Differentiation of SH-SY5Y neuroblastoma cells using retinoic acid and BDNF: a model for neuronal and synaptic differentiation in neurodegeneration.

There has been much interest in the use of cell culture models of neurones, to avoid the animal welfare and cost issues of using primary and human-induced pluripotent stem cell (hiPSC)-derived neurones respectively. The human neuroblastoma cell line, SH-SY5Y, is extensively used in laboratories as they can be readily expanded, are of low cost and can be differentiated into neuronal-like cells. However, much debate remains as to their phenotype once differentiated, and their ability to recapitulate the physiology of bona fide neurones.

SGIP1 binding to the α-helical H9 domain of cannabinoid receptor 1 promotes axonal surface expression.

Endocannabinoid signalling mediated by cannabinoid receptor 1 (CB1R, also known as CNR1) is critical for homeostatic neuromodulation of both excitatory and inhibitory synapses. This requires highly polarised axonal surface expression of CB1R, but how this is achieved remains unclear. We previously reported that the α-helical H9 domain in the intracellular C terminus of CB1R contributes to axonal surface expression by an unknown mechanism.

AuNP/MIL-88B-NH Nanocomposite for the Valorization of Nitroarene by Green Catalytic Hydrogenation.

The efficiency of a catalytic process is assessed based on conversion, yield, and time effectiveness. However, these parameters are insufficient for evaluating environmentally sustainable research. As the world is urged to shift towards green catalysis, additional factors such as reaction media, raw material availability, sustainability, waste minimization and catalyst biosafety, need to be considered to accurately determine the efficacy and sustainability of the process.

Impact of technological advances in treatment planning, image guidance, and treatment delivery on target margin design for prostate cancer radiotherapy: an updated review.

Recent innovations in image guidance, treatment delivery, and adaptive radiotherapy (RT) have created a new paradigm for planning target volume (PTV) margin design for patients with prostate cancer. We performed a review of the recent literature on PTV margin selection and design for intact prostate RT, excluding post-operative RT, brachytherapy, and proton therapy. Our review describes the increased focus on prostate and seminal vesicles as heterogenous deforming structures with further emergence of intra-prostatic GTV boost and concurrent pelvic lymph node treatment.

Proton Therapy Mediates Dose Reductions to Brain Structures Associated With Cognition in Children With Medulloblastoma.

Purpose: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy.

Methods And Materials: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed.

A feasibility study of adaptive radiation therapy for postprostatectomy prostate cancer.

Postoperative prostate radiotherapy requires large planning target volume (PTV) margins to account for motion and deformation of the prostate bed. Adaptive radiation therapy (ART) can incorporate image-guidance data to personalize PTVs that maintain coverage while reducing toxicity. We present feasibility and dosimetry results of a prospective study of postprostatectomy ART.

Liver SBRT dose accumulation to assess the impact of anatomic variations on normal tissue doses and toxicity in patients treated with concurrent sorafenib.

Background And Purpose: Unexpected liver volume reductions occurred during trials of liver SBRT and concurrent sorafenib. The aims were to accumulate liver SBRT doses to assess the impact of these anatomic variations on normal tissue dose parameters and toxicity.

Materials And Methods: Thirty-two patients with hepatocellular carcinoma (HCC) or metastases treated on trials of liver SBRT (30-57 Gy, 6 fractions) and concurrent sorafenib were analyzed.

Insights From Image Guided Radiation Therapy Credentialing for the NRG Oncology RTOG 1112 Liver Stereotactic Body Radiation Therapy Trial.

Purpose: NRG Oncology trial RTOG 1112 is a randomized phase 3 study of sorafenib with or without stereotactic body radiation therapy for locally advanced hepatocellular carcinoma. Image guided radiation therapy (IGRT) credentialing is essential for this study because of the high doses, respiratory motion, and variety of delivery technologies. This analysis presents the IGRT credentialing experience.

Long-term oncologic outcomes of low dose-rate brachytherapy compared to hypofractionated external beam radiotherapy for intermediate -risk prostate cancer.

Purpose: To compare the long-term oncologic outcomes of intermediate risk (IR) prostate cancer (PCa) patients treated with low dose-rate brachytherapy (LDR-BT) or moderate hypofractionated external beam radiotherapy (HF-EBRT).

Methods And Materials: Patients diagnosed with IR PCa and treated with LDR-BT or HF-EBRT between January 2005 and December 2013 were included. Brachytherapy treatment involved a transperineal implant of iodine-125 to a dose of 145 Gy to the PTV, while HF-EBRT was delivered using intensity modulated radiotherapy with 60 Gy in 20 fractions.

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer.

Background: This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy.

Materials And Methods: Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years).

Pan-Canadian consensus recommendations for proton beam therapy access in Canada.

Purpose: Proton Beam Therapy (PBT)is a treatment option for select cancer patients. It is currently not available in Canada. Assessment and referral processes for out-of-country treatment for eligible patients vary by jurisdiction, leading to variability in access to this treatment for Canadian cancer patients.

Structural basis for the in vitro efficacy of nirmatrelvir against SARS-CoV-2 variants.

The COVID-19 pandemic continues to be a public health threat with emerging variants of SARS-CoV-2. Nirmatrelvir (PF-07321332) is a reversible, covalent inhibitor targeting the main protease (M) of SARS-CoV-2 and the active protease inhibitor in PAXLOVID (nirmatrelvir tablets and ritonavir tablets). However, the efficacy of nirmatrelvir is underdetermined against evolving SARS-CoV-2 variants.

Impact of Definitive Chemoradiation on Quality-of-Life Changes for Patients With Anal Cancer: Long-term Results of a Prospective Study.

