Development of an intraventricular adeno-associated virus-based labeling strategy for glioblastoma cells nested in the subventricular zone.

Background: Glioblastoma (GBM) is a dreadful brain tumor, with a particular relationship to the adult subventricular zone (SVZ) that has been described as relevant to disease initiation, progression, and recurrence.

Methods: We propose a novel strategy for the detection and tracking of xenografted GBM cells that are located in the SVZ, based on an intracerebroventricular (icv) recombinant adeno-associated virus (AAV)-mediated color conversion method. We used different patient-derived GBM stem-like cells (GSCs), which we transduced first with a retroviral vector (LRLG) that included a lox-dsRed-STOP-lox cassette, upstream of the eGFP gene, then with rAAVs expressing the Cre-recombinase.

PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells.

Olaparib, a PARP inhibitor, is effective against various cancers, including prostate cancer. However, resistance to olaparib poses a significant challenge. This study uncovers that mitochondrial alterations and PINK1 gene overexpression contribute to this resistance in prostate cancer cells.

Diversity patterns of the South African azooxanthellate scleractinians (Cnidaria: Anthozoa), with considerations of environmental correlates.

Azooxanthellate scleractinian corals, a group of species that lack a symbiotic relationship with dinoflagellates, are influenced by environmental variables at various scales. As the global commitment to sustainably manage ocean ecosystems and resources rises, there is a growing need to describe biodiversity trends in previously unsampled areas. Benthic invertebrate research in South Africa is a developing field, and many taxa in deep water environments remain inadequately characterized.

LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.

The development of resistance to current standard-of-care treatments, such as androgen receptor (AR) targeting therapies, remains a major challenge in the management of advanced prostate cancer. There is an urgent need for new therapeutic strategies targeting key resistant drivers, such as AR variants like AR-V7, and steroidogenic enzymes, such as aldo-keto reductase 1C3 (AKR1C3), to overcome drug resistance and improve outcomes for patients with advanced prostate cancer. Here, we have designed, synthesized, and characterized a novel class of LX compounds targeting both the AR/AR variants and AKR1C3 pathways.

Machine-Learning Assisted Screening of Correlated Covariates: Application to Clinical Data of Desipramine.

Stepwise covariate modeling (SCM) has a high computational burden and can select the wrong covariates. Machine learning (ML) has been proposed as a screening tool to improve the efficiency of covariate selection, but little is known about how to apply ML on actual clinical data. First, we simulated datasets based on clinical data to compare the performance of various ML and traditional pharmacometrics (PMX) techniques with and without accounting for highly-correlated covariates.

IGFBP3 promotes resistance to Olaparib via modulating EGFR signaling in advanced prostate cancer.

Olaparib is a pioneering PARP inhibitor (PARPi) approved for treating castration-resistant prostate cancer (CRPC) tumors harboring DNA repair defects, but clinical resistance has been documented. To study acquired resistance, we developed Olaparib-resistant (OlapR) cell lines through chronic Olaparib treatment of LNCaP and C4-2B cell lines. Here, we found that IGFBP3 is highly expressed in acquired (OlapR) and intrinsic (Rv1) models of Olaparib resistance.

Therapeutic Resistance Models and Treatment Sequencing in Advanced Prostate Cancer.

Current common treatments for castration-resistant prostate cancer (CRPC) typically belong to one of three major categories: next-generation anti-androgen therapies (NGAT) including enzalutamide, abiraterone acetate, apalutamide, and darolutamide; taxane therapy represented by docetaxel; and PARP inhibitors (PARPi) like olaparib. Although these treatments have shown efficacy and have improved outcomes for many patients, some do not survive due to the emergence of therapeutic resistance. The clinical landscape is further complicated by limited knowledge about how the sequence of treatments impacts the development of therapeutic cross-resistance in CRPC.

Evaluating ecological benefits of oceanic protected areas.

Oceans beyond the continental shelf represent the largest yet least protected environments. The new agreement to increase protection targets to 30% by 2030 and the recent United Nations (UN) High Seas Treaty try to address this gap, and an increase in the declaration of oceanic Marine Protected Areas (oMPAs) in waters beyond 200 m in depth is likely. Here we find that there is contradictory evidence concerning the benefits of oMPAs in terms of protecting pelagic habitats, providing refuge for highly mobile species, and potential fisheries benefits.

Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone.

Pediatric high-grade gliomas (pHGG) are brain tumors occurring in children and adolescents associated with a dismal prognosis despite existing treatments. Therapeutic failure in both adult and pHGG has been partially imputed to glioma stem cells (GSC), a subset of cancer cells endowed with stem-like cell potential and malignant, invasive, adaptative, and treatment-resistant capabilities. Whereas GSC have largely been portrayed in adult tumors, less information has been provided in pHGG.

Self-reported effects of warm seasonal temperatures in persons with spinal cord injury.

Objective: Spinal cord injury (SCI) interrupts motor, sensory, and autonomic pathways, impairing mobility and increasing heat storage during warm seasonal temperatures due to compromised autonomic control of vasodilation and sweating and recognition of body temperature. Thus, persons with SCI are more vulnerable to hyperthermia and its adverse effects. However, information regarding how persons with SCI perceive warmer seasons and whether thermal discomfort during warmer seasons restricts routine activities remains anecdotal.

Geographical, temporal, and individual-based differences in the trophic ecology of female Cape fur seals.

Information on resource use and trophic dynamics of marine predators is important for understanding their role in ecosystem functioning and predicting population-level responses to environmental change. Where separate populations experience different local environmental conditions, geographic variability in their foraging ecology is often expected. Within populations, individuals also vary in morphology, physiology, and experience, resulting in specialization in resource use.

Autonomous Intersection Management: Optimal Trajectories and Efficient Scheduling.

Intersections are at the core of congestion in urban areas. After the end of the Second World War, the problem of intersection management has benefited from a growing body of advances to address the optimization of the traffic lights' phase splits, timing, and offset. These contributions have significantly improved traffic safety and efficiency in urban areas.

Erratum: Corrigendum: Filander ZN, Kitahara MV, Cairns SD, Sink KJ, Lombard AT (2021) Azooxanthellate Scleractinia (Cnidaria, Anthozoa) from South Africa. ZooKeys 1066: 1-198. https://doi.org/10.3897/zookeys.1066.69697.

[This corrects the article DOI: 10.3897/zookeys.1066.

Study of Strawberry Notch homolog 1 and 2 expression in human glioblastoma.

Purpose: In this work, we aimed to comprehensively document the expression of Strawberry Notch homolog (SBNO) 1 and 2 in glioblastoma (GBM) tissue and patient-derived GBM stem-like cell (GSC) cultures.

Methods: We investigated SBNO1 and SBNO2 expression at the RNA and protein levels in glioma patient tissue and GSCs, respectively by performing immunostainings and qPCR analyses. We also used publicly-available datasets for assessing SBNO1 and SBNO2 gene expression and related copy number alterations.

Incidence and epidemiology of conjunctival squamous cell carcinoma in relation to the HIV epidemic in South Africa: a 25-year analysis of the National Cancer Registry (1994-2018).

Aims: To describe the incidence and epidemiology of conjunctival squamous cell carcinoma (CSCC) in South Africa over a 25-year period (1994-2018), with particular reference to the HIV epidemic.

Methods: Incident cases of histologically diagnosed CSCC were identified from the pathology-based South African National Cancer Registry. Crude and direct age-standardised incidence rates (ASIRs) per 100 000 persons (Segi World Standard Population) were calculated using national population statistics and compared by age, sex and ethnicity.

Single-timepoint low-dimensional characterization and classification of acute versus chronic multiple sclerosis lesions using machine learning.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease characterized by the appearance of focal lesions across the central nervous system. The discrimination of acute from chronic MS lesions may yield novel biomarkers of inflammatory disease activity which may support patient management in the clinical setting and provide endpoints in clinical trials. On a single timepoint and in the absence of a prior reference scan, existing methods for acute lesion detection rely on the segmentation of hyperintense foci on post-gadolinium T1-weighted magnetic resonance imaging (MRI), which may underestimate recent acute lesion activity.

Wntless expression promotes lineage plasticity and is associated with neuroendocrine prostate cancer.

