Social-Economic Backgrounds to US County-Based COVID-19 Deaths: PLS-SEM Analysis.

Unlabelled: A complex interplay of social, economic, and environmental factors drove the COVID-19 epidemic. Understanding these factors is crucial in explaining the racial disparities observed in COVID-19 deaths. This research investigated various hypotheses, including ecological, racial, demographic, economic, and political party factors, to determine their impact on COVID-19 deaths.

Evaluating cPILOT Data toward Quality Control Implementation.

Multiplexing enables the monitoring of hundreds to thousands of proteins in quantitative proteomics analyses and increases sample throughput. In most mass-spectrometry-based proteomics workflows, multiplexing is achieved by labeling biological samples with heavy isotopes via precursor isotopic labeling or isobaric tagging. Enhanced multiplexing strategies, such as combined precursor isotopic labeling and isobaric tagging (cPILOT), combine multiple technologies to afford an even higher sample throughput.

Enhanced Multiplexing Technology for Proteomics.

The identification of thousands of proteins and their relative levels of expression has furthered understanding of biological processes and disease and stimulated new systems biology hypotheses. Quantitative proteomics workflows that rely on analytical assays such as mass spectrometry have facilitated high-throughput measurements of proteins partially due to multiplexing. Multiplexing allows proteome differences across multiple samples to be measured simultaneously, resulting in more accurate quantitation, increased statistical robustness, reduced analysis times, and lower experimental costs.

Intron-rich dinoflagellate genomes driven by Introner transposable elements of unprecedented diversity.

Spliceosomal introns, which interrupt nuclear genes, are ubiquitous features of eukaryotic nuclear genes. Spliceosomal intron evolution is complex, with different lineages ranging from virtually zero to thousands of newly created introns. This punctate phylogenetic distribution could be explained if intron creation is driven by specialized transposable elements ("Introners"), with Introner-containing lineages undergoing frequent intron gain.

Strain-triggered acidification in a double-network hydrogel enabled by multi-functional transduction of molecular mechanochemistry.

Recent work has demonstrated that force-triggered mechanochemical reactions within a polymeric material are capable of inducing measurable changes in macroscopic material properties, but examples of bulk property changes without irreversible changes in shape or structure are rare. Here, we report a double-network hydrogel that undergoes order-of-magnitude increases in acidity when strained, while recovering its initial shape after large deformation. The enabling mechanophore design is a 2-methoxy--dichlorocyclopropane mechanoacid that is gated within a fused methyl methoxycyclobutene carboxylate mechanophore structure.

Quantitative proteomics to study aging in rabbit spleen tissues.

Aging is a process that occurs in tissues and across species, leading to the degradation of many biological processes. We previously demonstrated that rabbits are a feasible model for studying aging due to their genetic homology and relatively short lifespan in comparison to humans. We utilized a cPILOT multiplexing strategy to identify proteomic changes in spleen tissues of young, middle, and old aged rabbits.

Analysis of a Real-World Progression Variable and Related Endpoints for Patients with Five Different Cancer Types.

Introduction: We previously demonstrated that real-world progression (rwP) can be ascertained from unstructured electronic health record (EHR)-derived documents using a novel abstraction approach for patients with advanced non-small cell lung cancer (base case). The objective of this methodological study was to assess the reliability, clinical relevance, and the need for disease-specific adjustments of this abstraction approach in five additional solid tumor types.

Methods: Patients with metastatic breast cancer (mBC), advanced melanoma (aMel), small cell lung cancer (SCLC), metastatic renal cell carcinoma (mRCC), and advanced gastric/esophageal cancer (aGEC) were selected from a real-world database.

Toughening hydrogels through force-triggered chemical reactions that lengthen polymer strands.

The utility and lifetime of materials made from polymer networks, including hydrogels, depend on their capacity to stretch and resist tearing. In gels and elastomers, those mechanical properties are often limited by the covalent chemical structure of the polymer strands between cross-links, which is typically fixed during the material synthesis. We report polymer networks in which the constituent strands lengthen through force-coupled reactions that are triggered as the strands reach their nominal breaking point.

Coupling of spliceosome complexity to intron diversity.

We determined that over 40 spliceosomal proteins are conserved between many fungal species and humans but were lost during the evolution of S. cerevisiae, an intron-poor yeast with unusually rigid splicing signals. We analyzed null mutations in a subset of these factors, most of which had not been investigated previously, in the intron-rich yeast Cryptococcus neoformans.

Effects of Overweight and Obesity on Running Mechanics in Children.

Purpose: The purpose of this study is to determine differences in running mechanics between healthy weight (HW) children and children classified as OW/OB.

Methods: Forty-two children (17 OW/OB, 25 HW) ran overground while kinematic and kinetic data were recorded using a motion capture system and force plate. Kinematic variables of interest included stance time, step length, and frontal and sagittal plane joint angles and excursions at the hip, knee, and ankle.

Single-Event Spectroscopy and Unravelling Kinetics of Covalent Domains Based on Cyclobutane Mechanophores.

Mechanochemical reactions that lead to an increase in polymer contour length have the potential to serve as covalent synthetic mimics of the mechanical unfolding of noncovalent "stored length" domains in structural proteins. Here we report the force-dependent kinetics of stored length release in a family of covalent domain polymers based on -1,2-substituted cyclobutane mechanophores. The stored length is determined by the size () of a fused ring in an [.

