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Functional Cooperativity Between the Trigger Factor Chaperone and the ClpXP Proteolytic Complex
A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close...
The Mitochondrial Protease LonP1 Promotes Proteasome Inhibitor Resistance in Multiple Myeloma
Multiple myeloma and its precursor plasma cell dyscrasias affect 3% of the elderly population in the US. Proteasome inhibitors are an essential part of several standard drug combinations used to ...
A Biallelic Pathogenic Variant in the Ogdh Gene Results in a Neurological Disorder With Features of a Mitochondrial Disease
2-Oxoglutarate dehydrogenase (OGDH) is a rate-limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α-Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in...
Functional Interpretation of ATAD3A Variants in Neuro-Mitochondrial Phenotypes
BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mi...
Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer's Disease
Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer's disease (AD) in a manner independent of amyloid ...
Deciphering the mechanism and function of Hsp100 unfoldases from protein structure.
Hsp100 chaperones, also known as Clp proteins, constitute a family of ring-forming ATPases that differ in 3D structure and cellular function from other stress-inducible molecular chaperones. Whil...
Atomic Structure of the Leishmania spp. Hsp100 N-domain
Hsp100 is an ATP-dependent unfoldase that promotes protein disaggregation or facilitates the unfolding of aggregation-prone polypeptides marked for degradation. Recently, new Hsp100 functions are...
Bi-allelic Variants in Ogdhl Cause a Neurodevelopmental Spe...eaturing Epilepsy, Hearing Loss, Visual Impairment, and Ataxia
The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to ...
Enniatin a Inhibits the Chaperone Hsp90 and Unleashes the Immune System Against Triple-Negative Breast Cancer
Low response rates and immune-related adverse events limit the remarkable impact of cancer immunotherapy. To improve clinical outcomes, preclinical studies have shown that combining immunotherapi...
Discovery and Characterization of Bromodomain 2-Specific Inhibitors of BRDT
Bromodomain testis (BRDT), a member of the bromodomain and extraterminal (BET) subfamily that includes the cancer targets BRD2, BRD3, and BRD4, is a validated contraceptive target. All BET subfam...
Cyclic Nucleotide Selectivity of Protein Kinase G Isozymes
The intrinsic activity of the C-terminal catalytic (C) domain of cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKG) is inhibited by interactions with the N-terminal regulatory ...
A Substitution in cGMP-Dependent Protein Kinase 1 Associate... Disease Induces an Active Conformation in the Absence of cGMP
Type 1 cGMP-dependent protein kinases (PKGs) play important roles in human cardiovascular physiology, regulating vascular tone and smooth-muscle cell phenotype. A mutation in the human PRKG1 gene...
Mechanism of Allosteric Inhibition in the Plasmodium falciparum cGMP-Dependent Protein Kinase
Most malaria deaths are caused by the protozoan parasite Plasmodium falciparum. Its life cycle is regulated by a cGMP-dependent protein kinase (PfPKG), whose inhibition is a promising antimalaria...
An auto-inhibited state of protein kinase G and implications for selective activation.
Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth ...
Discovery of Potent Bet Bromodomain 1 Stereoselective Inhibitors Using DNA-Encoded Chemical Library Selections
BET bromodomain inhibition is therapeutic in multiple diseases; however, pan-BET inhibitors have induced significant myelosuppression and gastrointestinal toxicity, perhaps due to inhibition of b...
Discovery of Potent Bet Bromodomain 1 Stereoselective Inhibitors Using DNA-Encoded Chemical Library Selections
Expression of a few master transcription factors can reprogram the epigenetic landscape and three-dimensional chromatin topology of differentiated cells and achieve pluripotency. During reprogram...
ERK Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro and In Vivo
Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell pr...
Dawn-to-Dusk Dry Fasting Induces Anti-atherosclerotic, Anti...al Blood Mononuclear Cells in Subjects With Metabolic Syndrome
BACKGROUND: Metabolic syndrome characterized by abdominal obesity, high blood pressure, elevated fasting glucose and triglyceride levels and low high-density lipoprotein cholesterol level is asso...
Functional Characterization of Age-Dependent p16 Epimutatio...ological Drivers and Therapeutic Targets for Colorectal Cancer
BACKGROUND: Methylation of the p16 promoter resulting in epigenetic gene silencing-known as p16 epimutation-is frequently found in human colorectal cancer and is also common in normal-appearing c...
3-Phosphoinositide-Dependent Kinase 1 Drives Acquired Resistance to Osimertinib
Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No ...
Purification and Characterization of Mitochondrial Mg2+-Independent Sphingomyelinase from Rat Brain
Sphingomyelinase (SMase) catalyzes ceramide production from sphingomyelin. Ceramides are critical in cellular responses such as apoptosis. They enhance mitochondrial outer membrane permeabilizati...
Speg Interactions That Regulate the Stability of Excitation-Contraction Coupling Protein Complexes in Triads and Dyads
Here we show that striated muscle preferentially expressed protein kinase α (Spegα) maintains cardiac function in hearts with Spegβ deficiency. Speg is required for stability of excitation-con...
Daam2 Phosphorylation by CK2α Negatively Regulates Wnt Activity During White Matter Development and Injury
Wnt signaling plays a vital role in oligodendrocyte (OL) development and has been implicated as an adverse event for myelin repair after white matter injury. Emerging studies have shed light on m...
Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.
Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both ly...
Role of Poly(A)-Binding Protein Cytoplasmic 1, a tRNA-Deriv...agment-Bound Protein, in Respiratory Syncytial Virus Infection
Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such ...
Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer.
Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unk...
RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus
SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could, thus, play important roles in viral replication and ho...
RNA-GPS Predicts High-Resolution RNA Subcellular Localization and Highlights the Role of Splicing
Subcellular localization is essential to RNA biogenesis, processing, and function across the gene expression life cycle. However, the specific nucleotide sequence motifs that direct RNA localizat...
Identifying the Reactive Metabolites of Tyrosine Kinase Inh...Pexidartinib In Vitro Using LC-MS-Based Metabolomic Approaches
Pexidartinib (PEX, TURALIO), a selective and potent inhibitor of the macrophage colony-stimulating factor-1 receptor, has been approved for the treatment of tenosynovial giant cell tumor. However...
Localization of RNAs to the Mitochondria-Mechanisms and Functions
The mammalian mitochondrial proteome comprises over 1000 proteins, with the majority translated from nuclear-encoded messenger RNAs (mRNAs). Mounting evidence suggests many of these mRNAs are loc...
Invariant natural killer T-cell subsets have diverse graft-versus-host-disease-preventing and antitumor effects.
Invariant natural killer T (iNKT) cells are a T-cell subset with potent immunomodulatory properties. Experimental evidence in mice and observational studies in humans indicate that iNKT cells hav...
Molecular and Physiological Changes in the SpaceX Inspiration4 Civilian Crew
Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1 , but new commercial spaceflight opportunities have opened spaceflight to a broader popula...
Nourishing the Brain on Deep Space Missions: Nutritional Psychiatry in Promoting Resilience
The grueling psychological demands of a journey into deep space coupled with ever-increasing distances away from home pose a unique problem: how can we best take advantage of the benefits of fres...
Microbiome for Mars: Surveying Microbiome Connections to He...ng-Duration Human Spaceflight, Virtual Workshop, July 13, 2020
The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate t...
Non-uniformity of projection distributions attenuates resolution in Cryo-EM.
Virtually all single-particle cryo-EM experiments currently suffer from specimen adherence to the air-water interface, leading to a non-uniform distribution in the set of projection views. Wherea...
Transformations Between Rotational and Translational Invariants Formulated in Reciprocal Spaces
Correlation functions play an important role in the theoretical underpinnings of many disparate areas of the physical sciences: in particular, scattering theory. More recently, they have become u...
Tools for Visualizing and Analyzing Fourier Space Sampling in Cryo-EM
A complete understanding of how an orientation distribution contributes to a cryo-EM reconstruction remains lacking. It is necessary to begin critically assessing the set of views to gain an unde...
