Diffusion-Based Generation of Neural Activity from Disentangled Latent Codes.

Recent advances in recording technology have allowed neuroscientists to monitor activity from thousands of neurons simultaneously. Latent variable models are increasingly valuable for distilling these recordings into compact and interpretable representations. Here we propose a new approach to neural data analysis that leverages advances in conditional generative modeling to enable the unsupervised inference of disentangled behavioral variables from recorded neural activity.

Expressive dynamics models with nonlinear injective readouts enable reliable recovery of latent features from neural activity.

The advent of large-scale neural recordings has enabled new approaches that aim to discover the computational mechanisms of neural circuits by understanding the rules that govern how their state evolves over time. While these cannot be directly measured, they can typically be approximated by low-dimensional models in a latent space. How these models represent the mapping from latent space to neural space can affect the interpretability of the latent representation.

Machine learning to develop a predictive model of pressure injury in persons with spinal cord injury.

Study Design: A 5-year longitudinal, retrospective, cohort study.

Objectives: Develop a prediction model based on electronic health record (EHR) data to identify veterans with spinal cord injury/diseases (SCI/D) at highest risk for new pressure injuries (PIs).

Setting: Structured (coded) and text EHR data, for veterans with SCI/D treated in a VHA SCI/D Center between October 1, 2008, and September 30, 2013.

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.

Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy.

Comparing Outcomes of the Veterans Health Administration's Traumatic Brain Injury and Mental Health Screening Programs: Types and Frequency of Specialty Services Used.

The Veterans Health Administration (VHA) screens veterans who deployed in support of the wars in Afghanistan and Iraq for traumatic brain injury (TBI) and mental health (MH) disorders. Chronic symptoms after mild TBI overlap with MH symptoms, for which there are already established screens within the VHA. It is unclear whether the TBI screen facilitates treatment for appropriate specialty care over and beyond the MH screens.

Measuring pain care quality in the Veterans Health Administration primary care setting.

The lack of a reliable approach to assess quality of pain care hinders quality improvement initiatives. Rule-based natural language processing algorithms were used to extract pain care quality (PCQ) indicators from documents of Veterans Health Administration primary care providers for veterans diagnosed within the past year with musculoskeletal disorders with moderate-to-severe pain intensity across 2 time periods 2013 to 2014 (fiscal year [FY] 2013) and 2017 to 2018 (FY 2017). Patterns of documentation of PCQ indicators for 64,444 veterans and 124,408 unique visits (FY 2013) and 63,427 veterans and 146,507 visits (FY 2017) are described.

Deletion of immunomodulatory genes as a novel approach to oncolytic vaccinia virus development.

Vaccinia virus (VV) has emerged as a promising platform for oncolytic virotherapy. Many clinical VV candidates, such as the double-deleted VV, vvDD, are engineered with deletions that enhance viral tumor selectivity based on cellular proliferation rates. An alternative approach is to exploit the dampened interferon-based innate immune responses of tumor cells by deleting one of the many VV immunomodulatory genes expressed to dismantle the antiviral response.

Cutting both ways: the innate immune response to oncolytic virotherapy.

Oncolytic viruses (OVs), above and beyond infecting and lysing malignant cells, interact with the immune system in complex ways that have important therapeutic significance. While investigation into these interactions is still in its early stages, important insights have been made over the past two decades that will help improve the clinical efficacy of OV-based management strategies in cancer care moving forward. The inherent immunosuppression that defines the tumor microenvironment can be modified by OV infection, and the subsequent recruitment and activation of innate immune cells, in particular, is central to this.

Canadian guidelines on the management of colorectal peritoneal metastases.

Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential.

Modeling oncolytic virus dynamics in the tumor microenvironment using zebrafish.

We have adapted a zebrafish (Danio rerio) tumor xenograft model for use in the study of oncolytic virotherapy. Following implantation of mammalian cancer cells into the perivitelline space of developing zebrafish embryos, both local and intravenous oncolytic virus treatments produce a tumor-specific infection with measurable antitumor effects. Tumor cells are injected at 48 h post fertilization, with oncolytic virus treatment then being administered 24 h later to allow for an initial period of tumor development and angiogenesis.

Impairments in Bowel Function, Social Function and Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can be associated with decreases in quality of life (QOL). Bowel-related QOL (BR-QOL) after CRS-HIPEC has not been previously studied. The objectives of the current study were to examine the effect of different types of bowel resection during CRS-HIPEC on overall QOL and BR-QOL.

Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials.

Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) (). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus.

