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Articles 3061 - 3090 of 10523

Full-Text Articles in Medicine and Health Sciences

Outcomes Of Limited Stage Primary Bone Diffuse Large B-Cell Lymphoma In The Rituximab Era: A Multicenter, Retrospective Study, Alexandra Rezazadeh, Nancy L. Bartlett, Et Al. May 2024

Outcomes Of Limited Stage Primary Bone Diffuse Large B-Cell Lymphoma In The Rituximab Era: A Multicenter, Retrospective Study, Alexandra Rezazadeh, Nancy L. Bartlett, Et Al.

2020-Current year OA Pubs

Primary bone diffuse large B-cell lymphoma is a rare variant of extranodal non-Hodgkin lymphoma historically treated with induction chemotherapy followed by consolidative radiation therapy (RT). It remains unknown whether RT confers additional benefit following rituximab-based chemoimmunotherapy (CIT) induction in patients with limited stage disease. We conducted a multicenter, retrospective analysis of patients treated between 2005 and 2019 using rituximab-based CIT regimens with or without consolidative RT to discern whether consolidative RT adds benefit in patients with stage I-II disease that could be encompassed in one radiation field. A total of 112 patients were included: 78 received CIT and radiation (RT …


Astrocytes As A Mechanism For Contextually-Guided Network Dynamics And Function, Lulu Gong, Fabio Pasqualetti, Thomas Papouin, Shinung Ching May 2024

Astrocytes As A Mechanism For Contextually-Guided Network Dynamics And Function, Lulu Gong, Fabio Pasqualetti, Thomas Papouin, Shinung Ching

2020-Current year OA Pubs

Astrocytes are a ubiquitous and enigmatic type of non-neuronal cell and are found in the brain of all vertebrates. While traditionally viewed as being supportive of neurons, it is increasingly recognized that astrocytes play a more direct and active role in brain function and neural computation. On account of their sensitivity to a host of physiological covariates and ability to modulate neuronal activity and connectivity on slower time scales, astrocytes may be particularly well poised to modulate the dynamics of neural circuits in functionally salient ways. In the current paper, we seek to capture these features via actionable abstractions within …


A Prospective Phase I/Ii Clinical Trial Of High-Dose Proton Therapy For Chordomas And Chondrosarcomas, Sana S Dastgheyb, Alexandra D Dreyfuss, Michael J Lariviere, Jahan J Mohiuddin, Brian C Baumann, Jacob Shabason, Robert A Lustig, Jay F Dorsey, Alexander Lin, Sean M Grady, Bert W O'Malley, John Y K Lee, Jason G Newman, James M Schuster, Michelle Alonso-Basanta May 2024

A Prospective Phase I/Ii Clinical Trial Of High-Dose Proton Therapy For Chordomas And Chondrosarcomas, Sana S Dastgheyb, Alexandra D Dreyfuss, Michael J Lariviere, Jahan J Mohiuddin, Brian C Baumann, Jacob Shabason, Robert A Lustig, Jay F Dorsey, Alexander Lin, Sean M Grady, Bert W O'Malley, John Y K Lee, Jason G Newman, James M Schuster, Michelle Alonso-Basanta

2020-Current year OA Pubs

PURPOSE: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and < 20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with magnetic resonance imaging or computed tomography at 3-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/intensity modulated radiation therapy (IMRT), or IMRT only.

RESULTS: Feasibility endpoints were met, with only 2 out of 54 patient radiation therapy plans failing to meet dosimetric constraints with protons, and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade …


Cardiovascular Safety Of Ozanimod In Patients With Ulcerative Colitis: True North And Open-Label Extension Analyses, Alessandro Armuzzi, Parakkal Deepak, Et Al. May 2024

Cardiovascular Safety Of Ozanimod In Patients With Ulcerative Colitis: True North And Open-Label Extension Analyses, Alessandro Armuzzi, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Evaluating cardiovascular safety of sphingosine 1-phosphate (S1P) receptor modulators is warranted due to S1P receptor expression on cardiomyocytes and vascular endothelial cells. This analysis reports the cardiovascular safety of ozanimod, an S1P receptor modulator, in patients with moderately to severely active ulcerative colitis from the phase 3 True North (TN) and open-label extension (OLE).

