The Biomechanics Research and Innovation Challenge: Development, Implementation, Uptake, and Reflections on the Inaugural Program.

Biomechanics as a discipline is ideally placed to increase awareness and participation of girls and women in science, technology, engineering, and mathematics. A nationwide Biomechanics and Research Innovation Challenge (BRInC) centered on mentoring and role modeling was developed to engage high school girls (mentees) and early-mid-career women (mentors) in the field of biomechanics through the completion of a 100-day research and/or innovation project. This manuscript describes the development, implementation, and uptake of the inaugural BRInC program and synthesizes the research and innovation projects undertaken, providing a framework for adoption of this program within the global biomechanics community.

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability.

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol).

Characterizing a panel of amino acid auxotrophs under auxotrophic starvation conditions.

Auxotrophic strains starving for their cognate nutrient, termed auxotrophic starvation, are characterized by a shorter lifespan, higher glucose wasting phenotype, and inability to accomplish cell cycle arrest when compared to a "natural starvation," where a cell is starving for natural environmental growth-limiting nutrients such as phosphate. Since evidence of this physiological response is limited to only a subset of auxotrophs, we evaluated a panel of auxotrophic mutants to determine whether these responses are characteristic of a broader range of amino acid auxotrophs. Based on the starvation survival kinetics, the panel of strains was grouped into three categories-short-lived strains, strains with survival similar to a prototrophic wild type strain, and long-lived strains.

Evaluating the sensitivity of newborn rats and newborn hamsters to oncogenic DNA.

To evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cell lines, we have been establishing in vivo assays to quantify the oncogenic activity of DNA. We had generated three oncogene-expression plasmids: pMSV-T24-H-ras, which expresses activated H-ras; pMSV-c-myc, which expresses c-myc; and pMSV-T24-H-ras/MSV-c-myc, which expresses both oncogenes. Tumors were induced in mice by pMSV-T24-H-ras plus pMSV-c-myc or by pMSV-T24-H-ras/MSV-c-myc.

Human Intestinal Dendritic Cells Can Overcome Retinoic Acid Signaling to Generate Proinflammatory CD4 T Cells with Both Gut and Skin Homing Properties.

Retinoic acid, produced by intestinal dendritic cells (DCs), promotes T cell trafficking to the intestinal mucosa by upregulating α4β7 integrin and inhibiting the generation of cutaneous leukocyte Ag (CLA) required for skin entry. In the present study, we report that activation of human naive CD4 T cells in an APC-free system generates cells expressing α4β7 alone; in contrast, activation by intestinal DCs that produce retinoic acid and induce high levels of α4β7 also results in CLA expression, generating CLA+α4β7+ "dual tropic" cells, with both gut and skin trafficking potential, that also express high levels of α4β1 integrin. DC generation of CLA+α4β7+ T cells is associated with upregulation of FUT7, a fucosyltransferase involved in CLA generation; requires cell contact; and is enhanced by IL-12/IL-23.

Immune Effects of Cryoablation in Woodchuck Hepatocellular Carcinoma.

Objectives: Local and systemic immune responses evoked by locoregional therapies such as cryoablation are incompletely understood. The aim of this study was to characterize cryoablation-related immune response and the capacity of immune drugs to augment immunity upon cryoablation for the treatment of hepatocellular carcinoma (HCC) using a woodchuck hepatocellular carcinoma model.

Materials And Methods: Twelve woodchucks chronically infected with woodchuck hepatitis virus and with hepatocellular carcinoma underwent imaging with contrast-enhanced CT.

Extremely thermoacidophilic archaea for metal bioleaching: What do their genomes tell Us?

Elevated temperatures favor bioleaching processes through faster kinetics, more favorable mineral chemistry, lower cooling requirements, and less surface passivation. Extremely thermoacidophilic archaea from the order Sulfolobales exhibit novel mechanisms for bioleaching metals from ores and have great potential. Genome sequences of many extreme thermoacidophiles are now available and provide new insights into their biochemistry, metabolism, physiology and ecology as these relate to metal mobilization from ores.

COVID-19 impact on facial trauma: Insights from Mississippi's only level 1 trauma center.

Purpose: Our primary aim was to understand and describe the impact of COVID-19 on the incidence and etiology of facial trauma in the state of Mississippi.

Methods: Retrospective review of facial trauma-related Emergency Department encounters in Mississippi from March 11, 2019 to March 10, 2021, divided into three time periods using the state of Mississippi's Governor's Office Executive Orders. Chi-square tests and segmented linear regressions were used for analysis.

Use of Resonant Acoustic Mixing Technology for Ultra-Low-Dose Blending in a Single-Step Mixing Process.

Purpose: To evaluate the use of resonant acoustic mixing (RAM) technology for homogenous blending of a morphologically challenging model API in low-dose concentrations (<0.1% w/w), and assess the potential for blend uniformity (BU) optimization.

Methods: Caffeine (CAF) mixing was carried out using a LabRAM I benchtop mixer.

Next-generation phenotyping: introducing phecodeX for enhanced discovery research in medical phenomics.

Motivation: Phecodes are widely used and easily adapted phenotypes based on International Classification of Diseases codes. The current version of phecodes (v1.2) was designed primarily to study common/complex diseases diagnosed in adults; however, there are numerous limitations in the codes and their structure.

The Psychosocial Impact of the COVID-19 Pandemic on Families of Youth of Color: A Prospective Cohort Study.

Objective: Prospectively examine racial and ethnic disparities in exposure to COVID-19-related stressors and their impact on families.