Background: Maintaining and improving quality of life (QOL) are important goals of anal cancer management. This disease is generally curable, with many long-term survivors.

Objective: Long-term QOL after chemoradiation for patients with anal cancer was evaluated.

Clinical integration of machine learning for curative-intent radiation treatment of patients with prostate cancer.

Machine learning (ML) holds great promise for impacting healthcare delivery; however, to date most methods are tested in 'simulated' environments that cannot recapitulate factors influencing real-world clinical practice. We prospectively deployed and evaluated a random forest algorithm for therapeutic curative-intent radiation therapy (RT) treatment planning for prostate cancer in a blinded, head-to-head study with full integration into the clinical workflow. ML- and human-generated RT treatment plans were directly compared in a retrospective simulation with retesting (n = 50) and a prospective clinical deployment (n = 50) phase.

Intellectual changes after radiation for children with brain tumors: which brain structures are most important?

Background: The objective of this study was to evaluate the contribution of radiation dose to different intracranial structures on changes in intellectual function for children with brain tumors.

Methods: We evaluated children with brain tumors treated in 2005-2017 who had longitudinal neuropsychological assessments and available photon dosimetric data (if radiation therapy [RT] given). Full Scale Intelligence Quotient (FSIQ) and index scores were evaluated (perceptual reasoning index [PRI], processing speed index [PSI], verbal comprehension index [VCI], and working memory index [WMI]).

Prostate or bone? Comparing the efficacy of image guidance surrogates for pelvis and prostate radiotherapy using accumulated delivered dose.

Introduction: This study assessed the impact of dosimetry to both the target and normal tissue when either bony anatomy (BA) or prostate (PRO) was used as surrogates for image guidance for pelvis and prostate radiotherapy using a dose accumulation process.

Methods: Thirty patients who were prescribed 50-54Gy to the pelvic lymph nodes (PLN) and 78Gy to the prostate/seminal vesicles were included. Daily acquired CBCTs were rigidly registered to the CT using BA and PRO to simulate two different treatment positions.

WT1 activates transcription of the splice factor kinase SRPK1 gene in PC3 and K562 cancer cells in the absence of corepressor BASP1.

Dysregulated alternative splicing plays a prominent role in all hallmarks of cancer. The splice factor kinase SRPK1 drives the activity of oncogenic splice factors such as SRSF1. SRSF1 in turn promotes the expression of splice isoforms that favour tumour growth, including proangiogenic VEGF.

Phosphorylation of Syntaxin-1a by casein kinase 2α regulates pre-synaptic vesicle exocytosis from the reserve pool.

The t-soluble NSF-attachment protein receptor protein Syntaxin-1a (Stx-1a) is abundantly expressed at pre-synaptic terminals where it plays a critical role in the exocytosis of neurotransmitter-containing synaptic vesicles. Stx-1a is phosphorylated by Casein kinase 2α (CK2α) at Ser14, which has been proposed to regulate the interaction of Stx-1a and Munc-18 to control of synaptic vesicle priming. However, the role of CK2α in synaptic vesicle dynamics remains unclear.

Tumor-targeted dose escalation for localized prostate cancer using MR-guided HDR brachytherapy (HDR) or integrated VMAT (IB-VMAT) boost: Dosimetry, toxicity and health related quality of life.

Purpose: To report dosimetry, preliminary toxicity and health-related quality of life (HRQoL) outcomes of tumor-targeted dose-escalation delivered by integrated boost volumetric arc therapy (IB-VMAT) or MR-guided HDR brachytherapy (HDR) boost for prostate cancer.

Materials And Methods: Patients diagnosed with localized prostate cancer, with at least 1 identifiable intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled in a prospective non-randomized phase II study. All patients received VMAT to the prostate alone (76 Gy in 38 fractions) plus a GTV boost: IB-VMAT (95 Gy in 38 fractions) or MR-guided HDR (10 Gy single fraction).

Can Conformity-Based Volumetric Modulated Arc Therapy Improve Dosimetry and Speed of Delivery in Radiation Therapy to Lumbosacral Spine Compared with Conventional Techniques?

Purpose: Volumetric modulated arc therapy (VMAT) has generally been perceived as too time and resource intensive for palliative radiation therapy mainly because of the need for extensive organs at risk contouring. Dose-limiting conformity-based objectives can be automatically generated and are commonly used to conform isodoses closely around the target volumes during inverse planning. The aim of this study was to determine if conformity-based objectives can be used to create VMAT plans for lumbosacral spine palliative radiation therapy without organs at risk contours, which will improve conformity, dose homogeneity, and speed of delivery compared with standard forward planning approaches.

Polydopamine-Lysophosphatidate-Functionalised Titanium: A Novel Hybrid Surface Finish for Bone Regenerative Applications.

Aseptic loosening of total joint replacements (TJRs) continues to be the main cause of implant failures. The socioeconomic impact of surgical revisions is hugely significant; in the United Kingdom alone, it is estimated that £135m is spent annually on revision arthroplasties. Enhancing the longevity of titanium implants will help reduce the incidence and overall cost of failed devices.

Treatment outcomes in oropharynx cancer patients who did not complete planned curative radiotherapy.

Purpose: To evaluate outcomes in oropharyngeal cancer (OPC) patients who did not complete their planned curative radiation therapy (RT).

Methods: OPC Patients who received less than planned curative RT dose between 2002 and 2016 were identified for analysis. HPV status was assessed.

Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes.

Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues today, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. One of the key pathological traits of this disease is insulin resistance at 'glucose sink' tissues (mostly skeletal muscle), and this remains one of the features of this disease most intractable to therapeutic intervention. Several lines of evidence have implicated the post-translational modification, SUMOylation, in insulin signalling and insulin resistance in skeletal muscle.