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Recent UMass Chan Publications
Total:
30
results
Reflections on Case Management-Past, Present, and Future
No abstract
Modelling the unexpected dynamics of COVID-19 in Manaus, Brazil
In late March 2020, SARS-CoV-2 arrived in Manaus, Brazil, and rapidly developed into a large-scale epidemic that collapsed the local health system and resulted in extreme death rates. Several key studies reported that ∼76% of residents of Manaus were infected (attack rate AR≃76%) by October 2020, suggesting protective herd immunity had been reached. Despite this, an unexpected second wave of COVID...
GnRH Induces Citrullination of the Cytoskeleton in Murine Gonadotrope Cells
Peptidylarginine deiminases (PADs or PADIs) catalyze the conversion of positively charged arginine to neutral citrulline, which alters target protein structure and function. Our previous work established that gonadotropin-releasing hormone agonist (GnRHa) stimulates PAD2-catalyzed histone citrullination to epigenetically regulate gonadotropin gene expression in the gonadotrope-derived LβT2 cell li...
Sex differences in time to initiate NSAIDs or bDMARDs among patients with axial spondyloarthritis
CONCLUSION: Prescription NSAID use was more common than initiation of bDMARDs among patients newly diagnosed with axSpA. Females appeared more likely to continue NSAIDs after diagnosis, and the time to initiation of bDMARDs was longer for females than males.
DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms
The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mec...
Targeting Solute Carrier Transporters (SLCs) as a Therapeutic Target in Different Cancers
Solute carrier (SLC) transporters constitute a vast superfamily of transmembrane proteins tasked with regulating the transport of various substances such as metabolites, nutrients, ions, and drugs across cellular membranes. SLC transporters exhibit coordinated expression patterns across normal tissues, suggesting a tightly regulated regulatory network governing normal cellular functions. These tra...
Development of a Sprayable Hydrogel-Based Wound Dressing: An In Vitro Model
Hydrogel-based dressings can effectively heal wounds by providing multiple functions, such as antibacterial, anti-inflammatory, and preangiogenic bioactivities. The ability to spray the dressing is important for the rapid and effective coverage of the wound surface. In this study, we developed a sprayable hydrogel-based wound dressing using naturally derived materials: hyaluronic acid and gelatin....
Development of AAV-Mediated Gene Therapy Approaches to Treat Skeletal Diseases
Adeno-associated viral (AAV) vectors have emerged as crucial tools in advancing gene therapy for skeletal diseases, offering the potential for sustained expression with low post-infection immunogenicity and pathogenicity. Preclinical studies support both the therapeutic efficacy and safety of these vectors, illustrating the promise of AAV-mediated gene therapy. Emerging technologies and innovation...
Patient-Reported Outcomes on Subjective Nipple Sensation After Double-Incision and Periareolar Mastectomy for Chest Masculinization: Subjective Nipple Sensation After Chest Masculinization
We evaluated patient-reported outcomes to assess for patient and procedural factors associated with postchest masculinization subjective nipple sensation. Patients who underwent double-incision or periareolar mastectomies for chest masculinization by a single senior surgeon (2015-2019) were surveyed at 2 time points regarding postoperative nipple sensation and satisfaction, including patient-repor...
Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk
CONCLUSION: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate t...
Tricuspid Regurgitation: Analysis of Outcomes and Risk Assessment
No abstract
Natural history of clonal haematopoiesis seen in real-world haematology settings
Recursive partitioning of healthy consortia led to the development of the Clonal Hematopoiesis Risk Score (CHRS) for clonal haematopoiesis (CH); however, in the practical setting, most cases of CH are diagnosed after patients present with cytopenias or related symptoms. To address this real-world population, we characterize the clinical trajectories of 94 patients with CH and distinguish CH harbou...
Sex differences in response inhibition-related neural predictors of PTSD in recent trauma-exposed civilians
CONCLUSIONS: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.
The Promise and Pitfalls of 3D Vena Contracta for Mitral Regurgitation
No abstract
FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells
The effectiveness of poly (ADP-ribose) polymerase inhibitors (PARPi) in creating single-stranded DNA gaps and inducing sensitivity requires the FANCJ DNA helicase. Yet, how FANCJ relates to PARP1 inhibition or trapping, which contribute to PARPi toxicity, remains unclear. Here, we find PARPi effectiveness hinges on S-phase PARP1 activity, which is reduced in FANCJ deficient cells as G-quadruplexes...
Mitotic chromosomes are self-entangled and disentangle through a topoisomerase-II-dependent two-stage exit from mitosis
The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase chromosomes are largely free of entanglements. Here, we use Hi-C, polymer simulations, and multi-contact 3C and find that, by contrast, mitotic chromosomes are self-entangled. We explore how a mitotic self-entangled state is converted into an unentangled interp...
Correlating Age and Hematoma Volume with Extent of Midline Shift in Acute Subdural Hematoma Patients: Validation of an Artificial Intelligence Tool for Volumetric Analysis
CONCLUSION: Commercially-available, automated, AI-based tools may be used for obtaining quantitative radiographic measurement data in patients with acute subdural hematoma. Our quantitative results are consistent with the qualitative relationship previously established between age, hematoma volume, and MLS, which supports the validity of using AI-based tools for acute subdural hematoma volume esti...
Correction: Minimising the payload solvent exposed hydrophobic surface area optimises the antibody-drug conjugate properties
[This corrects the article DOI: 10.1039/D3MD00540B.].
The medicinal chemistry evolution of antibody-drug conjugates
Antibody-drug conjugates (ADCs) comprise 3 components of wildly differing sizes: antibody (150 000 Da), linker (typically
Minimising the payload solvent exposed hydrophobic surface area optimises the antibody-drug conjugate properties
Glucocorticoid receptor modulators (GRMs) are an established and successful compound class for the treatment of multiple diseases. In addition, they are an area of high interest as payloads for antibody-drug conjugate s(ADCs) in both immunology and oncology. Solving the crystal structure of compound 2, the GRM payload from ABBV-3373 and ABBV-154, in the ligand binding domain of the glucocorticoid ...
Primary Sarcoidosis of the Temporal Bone a Clinical Pathologic Correlation
CONCLUSIONS: Sarcoidosis should be added to the differential diagnosis of lytic bone lesions in the temporal bone.
Extended stop codon context predicts nonsense codon readthrough efficiency in human cells
Protein synthesis terminates when a stop codon enters the ribosome's A-site. Although termination is efficient, stop codon readthrough can occur when a near-cognate tRNA outcompetes release factors during decoding. Seeking to understand readthrough regulation we used a machine learning approach to analyze readthrough efficiency data from published HEK293T ribosome profiling experiments and compare...
Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia
Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in ...
Translation-dependent and independent mRNA decay occur through mutually exclusive pathways defined by ribosome density during T Cell activation
mRNA translation and decay are tightly interconnected processes both in the context of mRNA quality control pathways and for the degradation of functional mRNAs. Cotranslational mRNA degradation through codon usage, ribosome collisions and through the recruitment of specific proteins to ribosomes are important determinants of mRNA turnover. However, the extent to which translation-dependent (TDD) ...
YAP/TAZ-mediated regulation of laminin 332 is enabled by β4 integrin repression of ZEB1 to promote ferroptosis resistance
We are interested in the contribution of integrins and the extracellular matrix to epithelial differentiation in carcinomas. This study was motivated by our finding that the Hippo effectors YAP and TAZ can sustain the expression of laminin 332 (LM332), the predominant ECM ligand for the integrin β4, in breast carcinoma cells with epithelial differentiation. More specifically, we observed that YAP ...
An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases
Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti-tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; th...
Room for improvement in patient compliance during peripheral vascular interventions
CONCLUSION: A significant fraction of PVI cases performed under PSA result in increased radiation and contrast exposure, sedative administration and procedural time due to inadequate patient cooperation. In certain cases, conversion to general anesthesia or case abortion is required. Further research should be performed to investigate strategies to minimize such adverse patient safety events.
Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic features
Some data suggest that antipsychotics may adversely affect brain structure. We examined the relationship among olanzapine exposure, relapse, and changes in brain structure in patients with major depressive disorder with psychotic features. We analyzed data from the Study of the Pharmacotherapy of Psychotic Depression II trial (STOP-PD II), a randomized, placebo-controlled trial in patients with ps...
Exercise-induced BDNF promotes PPARδ-dependent reprogramming of lipid metabolism in skeletal muscle during exercise recovery
Post-exercise recovery is essential to resolve metabolic perturbations and promote long-term cellular remodeling in response to exercise. Here, we report that muscle-generated brain-derived neurotrophic factor (BDNF) elicits post-exercise recovery and metabolic reprogramming in skeletal muscle. BDNF increased the post-exercise expression of the gene encoding PPARδ (peroxisome proliferator-activate...
AMPK Suppression Due to Obesity Drives Oocyte mtDNA Heteroplasmy via ATF5-POLG Axis
Due to the exclusive maternal transmission, oocyte mitochondrial dysfunction reduces fertility rates, affects embryonic development, and programs offspring to metabolic diseases. However, mitochondrial DNA (mtDNA) are vulnerable to mutations during oocyte maturation, leading to mitochondrial nucleotide variations (mtSNVs) within a single oocyte, referring to mtDNA heteroplasmy. Obesity (OB) accoun...
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