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Articles 4021 - 4050 of 7377
Full-Text Articles in Medicine and Health Sciences
Lipidome Of Mammographic Breast Density In Premenopausal Women, Kayla R Getz, Myung Sik Jeon, Chongliang Luo, Jingqin Luo, Adetunji T Toriola
Lipidome Of Mammographic Breast Density In Premenopausal Women, Kayla R Getz, Myung Sik Jeon, Chongliang Luo, Jingqin Luo, Adetunji T Toriola
2020-Current year OA Pubs
BACKGROUND: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women.
METHODS: Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon …
Metabolomic Phenotype Of Hepatic Steatosis And Fibrosis In Mexican Children Living With Obesity, Nayely Garibay-Nieto, Karen Pedraza-Escudero, Isabel Omaña-Guzmán, María José Garcés-Hernández, Eréndira Villanueva-Ortega, Mariana Flores-Torres, José Luis Pérez-Hernández, Mireya León-Hernández, Estibalitz Laresgoiti-Servitje, Berenice Palacios-González, Juan Carlos López-Alvarenga, Mauricio Lisker-Melman, Felipe Vadillo-Ortega
Metabolomic Phenotype Of Hepatic Steatosis And Fibrosis In Mexican Children Living With Obesity, Nayely Garibay-Nieto, Karen Pedraza-Escudero, Isabel Omaña-Guzmán, María José Garcés-Hernández, Eréndira Villanueva-Ortega, Mariana Flores-Torres, José Luis Pérez-Hernández, Mireya León-Hernández, Estibalitz Laresgoiti-Servitje, Berenice Palacios-González, Juan Carlos López-Alvarenga, Mauricio Lisker-Melman, Felipe Vadillo-Ortega
2020-Current year OA Pubs
No abstract provided.
Identification Of Post-Cardiac Arrest Blood Pressure Thresholds Associated With Outcomes In Children: An Icu-Resuscitation Study, Monique M Gardner, Stuart H Friess, Arushi Manga, Et Al.
Identification Of Post-Cardiac Arrest Blood Pressure Thresholds Associated With Outcomes In Children: An Icu-Resuscitation Study, Monique M Gardner, Stuart H Friess, Arushi Manga, Et Al.
2020-Current year OA Pubs
INTRODUCTION: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge.
METHODS: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled …
Open Structure And Gating Of The Arabidopsis Mechanosensitive Ion Channel Msl10, Jingying Zhang, Grigory Maksaev, Peng Yuan
Open Structure And Gating Of The Arabidopsis Mechanosensitive Ion Channel Msl10, Jingying Zhang, Grigory Maksaev, Peng Yuan
2020-Current year OA Pubs
Plants are challenged by drastically different osmotic environments during growth and development. Adaptation to these environments often involves mechanosensitive ion channels that can detect and respond to mechanical force. In the model plant Arabidopsis thaliana, the mechanosensitive channel MSL10 plays a crucial role in hypo-osmotic shock adaptation and programmed cell death induction, but the molecular basis of channel function remains poorly understood. Here, we report a structural and electrophysiological analysis of MSL10. The cryo-electron microscopy structures reveal a distinct heptameric channel assembly. Structures of the wild-type channel in detergent and lipid environments, and in the absence of membrane tension, capture …
Generalization Of Procedural Motor Sequence Learning After A Single Practice Trial, B P Johnson, I Iturrate, R Y Fakhreddine, M Bönstrup, E R Buch, E M Robertson, L G Cohen
Generalization Of Procedural Motor Sequence Learning After A Single Practice Trial, B P Johnson, I Iturrate, R Y Fakhreddine, M Bönstrup, E R Buch, E M Robertson, L G Cohen
2020-Current year OA Pubs
When humans begin learning new motor skills, they typically display early rapid performance improvements. It is not well understood how knowledge acquired during this early skill learning period generalizes to new, related skills. Here, we addressed this question by investigating factors influencing generalization of early learning from a skill A to a different, but related skill B. Early skill generalization was tested over four experiments (N = 2095). Subjects successively learned two related motor sequence skills (skills A and B) over different practice schedules. Skill A and B sequences shared ordinal (i.e., matching keypress locations), transitional (i.e., ordered keypress pairs), …
Characterizing The Patterns Of Electronic Health Record-Integrated Secure Messaging Use: Cross-Sectional Study, Laura R Baratta, Derek Harford, Christine A Sinsky, Thomas Kannampallil, Sunny S Lou
Characterizing The Patterns Of Electronic Health Record-Integrated Secure Messaging Use: Cross-Sectional Study, Laura R Baratta, Derek Harford, Christine A Sinsky, Thomas Kannampallil, Sunny S Lou
2020-Current year OA Pubs
BACKGROUND: Communication among health care professionals is essential for the delivery of safe clinical care. Secure messaging has rapidly emerged as a new mode of asynchronous communication. Despite its popularity, relatively little is known about how secure messaging is used and how such use contributes to communication burden.
OBJECTIVE: This study aims to characterize the use of an electronic health record-integrated secure messaging platform across 14 hospitals and 263 outpatient clinics within a large health care system.
METHODS: We collected metadata on the use of the Epic Systems Secure Chat platform for 6 months (July 2022 to January 2023). Information …
Yeast Rad52 Is A Homodecamer And Possesses Brca2-Like Bipartite Rad51 Binding Modes, Jaigeeth Deveryshetty, Rahul Chadda, Jenna R Mattice, Simrithaa Karunakaran, Michael J Rau, Katherine Basore, Nilisha Pokhrel, Noah Englander, James A J Fitzpatrick, Brian Bothner, Edwin Antony
Yeast Rad52 Is A Homodecamer And Possesses Brca2-Like Bipartite Rad51 Binding Modes, Jaigeeth Deveryshetty, Rahul Chadda, Jenna R Mattice, Simrithaa Karunakaran, Michael J Rau, Katherine Basore, Nilisha Pokhrel, Noah Englander, James A J Fitzpatrick, Brian Bothner, Edwin Antony
2020-Current year OA Pubs
Homologous recombination (HR) is an essential double-stranded DNA break repair pathway. In HR, Rad52 facilitates the formation of Rad51 nucleoprotein filaments on RPA-coated ssDNA. Here, we decipher how Rad52 functions using single-particle cryo-electron microscopy and biophysical approaches. We report that Rad52 is a homodecameric ring and each subunit possesses an ordered N-terminal and disordered C-terminal half. An intrinsic structural asymmetry is observed where a few of the C-terminal halves interact with the ordered ring. We describe two conserved charged patches in the C-terminal half that harbor Rad51 and RPA interacting motifs. Interactions between these patches regulate ssDNA binding. Surprisingly, Rad51 …
Immune Cell Deconvolution Reveals Possible Association Of Γδ T Cells With Poor Survival In Head And Neck Squamous Cell Carcinoma, Anuraag S Parikh, Yize Li, Angela Mazul, Wade Thorstad, Jason Rich, Randal C Paniello, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Zongtai Qi, Douglas Adkins, Li Ding, Sidharth V Puram, Et Al.
Immune Cell Deconvolution Reveals Possible Association Of Γδ T Cells With Poor Survival In Head And Neck Squamous Cell Carcinoma, Anuraag S Parikh, Yize Li, Angela Mazul, Wade Thorstad, Jason Rich, Randal C Paniello, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Zongtai Qi, Douglas Adkins, Li Ding, Sidharth V Puram, Et Al.
2020-Current year OA Pubs
(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating …
Multivariate Gwas Of Alzheimer's Disease Csf Biomarker Profiles Implies Grin2d In Synaptic Functioning, Alexander Neumann, Jigyasha Timsina, Thomas W Marsh, Priyanka Gorijala, Carlos Cruchaga, Et Al.
