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Various catalytic technologies are being developed to efficiently convert lignin into renewable chemicals. However, due to its complexity, catalytic lignin depolymerization often generates a wide and complex distribution of product compounds. Gas chromatography/mass spectrometry (GC-MS) is a common analytical technique to profile the compounds that comprise lignin depolymerization products. GC-MS is applied not only to determine the product composition, but also to develop an understanding of the catalytic reaction pathways and of the relationships among catalyst structure, reaction conditions, and the resulting compounds generated. Although a very useful tool, the analysis of lignin depolymerization products with GC-MS is limited by the quality and scope of the available mass spectral libraries and the ability to correlate changes in GC-MS chromatograms to changes in lignin structure, catalyst structure, and other reaction conditions. In this study, the GC-MS data of the depolymerization products generated from organosolv hybrid poplar lignin using a copper-doped porous metal oxide catalyst and a methanol/dimethyl carbonate co-solvent was analyzed by applying a factor analysis technique, positive matrix factorization (PMF). Several different solutions for the PMF model were explored. A 13-factor solution sufficiently explains the chemical changes occurring to lignin depolymerization products as a function of lignin, reaction time, catalyst, and solvent. Overall, seven factors were found to represent aromatic compounds, while one factor was defined by aliphatic compounds.

STUDY DESIGN: Retrospective review of a multi-institutional, multisurgeon database. OBJECTIVE: Assess for associations between bone morphogenetic protein (BMP) use and rate of complications in spinal fusion. SUMMARY OF BACKGROUND DATA: BMP is commonly used in spinal surgery to augment fusion; however, there is limited evidence demonstrating its associated complications. METHODS: We performed a retrospective analysis of all fusion cases submitted by members of the Scoliosis Research Society from 2004 to 2007. We stratified on the basis of the use of BMP and evaluated for complications and associated characteristics. RESULTS: A total of 55,862 cases of spinal fusion were identified with BMP used in 21% (11,933) of the cases. Excluding anterior cervical fusions, there were no significant differences between fusions with and without BMP with regard to overall complications (8.4% vs. 8.5%; P = 0.5), wound infections (2.4% vs. 2.4%; P = 0.8), or epidural hematomas/seromas (0.2% vs. 0.2%; P = 0.3). Anterior cervical fusions with BMP were associated with more overall complications (5.8% vs. 2.4%; P < 0.001) and more wound infections (2.1% vs. 0.4%; P < 0.001) than fusions without BMP. On multivariate analysis for thoracolumbar and posterior cervical fusions, BMP use was not a significant predictor of complications (P = 0.334; odds ratio = 1.039; 95% confidence interval = 0.961-1.124; covariates were BMP use, patient age, revision vs. primary surgery). Multivariate analysis for anterior cervical spinal fusion demonstrated that BMP use remained a significant predictor of complications (P < 0.001, odds ratio = 1.6; 95% confidence interval = 1.516-1.721), after adjusting for the effects of patient age and whether the surgery was a revision procedure. CONCLUSION: BMP use with anterior cervical fusion was associated with an increased incidence of complications. Use of BMP was not associated with more complications in thoracolumbar and posterior cervical fusions. [ABSTRACT FROM AUTHOR]

Spirituality is multifaceted as it is a nonphysical meaning placed upon existence and is unique to each individual. This exclusivity makes it difficult to measure or analyze, but the need remains to discover answers to questions regarding spirituality, human life, and its factors. This exploratory, pilot study involved interviewing three older adults to address issues of individual perceptions of spirituality, integration of spirituality in daily life, and utilization of spirituality to address individual needs. Thematic results indicate spirituality is a principle-based and intrinsic factor integrated into daily life. It involves motivation and meaning as spirituality addresses personal needs by providing strength and inspiration. Finally, spirituality affects chosen occupations by providing a sense of purpose. [ABSTRACT FROM AUTHOR]

