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Full-Text Articles in Medicine and Health Sciences

Global Prevalence Of Aspirin Use For Primary Prevention Of Cardiovascular Disease: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Sang Gune K Yoo, Mark D Huffman, Et Al. May 2024

Global Prevalence Of Aspirin Use For Primary Prevention Of Cardiovascular Disease: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Sang Gune K Yoo, Mark D Huffman, Et Al.

2020-Current year OA Pubs

No abstract provided.


Identifying Long-Term Survivors And Those At Higher Or Lower Risk Of Relapse Among Patients With Cytogenetically Normal Acute Myeloid Leukemia Using A High-Dimensional Mixture Cure Model, Kellie J Archer, Han Fu, Krzysztof Mrózek, Deedra Nicolet, Alice S Mims, Geoffrey L Uy, Wendy Stock, John C Byrd, Wolfgang Hiddemann, Jan Braess, Karsten Spiekermann, Klaus H Metzeler, Tobias Herold, Ann-Kathrin Eisfeld May 2024

Identifying Long-Term Survivors And Those At Higher Or Lower Risk Of Relapse Among Patients With Cytogenetically Normal Acute Myeloid Leukemia Using A High-Dimensional Mixture Cure Model, Kellie J Archer, Han Fu, Krzysztof Mrózek, Deedra Nicolet, Alice S Mims, Geoffrey L Uy, Wendy Stock, John C Byrd, Wolfgang Hiddemann, Jan Braess, Karsten Spiekermann, Klaus H Metzeler, Tobias Herold, Ann-Kathrin Eisfeld

2020-Current year OA Pubs

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) may harbor prognostically relevant gene mutations and thus be categorized into one of the three 2022 European LeukemiaNet (ELN) genetic-risk groups. Nevertheless, there remains heterogeneity with respect to relapse-free survival (RFS) within these genetic-risk groups. Our training set included 306 adults on Alliance for Clinical Trials in Oncology studies with de novo CN-AML aged <  60 years who achieved a complete remission and for whom centrally reviewed cytogenetics, RNA-sequencing, and gene mutation data from diagnostic samples were available (Alliance trial A152010). To overcome deficiencies of the Cox proportional hazards model when long-term survivors are present, we developed a penalized semi-parametric mixture cure model (MCM) to predict RFS where RNA-sequencing data comprised the predictor space. To validate model performance, we employed an independent test set from the German Acute Myeloid Leukemia Cooperative Group (AMLCG) consisting of 40 de novo CN-AML patients aged <  60 years who achieved a complete remission and had RNA-sequencing of their pre-treatment sample. For the training set, there was a significant non-zero cure fraction (p = 0.019) with 28.5% of patients estimated to be cured. Our MCM included 112 genes associated with cure, or long-term RFS, and 87 genes associated with latency, or shorter-term time-to-relapse. The area under the curve and C-statistic were respectively, 0.947 and 0.783 for our training set and 0.837 and 0.718 for our test set. We identified a novel, prognostically relevant molecular signature in CN-AML, which allows identification of patient subgroups independent of 2022 ELN genetic-risk groups.Trial registration Data from companion studies CALGB 8461, 9665 and 20202 (trials registered at www.clinicaltrials.gov as, respectively, NCT00048958, NCT00899223, and NCT00900224) were obtained from Alliance for Clinical Trials in Oncology under data sharing study A152010. Data from the AMLCG 2008 trial was registered at www.clinicaltrials.gov as NCT01382147.


The Long Non-Coding Rna Gene C027288.3 Plays A Role In Human Endometrial Stromal Fibroblast Decidualization, Rupak Thapa, Kevin Marmo, Liang Ma, Donald S Torry, Brent M Bany May 2024

The Long Non-Coding Rna Gene C027288.3 Plays A Role In Human Endometrial Stromal Fibroblast Decidualization, Rupak Thapa, Kevin Marmo, Liang Ma, Donald S Torry, Brent M Bany

2020-Current year OA Pubs

During the secretory phase of the menstrual cycle, endometrial fibroblast cells begin to change into large epithelial-like cells called decidual cells in a process called decidualization. This differentiation continues more broadly in the endometrium and forms the decidual tissue during early pregnancy. The cells undergoing decidualization as well as the resulting decidual cells, support successful implantation and placentation during early pregnancy. This study was carried out to identify new potentially important long non-coding RNA (lncRNA) genes that may play a role in human endometrial stromal fibroblast cells (hESF) undergoing decidualization in vitro, and several were found. The expression of nine …


Cytotoxic Sigma-2 Ligands Trigger Cancer Cell Death Via Cholesterol-Induced-Er-Stress, Rony Takchi, Bethany C Prudner, Qingqing Gong, Takaomi Hagi, Kenneth F Newcomer, Linda X Jin, Suwanna Vangveravong, Brian A Van Tine, William G Hawkins, Dirk Spitzer May 2024

Cytotoxic Sigma-2 Ligands Trigger Cancer Cell Death Via Cholesterol-Induced-Er-Stress, Rony Takchi, Bethany C Prudner, Qingqing Gong, Takaomi Hagi, Kenneth F Newcomer, Linda X Jin, Suwanna Vangveravong, Brian A Van Tine, William G Hawkins, Dirk Spitzer

2020-Current year OA Pubs

Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated. A series of high-affinity S2L were evaluated regarding their cytotoxicity profiles across cancer cell lines. While C6 and C10 displayed distinct cytotoxicities, C0 and ISO1 were essentially non-toxic. Confocal microscopy and lipidomics analysis in cellular and mouse models revealed that C10 …


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: …


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.


