Iyiyol, Nahyun Kong, Sheng Chih Jin, Michael C Kruer
2020-Current year OA Pubs
Cerebral palsy (CP) has historically been attributed to acquired insults, but emerging research suggests that genetic variations are also important causes of CP. While microarray and whole-exome sequencing based studies have been the primary methods for establishing new CP-gene relationships and providing a genetic etiology for individual patients, the cause of their condition remains unknown for many patients with CP. Recent advancements in genomic technologies offer additional opportunities to uncover variations in human genomes, transcriptomes, and epigenomes that have previously escaped detection. In this review, we outline the use of these state-of-the-art technologies to address the molecular diagnostic challenges experienced …
Association Between Interpregnancy Interval And The Labor Curve, Julia Burd, Candice Woolfolk, Antonina Frolova, Amanda Zofkie, Anthony Odibo, Ebony B Carter, Jeannie C Kelly, Alison G Cahill, Nandini Raghuraman
Association Between Interpregnancy Interval And The Labor Curve, Julia Burd, Candice Woolfolk, Antonina Frolova, Amanda Zofkie, Anthony Odibo, Ebony B Carter, Jeannie C Kelly, Alison G Cahill, Nandini Raghuraman
2020-Current year OA Pubs
BACKGROUND: Both short and long interpregnancy intervals are associated with adverse pregnancy outcomes; however, the impact of interpregnancy intervals on labor progression is unknown.
OBJECTIVE: We examined the impact of interpregnancy intervals on the labor curve, hypothesizing that those with a longer interpregnancy intervals would have slower labor progression.
STUDY DESIGN: This is a retrospective cohort study of patients with a history of one prior vaginal delivery admitted for induction of labor or spontaneous labor with a singleton gestation ≥37 weeks at an academic medical center between 2004 and 2015. Repeated measures regression was used to construct labor curves, which …
Estimation Of Differential Pathlength Factor From Nirs Measurement In Skeletal Muscle, B Koirala, A Concas, A Cincotti, Yi Sun, A Hernández, M L Goodwin, L B Gladden, N Lai
Estimation Of Differential Pathlength Factor From Nirs Measurement In Skeletal Muscle, B Koirala, A Concas, A Cincotti, Yi Sun, A Hernández, M L Goodwin, L B Gladden, N Lai
2020-Current year OA Pubs
The utilization of continuous wave (CW) near-infrared spectroscopy (NIRS) device to measure non-invasively muscle oxygenation in healthy and disease states is limited by the uncertainties related to the differential path length factor (DPF). DPF value is required to quantify oxygenated and deoxygenated heme groups' concentration changes from measurement of optical densities by NIRS. An integrated approach that combines animal and computational models of oxygen transport and utilization was used to estimate the DPF value in situ. The canine model of muscle oxidative metabolism allowed measurement of both venous oxygen content and tissue oxygenation by CW NIRS under different oxygen delivery …
Maldi-Tof Mass Spectrometry Misidentification Of Cutibacterium Namnetense And Cutibacterium Modestum: Implications For Multiplex Pcr Phylotyping Of Cutibacterium Acnes, Joseph Mclaughlin, Carey-Ann D Burnham, Andrew Mcdowell
Maldi-Tof Mass Spectrometry Misidentification Of Cutibacterium Namnetense And Cutibacterium Modestum: Implications For Multiplex Pcr Phylotyping Of Cutibacterium Acnes, Joseph Mclaughlin, Carey-Ann D Burnham, Andrew Mcdowell
2020-Current year OA Pubs
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can misidentify Cutibacterium namnetense and Cutibacterium modestum as Cutibacterium acnes. We now describe how such MALDI-TOF MS misidentification explains previous reports of C. acnes isolates that could not be characterised using a multiplex PCR phylotyping assay.