Missing Wedge Completion via Unsupervised Learning with Coordinate Networks
Cryogenic electron tomography (cryoET) is a powerful tool in structural biology, enabling detailed 3D imaging of biological specimens at a resolution of nanometers. Despite its potential, cryoET ...
Community Recommendations on cryoEM Data Archiving and Validation
In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for the deposition and validation of cryoEM structures, with a focus on single-particle analysis. The m...
Overcoming Resolution Attenuation During Tilted Cryo-EM Data Collection
Structural biology efforts using cryogenic electron microscopy are frequently stifled by specimens adopting "preferred orientations" on grids, leading to anisotropic map resolution and impeding s...
A Rare Case of Vulvar Discharge Associated With Exogenous Oestrogen Exposure in a Spayed Weimaraner Bitch
OBJECTIVE: This report documents a rare case of vulvar discharge associated with exogenous oestrogen exposure in a large-breed dog. CASE DESCRIPTION: A 4-year-old spayed Weimaraner bitch was pr...
A Retrospective Study of Canine Transmissible Venereal Tumour in Grenada, West Indies
BACKGROUND: Canine transmissible venereal tumour (CTVT) is a naturally occurring neoplasia affecting dogs worldwide. Previous CTVT studies in Grenada were limited to case records of dogs with neo...
Pharmacologically Induced Ex Copula Ejaculation in Horses and Donkeys
Pharmacologically induced ex copula ejaculation is a method used for collection of semen when the traditional methods of semen collection are not feasible. Common indications for this method incl...
Metagenomic Analysis Unravels Novel Taxonomic Differences i...e Microbiome Between Healthy Mares and Mares With Endometritis
BACKGROUND: The application of high throughput technologies has enabled unravelling of unique differences between healthy mares and mares with endometritis at transcriptomic and proteomic levels....
Bicuspid Aortic Valve in Pregnancy Complicated by Aortic Valve Vegetation, Aortic Root Abscess, and Aortic Insufficiency
A 39-year-old patient presented to our Labor and Delivery unit with fever and nausea in the context of recent bacteriuria. She was found to be in sepsis due to an incidental bicuspid aortic valve...
Neuron-Specific Mitochondrial Oxidative Stress Results in Epilepsy, Glucose Dysregulation and a Striking Astrocyte Response
Mitochondrial superoxide (O2.−) production is implicated in aging, neurodegenerative disease, and most recently epilepsy. Yet the specific contribution of neuronal O2.− to these phenomena is ...
Mitochondrial Transfer From Mesenchymal Stem Cells Improves...al Metabolism After Oxidant Injury In Vitro: The Role of Miro1
Stroke-induced cerebral ischemia is a major cause of death and disability. The disruption of blood flow results in neuronal and glial cell death leading to brain injury. Reperfusion restores oxyg...
Enhancing Glucose Metabolism via Gluconeogenesis Is Therapeutic in a Zebrafish Model of Dravet Syndrome
Energy-producing pathways are novel therapeutic targets for the treatment of neurodevelopmental disorders. Here, we focussed on correcting metabolic defects in a catastrophic paediatric epilepsy,...
Neuronal SIRT3 Deletion Predisposes to Female-Specific Alterations in Cellular Metabolism, Memory, and Network Excitability
Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment throu...
Successful Use of Continuous Erector Spinae Plane Blocks in a Patient With Variant Angina After Large Ventral Hernia Repair
Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympatheti...
Electric Potential Energy Optimized 3D Radial Sampling Trajectories for MRI
A novel method for creating “golden” 3D center-out radial MRI sampling trajectories was developed and analyzed. This method, called ELECTRO (ELECTRic potential energy Optimized), uses repulsi...
Increasing Glutathione Levels by a Novel Posttranslational Mechanism Inhibits Neuronal Hyperexcitability
Glutathione (GSH) depletion, and impaired redox homeostasis have been observed in experimental animal models and patients with epilepsy. Pleiotropic strategies that elevate GSH levels via transcr...
A Gain-of-Function TPC2 Variant R210C Increases Affinity to PI(3,5)P2 and Causes Lysosome Acidification and Hypopigmentation
Albinism is a group of inherited disorders mainly affecting skin, hair and eyes. Here we identify a de novo point mutation, p.R210C, in the TPCN2 gene which encodes Two Pore Channel 2 (TPC2) from...
Defining Cellular Population Dynamics at Single-Cell Resolution During Prostate Cancer Progression
Advanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigate pr...
Explainable Artificial Intelligence and Domain Adaptation for Predicting HIV Infection With Graph Neural Networks
OBJECTIVE: Investigation of explainable deep learning methods for graph neural networks to predict HIV infections with social network information and performing domain adaptation to evaluate mode...
Bcl-2 Inhibition Combined With PPARα Activation Synergisti...argets Leukemic Stem Cell-Like Cells in Acute Myeloid Leukemia
Persistence of leukemic stem cells (LSCs) is one of the determining factors to acute myeloid leukemia (AML) treatment failure and responsible for the poor prognosis of the disease. Hence, novel t...
Spatial Heterogeneity of Infiltrating T Cells in High-Grade Serous Ovarian Cancer Revealed by Multi-omics Analysis
Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spa...
Multiagent Chemotherapy and Stereotactic Body Radiation The...c Adenocarcinoma: A Prospective Nonrandomized Controlled Trial
PURPOSE: In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for local...
Machine Learning-Driven Exploration of Drug Therapies for Triple-Negative Breast Cancer Treatment
Breast cancer is the second leading cause of cancer death in women among all cancer types. It is highly heterogeneous in nature, which means that the tumors have different morphologies and there ...
deCS: A Tool for Systematic Cell Type Annotations of Single-cell RNA Sequencing Data among Human Tissues
Single-cell RNA sequencing (scRNA-seq) is revolutionizing the study of complex and dynamic cellular mechanisms. However, cell type annotation remains a main challenge as it largely relies on a pr...
Deep Learning for Detecting and Elucidating Human T-cell Leukemia Virus Type 1 Integration in the Human Genome
Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, is the causative agent for adult T cell leukemia/lymphoma and many other human diseases. Accurate and high throughput detection of HTLV-...
The Challenges and Opportunities of scRNA-Seq in COVID-19 Research and Clinical Translation
The application of single-cell RNA sequencing in COVID-19 research has greatly improved our understanding of COVID-19 pathogenesis and immunological characteristics. In this commentary, we discus...
MetaDegron: Multimodal Feature-Integrated Protein Language Model for Predicting E3 Ligase Targeted Degrons
Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequ...
Investigating Gene Functions and Single-Cell Expression Profiles of De Novo Variants in Orofacial Clefts
Orofacial clefts (OFCs) are common congenital birth defects with various etiologies, including genetic variants. Online Mendelian Inheritance in Man (OMIM) annotated several hundred genes involvi...
DegronMD: Leveraging Evolutionary and Structural Features f...-Targeted Degradation, Mutations, and Drug Response to Degrons
Protein-targeted degradation is an emerging and promising therapeutic approach. The specificity of degradation and the maintenance of cellular homeostasis are determined by the interactions betwe...
ImmuneAPP for Hla-I Epitope Prediction and Immunopeptidome Analysis
Advances in mass spectrometry accelerates the characterization of HLA ligandome, necessitating the development of efficient methods for immunopeptidomics analysis and (neo)antigen prediction. We ...
GENEVIC: GENetic data Exploration and Visualization via Intelligent interactive Console
The vast generation of genetic data poses a significant challenge in efficiently uncovering valuable knowledge. Introducing GENEVIC, an AI-driven chat framework that tackles this challenge by bri...
Alternative Splicing of Gsdmb Modulates Killer Lymphocyte-Triggered Pyroptosis
Granzyme A from killer lymphocytes cleaves gasdermin B (GSDMB) and triggers pyroptosis in targeted human tumor cells, eliciting antitumor immunity. However, GSDMB has a controversial role in pyro...
