Depression, Anxiety, and Neuropsychiatric Symptom Burden in a Longitudinal Cohort with Persistent Psychophysical Post-COVID Olfactory Dysfunction.

Background/objectives: Olfactory dysfunction (OD) is associated with a variety of neurologic deficits and impacts socialization decisions, mood, and overall quality of life. As a common symptom comprising the long COVID condition, persistent COVID-19-associated olfactory dysfunction (C19OD) may further impact the presentations of neuropsychiatric sequelae. Our study aims to characterize the longitudinal burden of depression, anxiety, and neuropsychiatric symptoms in a population with C19OD.

Advancements in TGF-β Targeting Therapies for Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide according to GLOBOCAN estimates from 2022. Current therapy options for recurrent or metastatic disease are limited to conventional cytotoxic chemotherapy and immunotherapy, with few targeted therapy options readily available. Recent single-cell transcriptomic analyses identified TGF-β signaling as an important mediator of functional interplays between cancer-associated fibroblasts and a subset of mesenchymal cancer cells.

Increasing the Soluble Expression and Whole-Cell Activity of the Plastic-Degrading Enzyme MHETase through Consensus Design.

The mono(2-hydroxyethyl) terephthalate hydrolase (MHETase) from carries out the second step in the enzymatic depolymerization of poly(ethylene terephthalate) (PET) plastic into the monomers terephthalic acid (TPA) and ethylene glycol (EG). Despite its potential industrial and environmental applications, poor recombinant expression of MHETase has been an obstacle to its industrial application. To overcome this barrier, we developed an assay allowing for the medium-throughput quantification of MHETase activity in cell lysates and whole-cell suspensions, which allowed us to screen a library of engineered variants.

A retrospective chart review assessing antibiotic treatment of hospitalized patients with discordant assays in an urban hospitalized setting.

infection (CDI) threatens vulnerable populations in health care. Two-step testing improves specificity, avoiding over-treatment. This study analyzed inpatient records to estimate diagnostic outcomes and identify characteristics associated with treatment after discordant testing.

Academic Half Day Improves Resident Perception of Education Without Compromising Patient Safety.

Background: Residency programs are required to offer a didactic curriculum and protect resident time for education. Our institution implemented an academic half day (AHD) in the 2021-2022 academic year to address issues related to the standard noon conference series.

Objective: Determine the impact of AHD implementation on education, patient safety, and workflow.

Do young adults complete health care proxies before anesthesia?

Background: Health care proxy (HCP) completion rates by older adults are relatively low; however, not much is known about proxy completion rates by younger adults.

Objectives: This study aimed to identify HCP completion rates amongst 18-21 year old young adults without intellectual disabilities admitted to a pediatric hospital peri-anesthesia care unit (PACU) and determine whether there was an association with any demographic factors.

Methods: Retrospective chart review was performed to describe demographic variables, presence of HCP, and relationship to proxy.

A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein.

The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics.

The more you know: Insights from integrated pre-visit surveys in a pediatric environmental health center.

The Pediatric Environmental Health Center (PEHC) at Boston Children's Hospital is a specialty referral clinic that provides consultation for approximately 250 patients annually. Identifying environmental hazards is key for clinical management. Exposure concerns include lead, mold, pesticides, perfluoroalkyl substances (PFAS), impaired air quality, and more.

Analysis of insertions and extensions in the functional evolution of the ribonucleotide reductase family.

Ribonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by primary sequence and cofactor requirement, while sharing a conserved fold and radical-based mechanism for nucleotide reduction. In this work, we expand on our recent phylogenetic inference of the entire RNR family and describe the evolutionarily relatedness of insertions and extensions around the structurally homologous catalytic barrel.

Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade.

Ribonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by primary sequence and cofactor requirement, while sharing a conserved fold and radical-based mechanism for nucleotide reduction. Here, we structurally aligned the diverse RNR family by the conserved catalytic barrel to reconstruct the first large-scale phylogeny consisting of 6779 sequences that unites all extant classes of the RNR family and performed evo-velocity analysis to independently validate our evolutionary model.

Ancestral Sequence Reconstruction Identifies Structural Changes Underlying the Evolution of PETase and Variants with Improved Stability and Activity.

The improved production, recycling, and removal of plastic waste, such as polyethylene terephthalate (PET), are pressing environmental and economic issues for society. Biocatalytic (enzymatic) PET depolymerization is potentially a sustainable, low-energy solution to PET recycling, especially when compared with current disposal methods such as landfills, incineration, or gasification. IsPETase has been extensively studied for its use in PET depolymerization; however, its evolution from cutinases is not fully understood, and most engineering studies have neglected the majority of the available sequence space remote from the active site.

Evo-velocity: Protein language modeling accelerates the study of evolution.

