UW Neurological Surgery Recent PubMed Publications

Treatment resistance remains a formidable barrier to curing lymphomas, driven in part by their ability to alter their phenotypic and molecular profiles under therapeutic pressure. A growing body of evidence suggests that a clinically minute population of drug-tolerant persister (DTP) cells, which undergo non-genetic adaptations to survive therapy, are responsible for seeding relapse. We highlight the substantial progress being made to characterize DTP populations, and postulate that they confer...

Creatine (CR) is essential for normal brain function. A lack of brain CR results in intellectual disability, epilepsy, and language delay in humans. The most common cause of CR deficiency in humans results from mutations in the CR transporter (SLC6A8). Several large deletion models of Slc6a8 have been characterized and are excellent models for global creatine loss. However, other SLC6A8 variants are reported in humans with creatine transporter deficiency (CTD), including missense mutations,...

While most meningiomas are benign and can be surgically removed, a subset behaves aggressively, recurs quickly, and can ultimately be fatal. Recent work has focused on defining this aggressive group. To better characterize this clinically distinct, high-risk group, we analyzed bulk RNA sequencing (RNA-seq) from human meningiomas using a dimension-reduced reference landscape. We identified an NF2 mutant subtype enriched for chromosome 10q loss and low PTEN expression, both of which were strongly...

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CONCLUSIONS: Together, these phenotypic findings indicate that NT5C2 is a conserved neuro-metabolic regulator, linking energy-related pathways to specific behavioral dimensions that may underlie its pleiotropic impact on psychiatric and metabolic risk.

Among the three classes of voltage-gated Ca2+ channels (CaV1, CaV2, and CaV3), CaV3 T-type channels are drug targets for disorders, including epilepsy and pain. Antagonists such as Z944 and ML218 are highly selective for CaV3 compared with the CaV1.2 L-type channel, but whether they have additional activity on other CaV1 subtypes is unknown. Here, we investigated the effects of Z944 and ML218 on the CaV1.4 channel, which regulates neurotransmitter release from retinal photoreceptors. In HEK293T...

The Glasgow Outcome Scale-Extended (GOSE) is the most frequently used outcome measure for traumatic brain injury (TBI) clinical trials. The GOSE may be administered several ways, the choice depending on the purpose of the research. For example, the GOSE can be administered to reflect functional limitations attributed to the overall injury, including extracranial injuries (GOSE-All), or to discount limitations attributed to extracranial injuries (GOSE-TBI). In this investigation, we assessed the...

Childhood adversity is associated with increased engagement in health risk behaviors (HRBs), such as substance use, violence, and risky sexual behaviors during adolescence, which contribute to leading causes of death and disability throughout the lifespan. Threat and deprivation are two dimensions of adversity that impact health and wellbeing through partially distinct developmental pathways, but no studies have examined if and how HRBs differ by adversity dimension. This pre-registered network...

CONCLUSION: The digital BSP atlas provides an explicit spatial representation of the BSP, enabling researchers to more efficiently locate, reference, and utilize postmortem samples. Implementing the BSP with modern neuroinformatics conventions provides a highly portable, quantitative reference that facilitates interdisciplinary collaboration, dynamic visualization, figure generation, protocol optimization, and integration with in-vivo neuroimaging. Ongoing extensions of this work include the...

Germline pathogenic variants that activate the Ras/mitogen-activated protein kinase (MAPK) pathway cause neurodevelopmental disorders called 'Rasopathies'. Because many affected proteins directly regulate Ras, causative mutations may alter other Ras-dependent pathways in addition to MAPK signaling. To better understand which Rasopathy sequelae result from hyperactivation of downstream MAP kinases, we engineered mice with a gain-of-function mutation in the terminal MAP kinase gene Mapk1 , which...

There is a critical need to understand pathophysiological mechanisms involved in injury from acute chlorine gas (Cl2) exposure. Limited information is available regarding time course and mechanisms of injury after acute Cl2 exposure due to lack of human clinical data and limited fidelity of pre-clinical animal models. We designed and integrated a Cl2 exposure platform to generate and deliver precise concentrations of Cl2 to a microfluidic human airway-on-a-chip microphysiological system in vitro...

CONCLUSION: onnecting the digital BSP atlas to an ecosystem of diverse neuroscience atlases provides a versatile, scalable, user-oriented, and explicit solution to characterizing and locating brain biorepository resources, optimizing their use for interdisciplinary ADRD research. Incorporating neuroinformatics conventions simplifies incorporating additional atlases and enables compatibility with freely-available tools for advanced analysis and visualization. The web-enabled interface facilitates...

CONCLUSION: Among patients with symptomatic subacute/chronic SDH, reoperation was associated with increased rates of mRS worsening and higher mRS scores at follow-up. Adjunctive Onyx MMAe resulted in lower rates of hematoma recurrence/progression and fewer unscheduled physician follow-up visits. Thus, in addition to reducing surgical reoperation rates, adjunctive MMAe led to improved clinical outcomes and reduced healthcare encounters.

CONCLUSIONS: Obesity and comorbidity profiles are associated with an inflammatory response with the potential to impact recovery; consideration of systemic health at the time of injury could improve recovery.

Patients with ischaemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. MicroRNAs (miRNAs), small non-coding RNAs involved in physiological and pathological processes, are released into circulation and remain stable. In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD....

Some patients with moderate to severe traumatic brain injury (TBI) make a full recovery, while others remain severely disabled. Accurate prognostication is important, because withdrawal of life-sustaining therapy based on perceived poor prognosis is the leading cause of death after TBI. Synchronized activity between brain regions, measurable with resting-state functional MRI (rs-fMRI), may underlie neurological recovery. However, which functional connections are critical for recovery, and...

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER-2 amplification, rendering it unresponsive to endocrine and HER2-targeted therapies. GRP78 (78 kDa glucose-regulated protein), a key endoplasmic reticulum (ER)-resident chaperone involved in protein folding and stress response, has been observed atypically localized on the cell surface of various cancer and stressed cell types, where it engages in non-canonical...

CONCLUSIONS: Isoflurane causes a failure of SERCA-dependent calcium removal by inhibition of mitochondrial production of ATP. The increase in intracellular calcium leads to early signs of cellular toxicity.

COVID-19 patients experience dynamic changes in immune and cellular function over time, similar to that in sepsis. However, there is insufficient research investigating, at the gene expression level, the mechanisms that become activated or suppressed over time as patients deteriorate or recover. This has potential prognostic and therapeutic implications. In this longitudinal study, 300 whole blood samples were analyzed from 128 adult patients throughout their COVID-19 hospitalization....

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