Glove and instrument changing to prevent tumour seeding in cancer surgery: a survey of surgeons' beliefs and practices.

Background: Some surgeons change gloves and instruments after the extirpative phase of cancer surgery with the intent of reducing the risk of local and wound recurrence. Although this practice is conceptually appealing, the evidence that gloves or instruments act as vectors of cancer-cell seeding in the clinical setting is weak. To determine the potential effect of further investigation of this question, we surveyed the practices and beliefs of a broad spectrum of surgeons who operate on cancer patients.

Management of complex polyps of the colon and rectum.

Puprpose: Benign polyps that are technically challenging and unsafe to remove via polypectomy are known as complex polyps. Concerns regarding safety and completeness of resection dictate they undergo advanced endoscopic techniques, such as endoscopic mucosal resection or surgery. We provide a comprehensive overview of complex polyps and current treatment options.

Leveraging Electronic Health Care Record Information to Measure Pressure Ulcer Risk in Veterans With Spinal Cord Injury: A Longitudinal Study Protocol.

Background: Pressure ulcers (PrUs) are a frequent, serious, and costly complication for veterans with spinal cord injury (SCI). The health care team should periodically identify PrU risk, although there is no tool in the literature that has been found to be reliable, valid, and sensitive enough to assess risk in this vulnerable population.

Objective: The immediate goal is to develop a risk assessment model that validly estimates the probability of developing a PrU.

Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies.

The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway.

Clinical features and outcomes of 20 patients with abdominopelvic desmoplastic small round cell tumor.

Introduction: Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal malignancy. We describe our experience with treating DSRCT at a large sarcoma referral center.

Methods: A retrospective chart review was performed on DSRCT patients referred to our institution (1998-2014).

Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients With Advanced Solid Cancers.

We have conducted a phase 1 study of intravenous vvDD, a Western Reserve strain oncolytic vaccinia virus, on 11 patients with standard treatment-refractory advanced colorectal or other solid cancers. The primary endpoints were maximum tolerated dose and associated toxicity while secondary endpoints were pharmacokinetics, pharmacodynamics, immune responses, and antitumor activity. No dose-limiting toxicities and treatment related severe adverse events were observed.

Impact of Major Complications on Patients' Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for selected patients with peritoneal surface malignancies (PSM). Although it can have significant morbidity, perioperative mortality is low. Little is known about whether major complications after CRS/HIPEC have a lasting impact on patients' quality of life (QOL).

Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques.

Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation.

Peritoneal Carcinomatosis from Colon Cancer: A Systematic Review of the Data for Cytoreduction and Intraperitoneal Chemotherapy.

A systematic review of the literature on the management of peritoneal carcinomatosis (PC) from colon cancer with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) was undertaken using OVID Medline. Forty-six relevant studies were reviewed. Mean weighted overall morbidity following CRS and IPC was 49% (range 22-76%) and mortality was 3.

Programmable insect cell carriers for systemic delivery of integrated cancer biotherapy.

Due to cancer's genetic complexity, significant advances in the treatment of metastatic disease will require sophisticated, multi-pronged therapeutic approaches. Here we demonstrate the utility of a Drosophila melanogaster cell platform for the production and in vivo delivery of multi-gene biotherapeutic systems. We show that cultured Drosophila S2 cell carriers can stably propagate oncolytic viral therapeutics that are highly cytotoxic for mammalian cancer cells without adverse effects on insect cell viability or gene expression.

VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor Vasculature to Oncolytic Virus Infection.

Oncolytic viruses designed to attack malignant cells can in addition infect and destroy tumor vascular endothelial cells. We show here that this expanded tropism of oncolytic vaccinia virus to the endothelial compartment is a consequence of VEGF-mediated suppression of the intrinsic antiviral response. VEGF/VEGFR2 signaling through Erk1/2 and Stat3 leads to upregulation, nuclear localization, and activation of the transcription repressor PRD1-BF1/Blimp1.

Oncolytic vaccinia virus synergizes with irinotecan in colorectal cancer.

Metastatic colorectal cancer (CRC) is complex clinical challenge for which there are limited treatment options. Chemotherapy with or without surgery provides moderate improvements in overall survival and quality of life; nevertheless the 5-year survival remains below 30%. Oncolytic vaccinia virus (VV) shows strong anti-tumour activity in models of CRC, however transient delays in disease progression are insufficient to lead to long-term survival.

Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms.

To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (psms), together with patient representatives, formed the Canadian HIPEC Collaborative Group (chicg). The group is dedicated to standardizing and improving the treatment of psm in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with psm are improved. Patients with resectable psm arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with psm.