Genetic and clinical study of in Japanese Parkinson's disease.

Background: Biallelic variants in , which encodes protein-nucleic acid deglycase DJ-1, can cause early-onset Parkinson's disease (PD). Although many patients with variants have been identified from European and Middle Eastern ethnic groups, there have been no reports in the Japanese population.

Objectives: To determine the prevalence and clinical features of patients with PD harboring variants in Japan.

KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution.

Rapid and accessible testing was paramount in the management of the COVID-19 pandemic. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva. Here, we describe our learnings and provide our blueprint for launching diagnostic laboratories, particularly in low-resource settings.

CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance.

Disseminated tuberculosis associated with fingolimod treatment in a patient with multiple sclerosis.

Fingolimod is a sphingosine-1-phosphate receptor modulator approved as a disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (MS). A woman in her 30s was treated with fingolimod for relapsing-remitting MS. After 7 years of treatment, she presented with non-productive cough, night sweats, breathlessness and unintentional weight loss.

Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease.

Introduction: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring.

Methods: We conducted a 1-year observational mixed-methods study.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

Background: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation.

Automated Digital Counseling Program (ODYSSEE-Kidney Health): A Pilot Study on Health-Related Quality of Life.

Key Points: Feasibility of implementing an automated, scalable, digital self-care program for patients with CKD was established. The primary outcome of improvement in health-related quality of life improved with the ODYSSEE-Kidney Health program. A dose relationship was shown between program engagement tertile and improvement in 4-month outcomes.

Diabetic retinopathy screening integrated in a multidisciplinary diabetes care clinic: a pilot project.

Objective: To characterize patients referred for diabetic retinopathy (DR) screening in a unique multidisciplinary diabetes care clinic at a tertiary care centre.

Methods: A retrospective study was conducted involving patients who were referred to the Cardiac and Renal Endocrine Clinic at a tertiary care centre (University Health Network) for DR screening between April 2019-March 2020 and November 2020-August 2021. Patients' demographics; micro- and macrovascular disease measurements; visual acuity, intraocular pressure, fundus imaging, and optical coherence tomography results were collected and analyzed.

Automated digital counselling with social network support as a novel intervention for patients with heart failure: protocol for randomised controlled trial.

Introduction: Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE-vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self-care materials, and health-related quality of life.

Methods And Analysis: Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months.

Combined Use of ECMO, Prone Positioning, and APRV in the Management of Severe COVID-19 Patients.

Background: Severe COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) may warrant extracorporeal membrane oxygenation (ECMO). We evaluated the safety and physiologic changes in oxygenation and hemodynamic profile during ECMO, prone positioning, and the two modalities combined in patients receiving veno-venous (VV) ECMO.

Methods: Cohort study of consecutive adult patients with COVID-19-associated ARDS requiring VV-ECMO, classified into three groups: ECMO support only; Prone positioning only; and Prone positioning during ECMO.

Asia Partnership Conference of Pharmaceutical Associations (APAC) Report on Regulatory Agility Implemented During the COVID-19 Pandemic: Inspiring Partnerships and Recommendations for the Way Forward.

Purpose: Asia Partnership Conference of Pharmaceutical Associations (APAC) promote regulatory agility of four important best practices i.e. reliance, digital platform, accepting electronic document and process integration.

Design and Development of a Digital Counseling Program for Chronic Kidney Disease.

Background: Self-management has shown to improve the quality of life in patients with chronic kidney disease (CKD). Readily accessible self-management tools are essential in promoting adherence to self-care behaviors. In recognizing that digital health facilitates efficient access to self-management programs, we developed a digital counseling program, ODYSSEE Kidney Health, to promote self-care behaviors while supporting health-related quality of life.

Video-Based Telemedicine for Kidney Disease Care: A Scoping Review.

Background And Objectives: Video-based telemedicine provides an alternative health care delivery model for patients with CKD. The objective was to provide an overview of the available evidence on the implementation and outcomes of adopting video-based telemedicine in nephrology.

Design, Setting, Participants, & Measurements: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL were searched in December 2019 and again in January 2021 for studies using video-based telemedicine for adults across the spectrum of kidney disease.

Chronic immune sensory polyradiculopathy (CISP).

Chronic immune sensory polyradiculopathy (CISP) is a rare variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We describe a man with isolated sensory ataxia whose initial investigations included normal nerve conduction studies and normal non-enhanced MR imaging of whole spine, but whose subsequent investigations showed delayed somatosensory evoked potential (SSEP) responses of the lower limbs, elevated cerebrospinal fluid (CSF) protein and lumbosacral nerve roots enhancement on MR imaging. We diagnosed CISP and he improved following intravenous immunoglobulin.

Inhibition of Granulocytic Myeloid-Derived Suppressor Cells Overcomes Resistance to Immune Checkpoint Inhibition in LKB1-Deficient Non-Small Cell Lung Cancer.

LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non-small cell lung cancer (NSCLC). Although treatment of NSCLC with immune checkpoint inhibitors (ICI) has resulted in improved overall survival in a subset of patients, studies have revealed that co-occurring KRAS/LKB1 mutations drive primary resistance to ICIs in NSCLC. Effective therapeutic options that overcome ICI resistance in LKB1-mutant NSCLC are limited.

Digital Applications Targeting Medication Safety in Ambulatory High-Risk CKD Patients: Randomized Controlled Clinical Trial.

Background And Objectives: Patients with CKD are at risk for adverse drug reactions, but effective community-based preventive programs remain elusive. In this study, we compared the effectiveness of two digital applications designed to improve outpatient medication safety.

Design, Setting, Participants, & Measurements: In a 1-year randomized controlled trial, 182 outpatients with advanced CKD were randomly assigned to receive a smartphone preloaded with either eKidneyCare (=89) or MyMedRec (=93).

Novel Kras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden.

Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establish Kras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [Kras (K), KrasTp53(KP), KrasTp53Lkb1 (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU).

Author Correction: Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure.

An Integrated Kidney Care eConsult Practice Model: Results from the iKinect Project.

Background: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple provider teams. Siloed care contributes to limited access between physicians, resulting in delays in the diagnosis and treatment of kidney disease and inappropriate use of healthcare resources. These gaps contribute to dissatisfied and disempowered providers and patients.

epsilon toxin vaccine candidate lacking toxicity to cells expressing myelin and lymphocyte protein.

A variant form of epsilon toxin (Y30A-Y196A) with mutations, which shows reduced binding to Madin-Darby canine kidney (MDCK) cells and reduced toxicity in mice, has been proposed as the next-generation enterotoxaemia vaccine. Here we show that, unexpectedly, the Y30A-Y196A variant does not show a reduction in toxicity towards Chinese hamster ovary (CHO) cells engineered to express the putative receptor for the toxin (myelin and lymphocyte protein; MAL). The further addition of mutations to residues in a second putative receptor binding site of the Y30A-Y196A variant further reduces toxicity, and we selected Y30A-Y196A-A168F for further study.