Liberating Structures in Strategic Planning: Methods to Foster Engagement.

This paper describes the innovative approach of using liberating structures to the development of the AUR 2023 strategic plan, and lessons learned in their application. The 2023 strategic plan built on the results and approach of the prior 2015 plan. Similar to the 2015 strategic plan, traditional tools such as a SWOT analysis and strategic retreat were used.

Proactive Decision Support for Glaucoma Treatment: Predicting Surgical Interventions with Clinically Available Data.

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery and 592 patients who did not undergo surgery. The data types used for prediction included patient demographics, history of systemic conditions, medication history, ophthalmic measurements, 24-2 VF results, and thickness measurements from OCT imaging.

Bioabsorbable Screw Fixation Provides Good Results With Low Failure Rates at Mid-term Follow-up of Stable Osteochondritis Dissecans Lesions That Do Not Improve With Initial Conservative Treatment.

Purpose: To evaluate the clinical and radiographic outcomes of patients who have undergone bioabsorbable screw fixation for intact, stable grade I and II osteochondritis dissecans (OCD) lesions for which at least 6 months of conservative management has failed.

Methods: A retrospective review of prospectively collected data from a single institution was performed to identify patients who underwent internal fixation of stable grade I and II OCD lesions (according to the Guhl classification) between January 2010 and January 2020. Patients were included regardless of the presence of concomitant procedures.

Whole-body galactose oxidation as a robust functional assay to assess the efficacy of gene-based therapies in a mouse model of Galactosemia.

Despite the implementation of lifesaving newborn screening programs and a galactose-restricted diet, many patients with classic galactosemia develop long-term debilitating neurological deficits and primary ovarian insufficiency. Previously, we showed that the administration of human mRNA predominantly expressed in the gene-trapped mouse liver augmented the expression of hepatic GALT activity, which decreased not only galactose-1 phosphate (gal-1P) in the liver but also peripheral tissues. Since each peripheral tissue requires distinct methods to examine the biomarker and/or GALT effect, this highlights the necessity for alternative strategies to evaluate the overall impact of therapies.

Oral COVID-19 Antiviral Uptake Among a Highly Vaccinated US Cohort of Adults With SARS-CoV-2 Infection Between December 2021 and October 2022.

Background: We described the oral nirmatrelvir/ritonavir (NMV/r) and molnupiravir (MOV) uptake among a subgroup of highly vaccinated adults in a US national prospective cohort who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 12/2021 and 10/2022.

Methods: We estimate antiviral uptake within 5 days of SARS-CoV-2 infection, as well as age- and gender-adjusted antiviral uptake prevalence ratios by antiviral eligibility (based on age and comorbidities), sociodemographic characteristics, and clinical characteristics including vaccination status and history of long coronavirus disease 2019 (COVID).

Results: NMV/r uptake was 13.

Change in Posterior Tibial Slope Angle After Displaced Pediatric Tibial Tubercle Fracture: A Model for Growth Modulation in the ACL-Deficient Knee.

Background: Increased posterior tibial slope angle (PTSA) has been shown to be an important risk factor for anterior cruciate ligament (ACL) injury. PTSA modulation is not utilized routinely to reduce risk of primary rupture or graft failure. Displaced tibial tubercle (TT) fractures in the skeletally immature are associated with potential growth arrest and may be used as a model to study PTSA changes in this setting.

Determination of sulfadoxine and pyrimethamine in microvolume human plasma using ultra high performance liquid chromatography-tandam mass spectrometry.

To support the pharmacokinetic study of sulfadoxine (SD) and pyrimethamine (PM) in pregnant women and children, sensitive methods with small sample volume are desirable. Here we report a method to determine SD and PM with microvolume plasma samples: 5 µL plasma samples were cleaned up by protein precipitation with acetonitrile. The deuterated analytes were used as the internal standards.

A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.

In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies.

Multispecies-targeting siRNAs for the modulation of JAK1 in the skin.

Identifying therapeutic oligonucleotides that are cross-reactive to experimental animal species can dramatically accelerate the process of preclinical development and clinical translation. Here, we identify fully chemically-modified small interfering RNAs (siRNAs) that are cross-reactive to Janus kinase 1 (JAK1) in humans and a large variety of other species. We validated the identified siRNAs in silencing JAK1 in cell lines and skin tissues of multiple species.

Integrated germline and somatic features reveal divergent immune pathways driving ICB response.

Immune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however mechanisms determining patient response remain poorly understood. Here we used machine learning to predict ICB response from germline and somatic biomarkers and interpreted the learned model to uncover putative mechanisms driving superior outcomes. Patients with higher T follicular helper infiltrates were robust to defects in the class-I Major Histocompatibility Complex (MHC-I).