Disruption Of Polyunsaturated Fatty Acid Biosynthesis Drives Sting-Dependent Acute Myeloid Leukemia Cell Maturation And Death, Joice Kanefsky, Mary Basse, Judith Sokei, Orsola Di Martino, Liana Valin, Jeffrey A Magee, Francesca Ferraro, Stephen M Sykes, Et Al. May 2024

Disruption Of Polyunsaturated Fatty Acid Biosynthesis Drives Sting-Dependent Acute Myeloid Leukemia Cell Maturation And Death, Joice Kanefsky, Mary Basse, Judith Sokei, Orsola Di Martino, Liana Valin, Jeffrey A Magee, Francesca Ferraro, Stephen M Sykes, Et Al.

2020-Current year OA Pubs

The role of polyunsaturated fatty acid (PUFA) biosynthesis in acute myeloid leukemia (AML) remains largely undefined. A comparative expression analysis of 35 genes encoding fatty acid biosynthesis enzymes showed that fatty acid desaturase 1 (FADS1) was highly expressed across multiple AML subtypes relative to healthy controls and that elevated FADS1 expression correlates with worse overall AML patient survival. Functionally, shRNA-mediated inhibition of FADS1 reduced AML cell growth in vitro and significantly delayed leukemia onset in an AML mouse model. AML cell lines depleted of FADS1 arrested in the G1/S-phase of the cell cycle, acquired characteristics of myeloid maturation and subsequently …


Modulation Of Host Immunity By Sensory Neurons, Telma Saraiva-Santos, Tiago H Zaninelli, Felipe A Pinho-Ribeiro May 2024

Modulation Of Host Immunity By Sensory Neurons, Telma Saraiva-Santos, Tiago H Zaninelli, Felipe A Pinho-Ribeiro

2020-Current year OA Pubs

Recent studies have uncovered a new role for sensory neurons in influencing mammalian host immunity, challenging conventional notions of the nervous and immune systems as separate entities. In this review we delve into this groundbreaking paradigm of neuroimmunology and discuss recent scientific evidence for the impact of sensory neurons on host responses against a wide range of pathogens and diseases, encompassing microbial infections and cancers. These valuable insights enhance our understanding of the interactions between the nervous and immune systems, and also pave the way for developing candidate innovative therapeutic interventions in immune-mediated diseases highlighting the importance of this interdisciplinary …


Cooking With Liquefied Petroleum Gas Or Biomass And Fetal Growth Outcomes: A Multi-Country Randomised Controlled Trial, William Checkley, Victor G Dávila-Román, Lisa De Las Fuentes, Et Al. May 2024

Cooking With Liquefied Petroleum Gas Or Biomass And Fetal Growth Outcomes: A Multi-Country Randomised Controlled Trial, William Checkley, Victor G Dávila-Román, Lisa De Las Fuentes, Et Al.

2020-Current year OA Pubs

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth.

METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. …


Inflammatory Myofibroblastic Tumor In A Patient With X-Linked Hypophosphatemia: A Case Of Occam's Razor Or Hickam's Dictum?, Farhan Chowdry, Kelsey M Miller, Ersan Altun, Sara E Wobker, Gary S Gottesman, Hikmat Al-Ahmadie, Tracy L Rose, Eric M Wallen, Matthew I Milowsky May 2024

Inflammatory Myofibroblastic Tumor In A Patient With X-Linked Hypophosphatemia: A Case Of Occam's Razor Or Hickam's Dictum?, Farhan Chowdry, Kelsey M Miller, Ersan Altun, Sara E Wobker, Gary S Gottesman, Hikmat Al-Ahmadie, Tracy L Rose, Eric M Wallen, Matthew I Milowsky

2020-Current year OA Pubs

We present the case of a patient with X-Linked Hypophosphatemia (XLH) and an inflammatory myofibroblastic tumor (IMT) of the bladder which prompted further investigation into the possible relationship between XLH and IMT i.e. a case of Occam's Razor or Hickam's Dictum?


Explainable Ai-Based Deep-Shap For Mapping The Multivariate Relationships Between Regional Neuroimaging Biomarkers And Cognition, Puskar Bhattarai, Deepa Singh Thakuri, Yuzheng Nie, Ganesh B Chand May 2024

Explainable Ai-Based Deep-Shap For Mapping The Multivariate Relationships Between Regional Neuroimaging Biomarkers And Cognition, Puskar Bhattarai, Deepa Singh Thakuri, Yuzheng Nie, Ganesh B Chand

2020-Current year OA Pubs

BACKGROUND: Mild cognitive impairment (MCI)/Alzheimer's disease (AD) is associated with cognitive decline beyond normal aging and linked to the alterations of brain volume quantified by magnetic resonance imaging (MRI) and amyloid-beta (Aβ) quantified by positron emission tomography (PET). Yet, the complex relationships between these regional imaging measures and cognition in MCI/AD remain unclear. Explainable artificial intelligence (AI) may uncover such relationships.

