Publications by authors named "Gustav Cederquist"

The contemporary landscape of systemic therapy options for hematologic malignancies involving the central nervous system (CNS-HM) is rapidly evolving; a key question is how radiotherapy (RT) can be optimally integrated to improve patient outcomes. Historically, use of RT to treat CNS-HM was defined by broad fields and high doses. While effective, this approach raised concerns of potential neurotoxicity which significantly decreased RT utilization.

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Purpose: In primary central nervous system lymphoma (PCNSL), the extent to which post-methotrexate consolidation contributes to neurotoxicity is unclear. Concerns for neurotoxicity from standard dose whole-brain radiation therapy (WBRT) have led to declining use. Cerebral atrophy is an established surrogate for neurotoxicity; however, the relative extent to which modern consolidation (ie, reduced-dose [RD-]WBRT ≤24 Gy, autologous hematopoietic cell transplant) contributes to cerebral atrophy is unclear.

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Despite the litany of pathogenic variants linked to neurodevelopmental disorders (NDD) including autism (ASD) and intellectual disability , our understanding of the underlying mechanisms caused by risk genes remain unclear. Here, we leveraged a human pluripotent stem cell model to uncover the neurodevelopmental consequences of mutations in , a newly implicated risk gene . ZMYND11, known for its tumor suppressor function, encodes a histone-reader that recognizes sites of transcriptional elongation and acts as a co-repressor .

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Article Synopsis
  • The study examines consolidation treatment options for patients with primary central nervous system lymphoma (PCNSL) after initial chemoimmunotherapy, focusing on whole-brain radiotherapy (WBRT), nonmyeloablative chemotherapy (NMC), and autologous hematopoietic cell transplantation (AHCT).
  • Data collected from 1983 to 2020 shows a decline in WBRT usage and an increase in AHCT and NMC, with notable differences in treatment approaches based on age and response to induction therapy.
  • Overall survival (OS) and progression-free survival (PFS) results did not reveal significant differences among the consolidation strategies, indicating that while NMC is becoming more popular, reduced-dose WBRT may still be
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Article Synopsis
  • The study examines relapse patterns and outcomes in primary CNS lymphoma (PCNSL) over several decades, focusing on factors affecting relapse in a large group of patients.
  • It analyzed patient responses to treatment from 1983 to 2020, categorizing relapses based on initial responses and the location of the relapse.
  • Findings show that deep structure involvement is linked to higher risk of local relapse, with a significant difference in relapse patterns between refractory patients and those who initially responded well to treatment.
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Chimeric antigen receptor (CAR) T-cell therapy (CART) for central nervous system lymphoma (CNSL) is a promising strategy, yet responses are frequently not durable. Bridging radiotherapy (BRT) is used for extracranial lymphoma in which it can improve CART outcomes through cytoreduction of high-risk lesions. We hypothesized that BRT would achieve similar, significant cytoreduction before CART for CNSL (CNS-BRT).

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The biological function and disease association of human endogenous retroviruses (HERVs) are largely elusive. HERV-K(HML-2) has been associated with neurotoxicity, but there is no clear understanding of its role or mechanistic basis. We addressed the physiological functions of HERV-K(HML-2) in neuronal differentiation using CRISPR engineering to activate or repress its expression levels in a human-pluripotent-stem-cell-based system.

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Autism is a clinically heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restricted interests, and repetitive behaviors. Despite significant advances in the genetics of autism, understanding how genetic changes perturb brain development and affect clinical symptoms remains elusive. Here, we present a multiplex human pluripotent stem cell (hPSC) platform, in which 30 isogenic disease lines are pooled in a single dish and differentiated into prefrontal cortex (PFC) lineages to efficiently test early-developmental hypotheses of autism.

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Human brain organoids generated with current technologies recapitulate histological features of the human brain, but they lack a reproducible topographic organization. During development, spatial topography is determined by gradients of signaling molecules released from discrete signaling centers. We hypothesized that introduction of a signaling center into forebrain organoids would specify the positional identity of neural tissue in a distance-dependent manner.

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Background: Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs.

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Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs.

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OBJECTIVE The authors of this study aimed to identify the incidence of and risk factors for preoperative deep venous thrombosis (DVT) in patients undergoing surgical treatment for spinal metastases. METHODS Univariate analysis of patient age, sex, ethnicity, laboratory values, comorbidities, preoperative ambulatory status, histopathological classification, spinal level, and surgical details was performed. Factors significantly associated with DVT univariately were entered into a multivariate logistic regression model.

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Background: Spine and nonspine skeletal metastases occur in more than 80% of patients with prostate cancer.

Objective: To examine the characteristics of the patient population undergoing surgery for the treatment of prostate cancer metastatic to the spine.

Methods: A retrospective chart review was performed on all patients treated at our institution from June 1993 to August 2014 for surgical management of metastatic spine disease from prostate cancer.

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Background: Survival duration and prognostic factors in adult high-grade glioma have been comprehensively analyzed, but less is known about factors contributing to overall survival (OS) and progression-free survival (PFS) in pediatric patients.

Objective: To identify these factors in the pediatric population.

Methods: We retrospectively reviewed institutional databases evaluating all patients ≤21 years with high-grade glioma treated between 1988 and 2010.

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The mammalian neocortex is parcellated into anatomically and functionally distinct areas. The establishment of area-specific neuronal diversity and circuit connectivity enables distinct neocortical regions to control diverse and specialized functional outputs, yet underlying molecular controls remain largely unknown. Here, we identify a central role for the transcriptional regulator Lim-only 4 (Lmo4) in establishing the diversity of neuronal subtypes within rostral mouse motor cortex, where projection neurons have particularly diverse and multi-projection connectivity compared with caudal motor cortex.

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Microtubules are essential components of axon guidance machinery. Among β-tubulin mutations, only those in TUBB3 have been shown to cause primary errors in axon guidance. All identified mutations in TUBB2B result in polymicrogyria, but it remains unclear whether TUBB2B mutations can cause axon dysinnervation as a primary phenotype.

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A spectrum of neurological disorders characterized by abnormal neuronal migration, differentiation, and axon guidance and maintenance have recently been attributed to missense and splice-site mutations in the genes that encode α-tubulin and β-tubulin isotypes TUBA1A, TUBA8, TUBB2B, and TUBB3, all of which putatively coassemble into neuronal microtubules. The resulting nervous system malformations can include different types of cortical malformations, defects in commissural fiber tracts, and degeneration of motor and sensory axons. Many clinical phenotypes and brain malformations are shared among the various mutations regardless of structural location and/or isotype, while others segregate with distinct amino acids or functional domains within tubulin.

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Molecular controls over the development of the exceptional neuronal subtype diversity of the cerebral cortex are now beginning to be identified. The initial subtype fate decision early in the life of a neuron, and the malleability of this fate when the balance of key postmitotic signals is modified, reveals not only that a neuron is deterministically set on a general developmental path at its birth, but also that this program must be precisely executed during postmitotic differentiation. Here, we show that callosal projection neurons (CPN) and subcerebral projection neurons (subcerebral PN) in layer V of the neocortex share aspects of molecular identity after their birth that are progressively resolved during differentiation.

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