Methods: A racially, ethnically, and socioeconomically diverse cohort of caregivers of youth (n = 1,581) representative of the population served by a pediatric healthcare system completed the COVID-19 Exposure and Family Impact Scales in Oct/Nov 2020 and March/April 2021. Linear mixed-effects models were used to examine exposure to COVID-19-related events (Exposure), impact of the pandemic on family functioning and well-being (Impact), and child and parent distress (Distress) across time and as a function of race and ethnicity, adjusting for other sociodemographic variables.

The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care.

Polygenic risk scores (PRSs) hold promise for disease risk assessment and prevention. The Genomic Medicine at Veterans Affairs (GenoVA) Study is addressing three main challenges to the clinical implementation of PRSs in preventive care: defining and determining their clinical utility, implementing them in time-constrained primary care settings, and countering their potential to exacerbate healthcare disparities. The study processes used to test patients, report their PRS results to them and their primary care providers (PCPs), and promote the use of those results in clinical decision-making are modeled on common practices in primary care.

Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology.

Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection.

The 2023 American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine Pediatric and Adult Brain Death/Death by Neurologic Criteria Determination Consensus Guidelines: What the Critical Care Team Needs to Know.

Guidelines for brain death/death by neurologic criteria (BD/DNC) determination were revised to provide a consistent and updated approach to BD/DNC evaluation across all ages by the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine. This article is intended to complement the guidelines and highlight aspects relevant to the critical care community; the actual guidelines should be used to update hospital protocols and dictate clinical practice. Because BD/DNC evaluations are conducted in the ICU, it is essential for members of the critical care community to familiarize themselves with these guidelines.

Detections in England, Jersey, and Guernsey during 2020-2023 Reveal Newly Affected Areas and Infections by the CHV1 Mycovirus.

In England, was detected for the first time in 2011 in a nursery and in 2016 in the wider environment. Surveys between 2017 and 2020 identified the disease at different sites in Berkshire, Buckinghamshire, Cornwall, Derbyshire, Devon, Dorset, London, West Sussex, and the island of Jersey, while the present study comprises the results of the 2020-2023 survey with findings in Derbyshire, Devon, Kent, Nottinghamshire, Herefordshire, Leicestershire, London, West Sussex, and the islands of Jersey and Guernsey. A total of 226 suspected samples were collected from 72 surveyed sites, as far north as Edinburgh and as far west as Plymouth (both of which were negative), and 112 samples tested positive by real-time PCR and isolation from 35 sites.

Unlocking Potentially Therapeutic Phytochemicals in Capadulla () from Guyana Using Untargeted Mass Spectrometry-Based Metabolomics.

is thought to have a wide variety of therapeutic phytochemicals that allegedly improve libido and cure impotence. Although a few biomarkers have been identified with potential antinociceptive and cytotoxic properties, an untargeted mass spectrometry-based metabolomics approach has never been undertaken to identify therapeutic biofingerprints for conditions, such as erectile dysfunction, in men. This study executes a preliminary phytochemical screening of the woody vine of two ecotypes of with renowned differences in therapeutic potential for erectile dysfunction.

A B7-H4-Targeting Antibody-Drug Conjugate Shows Antitumor Activity in PARPi and Platinum-Resistant Cancers with B7-H4 Expression.

Purpose: Platinum and PARP inhibitors (PARPi) demonstrate activity in breast and ovarian cancers, but drug resistance ultimately emerges. Here, we examine B7-H4 expression in primary and recurrent high-grade serous ovarian carcinoma (HGSOC) and the activity of a B7-H4-directed antibody-drug conjugate (B7-H4-ADC), using a pyrrolobenzodiazepine-dimer payload, in PARPi- and platinum-resistant HGSOC patient-derived xenograft (PDX) models.

Experimental Design: B7-H4 expression was quantified by flow cytometry and IHC.

The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF): feasibility trial protocol.

Background: Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible.

Perspectives of Medical Organizations, Organ Procurement Organizations, and Advocacy Organizations About Revising the Uniform Determination of Death Act (UDDA).

Background: The Uniform Law Commission paused work of the Drafting Committee to Revise the Uniform Determination of Death Act (UDDA) in September 2023.

Methods: Thematic review was performed of comments submitted to the Uniform Law Commission by medical organizations (MO), organ procurement organizations (OPO), and advocacy organizations (AO) from 1/1/2023 to 7/31/2023.

Results: Of comments from 41 organizations (22 AO, 15 MO, 4 OPO), 34 (83%) supported UDDA revision (50% OPO, 33% MO recommended against revision).

Low pre-albumin but not thiamine predicts cognitive deficits in adolescents post-Fontan and healthy controls.

Background: Low pre-albumin, body mass index, and thiamine levels have been associated with poor nutritional status and cognitive/memory deficits in adult heart failure patients. However, the relationship of these nutritional/dietary intake biomarkers to cognition has not been assessed in adolescents post-Fontan procedure and healthy controls.

Methods: This is a cross-sectional study.

Preparing Hematology/Oncology Fellows for Success: Implementing an Annual Career Development and Research Retreat.

Multiple factors, including job satisfaction, personality traits, and training experiences, influence the career trajectory of hematology/oncology fellows. In an effort to expose hematology/oncology fellows to (1) the various careers in oncology, (2) a diverse group of speakers for future mentorship, and (3) research opportunities, and grant writing experience, we established an annual career development and research retreat. During the retreat, we engaged speakers who covered a range of career trajectories, including academic, private practice, industry, government, and administrative paths.

Investigation of Cerebral Mitochondrial Injury in a Porcine Survivor Model of Carbon Monoxide Poisoning.

Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV).