Identification of Hypoxia Prognostic Signature in Glioblastoma Multiforme Based on Bulk and Single-Cell RNA-Seq.

Glioblastoma (GBM) represents a profoundly aggressive and heterogeneous brain neoplasm linked to a bleak prognosis. Hypoxia, a common feature in GBM, has been linked to tumor progression and therapy resistance. In this study, we aimed to identify hypoxia-related differentially expressed genes (DEGs) and construct a prognostic signature for GBM patients using multi-omics analysis. Patient cohorts were collected from publicly available databases, including the Gene Expression Omnibus (GEO), the Chinese Glioma Genome Atlas (CGGA), and The Cancer Genome Atlas-Glioblastoma Multiforme (TCGA-GBM), to facilitate a comprehensive analysis. Hypoxia-related genes (HRGs) were obtained from the Molecular Signatures Database (MSigDB). Differential expression analysis revealed 41 hypoxia-related DEGs in GBM patients. A consensus clustering approach, utilizing these DEGs' expression patterns, identified four distinct clusters, with cluster 1 showing significantly better overall survival. Machine learning techniques, including univariate Cox regression and LASSO regression, delineated a prognostic signature comprising six genes (ANXA1, CALD1, CP, IGFBP2, IGFBP5, and LOX). Multivariate Cox regression analysis substantiated the prognostic significance of a set of three optimal signature genes (CP, IGFBP2, and LOX). Using the hypoxia-related prognostic signature, patients were classified into high- and low-risk categories. Survival analysis demonstrated that the high-risk group exhibited inferior overall survival rates in comparison to the low-risk group. The prognostic signature showed good predictive performance, as indicated by the area under the curve (AUC) values for one-, three-, and five-year overall survival. Furthermore, functional enrichment analysis of the DEGs identified biological processes and pathways associated with hypoxia, providing insights into the underlying mechanisms of GBM. Delving into the tumor immune microenvironment, our analysis revealed correlations relating the hypoxia-related prognostic signature to the infiltration of immune cells in GBM. Overall, our study highlights the potential of a hypoxia-related prognostic signature as a valuable resource for forecasting the survival outcome of GBM patients. The multi-omics approach integrating bulk sequencing, single-cell analysis, and immune microenvironment assessment enhances our understanding of the intricate biology characterizing GBM, thereby potentially informing the tailored design of therapeutic interventions.

Cancer-Associated Fibroblasts in Gastrointestinal Cancers: Unveiling Their Dynamic Roles in the Tumor Microenvironment.

Gastrointestinal cancers are highly aggressive malignancies with significant mortality rates. Recent research emphasizes the critical role of the tumor microenvironment (TME) in these cancers, which includes cancer-associated fibroblasts (CAFs), a key component of the TME that have diverse origins, including fibroblasts, mesenchymal stem cells, and endothelial cells. Several markers, such as α-SMA and FAP, have been identified to label CAFs, and some specific markers may serve as potential therapeutic targets. In this review article, we summarize the literature on the multifaceted role of CAFs in tumor progression, including their effects on angiogenesis, immune suppression, invasion, and metastasis. In addition, we highlight the use of single-cell transcriptomics to understand CAF heterogeneity and their interactions within the TME. Moreover, we discuss the dynamic interplay between CAFs and the immune system, which contributes to immunosuppression in the TME, and the potential for CAF-targeted therapies and combination approaches with immunotherapy to improve cancer treatment outcomes.

Clinical and radiologic differences between early onset, late onset, and very late onset adult multiple sclerosis.

BACKGROUND: Previous studies suggested possible differences in clinical and radiologic characteristics between early-onset multiple sclerosis (EOMS) and late-onset MS (LOMS). However, differences between LOMS and very late onset MS (VLOMS) are largely unknown. METHODS: We performed a retrospective review of medical records of patients diagnosed with MS between 8/1/2017 and 3/1/2022 at the comprehensive MS center of the Froedtert and Medical College of Wisconsin. We included adult patients with MS diagnosis who were 60 years or older - VLOMS, 50-59 years old at diagnosis - LOMS, or were 18-30 years old at diagnosis - EOMS and had complete imaging and clinical records. Clinical presentation and location of demyelinating lesions at the onset of diagnosis were extracted and compared using the chi-square test, p<0.05. RESULTS: A total of 246 newly diagnosed patients were identified. Of which 54 were EOMS, 29 were LOMS, and 35 were VLOMS. The sex ratio was not different between groups. EOMS had a higher percentage of patients who self-identified as black, while LOMS had a higher percentage of patients who self-identified as white. LOMS and VLOMS showed significant differences in the presence of tremors and lesion distribution at the onset. Older onset patients were more likely to present with motor symptoms, sphincter dysfunction, fatigue, and tremor. EOMS was more likely to present with cerebellum and occipital lobe lesions, and lesions were more likely to show contrast enhancement on MRI at diagnosis. CONCLUSION: Our findings revealed novel clinical and imaging characteristics differences between VLOMS and LOMS. The current classification of LOMS may benefit from revision to better align with chronological age classification for old age >60 instead of the current standard in the literature of >50 years.

Rare Presentation of Morganella morganii Microorganism as Epidural and Subdural Empyema / Apresentação rara de Morganella morganii Microrganismo como Empiema Epidural e Subdural

Background Morganella morganii is a gram-negative bacterium that rarely infects the central nervous system (CNS). Few reports described such an infection in the CNS. We present a case of extremely invasive M. morganii infection in the CNS. In addition, we performed a literature review of M. morganii infection in the CNS. Case report A 53-year-old male was admitted to the hospital due to fever, general weakness, and left-sided facial muscle twitching. He had a history of diabetes mellitus, hypertension, brain tumor, and epilepsy. Multiple left frontal scalp ulcers were revealed. In addition, a computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a left side epidural abscess and subdural empyema. Moreover, the patient had left frontal bone osteomyelitis. The next day, the patient underwent craniectomy, was transferred to the intensive care unit and started an empirical antibiotic course. Morganella morganii was identified from the infected scalp ulcers. On the 13th day, the patient passed away due to uncontrolled status epilepticus. Conclusion M. morganii can cause isolated or multiple types of CNS infections, including brain abscess, meningitis, and subdural empyema. The mortality rate may differ according to age and to the use of surgical evacuation.

Introdução Morganella morganii é uma bactéria gram-negativa que raramente infecta o sistema nervoso central (SNC). Poucos relatos descreveram tal infecção no SNC. Apresentamos um caso de infecção extremamente invasiva por M. morganii no SNC. Além disso, realizamos uma revisão da literatura sobre a infecção por M. morganii no SNC. Relato de caso Um homem de 53 anos foi admitido no hospital devido a febre, fraqueza geral e espasmos da musculatura facial do lado esquerdo. Ele tinha história de diabetes mellitus, hipertensão, tumor cerebral e epilepsia. Múltiplas úlceras no couro cabeludo frontal esquerdo foram reveladas. Além disso, uma tomografia computadorizada (TC) e uma ressonância magnética (RM) revelaram um abscesso epidural do lado esquerdo e empiema subdural. Além disso, o paciente apresentava osteomielite do osso frontal esquerdo. No dia seguinte, o paciente foi submetido à craniectomia, foi transferido para a unidade de terapia intensiva e iniciou curso empírico de antibiótico. Morganella morganii foi identificada a partir das úlceras do couro cabeludo infectadas. No 13° dia, o paciente faleceu devido a estado de mal epiléptico não controlado. Conclusão M. morganii pode causar tipos isolados ou múltiplos de infecções do SNC, incluindo abscesso cerebral, meningite e empiema subdural. A taxa de mortalidade pode diferir de acordo com a idade e com o uso da evacuação cirúrgica.

Genomic and Transcriptomic Predictors of Response to Immune Checkpoint Inhibitors in Melanoma Patients: A Machine Learning Approach.

Immune checkpoint inhibitors (ICIs) became one of the most revolutionary cancer treatments, especially in melanoma. While they have been proven to prolong survival with lesser side effects compared to chemotherapy, the accurate prediction of response remains to be an unmet gap. Thus, we aim to identify accurate clinical and transcriptomic biomarkers for ICI response in melanoma. We also provide mechanistic insight into how high-performing markers impose their effect on the tumor microenvironment (TME). Clinical and transcriptomic data were retrieved from melanoma studies administering ICIs from cBioportal and GEO databases. Four machine learning models were developed using random-forest classification (RFC) entailing clinical and genomic features (RFC7), differentially expressed genes (DEGs, RFC-Seq), survival-related DEGs (RFC-Surv) and a combination model. The xCELL algorithm was used to investigate the TME. A total of 212 ICI-treated melanoma patients were identified. All models achieved a high area under the curve (AUC) and bootstrap estimate (RFC7: 0.71, 0.74; RFC-Seq: 0.87, 0.75; RFC-Surv: 0.76, 0.76, respectively). Tumor mutation burden, GSTA3, and VNN2 were the highest contributing features. Tumor infiltration analyses revealed a direct correlation between upregulated genes and CD8+, CD4+ T cells, and B cells and inversely correlated with myeloid-derived suppressor cells. Our findings confirmed the accuracy of several genomic, clinical, and transcriptomic-based RFC models, that could further support the use of TMB in predicting response to ICIs. Novel genes (GSTA3 and VNN2) were identified through RFC-seq and RFC-surv models that could serve as genomic biomarkers after robust validation.

Management of chronic subdural hematoma: A study from Jordan.

Objectives: Chronic subdural hematoma (CSDH) is a common condition encountered in neurosurgical practice. Few studies have reported the characteristics of CSDH patients in the Middle Eastern population. We describe the clinical presentation, surgical management, radiological findings, and post-operative outcomes in our hospital. Methods: We performed a retrospective cohort study in King Abdullah University Hospital, Northern Jordan, between 2009 and 2019. Data were extracted from patients' medical records and analyzed in patients treated with burr hole drainage (BHD). Univariate analysis was performed to identify correlations with age, laterality, and recurrence. Results: A total of 172 CSDH patients were identified, of whom 128 (74.4%) were treated surgically. The mean age of patients treated with BHD (n = 108) was 60.9 years with a male-to-female ratio of 2.38:1. Headache was the most common presenting symptom (64.81%) and was significant in patients aged 41-64 years (p = 0.004), whereas muscle weakness and unsteady gait were significant in patients ≥ 65 years (p = 0.004 and p = 0.033, respectively). A higher pre-operative maximum thickness was associated with bilateral presentation (p = 0.001), whereas a higher pre-operative midline shift was associated with unilateral presentation (p = 0.027). Regarding CSDH recurrence, only a preoperative midline shift was significant (p = 0.021). Conclusion: Clinical presentation was affected by age, as patients < 65 years commonly presented with headaches, whereas those ≥ 65 years presented with limb weakness, speech impairment, unsteady gait, and altered consciousness. BHD was the most utilized surgical option with low mortality and complication rates. Recurrence was only associated with a pre-operative midline shift.