Cancer-Associated Pyroptosis: A New License to Kill Tumor
Pyroptosis is a programmed necrotic cell death mediated by pore-forming Gasdermin (GSDM) proteins. After being unleashed from the C-terminal auto-inhibitory domains by proteolytic cleavage, the N...
Immune Checkpoint B7-H3 Is a Therapeutic Vulnerability in Prostate Cancer Harboring Pten and TP53 Deficiencies
Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint...
Targeting Branched N-glycans and Fucosylation Sensitizes Ovarian Tumors to Immune Checkpoint Blockade
Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be...
TXNRD1 Drives the Innate Immune Response in Senescent Cells With Implications for Age-Associated Inflammation
Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors colle...
Targeting Fatty Acid Reprogramming Suppresses CARM1-expressing Ovarian Cancer
The arginine methyltransferase CARM1 exhibits high expression levels in several human cancers, with the trend also observed in ovarian cancer. However, therapeutic approaches targeting tumors tha...
Redox Phospholipidomics Discovers Pro-ferroptotic Death Signals in A375 Melanoma Cells In Vitro and In Vivo
Growing cancer cells effectively evade most programs of regulated cell death, particularly apoptosis. This necessitates a search for alternative therapeutic modalities to cause cancer cell's demi...
Targeting the Mevalonate Pathway Suppresses ARID1A-Inactivated Cancers by Promoting Pyroptosis
ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in ∼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune...
Functional States of Myeloid Cells in Cancer
Myeloid cells, comprised of macrophages, dendritic cells, monocytes, and granulocytes, represent a major component of the tumor microenvironment (TME) and are critically involved in regulation of...
Identification of Molecular Signatures in Epicardial Adipose Tissue in Heart Failure With Preserved Ejection Fraction
AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this s...
Mutant NPM1 Hijacks Transcriptional Hubs to Maintain Pathogenic Gene Programs in Acute Myeloid Leukemia
Nucleophosmin (NPM1) is a ubiquitously expressed nucleolar protein with a wide range of biological functions. In 30% of acute myeloid leukemia (AML), the terminal exon of NPM1 is often found muta...
Endolysosomal Trafficking Controls Yolk Granule Biogenesis in Vitellogenic Drosophila Oocytes
Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly...
Fibrinogen-Like Protein 2: Its Biological Function Across C...Potential to Serve as an Immunotherapy Target for Brain Tumors
Brain tumors are among the 10 leading causes of cancer-related death and present unique treatment challenges due to their critical location, genetic heterogeneity, and the blood-brain barrier. Re...
Chronic Exposure to Carbon Black Ultrafine Particles Reprograms Macrophage Metabolism and Accelerates Lung Cancer
Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A-dependent emphysema. However, whether and how they alter t...
Impact of Select Actionable Genomic Alterations on Efficacy...djuvant Immunotherapy in Resectable Non-small Cell Lung Cancer
BACKGROUND: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of act...
Molecular Landscape of ERBB2 Alterations in 3000 Advanced NSCLC Patients
ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 altera...
Self-Assembling Peptides As Immunomodulatory Biomaterials
Self-assembling peptides are a type of biomaterial rapidly emerging in the fields of biomedicine and material sciences due to their promise in biocompatibility and effectiveness at controlled rel...
Dynamic Imine Bonding Facilitates Mannan Release from a Nanofibrous Peptide Hydrogel
Recently, there has been increased interest in using mannan as an immunomodulatory bioconjugate. Despite notable immunological and functional differences between the reduced (R-Man) and oxidized ...
From Pre-clinical to Translational Brain Metastasis Research: Current Challenges and Emerging Opportunities
Brain metastasis, characterized by poor clinical outcomes, is a devastating disease. Despite significant mechanistic and therapeutic advances in recent years, pivotal improvements in clinical int...
Targeting Alk Averts Ribonuclease 1-Induced Immunosuppression and Enhances Antitumor Immunity in Hepatocellular Carcinoma
Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of ...
Critical Functions of Extracellular Matrix in Brain Metastasis Seeding
Human brain is characterized by extremely sparse extracellular matrix (ECM). Despite its low abundance, the significance of brain ECM in both physiological and pathological conditions should not ...
Associations Between Kir/Kir-Ligand Genotypes and Clinical ...empeg Plus Nivolumab Combination Therapy in the Pivot-02 Trial
Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory an...
Ribonuclease 1 Enhances Antitumor Immunity Against Breast Cancer by Boosting T Cell Activation
The secretory enzyme human ribonuclease 1 (RNase1) is involved in innate immunity and anti-inflammation, achieving host defense and anti-cancer effects; however, whether RNase1 contributes to ada...
Disabling Uncompetitive Inhibition of Oncogenic IDH Mutations Drives Acquired Resistance
Mutations in IDH genes occur frequently in acute myeloid leukemia (AML) and other human cancers to generate the oncometabolite R-2HG. Allosteric inhibition of mutant IDH suppresses R-2HG producti...
Blockade of FGF2/FGFR2 Partially Overcomes Bone Marrow Mese...s Mediated Progression of T-cell Acute Lymphoblastic Leukaemia
The development of acute lymphoblastic leuakemia (ALL) is partly attributed to the effects of bone marrow (BM) microenvironment, especially mesenchymal stromal cells (MSCs), which interact bilate...
SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant C...roid Factor 2 Activity under Toxic Oxidative Stress Conditions
Healing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. He...
Revolutionizing Bone Regeneration: Advanced Biomaterials for Healing Compromised Bone Defects
In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects...
Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing for Craniomaxillofacial Bone Regeneration
Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolo...
Enhancement of Immunotherapies in Head and Neck Cancers Using Biomaterial-Based Treatment Strategies
Head and neck squamous cell carcinoma (HNSCC) is a challenging disease to treat because of typically late-stage diagnoses and tumor formation in difficult-to-treat areas, sensitive to aggressive ...
Targeting TMEM205 Mediated Drug Resistance in Ovarian Clear Cell Carcinoma Using Oncolytic Virus
BACKGROUND: Ovarian clear cell carcinoma (OCCC) accounts for approximately 8-10% of epithelial ovarian cancers in the United States. Although it is rare, OCCC usually presents with treatment chal...
Unraveling the Role of MiR-181 in Skin Fibrosis Pathogenesis by Targeting NUDT21
Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by widespread fibrosis in the skin and several internal organs. Nudix Hydrolase 21 (NUDT2 or CFIm25) downregulation...
From Primary Myelofibrosis to Chronic Myeloid Leukemia, BCR...ary Myelofibrosis: An Illustration of Dynamic Clonal Evolution
The simultaneous detection of BCR::ABL1 and JAK2 V617F was rarely reported and their clonal relationship and dynamic clonal shift were not characterized. Here, we described a unique case with the...
Elimination of Oncogenic Kras in Genetic Mouse Models Eradi...tic Cancer by Inducing Fas-Dependent Apoptosis by CD8+ T cells
Oncogenic KRASG12D (KRAS∗) is critical for the initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC) and is a known repressor of tumor immunity. Conditional elimination of KRAS...
KRASG12D Inhibition Reprograms the Microenvironment of Earl...creatic Cancer to Promote Fas-Mediated Killing by CD8+ T Cells
The KRASG12D mutation is present in nearly half of pancreatic adenocarcinomas (PDAC). We investigated the effects of inhibiting the KRASG12D mutant protein with MRTX1133, a non-covalent small mol...
A Comparative Analysis of the Immunoglobulin Repertoire in ...n Chinese Acute Myeloid Leukemia by High-Throughput Sequencing
It is common knowledge that immunoglobulin (Ig) is produced by B lymphocytes and mainly functions as an antibody. However, it has been shown recently that myeloblasts from acute myeloid leukemia ...