Characterization of a Real-World Response Variable and Comparison with RECIST-Based Response Rates from Clinical Trials in Advanced NSCLC.

Introduction: Effectiveness metrics for real-word research, analogous to clinical trial ones, are needed. This study aimed to develop a real-world response (rwR) variable applicable to solid tumors and to evaluate its clinical relevance and meaningfulness.

Methods: This retrospective study used patient cohorts with advanced non-small cell lung cancer from a nationwide, de-identified electronic health record (EHR)-derived database.

Substituent Effects in Mechanochemical Allowed and Forbidden Cyclobutene Ring-Opening Reactions.

Woodward and Hoffman once jested that a very powerful Maxwell demon could seize a molecule of cyclobutene at its methylene groups and tear it open in a disrotatory fashion to obtain butadiene (Woodward, R. B.; Hoffmann, R.

Mechanism Dictates Mechanics: A Molecular Substituent Effect in the Macroscopic Fracture of a Covalent Polymer Network.

The fracture of rubbery polymer networks involves a series of molecular events, beginning with conformational changes along the polymer backbone and culminating with a chain scission reaction. Here, we report covalent polymer gels in which the macroscopic fracture "reaction" is controlled by mechanophores embedded within mechanically active network strands. We synthesized poly(ethylene glycol) (PEG) gels through the end-linking of azide-terminated tetra-arm PEG ( = 5 kDa) with bis-alkyne linkers.

Detailed Protocol for the Novel and Scalable Viral Vector Upstream Process for AAV Gene Therapy Manufacturing.

Recombinant adeno-associated viral (rAAV) vector-based gene therapy has been adapted for use in more than 100 clinical trials. This is mainly because of its excellent safety profile, ability to target a wide range of tissues, stable transgene expression, and significant clinical benefit. However, the major challenge is to produce a high-titer, high-potency vector to achieve a better therapeutic effect.

Molecular Evolution: RNA Splicing Machinery Moonlights in Junk Removal.

A close relative of vertebrates solves the problem of gene-disrupting transposable element insertions by splicing them out at the RNA level. Why is such an elegant solution so rare across eukaryotes?

Generating Real-World Tumor Burden Endpoints from Electronic Health Record Data: Comparison of RECIST, Radiology-Anchored, and Clinician-Anchored Approaches for Abstracting Real-World Progression in Non-Small Cell Lung Cancer.

Introduction: Real-world evidence derived from electronic health records (EHRs) is increasingly recognized as a supplement to evidence generated from traditional clinical trials. In oncology, tumor-based Response Evaluation Criteria in Solid Tumors (RECIST) endpoints are standard clinical trial metrics. The best approach for collecting similar endpoints from EHRs remains unknown.

Association of Patient Characteristics and Tumor Genomics With Clinical Outcomes Among Patients With Non-Small Cell Lung Cancer Using a Clinicogenomic Database.

Importance: Data sets linking comprehensive genomic profiling (CGP) to clinical outcomes may accelerate precision medicine.

Objective: To assess whether a database that combines EHR-derived clinical data with CGP can identify and extend associations in non-small cell lung cancer (NSCLC).

Design, Setting, And Participants: Clinical data from EHRs were linked with CGP results for 28 998 patients from 275 US oncology practices.

Comparison of Surface-Bound and Free-Standing Variations of HKUST-1 MOFs: Effect of Activation and Ammonia Exposure on Morphology, Crystallinity, and Composition.

Metal-organic frameworks (MOFs) are extremely porous, crystalline materials with high surface area for potential use in gas storage, sequestration, and separations. Toward incorporation into structures for these applications, this study compares three variations of surface-bound and free-standing HKUST-1 MOF structures: surface-anchored MOF (surMOF) thin film, drop-cast film, and bulk powder. Herein, effects of HKUST-1 ammonia interaction and framework activation, which is removal of guest molecules via heat, are investigated.

Reducing Impact Loading in Runners: A One-Year Follow-up.

Unlabelled: Increased vertical impact loading during running has been associated with a variety of running related injuries including stress fractures, patellofemoral pain, and plantar fasciitis.

Purpose: The purpose of this study was to examine the acute and long-term effect of a gait retraining program aimed at teaching runners with high impact loading to run softer.

Methods: Nineteen runners with high tibial shock (TS) first underwent a control period of eight sessions of treadmill running over 2 wk, progressing from 15 to 30 min.

Effect of Footwear on Dynamic Stability during Single-leg Jump Landings.

Barefoot and minimal footwear running has led to greater interest in the biomechanical effects of different types of footwear. The effect of running footwear on dynamic stability is not well understood. The purpose of this study was to compare dynamic stability and impact loading across 3 footwear conditions; barefoot, minimal footwear and standard running shoes.

Is the New Heroin Epidemic Really New? Racializing Heroin.

Heroin abuse as an outcome of the prior use of painkillers increased rapidly over the past decade. This "new epidemic" is unique because the new heroin users are primarily young White Americans in rural areas of virtually every state. This commentary argues that the painkiller-to-heroin transition could not be the only cause of heroin use on such a scale and that the new and old heroin epidemics are linked.