Development of the Esterase PestE for Amide Bond Synthesis Under Aqueous Conditions: Enzyme Cascades for Converting Waste PET into Tamibarotene.

A growing number of hydrolase enzymes show promiscuous acyltransferase activity, even under aqueous conditions. Here we report, for the first time, the ability of Pyrobaculum calidifontis VA1 esterase (PestE) to catalyse the formation of a wide range of amides in buffer, where the acyl donor forms a significant structural component in the amide product. The reactions occur under mild conditions and can achieve conversions up to 97 % in 6 h for formation of N-benzylfuranamide as the model reaction.

Pregnancy and Long-Term Postnatal Outcomes of Congenital Sacrococcygeal Teratoma: A Single Institution's 18-Year Experience.

Objective: The objective of this study is to evaluate outcomes of fetal sacrococcygeal teratoma (SCT) from an academic tertiary center.

Study Design: This is a retrospective study evaluating pregnancy and postnatal outcomes of fetal SCT management at a single institution between 2006 and 2023. Results are reported as median (range).

Predictors of Human Papillomavirus Vaccination in the Postpartum Period for Individuals Aged 18-26.

Human papillomavirus (HPV) vaccination during the postpartum period is an opportunity for vaccine eligible individuals to be vaccinated. Identify predictors of vaccine acceptance in the postpartum period among patients aged 18-26. A retrospective chart review was conducted to evaluate the rate of HPV vaccination to eligible postpartum patients aged 18-26 who delivered between January 2021 and May 2023 at our institution.

Geographic Access to Urogynecology Care in the United States.

Importance: Although access to urogynecologic care is known to influence patient outcomes, less is known regarding geographic access to care and how it may vary by population characteristics.

Objective: The primary objective of this study was to estimate geographic accessibility of urogynecologic services in terms of drive time and by population demographics.

Study Design: We performed a descriptive study using practice location data by zip code for all board-certified urogynecologists who are American Urogynecologic Society members (n = 497) and pelvic floor physical therapists (n = 985).

Salience signaling and stimulus scaling of ventral tegmental area glutamate neuron subtypes.

Ventral tegmental area (VTA) glutamatergic neurons participate in reward, aversion, drug-seeking, and stress. Subsets of VTA VGluT2+ neurons are capable of co-transmitting glutamate and GABA (VGluT2+VGaT+ neurons), transmitting glutamate without GABA (VGluT2+VGaT- neurons), or co-transmitting glutamate and dopamine (VGluT2+TH+ neurons), but whether these molecularly distinct subpopulations show behavior-related differences is not wholly understood. We identified that neuronal activity of each VGluT2+ subpopulation is sensitive to reward value but signaled this in different ways.

Serial and parallel organ-at-risk-specific noncoplanar arc optimization for small versus large target volumes in liver SBRT.

Noncoplanar arc optimization has been shown to reduce OAR doses in SRS/SRT and has the potential to reduce doses to OARs in SBRT. Extracranial targets have additional considerations, including large OARs and, in the case of the liver, volume constraints on the healthy liver. Considering pathlengths through OARs that encompass target volumes may lead to specific dose reductions as in the encompassing healthy liver tissue.

Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial.

The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). In this observer-blind, placebo-controlled, phase 2 trial, healthy adults were randomized (4:1) to receive MVA-BN-Filo (dose 1) and Ad26.

Safety and Immunogenicity of Accelerated Heterologous 2-Dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa.

Background: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings.

Methods: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in 5 sub-Saharan African countries included people without human immunodeficiency virus (HIV) (PWOH, n = 249) and people with HIV (PWH, n = 250). Adult participants received 1 of 2 accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.

Curative Intent Radiation for Anal Cancer in Pelvic Kidney Transplant: A Case Report With an Eight-Year Follow-Up.

The incidence of malignancies seen after solid organ transplant is increasing, and oncologists are seeing more patients with transplanted organs. In this case report, we present how pelvic radiotherapy can be safely administered in a patient with a transplanted kidney by conducting a comprehensive chart review and analyzing the dosimetry in the radiotherapy planning software Eclipse. A 52-year-old female patient received a kidney transplant in 2002 and was diagnosed 11 years later with a cT3 N0 M0 squamous cell carcinoma of the anal canal.