Multivariate Gwas Of Alzheimer's Disease Csf Biomarker Profiles Implies Grin2d In Synaptic Functioning, Alexander Neumann, Jigyasha Timsina, Thomas W Marsh, Priyanka Gorijala, Carlos Cruchaga, Et Al.
2020-Current year OA Pubs
BACKGROUND: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.
METHODS: We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD …
Chemerin Triggers Migration Of A Cd8 T Cell Subset With Natural Killer Cell Functions, Romain Ballet, Melissa Lajevic, Noelle Huskey-Mullin, Rachel Roach, Kevin Brulois, Ying Huang, Muhammad A Saeed, Ha X Dang, Russell K Pachynski, Elizabeth Wilson, Eugene C Butcher, Brian A Zabel
Chemerin Triggers Migration Of A Cd8 T Cell Subset With Natural Killer Cell Functions, Romain Ballet, Melissa Lajevic, Noelle Huskey-Mullin, Rachel Roach, Kevin Brulois, Ying Huang, Muhammad A Saeed, Ha X Dang, Russell K Pachynski, Elizabeth Wilson, Eugene C Butcher, Brian A Zabel
2020-Current year OA Pubs
The recruitment of cells with effector functions into the tumor microenvironment holds potential for delaying cancer progression. We show that subsets of human CD28-effector CD8 T cells, CCR7
The Impact Of Helminth-Induced Immunity On Infection With Bacteria Or Viruses, Hong Chen, Zengguo Cao, Mingyuan Liu, Michael S Diamond, Xuemin Jin
The Impact Of Helminth-Induced Immunity On Infection With Bacteria Or Viruses, Hong Chen, Zengguo Cao, Mingyuan Liu, Michael S Diamond, Xuemin Jin
2020-Current year OA Pubs
Different human and animal pathogens trigger distinct immune responses in their hosts. The infection of bacteria or viruses can trigger type I pro-inflammatory immune responses (e.g., IFN-γ, TNF-α, T
Pet And Optical Imaging Of Caveolin-1 In Gastric Tumors, Sandeep Surendra Panikar, Shayla Shmuel, Jason S Lewis, Patrícia M R Pereira
Pet And Optical Imaging Of Caveolin-1 In Gastric Tumors, Sandeep Surendra Panikar, Shayla Shmuel, Jason S Lewis, Patrícia M R Pereira
2020-Current year OA Pubs
Previous studies have suggested tumoral caveolin-1 (CAV1) as a predictive biomarker for the response to anti-HER2 antibody drug therapies in gastric tumors. In this study, radiolabeled and fluorescently labeled anti-CAV1 antibodies were developed and tested as an immunoPET or optical imaging agent to detect CAV1 in HER2-positive/CAV1-high NCIN87 gastric tumors. The expression of CAV1 receptors in NCIN87 gastric tumors and nontumor murine organs was determined by Western blot. Binding assays were performed to validate the anti-CAV1 antibody specificity for CAV1-expressing NCIN87 cancer cells. Subcutaneous and orthotopic NCIN87 xenografts were used for PET imaging and
Was Covid-19 Associated With Worsening Inequities In Stroke Treatment And Outcomes?, Laurent G Glance, Curtis G Benesch, Karen E Joynt Maddox, Matthew T Bender, Jingjing Shang, Patricia W Stone, Stewart J Lustik, Jacob W Nadler, Christopher Galton, Andrew W Dick
Was Covid-19 Associated With Worsening Inequities In Stroke Treatment And Outcomes?, Laurent G Glance, Curtis G Benesch, Karen E Joynt Maddox, Matthew T Bender, Jingjing Shang, Patricia W Stone, Stewart J Lustik, Jacob W Nadler, Christopher Galton, Andrew W Dick
2020-Current year OA Pubs
Background COVID-19 stressed hospitals and may have disproportionately affected the stroke outcomes and treatment of Black and Hispanic individuals. Methods and Results This retrospective study used 100% Medicare Provider Analysis and Review file data from between 2016 and 2020. We used interrupted time series analyses to examine whether the COVID-19 pandemic exacerbated disparities in stroke outcomes and reperfusion therapy. Among 1 142 560 hospitalizations for acute ischemic strokes, 90 912 (8.0%) were Hispanic individuals; 162 752 (14.2%) were non-Hispanic Black individuals; and 888 896 (77.8%) were non-Hispanic White individuals. The adjusted odds of mortality increased by 51% (adjusted odds ratio …