STAT5B Mutations in Myeloid Neoplasms Differ by Disease Sub... Chronic Myeloid Neoplasms With Eosinophilia and/or Basophilia
STAT5B has been reported as a recurrent mutation in myeloid neoplasms with eosinophilia, but its overall frequency and importance across a spectrum of myeloid neoplasms are largely unknown. We co...
TET2 Modulates Spatial Relocalization of Heterochromatin in Aged Hematopoietic Stem and Progenitor Cells
DNA methylation deregulation at partially methylated domains (PMDs) represents an epigenetic signature of aging and cancer, yet the underlying molecular basis and resulting biological consequence...
Acute Myeloid Leukemia With Concurrent NPM1 and RUNX1 Mutations
NPM1 mutation, as a founding genetic event, cooperates with other gene mutations, such as DNMT3A and FLT3, to promote the development of acute myeloid leukemia. NPM1 mutation, however, has been r...
A Global Study for Acute Myeloid Leukemia With RARG Rearrangement
Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However,...
Model-Informed Drug Development of Autologous Car-T Cell Th...e Car-T Cell Exposure Leveraging Cell Kinetic/Dynamic Modeling
Autologous Chimeric antigen receptor (CAR-T) cell therapy has been highly successful in the treatment of aggressive hematological malignancies and is also being evaluated for the treatment of sol...
Single-Cell CRISPR Immune Screens Reveal Immunological Roles of Tumor Intrinsic Factors
Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms p...
Modulation of the Proteostasis Network Promotes Tumor Resistance to Oncogenic KRAS Inhibitors
Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier to progress. Here, we report proteostasis reprogramming as a key converg...
The Constitutively Active Form of a Key Cholesterol Synthes...roplet-Localized and Upregulated in Endometrial Cancer Tissues
Cholesterol is essential for both normal cell viability and cancer cell proliferation. Aberrant activity of squalene monooxygenase (SM, also known as squalene epoxidase), the rate-limiting enzyme...
Lipid Droplet Biogenesis and Functions in Health and Disease
Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances uncovering the intricacies of their...
Hypoxia Truncates and Constitutively Activates the Key Cholesterol Synthesis Enzyme Squalene Monooxygenase
Cholesterol synthesis is both energy- and oxygen-intensive, yet relatively little is known of the regulatory effects of hypoxia on pathway enzymes. We previously showed that the rate-limiting and...
Identification of Hypoxia-ALCAMhigh Macrophage- Exhausted T...Tumor Microenvironment Remodeling for Immunotherapy Resistance
Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elu...
Plumbing Mysterious RNAs in “Dark Genome” for the Conquest of Human Diseases
Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion transcribed into noncoding RNAs (ncRNAs). Among these, long nonco...
Hormonal Therapies Up-Regulate Manf and Overcome Female Susceptibility to Immune Checkpoint Inhibitor Myocarditis
Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment but are associated with myocarditis. Here, we report that tumor-bearing mice exhibited response...
Fully-Automated, CT-Only GTV Contouring for Palliative Head and Neck Radiotherapy
Planning for palliative radiotherapy is performed without the advantage of MR or PET imaging in many clinics. Here, we investigated CT-only GTV delineation for palliative treatment of head and ne...
Longitudinal Diffusion and Volumetric Kinetics of Head and ... 2a Imaging Biomarker Characterization/Pre-qualification Study
OBJECTIVES: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during ...
Automated Contouring and Planning in Radiation Therapy: What Is 'Clinically Acceptable'?
Developers and users of artificial-intelligence-based tools for automatic contouring and treatment planning in radiotherapy are expected to assess clinical acceptability of these tools. However, ...
Dose Accumulation for Mr-Guided Adaptive Radiotherapy: From...cal Considerations to State-of-the-Art Clinical Implementation
MRI-linear accelerator (MR-linac) devices have been introduced into clinical practice in recent years and have enabled MR-guided adaptive radiation therapy (MRgART). However, by accounting for an...
Bk Channel Modulation by Positively Charged Peptides and Auxiliary γ Subunits Mediated by the Ca2+-Bowl Site
The large-conductance, Ca2+-, and voltage-activated K+ (BK) channel consists of the pore-forming α (BKα) subunit and regulatory β and γ subunits. The γ1-3 subunits facilitate BK channel acti...
Mr-Linac-Guided Stereotactic Radiotherapy for Ct-Indiscernible Intravascular Renal Cell Carcinoma Tumours
Inferior vena cava tumour thrombus (IVC‐TT) is a life‐threatening complication of advanced renal cell carcinoma (RCC) occurring in 10%–25% of patients with RCC with one third of patients ha...
A Multi-institutional Comparison of Retrospective Deformabl...ion for Online Adaptive Magnetic Resonance-Guided Radiotherapy
BACKGROUND AND PURPOSE: Application of different deformable dose accumulation (DDA) solutions makes institutional comparisons after online-adaptive magnetic resonance-guided radiotherapy (OA-MRgR...
3q26.2/ MECOM Rearrangements by Pericentric Inv(3): Diagnostic Challenges and Clinicopathologic Features
MECOM rearrangement (MECOM-R) resulting from 3q26.2 aberrations is often associated with myeloid neoplasms and inferior prognosis in affected patients. Uncommonly, certain 3q26.2/MECOM-R can be s...
Vaccine Uptake and Intentions: Insights from a Texas Survey on Factors Influencing COVID-19 Vaccination Decisions
The effectiveness of COVID-19 vaccines depends on widespread vaccine uptake. Employing a telephone-administered weighted survey with 19,502 participants, we examined the determinants of COVID-19 ...
Parental Factors Associated with COVID-19 Vaccine Uptake for Children over 5 Years of Age in Texas
The COVID-19 vaccine is safe and effective for children, yet parental hesitancy towards vaccinating children against the virus persists. We conducted a telephone-administered weighted survey in T...
Blastoid B-Cell Neoplasms: Diagnostic Challenges and Solutions
Blastoid B-cell neoplasms mainly include B-lymphoblastic leukemia/lymphoma (B-ALL), blastoid mantle cell lymphoma, and high-grade B-cell lymphoma with blastoid morphologic features (blastoid HGBL...
Global Proteomic Identifies Multiple Cancer-Related Signali... Altered by a Gut Pathobiont Associated With Colorectal Cancer
In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 acceler...
Camonsertib in DNA Damage Response-Deficient Advanced Solid Tumors: Phase 1 Trial Results
Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic let...
Ataxia Telangiectasia and Rad3-Related (Atr) Inhibitor Camo...ts With Biomarker-Selected Advanced Solid Tumors (Tresr Study)
BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-ta...
Development of a Practical Nomogram for Personalized Anemia...h Ataxia Telangiectasia and Rad3-related Inhibitor Camonsertib
PURPOSE: Camonsertib is a highly selective and potent inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. Dose-dependent anemia is a class-related on-target adverse event often requ...
Reconstitution of Human Pdac Using Primary Cells Reveals Oncogenic Transcriptomic Features at Tumor Onset
Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar ce...
Fully Human Monoclonal Antibody Targeting Activated ADAM10 on Colorectal Cancer Cells
Metastasis and chemoresistance in colorectal cancer are mediated by certain poorly differentiated cancer cells, known as cancer stem cells, that are maintained by Notch downstream signaling initi...
Determinants and Mechanisms of the Low Fusogenicity and High Dependence on Endosomal Entry of Omicron Subvariants
The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit generally reduced fusogen...
Enhanced Neutralization Resistance of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2
The continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. Here, we examine the neutralization resista...
Antibody-Directed Evolution Reveals a Mechanism for Enhanced Neutralization at the HIV-1 Fusion Peptide Site
The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here...
Diverse Murine Vaccinations Reveal Distinct Antibody Classe... and Variation in Peptide Length to Improve HIV Neutralization
While neutralizing antibodies that target the HIV-1 fusion peptide have been elicited in mice by vaccination, antibodies reported thus far have been from only a single antibody class that could n...
Enhanced Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1, and CA.3.1 Variants
Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies sti...
SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies.
Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evo...