Strengthening Warfighter Resiliency Using Broad-Spectrum or Host-Directed Therapies within the Rapid Acquisition and Investigation of Drugs for Repurposing Program.

To maintain cadence with looming threats in a prolonged field-care environment, the broader medical countermeasure (MCM) enterprise must adopt new strategies for chemical, biological, radiological, and nuclear (CBRN)-addressing drug development. The Countering Emerging Threats - Rapid Acquisition and Investigation of Drugs for Repurposing (CET RAIDR) program within the Joint Program Manager for CBRN Medical is designed to rapidly tackle known, unknown, and emerging threats by utilizing late-stage or licensed therapeutics. The focus of the CET RAIDR effort is to bridge treatment gaps between threat identification and the implementation of licensed targeted MCMs, thereby strengthening warfighter resiliency.

Engineering a Carboxyl Methyltransferase for the Formation of a Furan-Based Bioplastic Precursor.

FtpM from Aspergillus fumigatus was the first carboxyl methyltransferase reported to catalyse the dimethylation of dicarboxylic acids. Here the creation of mutant R166M that can catalyse the quantitative conversion of bio-derived 2,5-furandicarboxylic acid (FDCA) to its dimethyl ester (FDME), a bioplastics precursor, was reported. Wild type FtpM gave low conversion due to its reduced catalytic efficiency for the second methylation step.

An evaluation of clinical psychology input into burns multidisciplinary follow-up clinics.

Introduction: Research highlights the complex psychological needs that patients and their families can face following a burn injury, regardless of the objective severity of the injury and often beyond the timeframe of physical healing. Identification of psychological needs at different stages post-burn recovery is therefore a key role of clinical psychologists working in burn care services.

Method: This paper presents audit data collected across a two-year period in routine paediatric and adult multidisciplinary team follow-up clinics in a UK burns service.

Adapting Simon's Two-Stage Design for Efficient Screening of Filovirus Vaccines in Non-Human Primates.

The cynomolgus monkey () non-human primate (NHP) is widely used for filovirus vaccine testing. To use limited BSL-4 resources efficiently and minimize NHP usage, Simon's two-stage design was adapted to screen candidate Ebola virus (EBOV) vaccines in up to six NHPs with two (optimal), three, or four NHPs in Stage 1. Using the optimal design, two NHPs were tested in Stage 1.

A U.S. Government-Coordinated Effort to Leverage Non-Human Primate Data to Facilitate Ebolavirus Vaccine Development.

A United States Government (USG) interagency group, the Filovirus Animal Non-Clinical Group (FANG), has been established to support the development of biodefense medical countermeasures (MCMs). As both vaccines and therapeutics are licensed using "non-traditional pathways", such as the U.S.

Carboxyl Methyltransferase Catalysed Formation of Mono- and Dimethyl Esters under Aqueous Conditions: Application in Cascade Biocatalysis.

Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono- and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl-l-tyrosine, trans, trans-muconic acid and a number of the dicarboxylic acids tested.

Determining Planning Priorities for SABR for Oligometastatic Disease: A Secondary Analysis of the SABR-COMET Phase II Randomized Trial.

Purpose: SABR may improve survival in patients with oligometastases, but for some lesions, safe delivery of SABR may require a reduction in delivered dose or target coverage. This study assessed the association between target coverage compromise and oncologic and survival outcomes.

Methods And Materials: Patients with a controlled primary malignancy and 1 to 5 oligometastases were randomized (1:2) between standard of care (SOC) treatment and SOC plus SABR.

Selection of Filovirus Isolates for Vaccine Development Programs.

The continuing outbreaks of ebola virus disease highlight the ongoing threat posed by filoviruses. Fortunately, licensed vaccines and therapeutics are now available for . However, effective medical countermeasures, such as vaccines for other filoviruses such as and the Marburg virus, are presently in early stages of development and, in the absence of a large outbreak, would require regulatory approval via the U.

Natural history of disease in cynomolgus monkeys exposed to Ebola virus Kikwit strain demonstrates the reliability of this non-human primate model for Ebola virus disease.