METHODS: All patients who received ozanimod in TN (n = 796) and all eligible TN patients who entered the OLE (n = 823) were included. Cardiovascular-related adverse events were evaluated in patients with up to 146 weeks of ozanimod exposure (2219 patient-years), which …


Deconstructing Pathological Tau By Biological Process In Early Stages Of Alzheimer Disease: A Method For Quantifying Tau Spatial Spread In Neuroimaging, Stephanie Doering, Austin Mccullough, Brian A Gordon, Charles D Chen, Nicole Mckay, Diana Hobbs, Sarah Keefe, Shaney Flores, Jalen Scott, Hunter Smith, Stephen Jarman, Kelley Jackson, Russ C Hornbeck, Beau M Ances, Chengjie Xiong, Andrew J Aschenbrenner, Jason Hassenstab, Carlos Cruchaga, Alisha Daniels, Randall J Bateman, John C Morris, Tammie L S Benzinger, Et Al. May 2024

Deconstructing Pathological Tau By Biological Process In Early Stages Of Alzheimer Disease: A Method For Quantifying Tau Spatial Spread In Neuroimaging, Stephanie Doering, Austin Mccullough, Brian A Gordon, Charles D Chen, Nicole Mckay, Diana Hobbs, Sarah Keefe, Shaney Flores, Jalen Scott, Hunter Smith, Stephen Jarman, Kelley Jackson, Russ C Hornbeck, Beau M Ances, Chengjie Xiong, Andrew J Aschenbrenner, Jason Hassenstab, Carlos Cruchaga, Alisha Daniels, Randall J Bateman, John C Morris, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD.

METHODS: 445 cross-sectional participants (aged ≥ 50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and …


Contemporary Management Of Aneurysmal Subarachnoid Haemorrhage. An Update For The Intensivist, Chiara Robba, Katharina M Busl, Jan Claassen, Michael N Diringer, Raimund Helbok, Soojin Park, Alejandro Rabinstein, Miriam Treggiari, Mervyn D I Vergouwen, Giuseppe Citerio May 2024

Contemporary Management Of Aneurysmal Subarachnoid Haemorrhage. An Update For The Intensivist, Chiara Robba, Katharina M Busl, Jan Claassen, Michael N Diringer, Raimund Helbok, Soojin Park, Alejandro Rabinstein, Miriam Treggiari, Mervyn D I Vergouwen, Giuseppe Citerio

2020-Current year OA Pubs

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare yet profoundly debilitating condition associated with high global case fatality and morbidity rates. The key determinants of functional outcome include early brain injury, rebleeding of the ruptured aneurysm and delayed cerebral ischaemia. The only effective way to reduce the risk of rebleeding is to secure the ruptured aneurysm quickly. Prompt diagnosis, transfer to specialized centers, and meticulous management in the intensive care unit (ICU) significantly improved the prognosis of aSAH. Recently, multimodality monitoring with specific interventions to correct pathophysiological imbalances has been proposed. Vigilance extends beyond intracranial concerns to encompass systemic respiratory and …


Person-Centred Interventions To Improve Patient-Provider Relationships For Hiv Services In Low- And Middle-Income Countries: A Systematic Review, Laura K Beres, Ashley Underwood, Noelle Le Tourneau, Christopher Galloway Kemp, Gauri Kore, Lauren Yaeger, Jingjia Li, Alec Aaron, Claire Keene, Deepthi Priyanka Mallela, Banda A A Khalifa, Aaloke Mody, Sheree Renae Schwartz, Stefan Baral, Chanda Mwamba, Kombatende Sikombe, Ingrid Eshun-Wilson, Elvin H Geng, Marie-Claude C Lavoie May 2024

Person-Centred Interventions To Improve Patient-Provider Relationships For Hiv Services In Low- And Middle-Income Countries: A Systematic Review, Laura K Beres, Ashley Underwood, Noelle Le Tourneau, Christopher Galloway Kemp, Gauri Kore, Lauren Yaeger, Jingjia Li, Alec Aaron, Claire Keene, Deepthi Priyanka Mallela, Banda A A Khalifa, Aaloke Mody, Sheree Renae Schwartz, Stefan Baral, Chanda Mwamba, Kombatende Sikombe, Ingrid Eshun-Wilson, Elvin H Geng, Marie-Claude C Lavoie

2020-Current year OA Pubs

INTRODUCTION: Person-centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient-provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient-provider interactions and how these interventions have improved HIV care continuum outcomes and person-reported outcomes (PROs) among people living with HIV in low- and middle-income countries.

METHODS: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January …


My Anesthesia Choice-Hf: Development And Preliminary Testing Of A Tool To Facilitate Conversations About Anesthesia For Hip Fracture Surgery, Mark D Neuman, Glyn Elwyn, Veena Graff, Viktoria Schmitz, Mary C Politi May 2024

My Anesthesia Choice-Hf: Development And Preliminary Testing Of A Tool To Facilitate Conversations About Anesthesia For Hip Fracture Surgery, Mark D Neuman, Glyn Elwyn, Veena Graff, Viktoria Schmitz, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Patients often desire involvement in anesthesia decisions, yet clinicians rarely explain anesthesia options or elicit preferences. We developed My Anesthesia Choice-Hip Fracture, a conversation aid about anesthesia options for hip fracture surgery and tested its preliminary efficacy and acceptability.

METHODS: We developed a 1-page, tabular format, plain-language conversation aid with feedback from anesthesiologists, decision scientists, and community advisors. We conducted an online survey of English-speaking adults aged 50 and older. Participants imagined choosing between spinal and general anesthesia for hip fracture surgery. Before and after viewing the aid, participants answered a series of questions regarding key outcomes, including decisional …


Evaluation Of An Automated Von Willebrand Factor Glycoprotein Ibm Activity Assay Compared With 3 Alternative Von Willebrand Factor Activity Assays, Kenneth D Friedman, Martina Böhm-Weigert, Nicole Desimone, Dennis J Dietzen, Charles Eby, Cynthia Flickinger, Walter Hoyer, Mareike Kahl, Kandice Kottke-Marchant, Thomas L Ortel, Jürgen Patzke, Steven W Pipe, Morgan Stuart, Ayse Anil Timur, Ravindra Sarode May 2024

Evaluation Of An Automated Von Willebrand Factor Glycoprotein Ibm Activity Assay Compared With 3 Alternative Von Willebrand Factor Activity Assays, Kenneth D Friedman, Martina Böhm-Weigert, Nicole Desimone, Dennis J Dietzen, Charles Eby, Cynthia Flickinger, Walter Hoyer, Mareike Kahl, Kandice Kottke-Marchant, Thomas L Ortel, Jürgen Patzke, Steven W Pipe, Morgan Stuart, Ayse Anil Timur, Ravindra Sarode

2020-Current year OA Pubs

BACKGROUND: To overcome deficiencies of the traditional von Willebrand factor (VWF) ristocetin cofactor activity assay (VWF:RCo), several automated assays for VWF platelet-binding activity have been developed. Information on the performance of these assays and their diagnostic utility remains limited.

OBJECTIVES: To validate the VWF:glycoprotein IbM assay INNOVANCE VWF Ac and compare it with an automated VWF:RCo assay as well as with an automated assay and a manual VWF:Ab assay and to generate reference ranges and analyze reproducibility of the VWF:glycoprotein IbM assay.

METHODS: Clinical sites enrolled healthy subjects and patients representing the intended use population; VWF activity assays were performed, …


Multi-Scale Cortical Bone Traits Vary In Females And Males From Two Mouse Models Of Genetic Diversity, Nicole Migotsky, Surabhi Kumar, John T Shuster, Jennifer C Coulombe, Bhavya Senwar, Adrian A Gestos, Charles R Farber, Virginia L Ferguson, Matthew J Silva May 2024

Multi-Scale Cortical Bone Traits Vary In Females And Males From Two Mouse Models Of Genetic Diversity, Nicole Migotsky, Surabhi Kumar, John T Shuster, Jennifer C Coulombe, Bhavya Senwar, Adrian A Gestos, Charles R Farber, Virginia L Ferguson, Matthew J Silva

2020-Current year OA Pubs

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that cannot easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of 3 long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from 2 populations of genetic diversity. Additionally, …


Onc201 (Dordaviprone) In Recurrent H3 K27m-Mutant Diffuse Midline Glioma, Isabel Arrillaga-Romany, Andrew Cluster, Et Al. May 2024

Onc201 (Dordaviprone) In Recurrent H3 K27m-Mutant Diffuse Midline Glioma, Isabel Arrillaga-Romany, Andrew Cluster, Et Al.

2020-Current year OA Pubs

PURPOSE: Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M-mutant DMG.