Long Trimer-Immunization Interval and Appropriate Adjuvant Reduce Immune Responses to the Soluble HIV-1-Envelope Trimer Base
Soluble 'SOSIP'-stabilized HIV-1 envelope glycoprotein (Env) trimers elicit dominant antibody responses targeting their glycan-free base regions, potentially diminishing neutralizing responses. P...
Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 BA.2.86 and FLip Variants
Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, B...
Immune Evasion and Membrane Fusion of SARS-CoV-2 XBB Subvariants EG.5.1 and XBB.2.3
Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we ...
Neutralization Escape, Infectivity, and Membrane Fusion of JN.1-Derived SARS-CoV-2 SLip, FLiRT, and KP.2 Variants
We investigate JN.1-derived subvariants SLip, FLiRT, and KP.2 for neutralization by antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pat...
Molecular Basis of Retinal Remodeling in a Zebrafish Model of Retinitis Pigmentosa
A hallmark of inherited retinal degenerative diseases such as retinitis pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degene...
Data Normalization for Addressing the Challenges in the Analysis of Single-Cell Transcriptomic Datasets
BACKGROUND: Normalization is a critical step in the analysis of single-cell RNA-sequencing (scRNA-seq) datasets. Its main goal is to make gene counts comparable within and between cells. To do so...
Global Trend in Exosome Isolation and Application: An Update Concept in Management of Diseases
Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype o...
Mincle-Gsdmd-Mediated Release of Il-1β Small Extracellular Vesicles From Hepatic Macrophages in Ethanol-Induced Liver Injury
BACKGROUND: Macrophage-inducible C-type lectin (Mincle) is expressed on hepatic macrophages and senses ethanol (EtOH)-induced danger signals released from dying hepatocytes and promotes IL-1β pr...
Macrophage-Derived Mlkl in Alcohol-Associated Liver Disease: Regulation of Phagocytosis
BACKGROUND AND AIMS: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regu...
Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease
Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD inc...
Protein-Centric Omics Analysis Reveals Circulating Compleme...d to Non-viral Liver Diseases As Potential Therapeutic Targets
BACKGROUND/AIMS: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. METHODS: We conducted Mendelian rand...
Receptor-Interacting Protein 1 and 3 Kinase Activity Are Required for High-Fat Diet Induced Liver Injury in Mice
BACKGROUND: The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical ro...
The Short- and Long-Term Readmission of Four Major Categori...ive System Cancers: Does Obesity or Metabolic Disorder Matter?
PURPOSE: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective coho...
5S rRNA Pseudogene Transcripts Are Associated With Interfer...ion and Inflammatory Responses in Alcohol-Associated Hepatitis
BACKGROUND AND AIMS: Interferon (IFN) signaling is critical to the pathogenesis of alcohol-associated hepatitis (AH), yet the mechanisms for activation of this system are elusive. We hypothesize ...
Mediators of Necroptosis: From Cell Death to Metabolic Regulation
Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized for its involvement in c...
Predictive Digital Twin for Optimizing Patient-Specific Radiotherapy Regimens Under Uncertainty in High-Grade Gliomas
We develop a methodology to create data-driven predictive digital twins for optimal risk-aware clinical decision-making. We illustrate the methodology as an enabler for an anticipatory personaliz...
An Untrained Deep Learning Method for Reconstructing Dynamic Mr Images From Accelerated Model-Based Data
PURPOSE: To implement physics-based regularization as a stopping condition in tuning an untrained deep neural network for reconstructing MR images from accelerated data. METHODS: The ConvDecode...
HicA Toxin-Based Counterselection Marker for Allelic Exchange Mutations in Fusobacterium nucleatum
The study of fusobacterial virulence factors has dramatically benefited from the creation of various genetic tools for DNA manipulation, including galK-based counterselection for in-frame deletio...
Spoken Word Recognition across Language Boundary: ERP Evidence of Prosodic Transfer Driven by Pitch
Extensive research has explored the perception of English lexical stress by Chinese EFL learners and tried to unveil the underlying mechanism of the prosodic transfer from a native tonal language...
Predicting the Spatio-Temporal Response of Recurrent Glioblastoma Treated With Rhenium-186 Labelled Nanoliposomes
Rhenium-186 (186Re) labeled nanoliposome (RNL) therapy for recurrent glioblastoma patients has shown promise to improve outcomes by locally delivering radiation to affected areas. To optimize the...
Modeling the Health Impact and Cost-Effectiveness of a Comb...Cervical Cancer Screening Program in Guangdong Province, China
Low human papillomavirus (HPV) vaccine uptake is a key barrier to cervical cancer elimination. We aimed to evaluate the health impact and cost-effectiveness of introducing different HPV vaccines ...
Language Nativeness Modulates Physiological Responses to Mo... from Event-Related Potential and Psychophysiological Measures
Morality has been an integral part of social cognition and our daily life, and different languages may exert distinct impacts on human moral judgment. However, it remains unclear how moral concep...
Development of a Xylose-Inducible Promoter and Riboswitch C...em for Manipulating Gene Expression In Fusobacterium nucleatum
Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expressi...
Beyond Valence and Arousal: The Role of Age of Acquisition in Emotion Word Recognition
Although the age of acquisition (AoA) effect has been established in numerous studies, how emotion word processing is modulated by AoA, along with affective factors, such as valence and arousal, ...
Grit and Second Language Learning Engagement: The Mediating Role of Affect Balance
The study of the relationship between key psychological attributes of learners and their engagement in second language (L2) learning helps to understand the critical personality mechanisms influe...
Use of CRISPR Interference for Efficient and Rapid Gene Inactivation in Fusobacterium nucleatum
Gene inactivation by creating in-frame deletion mutations in Fusobacterium nucleatum is time consuming, and most fusobacterial strains are genetically intractable. Addressing these problems, we i...
The Respiratory Enzyme Complex Rnf Is Vital for Metabolic Adaptation and Virulence in Fusobacterium nucleatum
The Gram-negative oral pathobiont Fusobacterium nucleatum can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. Ho...
Efficient Targeted Learning of Heterogeneous Treatment Effects for Multiple Subgroups
In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include esti...
Combined CRISPRi and Proteomics Screening Reveal a Cohesin-...Increased Expression of RUVBL1 and Prostate Cancer Progression
Genome-wide association studies along with expression quantitative trait locus (eQTL) mapping have identified hundreds of single-nucleotide polymorphisms (SNPs) and their target genes in prostate...
The Effect Direction Should Be Taken Into Account When Assessing Small-Study Effects
OBJECTIVE: Studies with statistically significant results are frequently more likely to be published than those with non-significant results. This phenomenon leads to publication bias or small-st...
Assessing the Most Vulnerable Subgroup to Type II Diabetes ...with Statin Usage: Evidence from Electronic Health Record Data
There have been increased concerns that the use of statins, one of the most commonly prescribed drugs for treating coronary artery disease, is potentially associated with the increased risk of ne...
Polygenic Risk Score Improves the Accuracy of a Clinical Risk Score for Coronary Artery Disease
BACKGROUND: The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine w...
Proteome-Wide Association Study and Functional Validation Identify Novel Protein Markers for Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomar...
Identification of Blood Protein Biomarkers Associated With ...g Genetic Prediction Models: Analysis of Over 140,000 Subjects
Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, ...
Regional Analysis to Delineate Intrasample Heterogeneity With RegionalST
MOTIVATION: Spatial transcriptomics has greatly contributed to our understanding of spatial and intra-sample heterogeneity, which could be crucial for deciphering the molecular basis of human dis...
Associations Between Genetically Predicted Plasma Protein L...imer’s Disease Risk: A Study Using Genetic Prediction Models
BACKGROUND: Specific peripheral proteins have been implicated to play an important role in the development of Alzheimer's disease (AD). However, the roles of additional novel protein biomarkers i...
Chronic Kidney Disease in Public Renal Practices in Queensland, Australia, 2011–2018
AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland. METHODS: 7,060 persons were recruited to a CK...
