Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

In-depth analysis of active compounds targeting tropomyosin-related kinase A via constructed lipid raft @capillary monolith affinity chromatography.

In order to enrich the selection of biological ligands, realize the miniaturization analysis, and broaden the application of monolith materials for active ingredients screening and separating, we sough to construct a lipid raft @capillary monolith microcolumn affinity chromatography model. Single factor experiments and various characterization methods, including scanning electron microscopy (SEM) and thermogravimetric analysis, were employed to investigate the polymerization of the monolith column under different material ratios to determine optimal preparation conditions. Subsequently, the lipid raft from U251 cells was integrated with the monolith materials based on epoxy-based covalent crosslinking principle and characterized through SEM and immunofluorescence methods.

Patient-Derived Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to multiple single agents cannot be delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.

Primary intracranial neuroendocrine tumor at the sphenoid ridge with metastasis to the spinal cord: A case report.

Rationale: Neuroendocrine tumors (NETs) originate from neuroendocrine cells and they are depicted with both nerve cells as well as hormone-producing cells. These tumors were initially discovered in extracranial locations and central nervous system involvement is often a result of metastasis. Herein, we present a very rare case of primary intracranial neuroendocrine tumor (PINET) that masqueraded as meningioma at the sphenoid ridge with metastasis to the spinal cord in a patient without a known history of extracranial NET at the time of diagnosis.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

Novel Biallelic Synonymous Exonic Variant in Affecting mRNA Splicing: Case Report.

Objectives: Chorea-acanthocytosis is an autosomal recessively inherited condition caused by loss-of-function pathogenic variants in . We identified a novel synonymous exonic variant leading to abnormal mRNA splicing in a patient with chorea-acanthocytosis.

Methods: A patient with focal epilepsy developed generalized chorea with orolingual dystonia, cognitive decline, and peripheral neuropathy, consistent with chorea-acanthocytosis.

High Abundance of Unusual High Mannose -Glycans Found in Beans.

High mannose -glycans extracted from eight different beans (black bean, soybean, pea, white kidney bean, pinto bean, mung bean, white hyacinth bean, and red bean) were studied using the state-of-the-art mass spectrometry method logically derived sequence tandem mass spectrometry (LODES/MS). These beans show very similar -glycan isomer profiles: one isomer of ManGlcNAc and ManGlcNAc, two isomers of ManGlcNAc, three isomers of ManGlcNAc, and five isomers of ManGlcNAc were found. Isomers not predicted by current -glycan biosynthetic pathways were found in all beans, indicating the possibility of alternative biosynthetic pathways in these plants.

Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.

Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective.

Impact of nebulization versus metered-dose inhaler utilization on viral particle dispersion in patients with COVID-19.

Background: Conflicting guidance exists regarding the characterization of nebulization as an aerosol-generating procedure and subsequent risk of transmission of SARS-CoV-2 to healthcare workers.

Aim/objective: This study sought to address whether SARS-CoV-2 viral load distribution was impacted by bronchodilator delivery via nebulizer versus metered-dose inhaler (MDI).

Methods: Adults infected with COVID-19 were enrolled and received a single dose of albuterol sulfate nebulized solution (2.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Dietary restriction impacts health and lifespan of genetically diverse mice.

Caloric restriction extends healthy lifespan in multiple species. Intermittent fasting, an alternative form of dietary restriction, is potentially more sustainable in humans, but its effectiveness remains largely unexplored. Identifying the most efficacious forms of dietary restriction is key for developing interventions to improve human health and longevity.

Calibrating Observational Health Record Data Against a Randomized Trial.

Importance: The conditions required for health record data sources to accurately assess treatment effectiveness remain unclear. Emulation of randomized clinical trials (RCTs) with health record data and subsequent calibration of the results can help elucidate this.

Objective: To pilot an emulation of the KEYNOTE-189 RCT using a commercially available electronic health record (EHR) data source.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Assessing the Performance of Models from the 2022 RSNA Cervical Spine Fracture Detection Competition at a Level I Trauma Center.

Purpose To evaluate the performance of the top models from the RSNA 2022 Cervical Spine Fracture Detection challenge on a clinical test dataset of both noncontrast and contrast-enhanced CT scans acquired at a level I trauma center. Materials and Methods Seven top-performing models in the RSNA 2022 Cervical Spine Fracture Detection challenge were retrospectively evaluated on a clinical test set of 1828 CT scans (from 1829 series: 130 positive for fracture, 1699 negative for fracture; 1308 noncontrast, 521 contrast enhanced) from 1779 patients (mean age, 55.8 years ± 22.

The Portfolio Diet and HbA1c in Adults Living with Type 2 Diabetes Mellitus: A Patient-Level Pooled Analysis of Two Randomized Dietary Trials.

The Portfolio Diet, a dietary pattern of cholesterol-lowering foods, is also rich in low glycemic index (GI) foods. While strong evidence supports clinically meaningful reductions in cholesterol, evidence on the relationship between the Portfolio Diet and diabetes management is lacking. To evaluate the relationship between the Portfolio Diet and glycated hemoglobin (HbA1c) as a determinant of glycemic control among adults living with type 2 diabetes mellitus (T2DM).

p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence-A Retrospective Study in a Longitudinal Cohort.

Grading of oral epithelial dysplasia (OED) can be challenging with considerable intraobserver and interobserver variability. Abnormal immunohistochemical staining patterns of the tumor suppressor protein, p53, have been recently shown to be potentially associated with progression in OED. We retrospectively identified 214 oral biopsies from 203 patients recruited in a longitudinal study between 2001 and 2008 with a diagnosis of reactive, nondysplastic lesions, low-grade lesions (mild OED and moderate OED) and high-grade lesions (HGLs; severe OED/carcinoma in situ).

Synergistic Catalysis of Water-Soluble Exogenous Catalysts and Reservoir Minerals during the Aquathermolysis of Heavy Oil.

Oil serves as the essential fuel and economic foundation of contemporary industry. However, the use of traditional light crude oil has exceeded its supply, making it challenging to meet the energy needs of humanity. Consequently, the extraction of heavy oil has become crucial in addressing this demand.

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.

pH-induced morphological transition of aggregates formed by miktoarm star polymers in dilute solution: a mesoscopic simulation study.

The self-assembly of miktoarm star polymers μ-A (B(D)) C in a neutral solution and the pH-responsive behaviors of vesicles and spherical micelles in an acidic solution have been investigated by DPD simulation. The results show that the self-assembled morphologies can be regulated by the lengths of pH-responsive arm B and hydrophilic arm C, leading to the formation of vesicles, discoidal micelles, and spherical micelles in a neutral solution. The dynamic evolution pathways of vesicles and spherical micelles are categorized into three stages: nucleation, coalescence, and growth.