Ancient genomes reveal a deep history of treponemal disease in the Americas.

Human treponemal infections are caused by a family of closely related Treponema pallidum that give rise to the diseases yaws, bejel, pinta and, most famously, syphilis. Debates on both a common origin for these pathogens and the history of syphilis itself has weighed evidence for the "Columbian hypothesis", which argues for an American origin, against that for the "pre-Columbian hypothesis", which argues for presence of the disease in Eurasia in the Medieval period and possibly earlier. While molecular data has provided a genetic basis for distinction of the typed subspecies, deep evolution of the complex has remained unresolved due to limitations in the conclusions that can be drawn from the sparse paleogenomic data currently available.

The effect of thoraco-lumbo-sacral orthosis wear time and clinical risk factors on curve progression for individuals with adolescent idiopathic scoliosis.

Background Context: The effectiveness of bracing with a thoraco-lumbo-sacral orthosis (TLSO) for adolescent idiopathic scoliosis (AIS) has been studied extensively, with a growing body of evidence supporting TLSO use. In this study we examine the effect of wear time and other important causal factors affecting curve progression and develop a risk model that can be applied to individual patients and is based on important casual factors.

Purpose: Understand the impact of TLSO wear time and other risk factors in order to guide optimal treatment.

Ancient Plasmodium genomes shed light on the history of human malaria.

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe. To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P.

Clinical perspectives on sampling and processing approaches for the management of infection in diabetic foot ulceration: A qualitative study.

Diabetic foot ulcers (DFUs) often become infected and are treated with antimicrobials, with samples collected to inform care. Swab samples are easier than tissue sampling but report fewer organisms. Compared with culture and sensitivity (C&S) methods, molecular microbiology identifies more organisms.

Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia.

Background: Distinct endothelial cell cycle states (early G1 versus late G1) provide different "windows of opportunity" to enable the differential expression of genes that regulate venous versus arterial specification, respectively. Endothelial cell cycle control and arteriovenous identities are disrupted in vascular malformations including arteriovenous shunts, the hallmark of hereditary hemorrhagic telangiectasia (HHT). To date, the mechanistic link between endothelial cell cycle regulation and the development of arteriovenous malformations (AVMs) in HHT is not known.

The long-term effects of aggressive spasticity reducing treatment, including selective dorsal rhizotomy, on joint kinematic outcomes of persons with cerebral palsy.

Background: Selective dorsal rhizotomy (SDR) creates a large and permanent reduction of spasticity for children with cerebral palsy (CP). Previous SDR outcomes studies have generally lacked appropriate control groups, had limited sample sizes, or reported short-term follow-up, limiting evidence for improvement in long-term gait function.

Research Question: Does aggressive spasticity management for individuals with CP improve long-term gait kinematics (discrete joint kinematics) compared to a control group of individuals with CP with minimal spasticity management?

Methods: This study was a secondary analysis - focused on joint-level kinematics - of a previous study evaluating the long-term outcomes of SDR.

14th century Yersinia pestis genomes support emergence of pestis secunda within Europe.

Pestis secunda (1356-1366 CE) is the first of a series of plague outbreaks in Europe that followed the Black Death (1346-1353 CE). Collectively this period is called the Second Pandemic. From a genomic perspective, the majority of post-Black Death strains of Yersinia pestis thus far identified in Europe display diversity accumulated over a period of centuries that form a terminal sub-branch of the Y.

Connexin 37 sequestering of activated-ERK in the cytoplasm promotes p27-mediated endothelial cell cycle arrest.

Connexin37-mediated regulation of cell cycle modulators and, consequently, growth arrest lack mechanistic understanding. We previously showed that arterial shear stress up-regulates Cx37 in endothelial cells and activates a Notch/Cx37/p27 signaling axis to promote G1 cell cycle arrest, and this is required to enable arterial gene expression. However, how induced expression of a gap junction protein, Cx37, up-regulates cyclin-dependent kinase inhibitor p27 to enable endothelial growth suppression and arterial specification is unclear.

Community partnerships are fundamental to ethical ancient DNA research.

The ethics of the scientific study of Ancestors has long been debated by archaeologists, bioanthropologists, and, more recently, ancient DNA (aDNA) researchers. This article responds to the article "Ethics of DNA research on human remains: five globally applicable guidelines" published in 2021 in by a large group of aDNA researchers and collaborators. We argue that these guidelines do not sufficiently consider the interests of community stakeholders, including descendant communities and communities with potential, but yet unestablished, ties to Ancestors.

Transformation of alignment files improves performance of variant callers for long-read RNA sequencing data.