Microfluidic Coaxial 3D Bioprinting of Cell-Laden Microfibers and Microtubes for Salivary Gland Tissue Engineering
Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar...
Hospitalizations Among Adults With CKD in Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia
RATIONALE & OBJECTIVE: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT). STUDY DESIG...
Visuo-Frontal Interactions During Social Learning in Freely Moving Macaques
Social interactions represent a ubiquitous aspect of our everyday life that we acquire by interpreting and responding to visual cues from conspecifics1 . However, despite the general acceptance o...
GSK-J4 Inhibition of KDM6B Histone Demethylase Blocks Adhes...Lymphoma Cells to Stromal Cells by Modulating NF-κB Signaling
Multiple signaling pathways facilitate the survival and drug resistance of malignant B-cells by regulating their migration and adhesion to microenvironmental niches. NF-κB pathways are commonly ...
Radiotherapy Use and Incidence of Locoregional Recurrence i..., Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial
IMPORTANCE: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favo...
Differential Gene Expression of Fresh Tissue and Patient-De... Breast Cancer Metastasis: The Possible Role of IL-6 and MCP-1
BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Change...
Population Coding of Strategic Variables During Foraging in Freely Moving Macaques
Until now, it has been difficult to examine the neural bases of foraging in naturalistic environments because previous approaches have relied on restrained animals performing trial-based foraging...
Evaluation of Treatment Parameters for Focused-Extracorpore...steoarthritis Patients With Bone Marrow Lesions: A Pilot Study
OBJECTIVES: To evaluate the effect of different dosage parameters of focused-extracorporeal shock wave therapy on pain and physical function in knee osteoarthritis patients with bone marrow lesio...
Deep Learning-Enabled Breast Cancer Endocrine Response Determination From H&E Staining Based on ESR1 Signaling Activity
Estrogen receptor (ER) positivity by immunohistochemistry has long been a main selection criterium for breast cancer patients to be treated with endocrine therapy. However, ER positivity might no...
Genome Protection by DNA Polymerase θ
DNA polymerase θ (Pol θ) is a DNA repair enzyme widely conserved in animals and plants. Pol θ uses short DNA sequence homologies to initiate repair of double-strand breaks by theta-mediated en...
Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma
To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and...
Association Between Helicobacter pylori Infection, Mismatch Repair, HER2 and Tumor-Infiltrating Lymphocytes in Gastric Cancer
BACKGROUND: The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studie...
Cancer Biomarkers: Emerging Trends and Clinical Implications for Personalized Treatment
The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The developme...
Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma
Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identificatio...
Deep Learning-Based H-Score Quantification of Immunohistochemistry-Stained Images
Immunohistochemistry (IHC) is a well-established and commonly used staining method for clinical diagnosis and biomedical research. In most IHC images, the target protein is conjugated with a spec...
Intragenic EGFR::EGFR.E1E8 Fusion (EGFRvIII) in 4331 Solid Tumors
Epidermal growth factor receptor variant III (EGFRvIII, the deletion of exons 2–7) is a recurrent intragenic EGFR::EGFR.E1E8 fusion that occurs in high-grade gliomas. The presence of EGFRvIII i...
Perioperative Chemoimmunotherapy Induces Strong Immune Resp...Patients With Hla Class I-deficient Non-small Cell Lung Cancer
BACKGROUND: Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) ...
Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight in Localized Non-small Cell Lung Cancer
Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the ...
Machine Learning Identifies Prognostic Subtypes of the Tumor Microenvironment of NSCLC
The tumor microenvironment (TME) plays a fundamental role in tumorigenesis, tumor progression, and anti-cancer immunity potential of emerging cancer therapeutics. Understanding inter-patient TME ...
HPV-Associated Anal Cancer Knowledge, Attitudes, and Health...IV/AIDS Service Organizations in Southern United States Region
Co-infection with HIV/HPV and bio-behavioral risk factors (e.g., immunodeficiency, un-protected sex) increase likelihood for developing anal and other HPV-associated cancers among people living w...
Detection of Early Myocardial Dysfunction by Imaging Biomar... Photon Beam vs. Proton Beam Radiotherapy: A Prospective Study
1. BACKGROUND: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle...
HIV/Aids-Associated Knowledge and Attitudes Towards Treatin...e-Community-Based Dental Education Dental Students in the U.S.
This study examines HIV/AIDS-associated knowledge and attitudes towards treating disadvantaged communities among predoctoral dental students in U.S. dental schools who have not yet commenced thei...
C4b-Binding Protein Inhibits Particulate- and Crystalline-Induced NLRP3 Inflammasome Activation
Dysregulated NLRP3 inflammasome activation drives a wide variety of diseases, while endogenous inhibition of this pathway is poorly characterised. The serum protein C4b-binding protein (C4BP) is ...
A Randomized, Phase III Trial to Evaluate Rucaparib Monothe...wly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45)
PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246 ) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or B...
Quality-Adjusted Survival in Women With Gynecologic Maligna...patient Rreported Ooutcome Study of NRG Oncology’s RTOG 1203
INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiot...
Targeting the PI3K Pathway in Gynecologic Malignancies
PURPOSE OF REVIEW: This review explores the PI3K pathway aberrations common in gynecologic malignancies, the relevant therapeutic targets that have been explored to date particularly given their ...
Adjuvant Therapy in Women With Early Stage Uterine Serous Carcinoma: A Multi-institutional Study
OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterin...
Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintena...ent for Advanced Endometrial Cancer: The Phase III DUO-E Trial
PURPOSE: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. ...
#HashtagThis – Everything You Need to Know About Launchin...eports and Society of Gynecologic Oncology Education Committee
On February 6th, 2024, Gynecologic Oncology Reports and the Society of Gynecologic Oncology Education Committee co-hosted a webinar about ways to use social media for career enhancement and for d...
Plastic, It's What's for Dinner: A Preliminary Comparison of Ingested Particles in Bottlenose Dolphins and Their Prey
Microplastic ingestion was reported for common bottlenose dolphins (Tursiops truncatus) inhabiting Sarasota Bay, FL, USA, a community that also has prevalent exposure to plasticizers (i.e., phtha...
Persistent Tailoring of MSC Activation Through Genetic Priming
Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molec...
First Evidence of Microplastic Inhalation Among Free-Ranging Small Cetaceans
Plastic is a ubiquitous environmental contaminant, resulting in widespread exposure across terrestrial and marine spaces. In the environment, plastics can degrade into microparticles where exposu...
An Analysis of Suspected Microplastics in the Muscle and Ga...sure and Implications for Apex Predators and Seafood Consumers
Microplastics have been found in the gastrointestinal (GI) fluid of bottlenose dolphins (Tursiops truncatus), inhabiting Sarasota Bay, FL, suggesting exposure by ingestion, possibly via contamina...
MASH: Mediation Analysis of Survival Outcome and High-Dimensional Omics Mediators With Application to Complex Diseases
Environmental exposures such as cigarette smoking influence health outcomes through intermediate molecular phenotypes, such as the methylome, transcriptome, and metabolome. Mediation analysis is ...
Combining Mendelian Randomization and Network Deconvolution for Inference of Causal Networks With GWAS Summary Data
Mendelian randomization (MR) has been increasingly applied for causal inference with observational data by using genetic variants as instrumental variables (IVs). However, the current practice of...
Identification of Novel Susceptibility Methylation Loci for Pancreatic Cancer in a Two-Phase Epigenome-Wide Association Study
The role of DNA methylation and its interplay with gene expression in the susceptibility to pancreatic cancer (PanC) remains largely unexplored. To fill in this gap, we conducted an integrative t...
Serinc5 Restricts HIV Membrane Fusion by Altering Lipid Order and Heterogeneity in the Viral Membrane
The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but no...
Neutrophil Elastase Remodels Mammary Tumors to Facilitate Lung Metastasis
Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protea...