METHODS: Fifty patients (pediatric, n = 4; adult, n = 46) with recurrent H3 K27M-mutant DMG who received oral ONC201 monotherapy in four clinical trials or one expanded access protocol were included. Eligible patients had measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria and performance score (PS) ≥60 and were ≥90 days from radiation; pontine and spinal tumors were ineligible. The …


Computationally Restoring The Potency Of A Clinical Antibody Against Omicron, Thomas A Desautels, Suzanne M Scheaffer, Bradley Whitener, James B Case, Larissa B Thackray, Michael S Diamond, Et Al. May 2024

Computationally Restoring The Potency Of A Clinical Antibody Against Omicron, Thomas A Desautels, Suzanne M Scheaffer, Bradley Whitener, James B Case, Larissa B Thackray, Michael S Diamond, Et Al.

2020-Current year OA Pubs

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs


Ligand Efficacy Modulates Conformational Dynamics Of The Μ-Opioid Receptor, Jiawei Zhao, Matthias Elgeti, Evan S O'Brien, Cecília P Sár, Amal Ei Daibani, Jie Heng, Xiaoou Sun, Elizabeth White, Tao Che, Wayne L Hubbell, Brian K Kobilka, Chunlai Chen May 2024

Ligand Efficacy Modulates Conformational Dynamics Of The Μ-Opioid Receptor, Jiawei Zhao, Matthias Elgeti, Evan S O'Brien, Cecília P Sár, Amal Ei Daibani, Jie Heng, Xiaoou Sun, Elizabeth White, Tao Che, Wayne L Hubbell, Brian K Kobilka, Chunlai Chen

2020-Current year OA Pubs

The µ-opioid receptor (µOR) is an important target for pain management


A Precision Functional Atlas Of Personalized Network Topography And Probabilities, Robert J M Hermosillo, Ally Dworetsky, Babatunde Adeyemo, Caterina Gratton, Steven Petersen, Nico U F Dosenbach, Et Al. May 2024

A Precision Functional Atlas Of Personalized Network Topography And Probabilities, Robert J M Hermosillo, Ally Dworetsky, Babatunde Adeyemo, Caterina Gratton, Steven Petersen, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases-the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a …


Phase Ii Trial Of Nab- Sirolimus In Patients With Advanced Malignant Perivascular Epithelioid Cell Tumors (Ampect): Long-Term Efficacy And Safety Update, Andrew J Wagner, Vinod Ravi, Richard F Riedel, Kristen Ganjoo, Brian A Van Tine, Rashmi Chugh, Lee Cranmer, Erlinda M Gordon, Jason L Hornick, Heng Du, Li Ding, Anita N Schmid, Willis H Navarro, David J Kwiatkowski, Mark A Dickson May 2024

Phase Ii Trial Of Nab- Sirolimus In Patients With Advanced Malignant Perivascular Epithelioid Cell Tumors (Ampect): Long-Term Efficacy And Safety Update, Andrew J Wagner, Vinod Ravi, Richard F Riedel, Kristen Ganjoo, Brian A Van Tine, Rashmi Chugh, Lee Cranmer, Erlinda M Gordon, Jason L Hornick, Heng Du, Li Ding, Anita N Schmid, Willis H Navarro, David J Kwiatkowski, Mark A Dickson

2020-Current year OA Pubs

No abstract provided.


Asct2-Targeting Antibody-Drug Conjugate Medi7247 In Adult Patients With Relapsed/Refractory Hematological Malignancies: A First-In-Human, Phase 1 Study, Michael Maris, Camille N Abboud, Et Al. May 2024

Asct2-Targeting Antibody-Drug Conjugate Medi7247 In Adult Patients With Relapsed/Refractory Hematological Malignancies: A First-In-Human, Phase 1 Study, Michael Maris, Camille N Abboud, Et Al.

2020-Current year OA Pubs

BACKGROUND: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer.

OBJECTIVE: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies.

PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included assessments of antitumor activity, pharmacokinetics (PK), and immunogenicity.

RESULTS: As of 26 March 2020, 67 patients were treated …


Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Li Ding, Et Al. May 2024

Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Li Ding, Et Al.