Association Between Socioeconomic Factors, Race, And Use Of A Specialty Memory Clinic, Abigail Lewis, Aditi Gupta, Inez Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Randi Foraker, Barbara Joy Snider, John C. Morris, Joyce Balls-Berry, Mahendra Gupta, Philip R. O. Payne, Albert M. Lai
Association Between Socioeconomic Factors, Race, And Use Of A Specialty Memory Clinic, Abigail Lewis, Aditi Gupta, Inez Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Randi Foraker, Barbara Joy Snider, John C. Morris, Joyce Balls-Berry, Mahendra Gupta, Philip R. O. Payne, Albert M. Lai
2020-Current year OA Pubs
BACKGROUND AND OBJECTIVES: The capacity of specialty memory clinics in the United States is very limited. If lower socioeconomic status or minoritized racial group is associated with reduced use of memory clinics, this could exacerbate health care disparities, especially if more effective treatments of Alzheimer disease become available. We aimed to understand how use of a memory clinic is associated with neighborhood-level measures of socioeconomic factors and the intersectionality of race.
METHODS: We conducted an observational cross-sectional study using electronic health record data to compare the neighborhood advantage of patients seen at the Washington University Memory Diagnostic Center with the …
Changes In Cardiovascular Spending, Care Utilization, And Clinical Outcomes Associated With Participation In Bundled Payments For Care Improvement - Advanced, Sukruth A. Shashikumar, Jie Zheng, E. John Orav, Arnold M. Epstein, Karen E. Joynt Maddox
Changes In Cardiovascular Spending, Care Utilization, And Clinical Outcomes Associated With Participation In Bundled Payments For Care Improvement - Advanced, Sukruth A. Shashikumar, Jie Zheng, E. John Orav, Arnold M. Epstein, Karen E. Joynt Maddox
2020-Current year OA Pubs
BACKGROUND: Bundled Payments for Care Improvement - Advanced (BPCI-A) is a Medicare initiative that aims to incentivize reductions in spending for episodes of care that start with a hospitalization and end 90 days after discharge. Cardiovascular disease, an important driver of Medicare spending, is one of the areas of focus BPCI-A. It is unknown whether BPCI-A is associated with spending reductions or quality improvements for the 3 cardiovascular medical events or 5 cardiovascular procedures in the model.
METHODS: In this retrospective cohort study, we conducted difference-in-differences analyses using Medicare claims for patients discharged between January 1, 2017, and September 30, …
Reduction Of Sparc Protects Mice Against Nlrp3 Inflammasome Activation And Obesity, Seungjin Ryu, Olga Spadaro, Sviatoslav Sidorov, Aileen H. Lee, Sonia Caprio, Christopher Morrison, Steven R. Smith, Eric Ravussin, Irina Shchukina, Maxim N. Artyomov, Yun-Hee Youm, Vishwa Deep Dixit
Reduction Of Sparc Protects Mice Against Nlrp3 Inflammasome Activation And Obesity, Seungjin Ryu, Olga Spadaro, Sviatoslav Sidorov, Aileen H. Lee, Sonia Caprio, Christopher Morrison, Steven R. Smith, Eric Ravussin, Irina Shchukina, Maxim N. Artyomov, Yun-Hee Youm, Vishwa Deep Dixit
2020-Current year OA Pubs
The comprehensive assessment of long-term effects of reducing intake of energy (CALERIE-II; NCT00427193) clinical trial established that caloric restriction (CR) in humans lowers inflammation. The identity and mechanism of endogenous CR-mimetics that can be deployed to control obesity-associated inflammation and diseases are not well understood. Our studies have found that 2 years of 14% sustained CR in humans inhibits the expression of the matricellular protein, secreted protein acidic and rich in cysteine (SPARC), in adipose tissue. In mice, adipose tissue remodeling caused by weight loss through CR and low-protein diet feeding decreased, while high-fat diet-induced (HFD-induced) obesity increased SPARC expression …
Safety And Immunogenicity Of Live Viral Vaccines In A Multicenter Cohort Of Pediatric Transplant Recipients, Amy G Feldman, Stacy Postma, Janis Stoll, Et Al.
