Expanding the RNA polymerase biocatalyst solution space for mRNA manufacture.

All mRNA products are currently manufactured in in vitro transcription (IVT) reactions that utilize single-subunit RNA polymerase (RNAP) biocatalysts. Although it is known that discrete polymerases exhibit highly variable bioproduction phenotypes, including different relative processivity rates and impurity generation profiles, only a handful of enzymes are generally available for mRNA biosynthesis. This limited RNAP toolbox restricts strategies to design and troubleshoot new mRNA manufacturing processes, which is particularly undesirable given the continuing diversification of mRNA product lines toward larger and more complex molecules.

Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation.

Unlabelled: An in-depth multiomic molecular characterization of PARP inhibitors revealed a distinct poly-pharmacology of niraparib (Zejula) mediated by its interaction with lanosterol synthase (LSS), which is not observed with other PARP inhibitors. Niraparib, in a similar way to the LSS inhibitor Ro-48-8071, induced activation of the 24,25-epoxysterol shunt pathway, which is a regulatory signaling branch of the cholesterol biosynthesis pathway. Interestingly, the combination of an LSS inhibitor with a PARP inhibitor that does not bind to LSS, such as olaparib, had an additive effect on killing cancer cells to levels comparable with niraparib as a single agent.

Recommendation endpoints and safety of an online self-triage for depression symptoms.

Introduction: Online symptom checkers are a way to address patient concerns and potentially offload a burdened healthcare system. However, safety outcomes of self-triage are unknown, so we reviewed triage recommendations and outcomes of our institution's depression symptom checker.

Methods: We examined endpoint recommendations and follow-up encounters seven days afterward during 2 December 2021 to 13 December 2022.

Engineering an Escherichia coli based in vivo mRNA manufacturing platform.

Synthetic mRNA is currently produced in standardized in vitro transcription systems. However, this one-size-fits-all approach has associated drawbacks in supply chain shortages, high reagent costs, complex product-related impurity profiles, and limited design options for molecule-specific optimization of product yield and quality. Herein, we describe for the first time development of an in vivo mRNA manufacturing platform, utilizing an Escherichia coli cell chassis.

A comprehensive clinically informed map of dependencies in cancer cells and framework for target prioritization.

Genetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities to functionally map genetic vulnerabilities. Here, we construct a second-generation map of cancer dependencies by annotating 930 cancer cell lines with multi-omic data and analyze relationships between molecular markers and cancer dependencies derived from CRISPR-Cas9 screens.

A novel multimodal framework for early diagnosis and classification of COPD based on CT scan images and multivariate pulmonary respiratory diseases.

Background And Objective: Chronic Obstructive Pulmonary Disease (COPD) is one of the world's worst diseases; its early diagnosis using existing methods like statistical machine learning techniques, medical diagnostic tools, conventional medical procedures, and other methods is challenging due to misclassification results of COPD diagnosis and takes a long time to perform accurate prediction. Due to the severe consequences of COPD, detection and accurate diagnosis of COPD at an early stage is essential. This paper aims to design and develop a multimodal framework for early diagnosis and accurate prediction of COPD patients based on prepared Computerized Tomography (CT) scan images and lung sound/cough (audio) samples using machine learning techniques, which are presented in this study.

Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment.

Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis.

Genome structure and population genomics of the canine heartworm Dirofilaria immitis.

The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of D.

Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes.

Limited evidence exists on the impact of spatial and temporal heterogeneity of high-grade serous ovarian cancer (HGSOC) on tumor evolution, clinical outcomes, and surgical operability. We perform systematic multi-site tumor mapping at presentation and matched relapse from 49 high-tumor-burden patients, operated up front. From SNP array-derived copy-number data, we categorize dendrograms representing tumor clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favor simpler sympodial evolution.

Non-invasive measurements of respiration and heart rate across wildlife species using Eulerian Video Magnification of infrared thermal imagery.

Background: An animal's metabolic rate, or energetic expenditure, both impacts and is impacted by interactions with its environment. However, techniques for obtaining measurements of metabolic rate are invasive, logistically difficult, and costly. Red-green-blue (RGB) imaging tools have been used in humans and select domestic mammals to accurately measure heart and respiration rate, as proxies of metabolic rate.

Assessing Dehydroepiandrosterone Sulfate (DHEAS) as a novel biomarker for monitoring estrus and successful reproduction in polar bears.

Polar bears (Ursus maritimus) in the wild are under threat due to climate change, primarily loss of sea ice, and experience poor reproductive success in zoos. The polar bear is a seasonally polyestrous species that exhibits embryonic diapause and pseudopregnancy, complicating characterization of reproductive function. Fecal excretion of testosterone and progesterone have been studied in polar bears, but accurately predicting reproductive success remains difficult.

Broadband infrared confocal imaging for applications in additive manufacturing.

We address new measurement challenges relating to 3D printing in metal powder using the powder bed fusion technique. Using a combination of confocal microscopy principles and fast, sensitive mid-infrared collection techniques, we present a compact and versatile method of measuring and analyzing broadband thermal emissions from the vicinity of the molten metal pool during the additive manufacturing process. We demonstrate the benefits of this instrumentation and potential for scientific research as well as in situ monitoring.

Genetic polymorphism, constitutive expression and tissue localization of Dirofilaria immitis P-glycoprotein 11: a putative marker of macrocyclic lactone resistance.

Background: Dirofilaria immitis causes dirofilariosis, a potentially fatal condition in canids. Dirofilaria infections can be prevented with a macrocyclic lactone (ML) prophylactic regimen. However, some D.