Resistance to androgen receptor (AR) targeted therapies remains as the main reason for most prostate cancer related deaths. Lineage plasticity resulting in altered, treatment insensitive prostate tumor cell phenotypes such neuroendocrine differentiated prostate cancer is a common manifestation within resistant tumors upon AR-targeted therapies. The mechanisms responsible for lineage plasticity in prostate cancer remain incompletely understood.

Activation of neural lineage networks and ARHGEF2 in enzalutamide-resistant and neuroendocrine prostate cancer and association with patient outcomes.

Background: Treatment-emergent neuroendocrine prostate cancer (NEPC) after androgen receptor (AR) targeted therapies is an aggressive variant of prostate cancer with an unfavorable prognosis. The underlying mechanisms for early neuroendocrine differentiation are poorly defined and diagnostic and prognostic biomarkers are needed.

Methods: We performed transcriptomic analysis on the enzalutamide-resistant prostate cancer cell line C4-2B MDVR and NEPC patient databases to identify neural lineage signature (NLS) genes.

Bioengineered BERA-Wnt5a siRNA Targeting Wnt5a/FZD2 Signaling Suppresses Advanced Prostate Cancer Tumor Growth and Enhances Enzalutamide Treatment.

The next-generation antiandrogen drugs such as enzalutamide and abiraterone extend survival times and improve quality of life in patients with advanced prostate cancer. However, resistance to both drugs occurs frequently through mechanisms that are incompletely understood. Wnt signaling, particularly through Wnt5a, plays vital roles in promoting prostate cancer progression and induction of resistance to enzalutamide and abiraterone.

Nanobody-based retargeting of an oncolytic herpesvirus for eliminating CXCR4 GBM cells: A proof of principle.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, which remains difficult to cure. The very high recurrence rate has been partly attributed to the presence of GBM stem-like cells (GSCs) within the tumors, which have been associated with elevated chemokine receptor 4 (CXCR4) expression. CXCR4 is frequently overexpressed in cancer tissues, including GBM, and usually correlates with a poor prognosis.

Sexual Dysfunction of Patients with Diffuse Low-Grade Glioma: A Qualitative Review of a Neglected Concern.

Diffuse low-grade gliomas (LGG) commonly affect young adults and display a slow evolution, with a life expectancy that can surpass 15 years, thanks to multimodal therapeutic management. Therefore, preservation of quality of life (QoL), including sexual health, is mandatory. We systematically searched available medical databases of Pubmed, Cochrane, and Scopus for studies that reported data on sexual activity or dysfunction (SD) in LGG patients.

Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.

In children, high-grade gliomas (HGG) and diffuse midline gliomas (DMG) account for a high proportion of death due to cancer. Glioma stem cells (GSCs) are tumor cells in a specific state defined by a tumor-initiating capacity following serial transplantation, self-renewal, and an ability to recapitulate tumor heterogeneity. Their presence was demonstrated several decades ago in adult glioblastoma (GBM), and more recently in pediatric HGG and DMG.

Surgical training during the COVID-19 pandemic - a single institution's trainee survey.

Background: Few studies have assessed the impact of COVID-19 on surgical training in low- and middle-income countries. The aim of this study was to survey the effect of the COVID-19 pandemic on postgraduate surgical training, research and registrar wellbeing in South Africa.

Methods: A cross-sectional study was conducted as an online survey from 5 October 2020 to 1 December 2020.

Olaparib-Induced Senescence Is Bypassed through G2-M Checkpoint Override in Olaparib-Resistant Prostate Cancer.

PARP inhibition represents the dawn of precision medicine for treating prostate cancer. Despite this advance, questions remain regarding the use of PARP inhibitors (PARPi) for the treatment of this disease, including (i) how specifically do PARPi-sensitive tumor cells respond to treatment, and (ii) how does PARPi resistance develop? To address these questions, we characterized response to olaparib in sensitive LNCaP and C4-2B cells and developed two olaparib-resistant derivative cell line models from each, termed LN-OlapR and 2B-OlapR, respectively. OlapR cells possess distinct morphology from parental cells and display robust resistance to olaparib and other clinically relevant PARPis, including rucaparib, niraparib, and talazoparib.