Long-read RNA sequencing (lrRNA-seq) produces detailed information about full-length transcripts, including novel and sample-specific isoforms. Furthermore, there is an opportunity to call variants directly from lrRNA-seq data. However, most state-of-the-art variant callers have been developed for genomic DNA.

Ancient Yersinia pestis and Salmonella enterica genomes from Bronze Age Crete.

During the late 3 millennium BCE, the Eastern Mediterranean and Near East witnessed societal changes in many regions, which are usually explained with a combination of social and climatic factors. However, recent archaeogenetic research forces us to rethink models regarding the role of infectious diseases in past societal trajectories. The plague bacterium Yersinia pestis, which was involved in some of the most destructive historical pandemics, circulated across Eurasia at least from the onset of the 3 millennium BCE, but the challenging preservation of ancient DNA in warmer climates has restricted the identification of Y.

Ten millennia of hepatitis B virus evolution.

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene.

The origin and legacy of the Etruscans through a 2000-year archeogenomic time transect.

The origin, development, and legacy of the enigmatic Etruscan civilization from the central region of the Italian peninsula known as Etruria have been debated for centuries. Here we report a genomic time transect of 82 individuals spanning almost two millennia (800 BCE to 1000 CE) across Etruria and southern Italy. During the Iron Age, we detect a component of Indo-European–associated steppe ancestry and the lack of recent Anatolian-related admixture among the putative non–Indo-European–speaking Etruscans.

Learning New Skills in Innovation, Leadership, and Discovery During a 9-Month Scholarly Concentration: Results from the First Cohort at a New Medical School.

Dell Medical School (DMS) has weaved health systems science (HSS) throughout its curriculum. During the third year, students complete a master's degree program or an immersive distinction in research or design during a 9-month Innovation, Leadership, and Discovery (ILD) block. Faculty assessments revealed all students met expectations, but dual-degree students were rated higher than distinction students in leading future innovative teams competencies.

Different measures of holistic face processing tap into distinct but partially overlapping mechanisms.

Holistic processing, which includes the integration of facial features and analysis of their relations to one another, is a hallmark of what makes faces 'special'. Various experimental paradigms purport to measure holistic processing but these have often produced inconsistent results. This has led researchers to question the nature and structure of the mechanism(s) underlying holistic processing.

Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells.

Blood vessels are ubiquitously distributed within all tissues of the body and perform diverse functions. Thus, derivation of mature vascular endothelial cells, which line blood vessel lumens, from human pluripotent stem cells is crucial for a multitude of tissue engineering and regeneration applications. In vivo, primordial endothelial cells are derived from the mesodermal lineage and are specified toward specific subtypes, including arterial, venous, capillary, hemogenic, and lymphatic.

Formulation, Stability, Pharmacokinetic, and Modeling Studies for Tests of Synergistic Combinations of Orally Available Approved Drugs against Ebola Virus In Vivo.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses.

Global health on the front lines: an innovative medical student elective combining education and service during the COVID-19 pandemic.

Background: An innovative medical student elective combined student-directed, faculty-supported online learning with COVID-19 response field placements. This study evaluated students' experience in the course, the curriculum content and format, and its short-term impact on students' knowledge and attitudes around COVID-19.

Methods: Students responded to discussion board prompts throughout the course and submitted pre-/post-course reflections.

Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs.

Neglected diseases caused by arenaviruses such as Lassa virus (LASV) and filoviruses like Ebola virus (EBOV) primarily afflict resource-limited countries, where antiviral drug development is often minimal. Previous studies have shown that many approved drugs developed for other clinical indications inhibit EBOV and LASV and that combinations of these drugs provide synergistic suppression of EBOV, often by blocking discrete steps in virus entry. We hypothesize that repurposing of combinations of orally administered approved drugs provides effective suppression of arenaviruses.

Ebola virus glycoprotein interacts with cholesterol to enhance membrane fusion and cell entry.

Cholesterol serves critical roles in enveloped virus fusion by modulating membrane properties. The glycoprotein (GP) of Ebola virus (EBOV) promotes fusion in the endosome, a process that requires the endosomal cholesterol transporter NPC1. However, the role of cholesterol in EBOV fusion is unclear.

From Knowing to Doing: Integrating Systems-Ready Physician Competencies in the Clerkship Setting.

There are increasing calls to graduate physicians with a strong understanding of health systems science (HSS). Many schools have incorporated didactics on health systems science content such as quality improvement, patient safety, or interprofessional education. Creating a systems-ready physician requires more than teaching content in classroom settings.