Filoviruses (Family Filoviridae genera Ebolavirus and Marburgvirus) are negative-stranded RNA viruses that cause severe health effects in humans and non-human primates, including death. Except in outbreak settings, vaccines and other medical countermeasures against Ebola virus (EBOV) will require testing under the FDA Animal Rule. Multiple vaccine candidates have been evaluated using cynomolgus monkeys (CM) exposed to EBOV Kikwit strain.

Safety and immunogenicity of a highly attenuated rVSVN4CT1-EBOVGP1 Ebola virus vaccine: a randomised, double-blind, placebo-controlled, phase 1 clinical trial.

Background: The safety and immunogenicity of a highly attenuated recombinant vesicular stomatitis virus (rVSV) expressing HIV-1 gag (rVSVN4CT1-HIV-1gag1) was shown in previous phase 1 clinical studies. An rVSV vector expressing Ebola virus glycoprotein (EBOV-GP) in place of HIV-1 gag (rVSVN4CT1-EBOVGP1) showed single-dose protection from lethal challenge with low passage Ebola virus in non-human primates. We aimed to evaluate the safety and immunogenicity of the rVSVN4CT1-EBOVGP1 vaccine in healthy adults.

Toward the combined optimization of dynamic axes (CODA) for stereotactic radiotherapy and radiosurgery using fixed couch trajectories.

Purpose: To develop a novel system for patient-specific combined optimization of couch, collimator, and gantry angles for use in volumetric modulated arc therapy (VMAT) treatment planning. The system was designed to produce highly compact dose distributions by extensively sampling the 4π space. Automated fixed couch trajectory planning was used to reduce normal tissue doses by avoiding beams-eye-view (BEV) overlap with organs-at-risk (OARs) and improve monitor unit (MU) efficiency through collimator angle optimization.

Approach to Strain Selection and the Propagation of Viral Stocks for Venezuelan Equine Encephalitis Virus Vaccine Efficacy Testing under the Animal Rule.

Licensure of a vaccine to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires use of the U.S. Food and Drug Administration (FDA) Animal Rule to assess vaccine efficacy as human studies are not feasible or ethical.

Development of a highly sensitive in vitro endothelial cell toxicity assay for evaluating ricin toxin A chain-based vaccines or therapeutics.

The ricin toxin A chain (RTA) is responsible for ricin intoxication due to inhibition of protein synthesis. RTA is also known to cause endothelial toxicity [via a 3 amino acid sequence (x)D(y) motif that acts as a natural disintegrin] resulting in vascular leak syndrome (VLS) in humans. An in vitro endothelial cell toxicity (ECT) assay was developed to evaluate if the ricin vaccine candidate (RVEc) exhibited endothelial toxicity, determined by altered transendothelial electrical resistance (TEER) across human umbilical vein endothelial cell (HUVEC) monolayers.

Intra-arc binary collimation algorithm for the optimization of stereotactic radiotherapy treatment of multiple metastases with multiple prescriptions.

Purpose: To design and implement a novel treatment planning algorithm based on a modification of dynamic conformal arc (DCA) therapy for the treatment of multiple cranial metastases with variable prescription doses.

Methods: A workflow was developed in which separate dose matrices were calculated for each target at each control point (i.e.

Comparison of Aerosol- and Percutaneous-acquired Venezuelan Equine Encephalitis in Humans and Nonhuman Primates for Suitability in Predicting Clinical Efficacy under the Animal Rule.

Licensure of medical countermeasure vaccines to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires the use of the Animal Rule to assess vaccine efficacy, because human studies are not feasible or ethical. We therefore performed a retrospective study of VEE cases that occurred in at-risk laboratory workers and support personnel during the United States Biowarfare Program (1943-1969) to better define percutaneous- and aerosol-acquired VEE in humans and to compare these results with those described for the NHP model (in which high-dose aerosol VEEV challenge led to more severe encephalitis than parenteral challenge). Record review and analysis of 17 aerosol- and 23 percutaneous-acquired human cases of VEE included incubation period, symptoms, physical examination findings, and markers of infection.

Situation awareness.

What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article discussed situation awareness, which refers to the ways people collect (perceive), interpret (comprehend) and use information and make decisions (projection).