Automatic detection of foreign body objects in neurosurgery using a deep learning approach on intraoperative ultrasound images: From animal models to first in-human testing.

Objects accidentally left behind in the brain following neurosurgical procedures may lead to life-threatening health complications and invasive reoperation. One of the most commonly retained surgical items is the cotton ball, which absorbs blood to clear the surgeon's field of view yet in the process becomes visually indistinguishable from the brain parenchyma. However, using ultrasound imaging, the different acoustic properties of cotton and brain tissue result in two discernible materials.

The Accuracy of In-State Prescription Monitoring Program Database and Electronic Medical Records Compared to Urine Toxicology Screening in Total Joint Arthroplasty Preoperative Evaluation.

Preoperative narcotic use is associated with poor postoperative pain management and worse outcomes after total joint arthroplasty (TJA). Therefore, identifying controlled substance use preoperatively is necessary. Electronic medical records (EMRs), prescription monitoring programs (PMP), or urine toxicology screening (UTS) are most commonly used.

Cell Chromatography: Biocompatible Chromatographic Separation and Interrogation of Microbial Cells.

The isolation of pure, single colonies lies at the heart of experimental microbiology. However, a microbial colony typically contains around 1 million cells at all stages of the life cycle. Here, we describe a novel cell chromatography method that facilitates the capture, purification, and interrogation of microbial cell populations from both single and mixed cultures.

Sit-Stand Desks and Physical Self-care Behaviors in a Family Medicine Residency.

Introduction: More than 50% of primary care physicians' practice involves sedentary desk work. Growing evidence suggests a link between sedentary workplace behaviors and increased morbidity and mortality. Research on the effects of sit-stand desks in the workplace suggests that sit-stand desks reduce sedentary behaviors.

: Genotyping Randomly Selected European Clinical Samples and USA Laboratory Isolates with Molecular Markers Associated with Macrocyclic Lactone Susceptibility and Resistance.

is a parasitic nematode and causes dirofilariosis, a potentially fatal pulmonary infection which primarily infects canids. Dirofilariosis infections are controlled via prophylactic macrocyclic lactone (ML) regimens. Recent evidence has confirmed the development of ML-resistant isolates in the USA, which are genetically distinct from wildtype populations.

Outcomes and complications of primary reverse shoulder arthroplasty with minimum of 2 years' follow-up: a systematic review and meta-analysis.

Background: Primary reverse shoulder arthroplasty (rTSA) is an effective treatment option for reducing pain and improving function for patients with rotator cuff tear arthropathy, irreparable rotator cuff tears, glenoid deformity, and other challenging clinical scenarios, including fracture sequelae and revision shoulder arthroplasty. There has been a wide range of reported outcomes and postoperative complication rates reported in the literature. The purpose of this systematic review and meta-analysis is to provide an updated review of the clinical outcomes and complication rates following primary rTSA.

Label-Free Quantification (LFQ) of Fecal Proteins for Potential Pregnancy Detection in Polar Bears.

Reliable pregnancy diagnostics would be beneficial for monitoring polar bear () populations both in situ and ex situ, but currently there is no method of non-invasive pregnancy detection in this species. Recent reports in several carnivore species described the identification of fecal proteins that may serve as pregnancy biomarkers; however, repeatability has been limited. The objective of the current analysis was to utilize an unbiased, antibody-free, label-free method for the identification and quantification of fecal proteins to determine if differences associated with pregnancy are detectable in polar bears.

Ultrasound monitoring of microcirculation: An original study from the laboratory bench to the clinic.

Objective: Monitoring microcirculation and visualizing microvasculature are critical for providing diagnosis to medical professionals and guiding clinical interventions. Ultrasound provides a medium for monitoring and visualization; however, there are challenges due to the complex microscale geometry of the vasculature and difficulties associated with quantifying perfusion. Here, we studied established and state-of-the-art ultrasonic modalities (using six probes) to compare their detection of slow flow in small microvasculature.

One Versus 2-Stage Revision for Shoulder Arthroplasty Infections: A Systematic Review and Analysis of Treatment Selection Bias.

Background: There is controversy regarding the optimal treatment for infection following shoulder arthroplasty. The purpose of this systematic review is to analyze the bias in treatment selection, infection clearance rates, and functional outcomes after 1 versus 2-stage revision surgery for periprosthetic shoulder infections.

Methods: A systematic search strategy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in 4 phases.

Advances in monitoring for acute spinal cord injury: a narrative review of current literature.

Spinal cord injury (SCI) is a devastating condition that affects about 17,000 individuals every year in the United States, with approximately 294,000 people living with the ramifications of the initial injury. After the initial primary injury, SCI has a secondary phase during which the spinal cord sustains further injury due to ischemia, excitotoxicity, immune-mediated damage, mitochondrial dysfunction, apoptosis, and oxidative stress. The multifaceted injury progression process requires a sophisticated injury-monitoring technique for an accurate assessment of SCI patients.

Development of a Smart Hospital Assistant: Integrating Artificial Intelligence and a Voice-User Interface for Improved Surgical Outcomes.

Patient safety and efficiency are top priorities in any surgical procedure. One effective way to achieve these objectives is to automate the logistical and routine tasks that occur in the operating suite. Inspired by smart assistant technology already widely used in the consumer sector, we engineered the Smart Hospital Assistant (SHA), a smart, voice-controlled virtual assistant that handles natural speech recognition while executing non-surgical functions to aid any surgery.