Recent UMass Chan Publications

The AMBASSADOR trial revealed improvement in disease-free survival with adjuvant pembrolizumab in patients with high-risk muscle-invasive urothelial carcinoma compared to observation.¹ In this Viewpoint, we discuss the clinical implications of these findings in the context of prior data from the CheckMate-274 and the recently published NIAGARA trial, envisioning the path forward for perioperative ...

CONCLUSIONS: Nonveteran postmenopausal women exhibit more complex pathways between SES and major CVD events than their veteran counterparts, informing the design, conduct, and evaluation of preventive strategies targeting CVD by veteran status.

eCD4-Ig is an entry inhibitor of the human immunodeficiency virus (HIV) that mimics the engagement of both CD4 and CCR5 with the HIV Envelope (Env) protein, a property which imbues it with remarkable potency and breadth. However, env is exceptionally genetically malleable and can evolve to escape a wide variety of entry inhibitors. Here we document the evolution of partial eCD4-Ig resistance in si...

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targ...

Patients receiving palliative care experience stigma associated with their illness, personal identity, and healthcare utilization. These stigmas can occur at any stage of the disease process. Varying stigmas combine to cause palliative care patients to feel misunderstood, contribute to treatment barriers, and further negative stereotypes held by clinicians. Stigma surrounding palliative care patie...

CONCLUSIONS: A customized, EHR based dynamic CDST can be highly accurate. Integrating a comprehensive dynamic CDST into existing workflows could improve attention and actions related to routine ICU quality metrics.

Cilia and flagella play a crucial role in the development and function of eukaryotes. The activity of thousands of dyneins is precisely regulated to generate flagellar motility. The complex proteome (600+ proteins) and architecture of the structural core of flagella, the axoneme, have made it challenging to dissect the functions of the different complexes, like the regulatory machinery. Previous r...

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Resting-state functional MRI (rs-fMRI), a promising method for interrogating different brain functional networks from a single MRI acquisition, is increasingly utilized in clinical presurgical and other pretherapeutic brain mapping. However, challenges in standardization of acquisition, preprocessing, and analysis methods across centers, and variability in results interpretation, complicate its cl...

To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in the field. While highlighting some common features of aging, the survey exposed broad disagreement on the foundational issues. What is aging? What causes it? When does it begin? What constitutes rejuvenation? Not only was there no consensus on these and other core questions, but no...

Breast cancer is the second leading cause of cancer deaths among women. Multiple microRNAs (miRNAs) have been reported to be associated with breast cancer progression or metastasis. The purpose of the current study was to identify plasma extracellular miRNAs associated with incident breast cancer. Levels of 166 plasma miRNA were measured using qRT-PCR in 2140 Framingham Heart Study female particip...

BACKGROUND: A wide variety of tumors can affect the nail unit, with some commonly mistaken as inflammatory or infectious diseases. Obtaining an optimal sample for histopathologic evaluation requires understanding of nail unit anatomy as well as the histopathology of the suspected nail tumor.

BACKGROUND: Nail avulsion is a procedure with numerous nuanced iterations and uses within the management of nail diseases, that when performed with intention and skill can imbue the clinician with the ability to manage myriad nail conditions.

Bone homeostasis within the skeletal system is predominantly maintained by bone formation and resorption. Where formation of new bone involves maturation of stromal cells to mineral and matrix secreting mature osteoblasts, which requires cellular energy or adenosine triphosphate (ATP). Alterations in systemic metabolism can influence osteoblast functioning. In line with this, type 2 diabetes melli...

Cerebral autoregulation (CA) is the mechanism that maintains stable cerebral blood flow (CBF) despite fluctuations in systemic blood pressure, crucial for brain homeostasis. Recent evidence highlights distinct regional variations in CA between the anterior (carotid) and posterior (vertebrobasilar) circulations. Non-invasive neuromonitoring techniques, such as transcranial Doppler, transfer functio...

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Gastrointestinal nematodes (GINs) are among the most common parasites of humans, livestock, and companion animals. GIN parasites infect 1-2 billion people worldwide, significantly impacting hundreds of millions of children, pregnant women, and adult workers, thereby perpetuating poverty. Two benzimidazoles with suboptimal efficacy are currently used to treat GINs in humans as part of mass drug adm...

CONCLUSION: The 10 domains identified through this exercise informed the proposed core domain set of GC effects to be considered for use in future clinical trials involving GCs. This core domain set was endorsed at the OMERACT 2020 virtual workshop.

BACKGROUND: The capacity to anticipate future health issues is important for both policy makers and practitioners in the USA, as such insights can facilitate effective planning, investment, and implementation strategies. Forecasting trends in disease and injury burden is not only crucial for policy makers but also garners substantial interest from the general populace and leads to a better-informe...

Though it has no catalytic activity toward GM2 ganglioside, the GM2 activator protein (GM2A) is essential for ganglioside hydrolysis by facilitating the action of lysosomal ß-N-acetylhexosaminidase. GM2A deficiency results in death in early childhood due to rapid central nervous system deterioration similar to the related GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease. This manuscript ...

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post trans...

CONCLUSIONS: Recruiting via social media platforms, especially Reddit, enhanced participant diversity and intervention accessibility. Researchers should identify recruitment methods that promote inclusivity while preserving safety and research integrity.

Amyloid-proteinopathy is observed in type 2 diabetes, where Islet amyloid polypeptide is secreted atypically and impedes cellular homeostasis. The thiazolidinediones family is reported to influence amyloid-beta aggregations. However, research on drug-based stimulation of insulin signaling to alleviate Islet amyloid aggregations is lacking. To understand the impact of pioglitazone on islet amyloid ...

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.