Racial And Geographic Disparities In Neonatal Brain Care, Zachary A Vesoulis, Stephanie Diggs, Cherise Brackett, Brynne Sullivan
Racial And Geographic Disparities In Neonatal Brain Care, Zachary A Vesoulis, Stephanie Diggs, Cherise Brackett, Brynne Sullivan
2020-Current year OA Pubs
In this review, we explore race-based disparities in neonatology and their impact on brain injury and neurodevelopmental outcomes. We discuss the historical context of healthcare discrimination, focusing on the post-Civil War era and the segregation of healthcare facilities. We highlight the increasing disparity in infant mortality rates between Black and White infants, with premature birth being a major contributing factor, and emphasize the role of prenatal factors such as metabolic syndrome and toxic stress in affecting neonatal health. Furthermore, we examine the geographic and historical aspects of racial disparities, including the consequences of redlining and limited access to healthcare facilities …
Population Pharmacokinetic Modelling And Simulation Of Tranexamic Acid In Adult Trauma Patients, Gideon Stitt, Philip C Spinella, Grant V Bochicchio, Ian Roberts, Kevin J Downes, Athena F Zuppa
Population Pharmacokinetic Modelling And Simulation Of Tranexamic Acid In Adult Trauma Patients, Gideon Stitt, Philip C Spinella, Grant V Bochicchio, Ian Roberts, Kevin J Downes, Athena F Zuppa
2020-Current year OA Pubs
AIMS: The aim of this study is to describe the disposition of tranexamic acid (TXA) in adult trauma patients and derive a dosing regimen that optimizes exposure based on a predefined exposure target.
METHODS: We performed a population pharmacokinetic (popPK) analysis of participants enrolled in the Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI) trial (≥18 years with traumatic injury, given ≥1 blood product and/or requiring immediate transfer to the operating room) who were randomized to a single dose of either 2 or 4 g of TXA ≤2 h from time of injury. PopPK analysis was conducted using nonlinear …
Advances In Blood Biomarkers For Alzheimer Disease (Ad): A Review, Araya Dimtsu Assfaw, Suzanne E Schindler, John C Morris
Advances In Blood Biomarkers For Alzheimer Disease (Ad): A Review, Araya Dimtsu Assfaw, Suzanne E Schindler, John C Morris
2020-Current year OA Pubs
Alzheimer disease (AD) and Alzheimer Disease and Related Dementias (AD/ADRD) are growing public health challenges globally affecting millions of older adults, necessitating concerted efforts to advance our understanding and management of these conditions. AD is a progressive neurodegenerative disorder characterized pathologically by amyloid plaques and tau neurofibrillary tangles that are the primary cause of dementia in older individuals. Early and accurate diagnosis of AD dementia is crucial for effective intervention and treatment but has proven challenging to accomplish. Although testing for AD brain pathology with cerebrospinal fluid (CSF) or positron emission tomography (PET) has been available for over 2 decades, …
Age-Related Dysregulation Of The Retinal Transcriptome In African Turquoise Killifish, Steven Bergmans, Nicole C L Noel, Luca Masin, Ellen G Harding, Aleksandra M Krzywańska, Julie D De Schutter, Rajagopal Ayana, Chi-Kuo Hu, Lut Arckens, Philip A Ruzycki, Ryan B Macdonald, Brian S Clark, Lieve Moons
Age-Related Dysregulation Of The Retinal Transcriptome In African Turquoise Killifish, Steven Bergmans, Nicole C L Noel, Luca Masin, Ellen G Harding, Aleksandra M Krzywańska, Julie D De Schutter, Rajagopal Ayana, Chi-Kuo Hu, Lut Arckens, Philip A Ruzycki, Ryan B Macdonald, Brian S Clark, Lieve Moons
2020-Current year OA Pubs
Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNAseq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in …
The Smc5/6 Complex Prevents Genotoxicity Upon Apobec3a-Mediated Replication Stress, Dylan F Fingerman, David R O'Leary, Ava R Hansen, Thi Tran, Brooke R Harris, Rachel A Deweerd, Mithila Tennakoon, Alice Meroni, Jessica Devenport, Danielle Lavigne, Jeffrey Bednarski, Alessandro Vindigni, Abby M Green, Et Al.
The Smc5/6 Complex Prevents Genotoxicity Upon Apobec3a-Mediated Replication Stress, Dylan F Fingerman, David R O'Leary, Ava R Hansen, Thi Tran, Brooke R Harris, Rachel A Deweerd, Mithila Tennakoon, Alice Meroni, Jessica Devenport, Danielle Lavigne, Jeffrey Bednarski, Alessandro Vindigni, Abby M Green, Et Al.
2020-Current year OA Pubs
Mutational patterns caused by APOBEC3 cytidine deaminase activity are evident throughout human cancer genomes. In particular, the APOBEC3A family member is a potent genotoxin that causes substantial DNA damage in experimental systems and human tumors. However, the mechanisms that ensure genome stability in cells with active APOBEC3A are unknown. Through an unbiased genome-wide screen, we define the Structural Maintenance of Chromosomes 5/6 (SMC5/6) complex as essential for cell viability when APOBEC3A is active. We observe an absence of APOBEC3A mutagenesis in human tumors with SMC5/6 dysfunction, consistent with synthetic lethality. Cancer cells depleted of SMC5/6 incur substantial genome damage from …
Dengue: A Focused Review For The Emergency Clinician, Michael J Pajor, Brit Long, Stephen Y Liang
Dengue: A Focused Review For The Emergency Clinician, Michael J Pajor, Brit Long, Stephen Y Liang
2020-Current year OA Pubs
Dengue is an arbovirus transmitted by the Aedes spp. mosquito. Approximately 390 million infections occur annually per World Health Organization estimates, with significant increases in infections throughout the last decade. The disease is endemic in warmer climates throughout the world, though cases may also be imported to non-endemic regions by returning travelers. Patients experience a wide variety of symptoms ranging from asymptomatic infection to severe disease requiring critical care. Emergency clinicians should consider the diagnosis of dengue in patients from endemic areas presenting with a flu-like illness, rash, and evidence of bleeding.
Obicetrapib On Top Of Maximally Tolerated Lipid-Modifying Therapies In Participants With Or At High Risk For Atherosclerotic Cardiovascular Disease: Rationale And Designs Of Broadway And Brooklyn, Stephen J Nicholls, Anne C Goldberg, Et Al.
Obicetrapib On Top Of Maximally Tolerated Lipid-Modifying Therapies In Participants With Or At High Risk For Atherosclerotic Cardiovascular Disease: Rationale And Designs Of Broadway And Brooklyn, Stephen J Nicholls, Anne C Goldberg, Et Al.
2020-Current year OA Pubs
BACKGROUND: Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events.
METHODS AND RESULTS: BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing …
Ai-Driven Deep Learning Techniques In Protein Structure Prediction, Lingtao Chen, Qiaomu Li, Kazi Fahim Ahmad Nasif, Ying Xie, Bobin Deng, Shuteng Niu, Seyedamin Pouriyeh, Zhiyu Dai, Jiawei Chen, Chloe Yixin Xie
Ai-Driven Deep Learning Techniques In Protein Structure Prediction, Lingtao Chen, Qiaomu Li, Kazi Fahim Ahmad Nasif, Ying Xie, Bobin Deng, Shuteng Niu, Seyedamin Pouriyeh, Zhiyu Dai, Jiawei Chen, Chloe Yixin Xie
2020-Current year OA Pubs
Protein structure prediction is important for understanding their function and behavior. This review study presents a comprehensive review of the computational models used in predicting protein structure. It covers the progression from established protein modeling to state-of-the-art artificial intelligence (AI) frameworks. The paper will start with a brief introduction to protein structures, protein modeling, and AI. The section on established protein modeling will discuss homology modeling, ab initio modeling, and threading. The next section is deep learning-based models. It introduces some state-of-the-art AI models, such as AlphaFold (AlphaFold, AlphaFold2, AlphaFold3), RoseTTAFold, ProteinBERT, etc. This section also discusses how AI techniques …
Medicare Utilization And Cost Trends For Car T Cell Therapies Across Settings Of Care In The Treatment Of Diffuse Large B-Cell Lymphoma, James Wu, Armin Ghobadi, Richard Maziarz, Krish Patel, Hil Hsu, Zihao Liu, Caitlin Sheetz, Peter Kardel, Christine Fu
Medicare Utilization And Cost Trends For Car T Cell Therapies Across Settings Of Care In The Treatment Of Diffuse Large B-Cell Lymphoma, James Wu, Armin Ghobadi, Richard Maziarz, Krish Patel, Hil Hsu, Zihao Liu, Caitlin Sheetz, Peter Kardel, Christine Fu
2020-Current year OA Pubs
INTRODUCTION: Chimeric antigen receptor T-cell (CAR T) therapies have transformed diffuse large B-cell lymphoma (DLBCL) treatment. It is important to better understand their use in Medicare Fee-for-Service (FFS) patients, who often differ from commercially insured populations in important ways.
