Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection.

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we sequenced saliva and nasal samples collected daily from vaccinated and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies.

Impact of COVID-19 infection on patients admitted with nonvariceal upper gastrointestinal bleeding: an analysis from the National Inpatient Sample.

Background: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a medical emergency that has significant morbidity and mortality. The available data about the impact of COVID-19 infection on mortality in patients with NVUGIB is limited.

Methods: We identified all hospitalizations with a principal diagnosis of NVUGIB in 2020.

Reflecting on gamified learning in medical education: a systematic literature review grounded in the Structure of Observed Learning Outcomes (SOLO) taxonomy 2012-2022.

Background: The acquisition of in-depth medical knowledge, skills, and competencies is of utmost importance when training future medical professionals. This systematic literature review delves into the empirical connection between gamified learning in medical education and the Structure of Observed Learning Outcomes (SOLO) taxonomy.

Methods: Following PRISMA guidelines, a systematic literature review was conducted in seven databases to identify empirical studies related to gamification and medical education.

A molecular toolkit for heterologous protein secretion across species.

species are abundant and prevalent stably colonizing members of the human gut microbiota, making them a promising chassis for developing long-term interventions for chronic diseases. Engineering these bacteria as on-site production and delivery vehicles for biologic drugs or diagnostics, however, requires efficient heterologous protein secretion tools, which are currently lacking. To address this limitation, we systematically investigated methods to enable heterologous protein secretion in using both endogenous and exogenous secretion systems.

Geospatial Evaluation of Disparities in Access to Cervical Spine Fusion in Metropolitan Areas Across the United States.

Study Design: Retrospective study with epidemiologic analysis of public Medicare data.

Objective: The purpose of this study is to use geospatial analysis to identify disparities in access to cervical spine fusions in metropolitan Medicare populations.

Summary Of Background Data: Cervical spine fusion is among the most common elective procedures performed by spine surgeons and is the most common surgical intervention for degenerative cervical spine disease.

Assessment of Mechanically Induced Changes in Helical Fiber Microstructure Using Diffusion Tensor Imaging.

Noninvasive methods to detect microstructural changes in collagen-based fibrous tissues are necessary to differentiate healthy from damaged tissues in vivo but are sparse. Diffusion Tensor Imaging (DTI) is a noninvasive imaging technique used to quantitatively infer tissue microstructure with previous work primarily focused in neuroimaging applications. Yet, it is still unclear how DTI metrics relate to fiber microstructure and function in musculoskeletal tissues such as ligament and tendon, in part because of the high heterogeneity inherent to such tissues.

Short-Term Outcomes of Expedited Arthroscopic Tensionable Knotless Biologic Tuberoplasty for Massive Irreparable Rotator Cuff Tears.

Massive irreparable rotator cuff tears in the nonarthritic patient are challenging because of the high failure rate and technical difficulty of intraoperative repair. We examined the outcomes of expedited arthroscopic tensionable knotless biologic tuberoplasty for massive irreparable rotator cuff tears. Eleven patients with an average follow-up of 8.

In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh.

As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism.

Initial validation of the university of Alabama Birmingham study of aging life-space assessment in older adults with multiple sclerosis.

Background: Older adults with multiple sclerosis (OAMS) have declines in walking and physical performance that may erode community mobility defined as the spatial extent of mobility in one's daily life and environment.

Objective: This study provided the first application and validation of the University of Alabama Birmingham Study of Aging Life-Space Assessment (UAB LSA) as a measure of community mobility in OAMS.

Methods: The sample included 97 OAMS and 108 healthy controls (HCs) who completed baseline assessments as part of an ongoing, longitudinal study.

Targeting neuraminidase: the next frontier for broadly protective influenza vaccines.

Current seasonal influenza vaccines, which mainly target hemagglutinin (HA), require annual updates due to the continuous antigenic drift of the influenza virus. Developing an influenza vaccine with increased breadth of protection will have significant public health benefits. The recent discovery of broadly protective antibodies to neuraminidase (NA) has provided important insights into developing a universal influenza vaccine, either by improving seasonal influenza vaccines or designing novel immunogens.

Protein Engineering Technologies for Development of Next-Generation Genome Editors.

Base editors and prime editors have emerged as promising tools for the modeling and treatment of genetic diseases due to their ability to introduce targeted modifications in the genomic DNA of living cells. Several engineering approaches have been applied to improve their performance, ranging from simple protein design approaches to complex directed evolution schemes that can probe a vast landscape of mutational variants with minimal user intervention. These extensive efforts have led to new generations of editors with enhanced properties such as increased editing activity, tailored editing windows, increased targetability, smaller construct size for viral delivery, and decreased off-target effects.

Predicting clinical progression trajectories of early Alzheimer's disease patients.

Background: Models for forecasting individual clinical progression trajectories in early Alzheimer's disease (AD) are needed for optimizing clinical studies and patient monitoring.

Methods: Prediction models were constructed using a clinical trial training cohort (TC; n = 934) via a gradient boosting algorithm and then evaluated in two validation cohorts (VC 1, n = 235; VC 2, n = 421). Model inputs included baseline clinical features (cognitive function assessments, APOE ε4 status, and demographics) and brain magnetic resonance imaging (MRI) measures.

Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning.

The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane fusion during virus entry and is part of a broadly neutralizing epitope. However, sequence determinants at the fusion peptide and its adjacent regions for pathogenicity and antigenicity remain elusive. In this study, we performed a series of deep mutational scanning (DMS) experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 in different cell lines and in the presence of broadly neutralizing antibodies.

Cardiorespiratory Responses to an Acute Bout of High Intensity Interval Training and Moderate Intensity Continuous Training on a Recumbent Handcycle in People With Spinal Cord Injury: A Within-Subject Design.

Objectives: To compare acute cardiorespiratory responses during high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on a recumbent handcycle in persons with spinal cord injury (PwSCI).

Methods: Eleven males and nine females with chronic SCI (T3 - L5), aged 23 (9) years, participated in this within-subject design. Based off peak power outputs from an incremental test to exhaustion, participants engaged in a HIIT and MICT session at matched workloads on a recumbent handcycle.

Impact of 8 lifestyle factors on mortality and life expectancy among United States veterans: The Million Veteran Program.

Background: Lifestyle medicine has been proposed as a way to address the root causes of chronic disease and their associated health care costs.

Objective: This study aimed to estimate mortality risk and longevity associated with individual lifestyle factors and comprehensive lifestyle therapy.

Methods: Age- and sex-specific mortality rates were calculated on the basis of 719,147 veterans aged 40-99 y enrolled in the Veteran Affairs Million Veteran Program (2011-2019).

Coordination Chemistry of Sulfur-Containing Bifunctional Chelators: Toward Stabilization of Cu PET Imaging Agents for Alzheimer's Disease.

The broader utilization of Cu positron emission tomography (PET) imaging agents has been hindered by the unproductive demetalation induced by bioreductants. To advance the development of Cu-based PET imaging tracers for Alzheimer's Disease (AD), there is a need for novel ligand design strategies. In this study, we developed sulfur-containing dithiapyridinophane (N2S2) bifunctional chelators (BFCs) as well as all nitrogen-based diazapyridinophane (N4) BFCs to compare their abilities to chelate Cu and target Aβ aggregates.

Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma.

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date).

A computational spatial whole-Cell model for hepatitis B viral infection and drug interactions.

Despite a vaccine, hepatitis B virus (HBV) remains a world-wide source of infections and deaths. We develop a whole-cell computational platform combining spatial and kinetic models describing the infection cycle of HBV in a hepatocyte host. We simulate key parts of the infection cycle with this whole-cell platform for 10 min of biological time, to predict infection progression, map out virus-host and virus-drug interactions.

Year-to-year variation in phthalate metabolites in the Midlife Women's Health Study.

Background: Humans are widely exposed to phthalates, which are metabolized in the body and excreted in urine. Phthalate metabolites are excreted within hours of exposure, making urinary phthalate biomarker concentrations highly variable.

Objective: The goal of this study was to characterize the long-term variability in phthalate biomarker concentrations in women across the midlife transition and to identify factors that may be associated with increased variability in those phthalate biomarker concentrations by analyzing longitudinal urinary phthalate metabolite data from the Midlife Women's Health Study (2006-2015).

Mucosal DNA methylome alteration in Crohn's disease: surgical and non-surgical groups.

Crohn's disease (CD) is characterized as a chronic, relapsing, and progressive disorder with a complex etiology involving interactions between host, microbiome, and the external environment. Genome wide association studies (GWAS) suggest several genetic variations in the diseased individuals but that explains only a small proportion of susceptibility to disease conditions. This indicates the possible role of epigenome which links environmental factors to the genetic variation in the disease etiology.

THE 2023 PRESIDENTAL ADDRESS. Celebrating advocacy: neurosurgeons as advocates.

The central focus of the 2023 annual gathering of the American Association of Neurological Surgeons in Los Angeles revolved around the concept of neurosurgeons as advocates. Beyond their roles in clinical practice and patient care, neurosurgeons frequently unite in their commitment to advocacy. This shared dedication empowers them to thrive in areas such as innovation, teaching, advanced research, and comprehensive training to shape the future of the neurosurgical field.

Revisiting bacterial cytolethal distending toxin structure and function.

Cytolethal distending toxins (CDTs) are intracellular-acting bacterial genotoxins generated by a diverse group of mucocutaneous human pathogens. CDTs must successfully bind to the plasma membrane of host cells in order to exert their modulatory effects. Maximal toxin activity requires all three toxin subunits, CdtA, CdtB, and CdtC, which, based primarily on high-resolution structural data, are believed to preassemble into a tripartite complex necessary for toxin activity.

Endovascular aspiration of native tricuspid valve vegetation using INARI catheter in a patient with methicillin-sensitive endocarditis.

A middle-aged man presented to the hospital with chief complaint of worsening chest pain and shortness of breath. He was found to have methicillin-sensitive (MSSA) bacteremia, acute hypoxic respiratory failure secondary to MSSA pneumonia and septic emboli. The patient underwent a transesophageal echocardiogram which revealed a large, mobile tricuspid valve vegetation secondary to endocarditis.