2020-Current year OA Pubs

Single-cell omics technologies enable molecular characterization of diverse cell types and states, but how the resulting transcriptional and epigenetic profiles depend on the cell's genetic background remains understudied. We describe Monopogen, a computational tool to detect single-nucleotide variants (SNVs) from single-cell sequencing data. Monopogen leverages linkage disequilibrium from external reference panels to identify germline SNVs and detects putative somatic SNVs using allele cosegregating patterns at the cell population level. It can identify 100 K to 3 M germline SNVs achieving a genotyping accuracy of 95%, together with hundreds of putative somatic SNVs. Monopogen-derived genotypes enable global and local ancestry inference …


Interferons And Tuft Cell Numbers Are Bottlenecks For Persistent Murine Norovirus Infection, Somya Aggarwal, Forrest C. Walker, James S. Weagley, Broc T. Mccune, Xiaofen Wu, Lawrence A. Schriefer, Heyde Makimaa, Dylan Lawrence, Pratyush Sridhar, Megan T. Baldridge May 2024

Interferons And Tuft Cell Numbers Are Bottlenecks For Persistent Murine Norovirus Infection, Somya Aggarwal, Forrest C. Walker, James S. Weagley, Broc T. Mccune, Xiaofen Wu, Lawrence A. Schriefer, Heyde Makimaa, Dylan Lawrence, Pratyush Sridhar, Megan T. Baldridge

2020-Current year OA Pubs

Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes …


Disease Staging Of Alzheimer's Disease Using A Csf-Based Biomarker Model, Gemma Salvadó, Kanta Horie, Nicolas R Barthélemy, Charles D Chen, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al. May 2024

Disease Staging Of Alzheimer's Disease Using A Csf-Based Biomarker Model, Gemma Salvadó, Kanta Horie, Nicolas R Barthélemy, Charles D Chen, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 and was validated in 222 participants from the Knight Alzheimer Disease Research Center cohort. SuStaIn identified a singular biomarker sequence and revealed that five CSF biomarkers effectively constituted a reliable staging model (ordered: Aβ42/40, pT217/T217, pT205/T205, MTBR-tau243 and non-phosphorylated mid-region tau). The …


Targeting Dendritic Cell Dysfunction To Circumvent Anti-Pd1 Resistance In Head And Neck Cancer, Shin Saito, Michihisa Kono, Hoang C B Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri May 2024

Targeting Dendritic Cell Dysfunction To Circumvent Anti-Pd1 Resistance In Head And Neck Cancer, Shin Saito, Michihisa Kono, Hoang C B Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri

2020-Current year OA Pubs

PURPOSE: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed.

EXPERIMENTAL DESIGN: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model.

RESULTS: An aPD1-resistant mouse model showed poor priming in the tumor DLN due …


Spatial Mapping Of Hematopoietic Clones In Human Bone Marrow, Andrew L Young, Hannah C Davis, Maggie J Cox, Tyler M Parsons, Samantha C Burkart, Diane E Bender, Lulu Sun, Stephen T Oh, Grant A Challen May 2024

Spatial Mapping Of Hematopoietic Clones In Human Bone Marrow, Andrew L Young, Hannah C Davis, Maggie J Cox, Tyler M Parsons, Samantha C Burkart, Diane E Bender, Lulu Sun, Stephen T Oh, Grant A Challen

2020-Current year OA Pubs

UNLABELLED: Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., >2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution …


Targeting Hematologic Malignancies By Inhibiting E-Selectin: A Sweet Spot For Aml Therapy?, Geoffrey L Uy, Daniel J Deangelo, Jay N Lozier, Dennis M Fisher, Brian A Jonas, John L Magnani, Pamela S Becker, Hillard M Lazarus, Ingrid G Winkler May 2024

Targeting Hematologic Malignancies By Inhibiting E-Selectin: A Sweet Spot For Aml Therapy?, Geoffrey L Uy, Daniel J Deangelo, Jay N Lozier, Dennis M Fisher, Brian A Jonas, John L Magnani, Pamela S Becker, Hillard M Lazarus, Ingrid G Winkler

2020-Current year OA Pubs

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewis


Impact Of Gram-Negative Bacilli Resistance Rates On Risk Of Death In Septic Shock And Pneumonia, Alison M Hixon, Scott Micek, Victoria J Fraser, Marin Kollef, M Cristina Vazquez Guillamet May 2024

Impact Of Gram-Negative Bacilli Resistance Rates On Risk Of Death In Septic Shock And Pneumonia, Alison M Hixon, Scott Micek, Victoria J Fraser, Marin Kollef, M Cristina Vazquez Guillamet

2020-Current year OA Pubs

BACKGROUND: Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship.