METHODS: We analyzed Medicare FFS claims data, focusing on the utilization patterns across three CAR T products-lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), and axicabtagene autoleucel (axi-cel)-which are indicated for the treatment of DLBCL. Our investigation covered the period from 2021 through 2022. This analysis spanned a 180-day period prior to CAR T procedure and extended to a 90-day post-CAR T. Utilization of …
Heroin Or Fentanyl: Prevalence Of Confirmed Fentanyl In Ed Patients With Suspected Heroin Overdose, Siri Shastry, Evan Schwarz, Et Al.
Heroin Or Fentanyl: Prevalence Of Confirmed Fentanyl In Ed Patients With Suspected Heroin Overdose, Siri Shastry, Evan Schwarz, Et Al.
2020-Current year OA Pubs
BACKGROUND: United States drug overdose deaths are being driven by the increasing prevalence of fentanyl, but whether patients are knowingly using fentanyl is unclear. We examined the analytical confirmation of fentanyl in emergency department (ED) patients with documented heroin overdose.
HYPOTHESIS: We hypothesized that the proportion of fentanyl and fentanyl analogs would be higher than that of confirmed heroin.
METHODS: This is a subgroup analysis from a prospective multicenter consecutive cohort of ED patients age 18+ with opioid overdose presenting to 10 US sites within the Toxicology Investigators Consortium from 2020 to 2021. Toxicology analysis was performed using liquid chromatography …
Association Of Surgical Approaches And Outcomes In Total Mesorectal Excision And Margin Status For Rectal Cancer, Muhammad Bilal Mirza, Adriana C Gamboa, Rebecca Irlmeier, Benjamin Hopkins, Scott E Regenbogen, Katherine A Hrebinko, Jennifer Holder-Murray, Jason T Wiseman, Aslam Ejaz, Paul E Wise, Fei Ye, Kamran Idrees, Alexander T Hawkins, Glen C Balch, Aimal Khan
Association Of Surgical Approaches And Outcomes In Total Mesorectal Excision And Margin Status For Rectal Cancer, Muhammad Bilal Mirza, Adriana C Gamboa, Rebecca Irlmeier, Benjamin Hopkins, Scott E Regenbogen, Katherine A Hrebinko, Jennifer Holder-Murray, Jason T Wiseman, Aslam Ejaz, Paul E Wise, Fei Ye, Kamran Idrees, Alexander T Hawkins, Glen C Balch, Aimal Khan
2020-Current year OA Pubs
INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer.
METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected …
Overall Survival In Patients With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel In The Randomized Engot-En6/Gog-3031/Ruby Trial, M A Powell, C Mccourt, Et Al.
Overall Survival In Patients With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel In The Randomized Engot-En6/Gog-3031/Ruby Trial, M A Powell, C Mccourt, Et Al.
2020-Current year OA Pubs
BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis.
PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were …
Psilocybin Desynchronizes The Human Brain, Joshua S Siegel, Demetrius Perry, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, T Rick Reneau, Nicholas V Metcalf, Samuel R Krimmel, Joshua S Shimony, Julie A Schweiger, Dean F Wong, David A Bender, Kristen M Scheidter, Forrest I Whiting, Jonah A Padawer-Curry, Eric J Lenze, Marcus E Raichle, Abraham Z Snyder, Ginger E Nicol, Nico U F Dosenbach, Et Al.
Psilocybin Desynchronizes The Human Brain, Joshua S Siegel, Demetrius Perry, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, T Rick Reneau, Nicholas V Metcalf, Samuel R Krimmel, Joshua S Shimony, Julie A Schweiger, Dean F Wong, David A Bender, Kristen M Scheidter, Forrest I Whiting, Jonah A Padawer-Curry, Eric J Lenze, Marcus E Raichle, Abraham Z Snyder, Ginger E Nicol, Nico U F Dosenbach, Et Al.
2020-Current year OA Pubs
A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials