NLS-binding deficient Kapβ2 reduces neurotoxicity via selective interaction with C9orf72-ALS/FTD dipeptide repeats.

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity.

Brown-Séquard syndrome after blunt cervical spine trauma in a patient with preinjury multilevel hemilaminectomies and OPLL: illustrative case.

Background: Brown-Séquard syndrome (BSS) is a rare neurological condition characterized by injury to one-half of the spinal cord. In the context of trauma, BSS is typically seen with penetrating injuries. Here, the authors present the unique case of a patient presenting with BSS after blunt trauma.

Perceptions and Needs for a Technology-Based Dyadic Intervention on Symptom Management Among Patients With Colorectal Cancer and Their Caregivers: A Qualitative Study.

Background: Colorectal cancer (CRC) patients and their caregivers often experience multiple co-occurring symptoms (eg, fatigue, depression, anxiety, and sleep disturbance). There is a noticeable gap in research regarding symptom management for patient-caregiver dyads, particularly using technology-based tools.

Objective: This study aimed to describe the needs and perceptions of patient-caregiver dyads regarding a technology-based tool to manage their multiple symptoms.

Higher Nodal expression is often associated with poorer survival in patients diagnosed with melanoma and treated with anti-PD1 therapy.

Advanced melanoma is considered the most aggressive and deadly form of skin cancer whose incidence has been rising over the past three decades. In the absence of treatment, the median overall survival for advanced-stage metastatic disease is less than 6 months. Although most melanomas detected at an early stage can be cured with surgery, a subset of these eventually metastasize.

Engineered NLS-chimera downregulates expression of aggregation-prone endogenous FUS.

Importin β-superfamily nuclear import receptors (NIRs) mitigate mislocalization and aggregation of RNA-binding proteins (RBPs), like FUS and TDP-43, which are implicated in neurodegenerative diseases. NIRs potently disaggregate RBPs by recognizing their nuclear localization signal (NLS). However, disease-causing mutations in NLS compromise NIR binding and activity.

PAI-1 Interaction with Sortilin Related Receptor-1 is Required for Lung Fibrosis.

Plasminogen activator inhibitor-1 (PAI-1) has been previously shown to promote lung fibrosis via a mechanism that requires an intact vitronectin (VTN) binding site. In the present study, employing two distinct murine fibrosis models, we find that VTN is not required for PAI-1 to drive lung scarring. This result suggested the existence of a previously unrecognized profibrotic PAI-1-protein interaction involving the VTN-binding site for PAI-1.

Apple Vision Pro Augmented Reality-Assisted Minimally Invasive Surgical Treatment of Spinal Dural Arteriovenous Fistula.

This report outlines the innovative use of augmented reality (AR) in the surgical planning and treatment of a spinal dural arteriovenous fistula (dAVF) via a minimally invasive technique. AR technology by way of an Apple Vision Pro headset was employed to enhance preoperative visualization and understanding of the pathology, leading to successful surgical ligation of the AVF. This case describes a 56-year-old male presenting with progressive weakness and thoracic myelopathy who showed marked improvement postoperatively, highlighting AR's potential to improve surgical approach and outcomes.

Personalized therapy in oncology: melanoma as a paradigm for molecular-targeted treatment approaches.

In recent decades, the field of systemic cancer treatment has seen remarkable changes due to advancements in the understanding of cancer's biology, immunology, and genetic makeup. As a result, individuals with late-stage cancers are now achieving survival rates that were previously unattainable. The goal of personalized cancer therapy is to enhance clinical outcomes by customizing drug treatments to suit the unique genetic and/or epigenetic profiles of each patient's tumor.

Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma.

Purpose: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma.

Next-generation IEDB tools: a platform for epitope prediction and analysis.

The Next-Generation (NG) IEDB Tools website (https://nextgen-tools.iedb.org) provides users with a redesigned interface to many of the algorithms for epitope prediction and analysis that were originally released on the legacy IEDB Tools website.

Collagen fibril formation at the plasma membrane occurs independently from collagen secretion.

Collagen fibrils are the primary supporting scaffold of vertebrate tissues but how they are assembled is unclear. Here, using CRISPR-tagging of type I collagen and SILAC labelling, we elucidate the cellular mechanism for the spatiotemporal assembly of collagen fibrils, in cultured fibroblasts. Our findings reveal multifaceted trafficking of collagen, including constitutive secretion, intracellular pooling, and plasma membrane-directed fibrillogenesis.

Feasibility of a novel augmented reality overlay for cervical screw placement in phantom spine models.

Study Design: Feasibility study.

Purpose: A phantom model was used to evaluate the accuracy of a novel augmented reality (AR) system for cervical screw placement.

Overview Of Literature: The use of navigation systems is becoming increasingly common in spine procedures.

Positive Bacterial Cultures on Spinal Wound Closure Do Not Predict Postoperative Outcomes.

Background: Complex surgical back wounds represent significant morbidity in patients who have undergone spinal procedures requiring closure or revision by plastic surgeons. This study aimed to assess the utility of bacterial wound culture data for predicting surgical outcomes of wound management.

Methods: This study is a single-institution retrospective review of consecutive patients who required plastic surgery intervention for wound infection following spinal procedures between the years 2010 and 2021 (n = 70).

The Molecular Evolution of Melanoma Distant Metastases.

The evolution of primary melanoma to lymph node and distant metastasis is incompletely understood. We examined the genomic diversity in melanoma progression in matched primary melanomas and lymph node and distant metastases from 17 patients. FISH analysis revealed cancer cell fractions with monotonic copy number alterations, including PHIP gain and PTEN loss, in the metastatic cascade.

Hepatic veno-occlusive disease complicated with extreme hyperammonaemia (920 µmol/L) treated with defibrotide, lactulose, rifampin and haemodialysis.

Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS) is a severe complication that can occur following haematopoietic stem cell transplant (HSCT) with high-intensity conditioning chemotherapy regimens. Severe VOD/SOS, often characterised by multiorgan failure, is associated with a high mortality rate. This case report details the complex clinical course of a male patient in his mid-20s, recently diagnosed with B cell acute lymphoblastic leukaemia, who underwent allogeneic HSCT.

A direct aorta to segmental artery bypass for prevention of spinal cord ischemia after endovascular aortic repair.

Spinal cord ischemia remains a persistent challenge after endovascular aortic aneurysm repair. We present a novel direct aorta to segmental artery bypass before aneurysm repair in a 64-year-old woman presenting with an enlarging aneurysm following dissection. Through an eighth intercostal incision, a polyester graft was sewn into the aorta using pledgeted sutures.

The Apple Vision Pro as a Neurosurgical Planning Tool: A Case Report.

With its recent release, the Apple Vision Pro (Apple Inc., Cupertino, CA) represents a promising technological advancement of mixed reality in the field of neurosurgery and medicine more broadly. With all new technologies, it is critical to facilitate early use and assessment of the technology to facilitate adoption by the larger medical community.

High-Dimensional Analyses Reveal IL15 Enhances Activation of Sipuleucel-T Lymphocyte Subsets and Reverses Immunoresistance.

Sipuleucel-T (sip-T) is the only FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). To elucidate parameters of the response profile to this therapy, we report high-dimensional analyses of sip-T using cytometry by time of flight (CyTOF) and show a lymphoid predominance, with CD3+ T cells constituting the highest proportion (median ∼60%) of sip-T, followed by B cells, and natural killer (NK) and NKT cells. We hypothesized that treatment of sip-T with homeostatic cytokines known to activate/expand effector lymphocytes could augment efficacy against prostate tumors.

Augmented Reality-Assisted Placement of Ommaya Reservoir for Cyst Aspiration: A Case Report.

Image guidance technologies can significantly improve the accuracy and safety of intracranial catheter insertions. Augmented reality (AR) allows surgeons to visualize 3D information overlaid onto a patient's head. As such, AR has emerged as a novel image guidance technology that offers unique advantages when navigating intracranial targets.

ARID2 mutations may relay a distinct subset of cutaneous melanoma patients with different outcomes.

ARID genes encode subunits of SWI/SNF chromatin remodeling complexes and are frequently mutated in human cancers. We investigated the correlation between ARID mutations, molecular features, and clinical outcomes in melanoma patients. Cutaneous melanoma samples (n = 1577) were analyzed by next-generation sequencing.

Discoidin domain receptor 2 signaling through PIK3C2α in fibroblasts promotes lung fibrosis.

Pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), portends significant morbidity and mortality, and current therapeutic options are suboptimal. We have previously shown that type I collagen signaling through discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase expressed by fibroblasts, is critical for the regulation of fibroblast apoptosis and progressive fibrosis. However, the downstream signaling pathways for DDR2 remain poorly defined and could also be attractive potential targets for therapy.

A phase 1 study of triple-targeted therapy with BRAF, MEK, and AKT inhibitors for patients with BRAF-mutated cancers.

Background: Aberrant PI3K/AKT signaling in BRAF-mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF-mutated solid tumors (ClinicalTrials.gov identifier NCT01902173).