Understanding how protein sequences have evolved is one of the defining challenges in modern biology. In this issue of Cell Systems, Hie et al. describe a novel phylogenetic approach, dubbed "evo-velocity," that exploits protein language modeling to overcome many limitations of traditional phylogenetic analysis.

Postoperative Use of Ketorolac Improves Pain Management and Decreases Narcotic Use Following Primary Cleft Palate Surgery.

Objective: To study the efficacy and safety profile of ketorolac in cleft palate surgery.

Design: Retrospective analysis of patients who underwent primary cleft palate surgery and received either postoperative ketorolac or opioids.

Setting: Tertiary care children's hospital.

The effect of nutritional status on post-operative outcomes in pediatric otolaryngology-head and neck surgery.

Introduction: Nutritional status can affect surgical patients in terms of stress response, healing time, and outcomes. Several abnormalities are known to have a high prevalence in the general population such as vitamin D deficiency (VDD) and subclinical hypothyroidism. We hypothesized that there will be elevated rates of nutritional deficiencies in preoperative patients which may adversely affect postoperative outcomes following pediatric otolaryngology surgery.

micro-RNA-486-5p protects against kidney ischemic injury and modifies the apoptotic transcriptome in proximal tubules.

Acute kidney injury (AKI) carries high morbidity and mortality, and effective treatments are lacking. Preclinical models support involvement of micro-RNAs (miRs) in AKI pathogenesis, although effects on the kidney transcriptome are unclear. We previously showed that injection of cord blood endothelial colony forming cell-derived exosomes, enriched in miR-486-5p, prevented ischemic AKI in mice.

Longitudinal typing of molecular HIV clusters in a statewide epidemic.

Background: HIV molecular epidemiology is increasingly integrated into public health prevention. We conducted cluster typing to enhance characterization of a densely sampled statewide epidemic towards informing public health.

Methods: We identified HIV clusters, categorized them into types, and evaluated their dynamics between 2004 and 2019 in Rhode Island.

Ancestral sequence reconstruction for protein engineers.

In addition to its value in the study of molecular evolution, ancestral sequence reconstruction (ASR) has emerged as a useful methodology for engineering proteins with enhanced properties. Proteins generated by ASR often exhibit unique or improved activity, stability, and/or promiscuity, all of which are properties that are valued by protein engineers. Comparison between extant proteins and evolutionary intermediates generated by ASR also allows protein engineers to identify substitutions that have contributed to functional innovation or diversification within protein families.

A Comprehensive Phylogenetic Analysis of the Serpin Superfamily.

Serine protease inhibitors (serpins) are found in all kingdoms of life and play essential roles in multiple physiological processes. Owing to the diversity of the superfamily, phylogenetic analysis is challenging and prokaryotic serpins have been speculated to have been acquired from Metazoa through horizontal gene transfer due to their unexpectedly high homology. Here, we have leveraged a structural alignment of diverse serpins to generate a comprehensive 6,000-sequence phylogeny that encompasses serpins from all kingdoms of life.

Pharmacists' nonprescription syringe dispensing perceptions and behaviors: A three-state descriptive analysis.

Background: One approach to increasing the reach of syringe programs in rural areas could be through provision of syringes at community pharmacies. This study evaluated relationships between state-specific syringe policies, pharmacy, and pharmacist characteristics and pharmacists' nonprescription syringe dispensing behaviors in a 3- state Appalachian region at high risk for HIV and HCV transmission.

Methods: We conducted a telephone census of community pharmacies in the Appalachian counties of North Carolina, Tennessee, and Virginia from April-June 2018.

Empirical comparison of analytical approaches for identifying molecular HIV-1 clusters.

Public health interventions guided by clustering of HIV-1 molecular sequences may be impacted by choices of analytical approaches. We identified commonly-used clustering analytical approaches, applied them to 1886 HIV-1 Rhode Island sequences from 2004-2018, and compared concordance in identifying molecular HIV-1 clusters within and between approaches. We used strict (topological support ≥ 0.

Challenges in evaluating the use of viral sequence data to identify HIV transmission networks for public health.

Great efforts are devoted to end the HIV epidemic as it continues to have profound public health consequences in the United States and throughout the world, and new interventions and strategies are continuously needed. The use of HIV sequence data to infer transmission networks holds much promise to direct public heath interventions where they are most needed. As these new methods are being implemented, evaluating their benefits is essential.

Novel Use of Biphasic Cuirass Ventilation During Definitive Radiation Therapy: A Technical Report.

The use of biphasic cuirass ventilator supported radiation therapy has never been documented. We present the first technical report here. A 57-year-old man with obstructive sleep apnea presented with a T0N1M0 right sided, human papillomavirus related head and neck cancer diagnosed on excisional lymph node biopsy.