Safety And Immunogenicity Of Live Viral Vaccines In A Multicenter Cohort Of Pediatric Transplant Recipients, Amy G Feldman, Stacy Postma, Janis Stoll, Et Al.
2020-Current year OA Pubs
IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.
OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody …
Interplay Between Esr1/Pik3ca Codon Variants, Oncogenic Pathway Alterations And Clinical Phenotype In Patients With Metastatic Breast Cancer (Mbc): Comprehensive Circulating Tumor Dna (Ctdna) Analysis, Lorenzo Gerratana, Andrew A Davis, Katherine Clifton, Whitney L Hensing, Cynthia X Ma, Et Al.
Interplay Between Esr1/Pik3ca Codon Variants, Oncogenic Pathway Alterations And Clinical Phenotype In Patients With Metastatic Breast Cancer (Mbc): Comprehensive Circulating Tumor Dna (Ctdna) Analysis, Lorenzo Gerratana, Andrew A Davis, Katherine Clifton, Whitney L Hensing, Cynthia X Ma, Et Al.
2020-Current year OA Pubs
BACKGROUND: although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice.
METHODS: The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among …
Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al.
Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al.
2020-Current year OA Pubs
UNLABELLED: Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF …
Accuracy And Reliability Of Chatbot Responses To Physician Questions, Rachel S Goodman, Isik Turker, Et Al.
Accuracy And Reliability Of Chatbot Responses To Physician Questions, Rachel S Goodman, Isik Turker, Et Al.
2020-Current year OA Pubs
IMPORTANCE: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency.
OBJECTIVE: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information.
DESIGN, SETTING, AND PARTICIPANTS: Thirty-three physicians across 17 specialties generated 284 medical questions that they …
Il-6 Selectively Suppresses Cdc1 Specification Via C/Ebpβ, Sunkyung Kim, Jing Chen, Suin Jo, Feiya Ou, Stephen T Ferris, Tian-Tian Liu, Ray A Ohara, David A Anderson, Renee Wu, Michael Y Chen, William E Gillanders, William E Gillanders, Theresa L Murphy, Kenneth M Murphy
Il-6 Selectively Suppresses Cdc1 Specification Via C/Ebpβ, Sunkyung Kim, Jing Chen, Suin Jo, Feiya Ou, Stephen T Ferris, Tian-Tian Liu, Ray A Ohara, David A Anderson, Renee Wu, Michael Y Chen, William E Gillanders, William E Gillanders, Theresa L Murphy, Kenneth M Murphy
2020-Current year OA Pubs
Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPβ expression in …
Tipifarnib Potentiates The Antitumor Effects Of Pi3kα Inhibition In Pik3ca- And Hras-Dysregulated Hnscc Via Convergent Inhibition Of Mtor Activity, Alison E Smith, Douglas R Adkins, Et Al.
Tipifarnib Potentiates The Antitumor Effects Of Pi3kα Inhibition In Pik3ca- And Hras-Dysregulated Hnscc Via Convergent Inhibition Of Mtor Activity, Alison E Smith, Douglas R Adkins, Et Al.