Absolute Photoionization Cross Section and Dissociative Ionization Pathways of Alpha-Pinene.

The absolute photoionization cross section of the monoterpenoid, alpha-pinene (AP), is presented together with the relative photoionization cross sections of its dissociative fragments for the first time. Experiments are performed via multiplexed vacuum ultraviolet (VUV) synchrotron photoionization (PI) mass spectrometry in the 8.0-11.

XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells.

Emerging data suggest that induction of viral mimicry responses through activation of double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy. One approach to induce viral mimicry is to target molecular regulators of dsRNA sensing pathways. Here, we show that the exoribonuclease XRN1 is a negative regulator of the dsRNA sensor protein kinase R (PKR) in cancer cells with high interferon-stimulated gene expression.

Methylation of NRIP3 Is a Synthetic Lethal Marker for Combined PI3K and ATR/ATM Inhibitors in Colorectal Cancer.

Introduction: The aim of this study was to investigate the epigenetic regulation and underlying mechanism of NRIP3 in colorectal cancer (CRC).

Methods: Eight cell lines (SW480, SW620, DKO, LOVO, HT29, HCT116, DLD1, and RKO), 187 resected margin samples from colorectal cancer tissue, 146 cases with colorectal adenomatous polyps, and 308 colorectal cancer samples were used. Methylation-specific PCR, Western blotting, RNA interference assay, and a xenograft mouse model were used.

Vaginal fatty acid response mechanisms reveal a novel strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by -deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by instead of , which has more beneficial health associations. Strategies to promote and inhibit are thus needed.

HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant.

Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection.

Kids name the darndest things: confrontation naming in pediatric neuropsychology.

Few confrontation naming tests are designed for pediatric populations. The Children's Visual Naming Test (cVNT; Hamberger et al., 2018) was developed to fill this gap.

Ion emission from 1-10 MDa salt clusters: individual charge state resolution with charge detection mass spectrometry.

Salt cluster ions produced by electrospray ionization are used for mass calibration and fundamental investigations into cluster stability and charge separation processes. However, previous studies have been limited to relatively small clusters owing to the heterogeneity associated with large, multiply-charged clusters that leads to unresolved signals in conventional / spectra. Here, charge detection mass spectrometry is used to measure both the mass and charge distributions of positively charged clusters of KCl, CaCl, and LaCl with masses between ∼1 and 10 MDa by dynamically measuring the energy per charge, /, charge, and mass of simultaneously trapped individual ions throughout a 1 s trapping time.

A randomised, double-blind, comparative study of preoperative magnesium sulphate versus zinc sulphate gargle for prevention of postoperative sore throat following endotracheal intubation.

Background And Aims: Magnesium sulphate and zinc sulphate have been reported to attenuate postoperative sore throat (POST). The study aims to compare the effect of preoperative magnesium sulphate and zinc sulphate gargle on the incidence and severity of POST following endotracheal intubation within 24 h.

Methods: After ethics committee approval, 132 patients were randomly allocated to three groups (M, Z and D).

Deconvolution of multichannel LC-MS/MS chromatograms of glucosamine-phosphates: Evidence of a GlmS regulatory difference between and .

Resolving isomeric analytes is challenging given their physical similarity - making chromatographic resolution difficult, and their identical masses - making simple mass resolution impossible. MS/MS data provides a means to resolve isomeric analytes if their MS/MS intensity profiles are sufficiently different. Glucosamine-6-phosphate (GlcN-6P) and glucosamine-1-phosphate (GlcN-1P) are early bacterial cell wall intermediates.

Development and application of LC-MS/MS method for the quantification of hydrogen sulfide in the eye.

There are limited studies that report the physiological levels of HS in the eye. The currently available UV/Vis methods lack the required sensitivity and precision. Hence, the purpose of this study was to develop and validate a sensitive and robust pre-column derivatization LC-MS/MS method to measure changes in HS levels in tissues from isolated porcine eyes.

Effects of ozone dose on brominated DBPs in subsequent chlor(am)ination: A comprehensive study of aliphatic, alicyclic and aromatic DBPs.

Ozone‒chlor(am)ine is a commonly used combination of disinfectants in drinking water treatment. Although there are quite a few studies on the formation of some individual DBPs in the ozone‒chlor(am)ine disinfection, an overall picture of the DBP formation in the combined disinfection is largely unavailable. In this study, the effects of ozone dose on the formation and speciation of organic brominated disinfection byproducts (DBPs) in subsequent chlorination, chloramination, or chlorination‒chloramination of simulated drinking water were investigated.

Cardiac-Targeting Peptide: From Discovery to Applications.

Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adenoviral, lentiviral, and adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell-penetrating peptides (CPP) are 5-30-amino-acid-long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form.