We investigated the psychological functioning of parents of children suffering from pediatric cancer using a prospective design over a five-year time period. Parents of children diagnosed with cancer participated at diagnosis (T1), six months (T2), twelve months (T3), and five years later (T4, n = 115). Repeated measures ANOVAs were calculated for the three measures of psychological distress (GHQ, SCL-90 and STAI-S) to examine changes over time and gender differences. Independent T-tests were computed to examine differences between the mean scores of the parents at T4 and the norm groups. The effects of health status and earlier levels of distress on T4 functioning were examined using ANOVA and partial correlational analysis. Results showed that levels of reported distress, psychoneurotic symptoms and state anxiety significantly decreased across time to normal levels at T4 except on the GHQ. A significantly higher percentage of parents (27%) than in the norm group (15%) showed clinically elevated scores on the GHQ. Mothers had higher scores than fathers only on state anxiety. Parents of relapsed children reported higher anxiety levels than parents of surviving and deceased children. Psychological functioning at T1 was significantly related to functioning at T4. These results support the conclusion that although parental distress decreases with time, a significant number of parents still suffer from clinical distress after five years. Parents of relapsed children are at risk for long-term psychological problems as are those with higher levels of psychosomatic complaints at diagnosis. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Gilliam Autism Rating Scale (GARS) was developed as a relatively easy, inexpensive aid in the surveillance and diagnosis of autism. This study examined the validity of the GARS when used with a sample of 119 children with strict DSM-IV diagnoses of autism, ascertained from both clinical and research settings. The GARS consistently underestimated the likelihood that autistic children in this sample would be classified as having autism. The sample mean for the Autism Quotient, a hypothesized index of the likelihood of having autism, was 90.10, significantly below the reference mean of 100. Diagnostic classification according to criteria specified by the GARS resulted in a sensitivity of only .48. Limitations of rating scales in general and of the GARS specifically are discussed. It is recommended that clinicians and researchers using or considering using the GARS for autism diagnosis or ratings of autism severity recognize the need for further research regarding its use. [ABSTRACT FROM AUTHOR]

Intracranial epidermoid cysts (ECs) are rare, benign lesions typically found in the cerebellopontine angle, suprasellar spaces, and middle cranial fossa. While these cysts are congenital, originating from ectodermal cell remnants during embryogenesis, it is not until middle age that patients present with symptoms secondary to local mass effect. Here, we present an interesting case of an EC arising from the midline anterior skull base in a 69-year-old male, presenting with symptoms ensuing from the spontaneous rupture of cyst contents into the brain parenchyma. As this is a highly unusual location and presentation for intracranial ECs, this report provides valuable information to the literature on ECs., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Leavitt et al.)

Background and Objectives: Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA)., Methods: The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed. SRS-treated AVMs with IAs were included. Patients were categorized into those treated with upfront embolization (E + SRS) vs stand-alone SRS (SRS). Primary end point was a favorable outcome (AVM obliteration + no permanent radiation-induced changes or post-SRS hemorrhage). Secondary outcomes included AVM obliteration, mortality, follow-up modified Rankin Scale, post-SRS hemorrhage, and radiation-induced changes., Results: Forty four AVM patients with associated IAs were included, of which 23 (52.3%) underwent pre-SRS embolization and 21 (47.7%) SRS only. Significant differences between the E + SRS vs SRS groups were found for AVM maximum diameter (1.5 ± 0.5 vs 1.1 ± 0.4 cm3, P = .019) and SRS treatment volume (9.3 ± 8.3 vs 4.3 ± 3.3 cm3, P = .025). A favorable outcome was achieved in 45.4% of patients in the E + SRS group and 38.1% in the SRS group (P = .625). Obliteration rates were comparable (56.5% for E + SRS vs 47.6% for SRS, P = .555), whereas a higher mortality rate was found in the SRS group (19.1% vs 0%, P = .048). After adjusting for AVM maximum diameter, SRS treatment volume, and maximum radiation dose, the likelihood of achieving favorable outcome and AVM obliteration did not differ between groups (P = .475 and P = .820, respectively)., Conclusion: The likelihood of a favorable outcome and AVM obliteration after SRS with neoadjuvant embolization in AVMs with concomitant IA seems to be comparable with stand-alone SRS, even after adjusting for AVM volume and SRS maximum dose. However, the increased mortality among the stand-alone SRS group and relatively low risk of embolization-related complications suggest that these patients may benefit from a combined treatment approach., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Federally qualified health centers (FQHC) aim to improve cancer prevention by providing screening options and efforts to prevent harmful behavior. Patient portals are increasingly being used to deliver health promotion initiatives. However, little is known about patient portal activation rates in FQHC settings and the factors associated with activation. This study examined patient portal activation among FQHC patients and assessed correlations with demographic, clinical, and health service use variables. We analyzed electronic health record data from adults >18 years old with at least one appointment. Data were accessed from the electronic health records for patients seen between 1 September 2018 and 31 August 2022 (n = 40,852 patients). We used multivariate logistic regression models to examine the correlates of having an activated EPIC-supported MyChart patient portal account. One-third of patients had an activated MyChart portal account. Overall, 35% of patients with an activated account had read at least one portal message, 69% used the portal to schedule an appointment, and 90% viewed lab results. Demographic and clinical factors associated with activation included younger age, female sex, white race, English language, being partnered, privately insured, non-smoking, and diagnosed with a chronic disease. More frequent healthcare visits were also associated with an activated account. Whether or not a patient had an email address in the EHR yielded the strongest association with patient portal activation. Overall, 39% of patients did not have an email address; only 2% of those patients had activated their accounts, compared to 54% of those with an email address. Patient portal activation rates were modest and associated with demographic, clinical, and healthcare utilization factors. Patient portal usage to manage one's healthcare needs is increasing nationally. As such, FQHC clinics should enhance efforts to improve the uptake and usage of patient portals, including educational campaigns and eliminating email requirements for portal activation, to reinforce cancer prevention efforts.

Objective: Assess the feasibility and concurrent validity of a modified Uniform Data Set version 3 (UDSv3) for remote administration for individuals with normal cognition (NC), mild cognitive impairment (MCI), and early dementia., Method: Participants (N = 93) (age: 72.8 [8.9] years; education: 15.6 [2.5] years; 72% female; 84% White) were enrolled from the Wake Forest ADRC. Portions of the UDSv3 cognitive battery, plus the Rey Auditory Verbal Learning Test, were completed by telephone or video within ~6 months of participant's in-person visit. Adaptations for phone administration (e.g., Oral Trails for Trail Making Test [TMT] and Blind Montreal Cognitive Assessment [MoCA] for MoCA) were made. Participants reported on the pleasantness, difficulty, and preference for each modality. Staff provided validity ratings for assessments. Participants' remote data were adjudicated by cognitive experts blinded to the in person-diagnosis (NC [N = 44], MCI [N = 35], Dementia [N = 11], or other [N = 3])., Results: Remote assessments were rated as pleasant as in-person assessments by 74% of participants and equally difficult by 75%. Staff validity rating (video = 92%; phone = 87.5%) was good. Concordance between remote/in-person scores was generally moderate to good (r = .3 -.8; p < .05) except for TMT-A/OTMT-A (r = .3; p > .05). Agreement between remote/in-person adjudicated cognitive status was good (k = .61-.64)., Conclusions: We found preliminary evidence that older adults, including those with cognitive impairment, can be assessed remotely using a modified UDSv3 research battery. Adjudication of cognitive status that relies on remotely collected data is comparable to classifications using in-person assessments., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Intraoperative rupture (IOR) is the most common adverse event encountered during surgical clip obliteration of ruptured intracranial aneurysms. Besides increasing surgeon experience and early proximal control, no methods exist to decrease IOR risk. Thus, our objective was to assess if partial endovascular coil embolization to protect the aneurysm before clipping decreases IOR., Methods: We conducted a retrospective analysis of patients with ruptured intracranial aneurysms that were treated with surgical clipping at two tertiary academic centers. We compared patient characteristics and outcomes of those who underwent partial endovascular coil embolization to protect the aneurysm before clipping to those who did not. The primary outcome was IOR. Secondary outcomes were inpatient mortality and discharge destination., Results: We analyzed 100 patients. Partial endovascular aneurysm protection was performed in 27 patients. Age, sex, subarachnoid hemorrhage severity, and aneurysm location were similar between the partially-embolized and non-embolized groups. The median size of the partially-embolized aneurysms was larger (7.0 mm [interquartile range 5.95-8.7] vs. 4.6 mm [3.3-6.0]; P < 0.001). During surgical clipping, IOR occurred less frequently in the partially-embolized aneurysms than non-embolized aneurysms (2/27, 7.4%, vs. 30/73, 41%; P = 0.001). Inpatient mortality was 14.8% (4/27) in patients with partially-embolized aneurysms and 28.8% (21/73) in patients without embolization (P = 0.20). Discharge to home or inpatient rehabilitation was 74.0% in patients with partially-embolized aneurysms and 56.2% in patients without embolization (P = 0.11). A complication from partial embolization occurred in 2/27 (7.4%) patients., Conclusions: Preoperative partial endovascular coil embolization of ruptured aneurysms is associated with a reduced frequency of IOR during definitive treatment with surgical clip obliteration. These results and the impact of preoperative partial endovascular coil embolization on functional outcomes should be confirmed with a randomized trial., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: A growing body of literature examines the utility of emotion-focused parenting programs, as behaviorally based programs currently dominate the parenting literature. Few of those studies examine differences in how Black parents may benefit. This mixed-methods pilot study examined preliminary fidelity, efficacy, and acceptability of Tuning in to Kids (TIK), an emotion-focused parenting program targeting parenting practices and children's emotion regulation through a strengths-based approach., Methods: Pre, post, and one-month follow-up measurements were collected from 21 parents in the United States who were randomly assigned to a treatment (i.e., TIK) or waitlist control group. They were assessed across several self-report parent measures (parental emotion regulation, emotion socialization parenting practices and beliefs) and parent-report of children's social-emotional competence. Parents in the TIK group completed interviews to further understand their experience participating in the intervention., Results: Descriptive analyses showed general improvements and positive change in parenting practices, beliefs, parental emotion regulation, and children's self-regulation. Large effect sizes indicate reductions of parents emotion dismissing and distressed reactions to children's negative emotions. TIK was overall rated as a highly acceptable intervention. Parent interviews offer essential information to provide context to Black parents' experiences utilizing TIK as well as themes related to challenges in raising Black children with self-regulation difficulties., Conclusions: Overall, these preliminary mixed-methods outcomes suggest that TIK is a promising parenting program to improve Black parents' emotion regulation, emotion coaching beliefs and positive parenting practices. Further research is needed to investigate the effectiveness of TIK and other emotion-focused parenting programs with Black parents and assess the necessity of future cultural adaptations.