METHODS: We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We …


Loss Of Katnal2 Leads To Ependymal Ciliary Hyperfunction And Autism-Related Phenotypes In Mice, Ryeonghwa Kang, Zachary Papadopoulos, Jonathan Kipnis, Et Al. May 2024

Loss Of Katnal2 Leads To Ependymal Ciliary Hyperfunction And Autism-Related Phenotypes In Mice, Ryeonghwa Kang, Zachary Papadopoulos, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early …


High Rates Of Missed Hiv Testing Among Oral Prep Users In The United States From 2018-2021: A National Assessment On Compliance With Hiv Testing Recommendations Of The Cdc Prep Guidelines, Jason Baron, Tamar Tchelidze, Benjamin Labrot, Joseph Yao, Kenneth H Mayer, Daniel Kuritzkes, Nicole Robinson, Rupa R Patel May 2024

High Rates Of Missed Hiv Testing Among Oral Prep Users In The United States From 2018-2021: A National Assessment On Compliance With Hiv Testing Recommendations Of The Cdc Prep Guidelines, Jason Baron, Tamar Tchelidze, Benjamin Labrot, Joseph Yao, Kenneth H Mayer, Daniel Kuritzkes, Nicole Robinson, Rupa R Patel

2020-Current year OA Pubs

BACKGROUND: The US Centers for Disease Control and Prevention recommends HIV testing every 3 months in oral PrEP users. We performed a national assessment of HIV testing compliance among oral PrEP users.

METHODS: We analyzed 408 910 PrEP prescriptions issued to 39 809 PrEP users using a national insurance claims database that contained commercial and Medicaid claims. We identified PrEP use based on pharmacy claims and outpatient diagnostic coding. We evaluated the percentage of PrEP prescription refills without HIV testing (identified by CPT codes) within the prior 3, 6, and 12 months using time to event methods. We performed subgroup …


From Chest Trauma To Coronary Artery Dissection, Hakob Harutyunyan, Nnamdi Chukwuka, Arafat Ali Farooqui, Vahagn Tamazyan, Ashot Batikyan, Aleksan Khachatryan, Elliot Borgen, Joshua Kerstein May 2024

From Chest Trauma To Coronary Artery Dissection, Hakob Harutyunyan, Nnamdi Chukwuka, Arafat Ali Farooqui, Vahagn Tamazyan, Ashot Batikyan, Aleksan Khachatryan, Elliot Borgen, Joshua Kerstein

2020-Current year OA Pubs

Despite being rare, traumatic coronary artery dissection after blunt chest trauma can lead to life-threatening consequences that can be fatal. This case report focuses on a 51-year-old woman who suffered chest trauma at home and was later found to have right coronary artery dissection. This manuscript aims to elucidate the risk factors, diagnostic challenges, and management strategies associated with traumatic coronary artery dissection. This case report emphasizes the evaluation of risk factors, the significance of early detection with appropriate imaging modalities while maintaining high clinical suspicion, and the critical necessity of optimizing patient outcomes in such circumstances.


Clinical Outcomes, Return To Sport, And Complications After Isolated Primary Latarjet Versus Latarjet As A Revision Procedure: A Systematic Review And Meta-Analysis, Garrett R Jackson, Trevor Tuthill, Shaan Asif, Daniel Dewald, Morgan Wessels, Johnathon R Mccormick, Enzo S Mameri, Derrick M Knapik, Filippo Familiari, Mario Hevesi, Anjay K Batra, Jorge Chahla, Nikhil N Verma May 2024

Clinical Outcomes, Return To Sport, And Complications After Isolated Primary Latarjet Versus Latarjet As A Revision Procedure: A Systematic Review And Meta-Analysis, Garrett R Jackson, Trevor Tuthill, Shaan Asif, Daniel Dewald, Morgan Wessels, Johnathon R Mccormick, Enzo S Mameri, Derrick M Knapik, Filippo Familiari, Mario Hevesi, Anjay K Batra, Jorge Chahla, Nikhil N Verma

2020-Current year OA Pubs

BACKGROUND: The purpose of this review was to compare clinical outcomes, return to sport (RTS), and complications in comparative studies examining patients undergoing primary Latarjet procedure versus Latarjet in the revision setting following soft tissue stabilization.

