Repeated 5-aminolevulinic acid mediated sonodynamic therapy using magnetic resonance guided focused ultrasound in rat brain tumour models.

Sonodynamic therapy is an emerging therapeutic approach against brain tumours. However, the treatment scheme and ultrasound parameters have yet to be explored for clinical translation. Our study aimed to optimize ultrasound parameters for sonodynamic therapy (SDT) with 5-ALA as a sonosensitizing agent and to evaluate its therapeutic outcome on the rodent 9L gliosarcoma and the human U87 glioblastoma models.

Antisense Oligonucleotide Therapy for Calmodulinopathy.

Background: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in , , or , which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function.

Methods: We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of pathogenic variants.

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II hepatocellular carcinoma undergoing surgery? An observational cohort study.

Introduction: The influence of deranged body composition on stage I/II hepatocellular carcinoma (HCC) after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed.

Selective haematological cancer eradication with preserved haematopoiesis.

Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on untargeted chemotherapies and limited possibilities to treat malignant cells after HSCT without affecting the transplanted healthy cells. Antigen-specific cell-depleting therapies hold the promise of much more targeted elimination of diseased cells, as witnessed in the past decade by the revolution of clinical practice for B cell malignancies. However, target selection is complex and limited to antigens expressed on subsets of haematopoietic cells, resulting in a fragmented therapy landscape with high development costs.

POLARIS: A phase 2 trial of encorafenib plus binimetinib evaluating high-dose and standard-dose regimens in patients with V600-mutant melanoma with brain metastasis.

Background: POLARIS (phase 2 [ph2]; NCT03911869) evaluated encorafenib (BRAF inhibitor) in combination with binimetinib (MEK1/2 inhibitor) in BRAF/MEK inhibitor-naïve patients with V600-mutant melanoma with asymptomatic brain metastases.

Methods: The safety lead-in (SLI) assessed tolerability for high-dose encorafenib 300 mg twice daily (BID) plus binimetinib 45 mg BID. If the high dose was tolerable in ph2, patients would be randomized to receive high or standard dose (encorafenib 450 mg once daily [QD] plus binimetinib 45 mg BID).

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

Background: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.

The Pressurized Skin: A Review on the Pathological Effect of Mechanical Pressure on the Skin from the Cellular Perspective.

Since human skin is the primary interface responding to external mechanical stimuli, extrinsic forces can disrupt its balanced microenvironment and lead to cutaneous lesions. We performed this review to delve into the pathological effects of mechanical pressure on skin from the cellular perspective. Fibroblasts of different subsets act as heterogeneous responders to mechanical load and express diverse functionalities.

Recombinant lipidated FLIPr effectively enhances mucosal and systemic immune responses for various vaccine types.

Formyl peptide receptor-like 1 inhibitor protein (FLIPr) is an immune evasion protein produced by Staphylococcus aureus, and FLIPr is a potential vaccine candidate for reducing Staphylococcus aureus virulence and biofilm formation. We produced recombinant lipidated FLIPr (rLF) to increase the immunogenicity of FLIPr and showed that rLF alone elicited potent anti-FLIPr antibody responses to overcome the FLIPr-mediated inhibition of phagocytosis. In addition, rLF has potent immunostimulatory properties.

Identification of CD8 + T-Cell-Immune Cell Communications in Ileal Crohn's Disease.

Introduction: Crohn's disease (CD) is a major subtype of inflammatory bowel disease (IBD), a spectrum of chronic intestinal disorders caused by dysregulated immune responses to gut microbiota. Although transcriptional and functional changes in a number of immune cell types have been implicated in the pathogenesis of IBD, the cellular interactions and signals that drive these changes have been less well-studied.

Methods: We performed Cellular Indexing of Transcriptomes and Epitopes by sequencing on peripheral blood, colon, and ileal immune cells derived from healthy subjects and patients with CD.

REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis: A Canadian IBD Research Consortium Multicenter National Cohort Study.

Introduction: We aimed to evaluate the real-world effectiveness and safety of tofacitinib for the treatment of ulcerative colitis (UC).

Methods: REMIT-UC is a Canadian multicenter cohort study. Standardized data collection was performed on 334 consecutive adult outpatients with UC treated with tofacitinib.

Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis.

Purpose: Metformin is a biguanide derivative that is commonly used for the treatment of diabetes mellitus (DM). It demonstrates antioxidative, anti-inflammatory, and antiangiogenic activity within the ocular tissue and thus may be implicated in the treatment of age-related macular degeneration (AMD). However, epidemiological studies have shown conflicting results.

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

Background And Objectives: COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.

Methods: This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection.

Interstitial Control-Released Polymer Carrying a Targeting Small-Molecule Drug Reduces PD-L1 and MGMT Expression in Recurrent High-Grade Gliomas with TMZ Resistance.

In recurrent glioblastoma, Gliadel wafer implantation after surgery has been shown to result in incomplete chemical removal of residual tumor and development of brain edema. Furthermore, temozolomide (TMZ) resistance caused by O-methylguanine-DNA-methyltransferase (MGMT) activation and programmed cell death-ligand 1 (PD-L1) expression leads to immune-cold lesions that result in poorer prognosis. Cerebraca wafer, a biodegradable polymer containing (Z)--butylidenephthalide (BP), is designed to eliminate residual tumor after glioma resection.

Heat-Killed Lactobacilli Preparations Promote Healing in the Experimental Cutaneous Wounds.

Probiotics are defined as microorganisms with beneficial health effects when consumed by humans, being applied mainly to improve allergic or intestinal diseases. Due to the increasing resistance of pathogens to antibiotics, the abuse of antibiotics becomes inefficient in the skin and in systemic infections, and probiotics may also provide the protective effect for repairing the healing of infected cutaneous wounds. Here we selected two Lactobacillus strains, GMNL-6 and GMNL-653, in heat-killed format to examine the beneficial effect in skin wound repair through the selection by promoting collagen synthesis in Hs68 fibroblast cells.

Increased Risk of Stroke in Patients With Obsessive-Compulsive Disorder: A Nationwide Longitudinal Study.

Background And Purpose: Patients with obsessive-compulsive disorder (OCD) tend to be comorbid with stroke-related risk factors, including obesity, hypertension, and diabetes. However, the temporal association between OCD and subsequent stroke risk is unclear.

Methods: Using data collected between 2001 and 2010 by Taiwan’s National Health Insurance Research Database, 28 064 adult patients with OCD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code: 300.

Clinical implications of sequential MRD monitoring by NGS at 2 time points after chemotherapy in patients with AML.

Next-generation sequencing (NGS) has been applied to measurable/minimal residual disease (MRD) monitoring after induction chemotherapy in patients with acute myeloid leukemia (AML), but the optimal time point for the test remains unclear. In this study, we aimed to investigate the clinical significance of NGS MRD at 2 different time points. We performed targeted NGS of 54 genes in bone marrow cells serially obtained at diagnosis, first complete remission (first time point), and after the first consolidation chemotherapy (second time point) from 335 de novo AML patients.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Somatic Mutations in Aldosterone-Producing Adenoma Are Associated With a Worse Baseline Status and Better Recovery of Left Ventricular Remodeling and Diastolic Function.

Primary aldosteronism is the most common secondary endocrine form of hypertension and causes many cardiovascular injuries. somatic mutations have recently been identified in aldosterone-producing adenoma. However, their impacts on left ventricular remodeling precluding the interference of age, sex, and blood pressure are still uncertain.

Gal-1 (Galectin-1) Upregulation Contributes to Abdominal Aortic Aneurysm Progression by Enhancing Vascular Inflammation.

Objective: Abdominal aortic aneurysm (AAA) is a vascular degenerative disease causing sudden rupture of aorta and significant mortality in elders. Nevertheless, no prognostic and therapeutic target is available for disease management. Gal-1 (galectin-1) is a β-galactoside-binding lectin constitutively expressed in vasculature with roles in maintaining vascular homeostasis.

Small fiber pathology in autism and clinical implications.

Objective: To investigate small fiber innervation of the skin and its relationships with clinicometry of autism and peripheral afferents for contact heat-evoked potential (CHEP) and psychophysical measures of thermal thresholds.

Methods: We recruited 32 men with autism (26.5 ± 5.

Automated Recognition of Regional Wall Motion Abnormalities Through Deep Neural Network Interpretation of Transthoracic Echocardiography.

Background: Automated interpretation of echocardiography by deep neural networks could support clinical reporting and improve efficiency. Whereas previous studies have evaluated spatial relationships using still frame images, we aimed to train and test a deep neural network for video analysis by combining spatial and temporal information, to automate the recognition of left ventricular regional wall motion abnormalities.

Methods: We collected a series of transthoracic echocardiography examinations performed between July 2017 and April 2018 in 2 tertiary care hospitals.