Glioblastoma (GBM) is a highly invasive, aggressive brain cancer that carries a median survival of 15 months and is resistant to standard therapeutics. Recent studies have demonstrated that intratumoral heterogeneity plays a critical role in promoting resistance by mediating tumor adaptation through microenvironmental cues. GBM can be separated into two distinct regions-a core and a rim, which are thought to drive specific aspects of tumor evolution. These differences in tumor progression are regulated by the diverse biomolecular and biophysical signals in these regions, but the acellular biophysical characteristics remain poorly described. This study investigates the mechanical and ultrastructural characteristics of the tumor extracellular matrix (ECM) in patient-matched GBM core and rim tissues. Seven patient-matched tumor core and rim samples and one non-neoplastic control were analyzed using atomic force microscopy, scanning electron microscopy, and immunofluorescence imaging to quantify mechanical, ultrastructural, and ECM composition changes. The results reveal significant differences in biophysical parameters between GBM core, rim, and non-neoplastic tissues. The GBM core is stiffer, denser, and is rich in ECM proteins hyaluronic acid and tenascin-C when compared to tumor rim and non-neoplastic tissues. These alterations are intimately related and have prognostic effect with stiff, dense tissue correlating with longer progression-free survival. These findings reveal new insights into the spatial heterogeneity of biophysical parameters in the GBM tumor microenvironment and identify a set of characteristics that may correlate with patient prognosis. In the long term, these characteristics may aid in the development of strategies to combat therapeutic resistance., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Digital pathology (the technology whereby glass histology slides are scanned at high resolution, digitised, stored and shared with pathologists, who can view them using microscopy software on a screen) is transforming the delivery of clinical diagnostic pathology services around the world. In addition to adding value to clinical histopathology practice, digital histology slides provide a versatile medium to achieve the educational needs of a variety of learners including undergraduate students, postgraduate doctors in training and those pursuing continuing professional development portfolios. In this guide, we will review the principal use cases for digital slides in training and education and I will share tips for successful use of digital pathology to support a range of learners based on experience gathered at Leeds Teaching Hospitals National Health Service Trust and the National Pathology Imaging Co-Operative during the last 5 years of digital slide usage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Glioblastoma (GBM) tumors are rich in tumor-associated microglia/macrophages. Changes associated with treatment in this specific cell population are poorly understood. Therefore, we studied changes in gene expression of tumor-associated microglia/macrophages (Iba1+) cells in de novo versus recurrent GBMs., Methods: NanoString GeoMx ® Digital Spatial Transcriptomic Profiling of microglia/macrophages (Iba1+) and glial cells (Gfap+) cells identified on tumor sections was performed on paired de novo and recurrent samples obtained from three IDH-wildtype GBM patients. The impact of differentially expressed genes on patient survival was evaluated using publicly available data., Results: Unsupervised analyses of the NanoString GeoMx ® Digital Spatial Profiling data revealed clustering based on the transcriptomic data from Iba1+ and Gfap+ cells. As expected, conventional differential gene expression and enrichment analyses revealed upregulation of immune-function-related genes in Iba1+ cells compared to Gfap+ cells. A focused differential gene expression analysis revealed upregulation of phagocytosis and fatty acid/lipid metabolism genes in Iba1+ cells in recurrent GBM samples compared to de novo GBM samples. Importantly, of these genes, the lipid metabolism gene PLD3 consistently correlated with survival in multiple different publicly available datasets., Conclusion: Tumor-associated microglia/macrophages in recurrent GBM overexpress genes involved in fatty acid/lipid metabolism. Further investigation is needed to fully delineate the role of PLD phospholipases in GBM progression.

The Alaskan Layered Pollution And Chemical Analysis (ALPACA) field experiment was a collaborative study designed to improve understanding of pollution sources and chemical processes during winter (cold climate and low-photochemical activity), to investigate indoor pollution, and to study dispersion of pollution as affected by frequent temperature inversions. A number of the research goals were motivated by questions raised by residents of Fairbanks, Alaska, where the study was held. This paper describes the measurement strategies and the conditions encountered during the January and February 2022 field experiment, and reports early examples of how the measurements addressed research goals, particularly those of interest to the residents. Outdoor air measurements showed high concentrations of particulate matter and pollutant gases including volatile organic carbon species. During pollution events, low winds and extremely stable atmospheric conditions trapped pollution below 73 m, an extremely shallow vertical scale. Tethered-balloon-based measurements intercepted plumes aloft, which were associated with power plant point sources through transport modeling. Because cold climate residents spend much of their time indoors, the study included an indoor air quality component, where measurements were made inside and outside a house to study infiltration and indoor sources. In the absence of indoor activities such as cooking and/or heating with a pellet stove, indoor particulate matter concentrations were lower than outdoors; however, cooking and pellet stove burns often caused higher indoor particulate matter concentrations than outdoors. The mass-normalized particulate matter oxidative potential, a health-relevant property measured here by the reactivity with dithiothreiol, of indoor particles varied by source, with cooking particles having less oxidative potential per mass than pellet stove particles., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans., Methods: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER., Results: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing., Discussion: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: The preclinical Alzheimer's cognitive composite (PACC) was developed for in-person administration to capture subtle cognitive decline. At the outset of the COVID-19 pandemic, cognitive testing was increasingly performed remotely by telephone or video administration. It is desirable to have a harmonized composite measurement derived from both in-person and remote assessments for identifying cognitive changes and to examine its relationship with common neuroimaging biomarkers., Objective: We defined a telehealth compatible PACC (tPACC) and examined its relationship with neuroimaging biomarkers related to neurodegeneration, brain function and perfusion, white matter integrity, and amyloid-β., Methods: We examined 648 participants' neuroimaging and in-person and remote cognitive testing data from the Wake Forest Alzheimer's Disease Research Center's Clinical Core cohort (observational study) to calculate a modified PACC (PACC5-RAVLT) score and tPACC scores (in-person and remote). We performed Spearman/intraclass correlation coefficient (ICC) analyses for reliability of tPACC scores and linear regression models to evaluate associations between tPACC and neuroimaging. Bland-Altman plots for agreement were constructed across cognitively normal and impaired (mild cognitive impairment and dementia) participants., Results: There was a significant positive relationship between tPACCin - person and PACC5-RAVLT (Overall group: r2 = 0.94, N = 648), and tPACCin - person and tPACCremote (validation subgroup: ICC = 0.82, n = 53). Overall, tPACC showed significant associations with brain thickness/volume, gray matter perfusion, white matter free water, and amyloid-β deposition., Conclusions: There is a good agreement between tPACCand PACC5-RAVLTfor cognitively normal and impaired individuals. The tPACC is associated with common neuroimaging markers of Alzheimer's disease.

Introduction: We assessed the effects of multivitamin-mineral and cocoa extract supplementation on incident mild cognitive impairment (MCI) and all-cause probable dementia., Methods: COSMOS-Mind (N = 2262), a 2 × 2 factorial, randomized-controlled clinical trial administered a telephone-based cognitive battery at baseline and annually for 3 years. Incidence rates of MCI, and separately dementia, were compared among treatment arms with proportional hazards regression., Results: Over 3 years, 110 incident MCI and 14 incident dementia cases were adjudicated. Incidence rates did not vary by assignment to multivitamin-mineral or cocoa extract (all p's ≥ 0.05); however, statistical power was low. When participants assigned to multivitamin-mineral versus placebo converted to MCI, their scores for global cognition (p = 0.03) and executive function (p < 0.001) were higher and had declined less relative to the previous year (p = 0.03 for global cognition; p = 0.004 for executive function)., Discussion: Multivitamin-mineral therapy may provide cognitive resilience, countering conversion to MCI, but not significantly reduce its incidence over 3 years., Highlights: Multivitamin-mineral supplementation did not reduce risks for cognitive impairment. Cocoa extract supplementation did not reduce risks for cognitive impairment. Multivitamin-mineral supplementation slowed cognitive declines for incident mild cognitive impairment., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Glioblastoma (GBM), the most common human brain tumor, has been notoriously resistant to treatment. As a result, the dismal overall survival of GBM patients has not changed over the past three decades. GBM has been stubbornly resistant to checkpoint inhibitor immunotherapies, which have been remarkably effective in the treatment of other tumors. It is clear that GBM resistance to therapy is multifactorial. Although therapeutic transport into brain tumors is inhibited by the blood brain barrier, there is evolving evidence that overcoming this barrier is not the predominant factor. GBMs generally have a low mutation burden, exist in an immunosuppressed environment and they are inherently resistant to immune stimulation, all of which contribute to treatment resistance. In this review, we evaluate the contribution of multi-omic approaches (genomic and metabolomic) along with analyzing immune cell populations and tumor biophysical characteristics to better understand and overcome GBM multifactorial resistance to treatment., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)