METHODS: A literature search was conducted using PubMed and Scopus databases using Preferred Reporting Items for Systematic Meta-Analyses guidelines. Inclusion criteria consisted of level I to III human clinical studies reporting clinical outcomes (Visual Analogue Pain Scale [VAS]), RTS metrics, and complications in patients following primary versus revision Latarjet procedures. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria.

RESULTS: …


Implementation Of Health It For Cancer Screening In Us Primary Care: Scoping Review, Constance Owens-Jasey, Maura M Kepper, Alex T Ramsey, Et Al. Apr 2024

Implementation Of Health It For Cancer Screening In Us Primary Care: Scoping Review, Constance Owens-Jasey, Maura M Kepper, Alex T Ramsey, Et Al.

2020-Current year OA Pubs

BACKGROUND: A substantial percentage of the US population is not up to date on guideline-recommended cancer screenings. Identifying interventions that effectively improve screening rates would enhance the delivery of such screening. Interventions involving health IT (HIT) show promise, but much remains unknown about how HIT is optimized to support cancer screening in primary care.

OBJECTIVE: This scoping review aims to identify (1) HIT-based interventions that effectively support guideline concordance in breast, cervical, and colorectal cancer screening provision and follow-up in the primary care setting and (2) barriers or facilitators to the implementation of effective HIT in this setting.

METHODS: Following …


Pml::Rara And Gata2 Proteins Interact Via Dna Templates To Induce Aberrant Self-Renewal In Mouse And Human Hematopoietic Cells, Casey D S Katerndahl, Olivia R S Rogers, Ryan B Day, Ziheng Xu, Nichole M Helton, Sai Mukund Ramakrishnan, Christopher A Miller, Timothy J Ley Apr 2024

Pml::Rara And Gata2 Proteins Interact Via Dna Templates To Induce Aberrant Self-Renewal In Mouse And Human Hematopoietic Cells, Casey D S Katerndahl, Olivia R S Rogers, Ryan B Day, Ziheng Xu, Nichole M Helton, Sai Mukund Ramakrishnan, Christopher A Miller, Timothy J Ley

2020-Current year OA Pubs

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5-tagged PML::RARA, using anti-V5-PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin-accessible (defined by ATAC-seq) in unmanipulated, wild-type promyelocytes, suggesting that these regions are "open" prior to PML::RARA expression. We found that GATA binding motifs, and the direct binding of the chromatin "pioneering factor" GATA2, were significantly enriched near PML::RARA binding sites. Proximity labeling studies …


Expanding Youth-Friendly Hiv Self-Testing Services During The Covid-19 Pandemic: Qualitative Analysis Of A Crowdsourcing Open Call In Nigeria, Onyekachukwu Anikamadu, Oliver Ezechi, Alexis Engelhart, Ucheoma Nwaozuru, Chisom Obiezu-Umeh, Ponmile Ogunjemite, Babatunde Ismail Bale, Daniel Nwachukwu, Titilola Gbaja-Biamila, David Oladele, Adesola Z Musa, Stacey Mason, Temitope Ojo, Joseph Tucker, Juliet Iwelunmor Apr 2024

Expanding Youth-Friendly Hiv Self-Testing Services During The Covid-19 Pandemic: Qualitative Analysis Of A Crowdsourcing Open Call In Nigeria, Onyekachukwu Anikamadu, Oliver Ezechi, Alexis Engelhart, Ucheoma Nwaozuru, Chisom Obiezu-Umeh, Ponmile Ogunjemite, Babatunde Ismail Bale, Daniel Nwachukwu, Titilola Gbaja-Biamila, David Oladele, Adesola Z Musa, Stacey Mason, Temitope Ojo, Joseph Tucker, Juliet Iwelunmor

2020-Current year OA Pubs

BACKGROUND: HIV self-testing (HIVST) among young people is an effective approach to enhance the uptake of HIV testing recommended by the World Health Organization. However, the COVID-19 pandemic disrupted conventional facility-based HIV testing services, necessitating the exploration of innovative strategies for the effective delivery of HIVST.

OBJECTIVE: This study analyzed the outcomes of a digital World AIDS Day crowdsourcing open call, designed to elicit youth responses on innovative approaches to promote HIVST among young people (14-24 years) in Nigeria during COVID-19 restrictions.

METHODS: From November 2 to 22, 2020, a World AIDS Day 2020 crowdsourcing open call was held digitally …