METHOD: We integrate the AI-based deep learning neural network and Shapley additive explanations (SHAP) approaches and introduce the Deep-SHAP method to investigate the multivariate relationships between regional imaging measures and cognition. After validating this approach on simulated data, we …


Plecanatide Improves Abdominal Bloating And Bowel Symptoms Of Irritable Bowel Syndrome With Constipation, Darren M Brenner, Amol Sharma, Satish S C Rao, Adam P Laitman, Zeev Heimanson, Christopher Allen, Gregory S Sayuk May 2024

Plecanatide Improves Abdominal Bloating And Bowel Symptoms Of Irritable Bowel Syndrome With Constipation, Darren M Brenner, Amol Sharma, Satish S C Rao, Adam P Laitman, Zeev Heimanson, Christopher Allen, Gregory S Sayuk

2020-Current year OA Pubs

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C).

AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity.

METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in …


Mapping Brain Function In Adults And Young Children During Naturalistic Viewing With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Morgan Fogarty, Alexandra M Svoboda, Mariel L Schroeder, Sean M Rafferty, Edward J Richter, Christopher Tracy, Patricia K Mansfield, Madison Booth, Andrew K Fishell, Arefeh Sherafati, Zachary E Markow, Muriah D Wheelock, Ana María Arbeláez, Bradley L Schlaggar, Christopher D Smyser, Adam T Eggebrecht, Joseph P Culver May 2024

Mapping Brain Function In Adults And Young Children During Naturalistic Viewing With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Morgan Fogarty, Alexandra M Svoboda, Mariel L Schroeder, Sean M Rafferty, Edward J Richter, Christopher Tracy, Patricia K Mansfield, Madison Booth, Andrew K Fishell, Arefeh Sherafati, Zachary E Markow, Muriah D Wheelock, Ana María Arbeláez, Bradley L Schlaggar, Christopher D Smyser, Adam T Eggebrecht, Joseph P Culver

2020-Current year OA Pubs

Human studies of early brain development have been limited by extant neuroimaging methods. MRI scanners present logistical challenges for imaging young children, while alternative modalities like functional near-infrared spectroscopy have traditionally been limited by image quality due to sparse sampling. In addition, conventional tasks for brain mapping elicit low task engagement, high head motion, and considerable participant attrition in pediatric populations. As a result, typical and atypical developmental trajectories of processes such as language acquisition remain understudied during sensitive periods over the first years of life. We evaluate high-density diffuse optical tomography (HD-DOT) imaging combined with movie stimuli for high …


Image Quality Characterization Of An Ultra-High-Speed Kilovoltage Cone-Beam Computed Tomography Imaging System On An O-Ring Linear Accelerator, Euidam Kim, Yang Kyun Park, Tianyu Zhao, Eric Laugeman, Xiaodong Neo Zhao, Yao Hao, Yoonsun Chung, Hugh Lee May 2024

Image Quality Characterization Of An Ultra-High-Speed Kilovoltage Cone-Beam Computed Tomography Imaging System On An O-Ring Linear Accelerator, Euidam Kim, Yang Kyun Park, Tianyu Zhao, Eric Laugeman, Xiaodong Neo Zhao, Yao Hao, Yoonsun Chung, Hugh Lee

2020-Current year OA Pubs

PURPOSE: The quality of on-board imaging systems, including cone-beam computed tomography (CBCT), plays a vital role in image-guided radiation therapy (IGRT) and adaptive radiotherapy. Recently, there has been an upgrade of the CBCT systems fused in the O-ring linear accelerators called HyperSight, featuring a high imaging performance. As the characterization of a new imaging system is essential, we evaluated the image quality of the HyperSight system by comparing it with Halcyon 3.0 CBCT and providing benchmark data for routine imaging quality assurance.

METHODS: The HyperSight features ultra-fast scan time, a larger kilovoltage (kV) detector, a more substantial kV tube, and …


Assessment Of Illness Severity In Adults Hospitalized With Acute Respiratory Tract Infection Due To Influenza, Respiratory Syncytial Virus, Or Human Metapneumovirus, Ann R Falsey, Edward E Walsh, Stacey L House, Yannick Vandendijck, Marita Stevens, Eric K H Chan, Gabriela Ispas May 2024

Assessment Of Illness Severity In Adults Hospitalized With Acute Respiratory Tract Infection Due To Influenza, Respiratory Syncytial Virus, Or Human Metapneumovirus, Ann R Falsey, Edward E Walsh, Stacey L House, Yannick Vandendijck, Marita Stevens, Eric K H Chan, Gabriela Ispas

2020-Current year OA Pubs

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs).

METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection …