Recent UMass Chan Publications

A 47-year-old woman presents to our clinic with a chief complaint of rhinorrhea; she had chronic hypertension managed with four antihypertensive drugs, including an ACE inhibitor. While dry cough is a well-known side effect associated with ACE inhibitors, this case highlights a common chief complaint yet less recognized side effect of ACE inhibitors and further emphasizes the idea that overall, an...

The tobacco epidemic has claimed countless lives, caused significant morbidity, and cost billions of dollars in direct costs and lost productivity. Despite its acute vascular effects, nicotine alone has not been definitively linked to cardiovascular events. Rather, additives found in cigarettes and other tobacco products likely play a bigger role in tobacco's link to cardiovascular events. The eme...

GCN2 is a conserved receptor kinase activating the integrated stress response (ISR) in eukaryotic cells. The ISR kinases detect accumulation of stress molecules and reprogram translation from basal tasks to preferred production of cytoprotective proteins. GCN2 stands out evolutionarily among all protein kinases due to the presence of a histidyl-tRNA synthetase-like (HRSL) domain, which arises only...

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CONCLUSIONS: In this pre-COVID study of U.S. rural PWUD, those who reported opioid use alone had a lower prevalence of reported HCV testing. Those diagnosed with HCV and reported both opioid and stimulant use were less likely to report ever taking anti-HCV medication.

CONCLUSIONS: EVT showed high procedural success but did not significantly improve functional outcomes or mortality compared with BMT in patients with ACAo. Further randomized trials are needed to clarify EVT's role in ACAo.

Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 in autoinhibited states, which reveal dynamic interactions at the auto...

Human cytomegalovirus (HCMV) is a β-herpesvirus that contributes to the disease burden of immunocompromised and immunomodulated individuals, including transplant recipients and newborns. The FDA-approved HCMV drugs can exhibit drug resistance and severe side effects including bone marrow toxicity, gastrointestinal disruption, and nephrotoxicity. In a previous study, we identified the N-arylpyrimid...

This position statement explores the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.e., phosphatidylethanol), use of ...

CONCLUSIONS: A multimodal intervention combining preventative care, symptom and biometric monitoring, and home treatment was feasible in adults living with COPD. Participants demonstrated high protocol fidelity and engagement and reported improved quality of life.

CONCLUSION: Our findings suggest that the neurocircuitry underlying the response to social threat cues are facilitated through broader pathways that involve the posterior hub of the default mode network.

Astrocyte secreted signals substantially affect disease pathology in neurodegenerative diseases. It remains little understood about how proinflammatory cytokines, such as interleukin-1α/tumor necrosis factor-α/C1q (ITC), often elevated in neurodegenerative diseases, alter astrocyte-secreted signals and their effects in disease pathogenesis. By selectively isolating astrocyte exosomes (A-Exo.) and ...

CONCLUSIONS: In this older adult cohort undergoing mHealth-CR, we found three main engagement groups with declining engagement over time in two of the three groups. These patterns can inform future mHealth-CR interventions.

While breast cancer screening reduces mortality, disparities in access continue to limit equitable care. Medically underserved groups-including American Indian or Alaska Native, Black, Hispanic, disabled, and LGBTQ+ individuals-face significant barriers in accessing screening mammography services. This AJR Expert Panel Narrative Review leverages the National Institute on Minority Health and Health...

CONCLUSION: Lung cancer screening rates have increased; however, it remains low. Adults with COPD and ACO are more likely to undergo lung cancer screening.

CONCLUSION: Patient portal use in otolaryngology has markedly increased over the last 3 years, but utilization varies across demographic groups. This provides an opportunity to improve patient portal content and outreach, and ultimately make portals more accessible to diverse patient populations.

Infection by retroviruses and the mobilization of transposable elements cause DNA damage that can be catastrophic for a cell. If the cell survives, the mutations generated by retrotransposition may confer a selective advantage, although, more commonly, the effect of new integrants is neutral or detrimental. If retrotransposition occurs in gametes or in the early embryo, it introduces genetic modif...

Atherosclerosis (AS) is a chronic inflammatory condition of the arteries, characterized by plaque formation that can restrict blood flow and lead to potentially fatal cardiovascular events. Given that AS is responsible for a quarter of global deaths, this study aimed to develop a systematic bioinformatics approach to identify biomarkers and regulatory targets involved in plaque development, with t...

8-oxoguanine DNA glycosylase-1 (OGG1) is a DNA glycosylase mediating the first step in base excision repair which removes 7,8-dihydro-8-oxoguanine (8-oxoG) and repairs oxidized nuclear and mitochondrial DNA. Previous studies showed that OGG1 deficiency results in an increased susceptibility to high-fat diet (HFD)-induced obesity and metabolic dysfunction in mice, suggesting a crucial role of OGG1 ...

Older adults with lung cancer experience inferior clinical outcomes compared to their younger counterparts. This review provides the scaffolding to address these disparities by delineating (1) the distinct and varied care needs of older adults with lung malignancies, (2) evidence-based measures for identifying subgroups within this population meriting tailored approaches to care, (3) age-specific ...

Gene expression is controlled by dynamic localization of thousands of regulatory proteins to precise genomic regions. Understanding this cell type-specific process has been a longstanding goal yet remains challenging because DNA-protein mapping methods generally study one protein at a time. Here, to address this, we developed chromatin immunoprecipitation done in parallel (ChIP-DIP) to generate ge...

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Significant aggregation challenges were encountered during the manufacturing processing of an immunocytokine diabody fusion protein. To mitigate this issue and reduce aggregates in the purification process, a variety of depth filters were evaluated for harvest clarification and post-Protein A intermediate filtration. Emphaze™ AEX Hybrid Purifier, a fully synthetic quaternary amine functionalized a...

Huntington's disease (HD) arises from a CAG expansion in the huntingtin (HTT) gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant HTT mRNA (mHTT) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in HTT's CAG repeat - whereby it lengthe...

We review and salute the third edition of E.B. Wilson's "The Cell in Development and Heredity" published a century ago, noting its unique features and placing them in context. Brief commentaries from colleagues convey how they have encountered and have been influenced by The Cell. Although soon to be 100 years old, Wilson's 1925 edition is a hallmark of our profession, reminding us of a time when ...

Multiple sclerosis (MS) is initially characterized by myelin and axonal damage in central nervous system white matter lesions, but their causal role in synapse loss remains undefined. Gray matter atrophy is also present early in MS, making it unclear if synaptic alterations are driven by white matter demyelinating lesions or primary gray matter damage. Furthermore, whether axonal pathology occurs ...

A new and highly efficient ring-closing metathesis-based strategy was developed for the synthesis of the cyclic urea 1,3-diazepinone, presenting significant improvement upon previous methods. Using a direct glycosylation approach, analogues of the potent cytidine deaminase (CDA) inhibitor diazepinone riboside were then synthesized including 2'-deoxyribo-, 2'-deoxy-2'-fluoroarabino-, and 2'-deoxy-2...

Solute carrier proteins (SLCs) are pivotal for maintaining cellular homeostasis by transporting small molecules across cellular membranes. Recent discoveries have uncovered their involvement in modulating innate immunity, particularly within the cytosol. We review emerging evidence that links SLC transporters to cytosolic innate immune recognition and highlight their role in regulating inflammatio...

Long-read sequencing (LRS) technologies have the potential to revolutionize scientific discoveries in RNA biology through the comprehensive identification and quantification of full-length mRNA isoforms. Despite great promise, challenges remain in the widespread implementation of LRS technologies for RNA-based applications, including concerns about low coverage, high sequencing error, and robust c...

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