CD103+ cDC1 Dendritic Cell Vaccine Therapy for Osteosarcoma Lung Metastases
Background: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immu...
Fucosylation of Hla-DRB1 Regulates CD4+ T Cell-Mediated Anti-melanoma Immunity and Enhances Immunotherapy Efficacy
Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment...
Monitoring and Modulating Diet and Gut Microbes to Enhance Response and Reduce Toxicity to Cancer Treatment
The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis....
Efficacy of Immune Checkpoint Inhibitors for the Treatment ...noma in Patients With Concomitant Chronic Lymphocytic Leukemia
BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, t...
Gut OncoMicrobiome Signatures (GOMS) As Next-Generation Biomarkers for Cancer Immunotherapy
Oncogenesis is associated with intestinal dysbiosis, and stool shotgun metagenomic sequencing in individuals with this condition might constitute a non-invasive approach for the early diagnosis o...
Diverse Clonal Fates Emerge Upon Drug Treatment of Homogeneous Cancer Cells
Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells1 -7 . Molecular differences in rare individual cells in the initial popu...
From Bugs to Drugs: Bacterial 3-Iaa Enhances Efficacy of Chemotherapy in Pancreatic Cancer
Tintelnot et al. identified enrichment of indole-3-acetic acid (3-IAA), a tryptophan metabolite produced by gut microbiota, as a predictor of chemotherapy response in pancreatic adenocarcinoma. R...
Targeting Pd-L2-RGMb Overcomes Microbiome-Related Immunotherapy Resistance
The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors...
Young-onset Rectal Cancer: Unique Tumoral Microbiome and Correlation With Response to Neoadjuvant Therapy
OBJECTIVE: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correl...
TIME for Bugs: The Immune Microenvironment and Microbes in Precancer
Major advances in our understanding of the tumor immune microenvironment (TIME) in established cancer have been made, including the influence of host-intrinsic (host genomics) and -extrinsic fact...
Androgen Drives Melanoma Invasiveness and Metastatic Spread by Inducing Tumorigenic Fucosylation
Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor ...
Humoral Immunity and Antibody Responses against Diphtheria,...ccus after Immune Effector Cell Therapies: A Prospective Study
Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT...
Challenges and Opportunities in Cancer Immunotherapy: A Society for Immunotherapy of Cancer (SITC) Strategic Vision
Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct cl...
Artificial Intelligence-based Segmentation of Residual Panc...ent (ISGPP-2): International Improvement and Validation Study.
Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. Ho...
The Association between Sampling and Survival in Patients w...a Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy
Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limi...
Loss of p53 and SMAD4 Induces Adenosquamous Subtype Pancreatic Cancer in the Absence of an Oncogenic KRAS Mutation
Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). Thi...
Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series
OBJECTIVES: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcino...
Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis
BACKGROUND: The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entitie...
Tumor-Infiltrating Mast Cells Confer Resistance to Immunotherapy in Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) exhibits an immunosuppressive tumor microenvironment (TME) contributing to its therapeutic resistance. Following our previous studies, we report that mast ...
Cardiac Neural Crest and Cardiac Regeneration
Neural crest cells (NCCs) are a vertebrate-specific, multipotent stem cell population that have the ability to migrate and differentiate into various cell populations throughout the embryo during...
Fgf Signaling in Cranial Suture Development and Related Diseases
Suture mesenchymal stem cells (SMSCs) are a heterogeneous stem cell population with the ability to self-renew and differentiate into multiple cell lineages. The cranial suture provides a niche fo...
DeepMiceTL: A Deep Transfer Learning Based Prediction of Mice Cardiac Conduction Diseases Using Early Electrocardiograms
Cardiac conduction disease is a major cause of morbidity and mortality worldwide. There is considerable clinical significance and an emerging need of early detection of these diseases for prevent...
Myosin Light-Chain 4 Gene-Transfer Attenuates Atrial Fibrosis While Correcting Autophagic Flux Dysregulation
OBJECTIVES: To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy. BACKGROUND: We have previously demonstrated that the atrial-spe...
PRMT3-Mediated Arginine Methylation of IGF2BP1 Promotes Oxaliplatin Resistance in Liver Cancer
Although oxaliplatin-based chemotherapy has been effective in the treatment of hepatocellular carcinoma (HCC), primary or acquired resistance to oxaliplatin remains a major challenge in the clini...
Emerging Signaling Regulation of Sinoatrial Node Dysfunction
PURPOSE OF REVIEW: The sinoatrial node (SAN), the natural pacemaker of the heart, is responsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND...
Accelerated Somatic Mutation Calling for Whole-Genome and Whole-Exome Sequencing Data From Heterogenous Tumor Samples
Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenges were overcome by consensus mutation calling from f...
Reactivation of the G1 Enhancer Landscape Underlies Core Circuitry Addiction to SWI/SNF
Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in...
Targeting PRMT3 Impairs Methylation and Oligomerization of ...o Boost Anti-tumor Immunity by Activating cGAS/Sting Signaling
Immune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), but resistance to ICB occurs and patient responses vary. Here, we uncover protei...
The Role of Ganglioside GD2 and GD3 Synthase (ST8SIA1) in the Regulation of Immune Suppression in Breast Cancer
Gangliosides are acidic glycosphingolipids involved in cell adhesion, proliferation, and modulation of signal transduction pathways. It has been reported that tumor-shed gangliosides influence th...
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1401
Interpreting the Biological Effects of Protons as a Functio...ear Energy Transfer or Microdosimetric Lineal Energy Spectrum?
The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypot...
Dosimetric Response of Gafchromic™ EBT-XD Film to Therapeutic Protons
The EBT-XD model of Gafchromic™ films has a broader optimal dynamic dose range, up to 40 Gy, compared with its predecessor models. This characteristic has made EBT-XD films suitable for high-do...
Identification of Key Genes Associated With Cancer Stem Cel...acteristics in Wilms’ Tumor Based on Bioinformatics Analysis
BACKGROUND: Nephroblastoma, also known as Wilms' tumor (WT), remains one of the major causes of tumor-related deaths worldwide in children. Cancer stem cells (CSCs) are considered to be the main ...
Single-Incision Laparoscopic Splenectomy in Children With Massive Splenomegaly: A Prospective, Monocentric Pilot Study
BACKGROUND: Single-incision laparoscopic splenectomy (SILS) remains a challenging procedure because of the technical difficulty. In this prospective study, we aimed to evaluate the efficacy and s...
Hormone Replacement Therapy and Risk of Pancreatic Cancer i...en: Evidence From the US National Inpatient Sample 2008–2018
BACKGROUND: Pancreatic cancer is a serious, usually fatal disease and one of the most aggressive malignancies. Research into whether hormone replacement therapy (HRT) might protect against pancre...
High-Performance Cementitious Composites Containing Nanostructured Carbon Additives Made From Charred Coal Fines
Carbon-based nanomaterials, such as carbon nanoplatelets, graphene oxide, and carbon quantum dots, have many possible end-use applications due to their ability to impart unique mechanical, electr...
Selection of Surgical Modality for Massive Splenomegaly in Children
BACKGROUND: Laparoscopic splenectomy (LS), a treatment for both benign and malignant splenic diseases, can prove technically challenging in patients with massive splenomegaly. In particular, the ...
CLIC1-Mediated Autophagy Confers Resistance to DDP in Gastric Cancer
Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditio...
Prevalence of Pituitary Hormone Dysfunction Following Radiotherapy for Sinonasal and Nasopharyngeal Malignancies.
BACKGROUND: There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation. METHODS: Cross-sectional study of 50 consecu...
Automated Capture and Analysis of Circulating Tumor Cells i...nt and Young Adult Patients with Central Nervous System Tumors
Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are cha...
A Look-Up-Table Development to Facilitate CT Simulation of MR-Linac Treatment
While current MR-Linac (MRL) treatment workflows utilize a large table overlay during CT simulation to convert indexing between the two machines, we developed a look-up-table (LUT) as an alternat...