2020-Current year OA Pubs
UNLABELLED: Outcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival (OS) ranging from 6 to 18 months. For those who progress on standard-of-care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K-mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase (FTase) inhibitor, and alpelisib, a PI3Kα inhibitor, in multiple molecularly defined subsets of HNSCC. Tipifarnib synergized with alpelisib at the level of mTOR in PI3Kα- or HRAS-dependent HNSCCs, leading to marked cytotoxicity in vitro and tumor …
Alvin J. Siteman Cancer Center: Cancer Prevention Perspective, Graham A Colditz, Bettina F Drake, Timothy J Eberlein
Alvin J. Siteman Cancer Center: Cancer Prevention Perspective, Graham A Colditz, Bettina F Drake, Timothy J Eberlein
2020-Current year OA Pubs
We summarize Siteman Cancer Center catchment that covers 82 counties in southern Illinois and eastern Missouri. We note both the high poverty and cancer rates in many rural counties. Siteman Community Outreach and Engagement has developed a number of strategies to move towards achieving health equity. These include NCI-funded research projects in rural clinics and outreach to improve access to cancer prevention services. To increase capacity for community-engaged research, we have developed and refined a Community Research Fellows Training Program.
Diagnostic Criteria For Identifying Individuals At High Risk Of Progression From Mild Or Moderate To Severe Alcohol Use Disorder, Alex P Miller, Emma C Johnson, Rebecca Tillman, Vivia V Mccutcheon, Kathleen K Bucholz, Arpana Agrawal, Et Al.
Diagnostic Criteria For Identifying Individuals At High Risk Of Progression From Mild Or Moderate To Severe Alcohol Use Disorder, Alex P Miller, Emma C Johnson, Rebecca Tillman, Vivia V Mccutcheon, Kathleen K Bucholz, Arpana Agrawal, Et Al.
2020-Current year OA Pubs
IMPORTANCE: Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnoses of substance use disorders rely on criterion count-based approaches, disregarding severity grading indexed by individual criteria.
OBJECTIVE: To examine correlates of alcohol use disorder (AUD) across count-based severity groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative of greater severity, and evaluate whether specific criteria within mild-to-moderate AUD differentiate across relevant correlates and manifest in greater hazards of severe AUD development.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved 2 cohorts from the family-based Collaborative Study on the Genetics of Alcoholism (COGA) with 7 sites …
Pre-Radiotherapy Ctdna Liquid Biopsy For Risk Stratification Of Oligometastatic Non-Small Cell Lung Cancer, Nicholas P Semenkovich, Shahed N Badiyan, Pamela P Samson, Hayley B Stowe, Yun E Wang, Rachel Star, Siddhartha Devarakonda, Ramaswamy Govindan, Saiama N Waqar, Clifford G Robinson, Gregory Vlacich, Bruna Pellini, Aadel A Chaudhuri
Pre-Radiotherapy Ctdna Liquid Biopsy For Risk Stratification Of Oligometastatic Non-Small Cell Lung Cancer, Nicholas P Semenkovich, Shahed N Badiyan, Pamela P Samson, Hayley B Stowe, Yun E Wang, Rachel Star, Siddhartha Devarakonda, Ramaswamy Govindan, Saiama N Waqar, Clifford G Robinson, Gregory Vlacich, Bruna Pellini, Aadel A Chaudhuri
2020-Current year OA Pubs
The optimal treatment paradigm for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below limits of detection by imaging) and benefit from systemic therapy. To risk-stratify and identify the patients most likely to benefit from locally consolidative RT, we performed a multi-institutional cohort study of 1487 patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA). In total, 1880 liquid biopsies were performed and approximately 20% of patients (n = 309) had ctDNA measured prior to …
Optimizing The Utility Of Anorectal Manometry For Diagnosis And Therapy: A Roundtable Review And Recommendations, Satish S C Rao, Gregory S Sayuk, Et Al.
Optimizing The Utility Of Anorectal Manometry For Diagnosis And Therapy: A Roundtable Review And Recommendations, Satish S C Rao, Gregory S Sayuk, Et Al.
2020-Current year OA Pubs
BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings.
METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic …
Sustained Antidepressant Effect Of Ketamine Through Nmdar Trapping In The Lhb, Shuangshuang Ma, Christopher J Lingle, Et Al.
Sustained Antidepressant Effect Of Ketamine Through Nmdar Trapping In The Lhb, Shuangshuang Ma, Christopher J Lingle, Et Al.
2020-Current year OA Pubs
Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist
The Vcam1-Apoe Pathway Directs Microglial Chemotaxis And Alleviates Alzheimer's Disease Pathology, Shun-Fat Lau, Wei Wu, Hiu Yi Wong, Li Ouyang, Yi Qiao, Jiahui Xu, Jessica Hiu-Yan Lau, Carlton Wong, Yuanbing Jiang, David M Holtzman, Amy K Y Fu, Nancy Y Ip
The Vcam1-Apoe Pathway Directs Microglial Chemotaxis And Alleviates Alzheimer's Disease Pathology, Shun-Fat Lau, Wei Wu, Hiu Yi Wong, Li Ouyang, Yi Qiao, Jiahui Xu, Jessica Hiu-Yan Lau, Carlton Wong, Yuanbing Jiang, David M Holtzman, Amy K Y Fu, Nancy Y Ip
2020-Current year OA Pubs
In Alzheimer's disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. Although extrinsic signals, including interleukin-33 (IL-33), can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, and leads to Aβ clearance. We show that IL-33 stimulates a chemotactic state in microglia, characterized by Aβ-directed migration. Functional screening identified that VCAM1 directs microglial Aβ chemotaxis by sensing Aβ plaque-associated ApoE. Moreover, we found …
Organizational Preparedness For The Use Of Large Language Models In Pathology Informatics, Steven N Hart, Noah G Hoffman, Peter Gershkovich, Chancey Christenson, David S Mcclintock, Lauren J Miller, Ronald Jackups, Vahid Azimi, Nicholas Spies, Victor Brodsky
Organizational Preparedness For The Use Of Large Language Models In Pathology Informatics, Steven N Hart, Noah G Hoffman, Peter Gershkovich, Chancey Christenson, David S Mcclintock, Lauren J Miller, Ronald Jackups, Vahid Azimi, Nicholas Spies, Victor Brodsky
2020-Current year OA Pubs
In this paper, we consider the current and potential role of the latest generation of Large Language Models (LLMs) in medical informatics, particularly within the realms of clinical and anatomic pathology. We aim to provide a thorough understanding of the considerations that arise when employing LLMs in healthcare settings, such as determining appropriate use cases and evaluating the advantages and limitations of these models. Furthermore, this paper will consider the infrastructural and organizational requirements necessary for the successful implementation and utilization of LLMs in healthcare environments. We will discuss the importance of addressing education, security, bias, and privacy concerns associated …
Investigating Weekend Effect In The Management Of Upper And Lower Extremity Degloving Injuries, Kaamya Varagur, Janessa Sullivan, Sarah N. Chiang, Gary B. Skolnick, Justin M. Sacks, Joani M. Christensen
Investigating Weekend Effect In The Management Of Upper And Lower Extremity Degloving Injuries, Kaamya Varagur, Janessa Sullivan, Sarah N. Chiang, Gary B. Skolnick, Justin M. Sacks, Joani M. Christensen
2020-Current year OA Pubs
BACKGROUND: Weekend presentation has been associated with adverse outcomes in emergent conditions, including stroke, myocardial infarction, and critical limb ischemia. We examine whether a weekend effect exists in the management of and outcomes after extremity degloving injuries.
METHODS: The cohort included adults presenting with open extremity degloving injuries to a tertiary level one trauma center between June 2018 and May 2022. We collected demographics, comorbidities, injury information, interventions, and complications. Propensity score weighting was used to minimize confounding differences between those presenting on weekends (Sat-Sun) versus weekdays (Mon-Fri). Weighted regressions were used to examine differences in interventions by day of …