Multi-Parametric MRI for Radiotherapy Simulation
Magnetic resonance imaging (MRI) has become an important imaging modality in the field of radiotherapy (RT) in the past decade, especially with the development of various novel MRI and image-guid...
Prospective Evaluation of In Vivo and Phantom Repeatability... (MR-Linac) and MR Simulator Devices for Head and Neck Cancers
INTRODUCTION: Diffusion-weighted imaging (DWI) on MRI-linear accelerator (MR-linac) systems can potentially be used for monitoring treatment response and adaptive radiotherapy in head and neck ca...
Transcriptome-Wide Profiling of Acute Stress Induced Changes in Ribosome Occupancy Level Using External Standards
Acute cellular stress is known to induce a global reduction in mRNA translation through suppression of cap dependent translation. Selective translation in response to acute stress has been shown ...
Disease Modeling and Gene Correction of LGMDR21 iPSCs Eluci...Muscle Maintenance, Regeneration, and the Satellite Cell Niche
Autosomal recessive limb-girdle muscular dystrophy 21 (LGMDR21) is caused by pathogenic variants in protein O-glucosyltransferase 1 (POGLUT1), which is responsible for O-glucosylation of specific...
Evaluating Performance and Applications of Sample-Wise Cell Deconvolution Methods on Human Brain Transcriptomic Data
Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in ...
Induction of Long-Term Hyperexcitability by Memory-Related cAMP Signaling in Isolated Nociceptor Cell Bodies
Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hypera...
Persistent Nociceptor Hyperactivity as a Painful Evolutionary Adaptation
Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect...
Fitness Consequences of Depressive Symptoms Vary Between Ge... Evidence From a Large Cohort of Women Across the 20th Century
Depression has strong negative impacts on how individuals function, leading to the assumption that there is strong negative selection on this trait that should deplete genetic variation and decre...
Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis...nia Susceptibility Gene Network within the Mouse Dentate Gyrus
Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional s...
Neuroecological links of the exposome and One Health
This NeuroView assesses the interplay among exposome, One Health, and brain capital in health and disease. Physical and social exposomes affect brain health, and green brain skills are required f...
Emphasizing Others’ Persistence Can Promote Unwarranted Social Inferences in Children and Adults
People often hear stories about individuals who persist to overcome their constraints. While these stories can be motivating, emphasizing others’ persistence may promote unwarranted judgments a...
Cell Entry and Release of Quasi-enveloped Human Hepatitis Viruses
Infectious hepatitis type A and type E are caused by phylogenetically distinct single-stranded, positive-sense RNA viruses that were once considered to be non-enveloped. However, studies show tha...
Treatment Outcomes for Rheumatoid Arthritis-Associated Inte...e Impact of Immunosuppression on Pulmonary Function Trajectory
BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled ...
Phenotype and Fate of Liver-Resident CD8 T Cells During Acute and Chronic Hepacivirus Infection
Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like vi...
Immunological Monitoring in Hepatitis C Virus Controlled Human Infection Model
Controlled human infection model trials for hepatitis C virus represent an important opportunity to identify correlates of protective immunity against a well-characterized inoculum of hepatitis C...
Paleoamerican Exploitation of Extinct Megafauna Revealed Th... Residue and Microwear Analysis, North and South Carolina, USA
Previous immunological studies in the eastern USA have failed to establish a direct connection between Paleoamericans and extinct megafauna species. The lack of physical evidence for the presence...
Staphylococcus aureus Breast Implant Infection Isolates Display Recalcitrance to Antibiotic Pocket Irrigants
Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence of breast cancer, reconstr...
In Vitro Antibacterial, Antibiofilm Activities, and Phytoch...idonia oceanica (L.) Delile: An Endemic Mediterranean Seagrass
In the antibiotic resistance era, utilizing understudied sources for novel antimicrobials or antivirulence agents can provide new advances against antimicrobial resistant pathogens. In this study...
Defining the Roles of Pyruvate Oxidation, TCA Cycle, and Ma...phylococcus aureus Catheter-Associated Urinary Tract Infection
Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports hav...
Activation of Endogenous Retroviruses and Induction of Viral Mimicry by MEK1/2 Inhibition in Pancreatic Cancer
While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of t...
Differential Integrated Stress Response and Asparagine Prod...osis and Therapy Resistance of Pancreatic Adenocarcinoma Cells
The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer su...
Neuroaffective Reactivity Profiles Are Associated With Vulnerability to E-cigarette Use
BACKGROUND: We tested whether neuroaffective responses to motivationally salient stimuli are associated with vulnerability to cue-induced e-cigarette use in e-cigarette naïve adults who smoke da...
Towards Neuromarkers for Tailored Smoking Cessation Treatments
Vulnerability to compulsive drug use stems from dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that a) attributing high...
Impact of Psychosocial, Behavioral and Lifestyle Factors on...ty of Life in a Large Cohort of Italian Breast Cancer Patients
The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer relate...
Electrophysiological Normative Responses to Emotional, Neutral, and Cigarette-Related Images
To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotio...
Improved Data Quality and Statistical Power of Trial-Level ...lated Potentials With Bayesian Random-Shift Gaussian Processes
Studies of cognitive processes via electroencephalogram (EEG) recordings often analyze group-level event-related potentials (ERPs) averaged over multiple subjects and trials. This averaging proce...
Individual Differences in Late Positive Potential Amplitude and Theta Power Predict Cue-Induced Eating
Cue-induced reward-seeking behaviors are regulated by both the affective and cognitive control systems of the brain. This study aimed at investigating how individual differences in affective and ...
Clinical, Endoscopic, and Histopathologic Gastrointestinal Disease in an American Cohort With Behçet's Disease
INTRODUCTION: Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disea...
Designing Clinical Trials for Patients Who Are Not Average
The heterogeneity inherent in cancer means that even a successful clinical trial merely results in a therapeutic regimen that achieves, on average, a positive result only in a subset of patients....
Evaluating Clinical Outcomes in Patients Being Treated Exclusively via Telepsychiatry: Retrospective Data Analysis
BACKGROUND: Depression and anxiety are highly prevalent conditions in the United States. Despite the availability of suitable therapeutic options, limited access to high-quality psychiatrists rep...
DUSP22 Rearrangement Is Associated With a Distinctive Immun...ents With Systemic Alk-Negative Anaplastic Large Cell Lymphoma
DUSP22 rearrangement (R) has been associated with a favorable outcome in systemic ALK-negative anaplastic large cell lymphoma (ALCL). However, a recent study found that patients with DUSP22-R ALK...
Pd-L1 + Macrophages Are Associated With Favorable Features in Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a rare, aggressive subtype of non-Hodgkin lymphoma and has a complex inflammatory microenvironment. Although most patients can be cur...
Immune-Depleted Tumor Microenvironment Is Associated With Poor Outcomes and Btk Inhibitor Resistance in Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is a generally aggressive B cell non-Hodgkin lymphoma (B-NHL). Outcomes of patients have improved in the era of Bruton’s tyrosine kinase inhibitors (BTKi). However, M...
Blastoid and Pleomorphic Mantle Cell Lymphoma Demonstrate Distinct Clinicopathologic and Genetic Features
The blastoid (B) and pleomorphic (P) variants of mantle cell lymphoma (MCL) are associated with aggressive clinical behavior. In this study, we collected 102 cases of B-MCL and P-MCL from untreat...
The Swi/Snf Chromatin-Remodeling Subunit DPF2 Facilitates NRF2-Dependent Antiinflammatory and Antioxidant Gene Expression
During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury....
Impact of Cumulative Dose of Brentuximab Vedotin on Outcomes of Frontline Therapy for Advanced-Stage Hodgkin Lymphoma
In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of adv...
Accumulation of Sublethal Radiation Damage and Its Effect on Cell Survival
Objective. Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival. Approach. We devel...
Impact of Patient Demographics and Neighborhood Socioeconomic Variables on Clinical Trial Participation Patterns for NHL
Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective a...