Biomarkers.

Background: AD is defined by cortical amyloid-β (Aβ), tau neurofibrillary tangles, and neurodegeneration, pathological processes which may contribute to cognitive decline by altering large scale functional brain networks. To test this hypothesis, we examined whether plasma biomarkers of AD pathology (Aβ, phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) related to longitudinal changes in resting-state functional connectivity (rsFC) in cognitively unimpaired participants from the Baltimore Longitudinal Study of Aging.

Method: Baseline plasma biomarkers were measured with Quanterix SIMOA assays.

Developing Topics.

Background: To further understand the neural basis of memory failure in the older brain, we examined the medial temporal lobe (MTL) memory system in 297 cognitively normal participants (mean age = 74.46 (4.95 SD)) from the Baltimore Longitudinal Study of Aging (BLSA).

Alzheimer's Imaging Consortium.

Background: AD is defined by cortical amyloid-ß (Aß), tau neurofibrillary tangles, and neurodegeneration, pathological processes which may contribute to cognitive decline by altering large scale functional brain networks. To test this hypothesis, we examined whether plasma biomarkers of AD pathology (Aß42/40, phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) related to longitudinal changes in resting-state functional connectivity (rsFC) in cognitively unimpaired participants from the Baltimore Longitudinal Study of Aging.

Method: Baseline plasma biomarkers were measured with Quanterix SIMOA assays.

Runs of Homozygosity and Inferences in Wild Populations.

Long homozygous chromosome segments are known as runs of homozygosity (ROH); these reflect patterns of identity by descent and can be used to measure individual inbreeding, map recessive traits, and reconstruct demographic histories. Here, we review some key considerations with ROH detection and the inferences pertaining to inbreeding and demographic analyses in wild populations.

Humans exploit the trade-off between lateral stability and manoeuvrability during walking.

People use the mechanical interplay between stability and manoeuvrability to successfully walk. During single-limb support, body states (position and velocity) that increase in lateral stability will inherently resist lateral manoeuvres, decrease medial stability and facilitate medial manoeuvres. Although not well understood, people can make behavioural decisions exploiting this relationship in anticipation of perturbations or direction changes.

Improving representation of Hispanic adults in a population-based cancer genetics cohort: Qualitative findings from the Healthy Oregon Project.

Background: Members of many racial and ethnic population subgroups are underrepresented in clinical trials and research. We present perspectives on barriers and facilitators to study participation gathered from Hispanic participants in a population-based genetic screening study.

Methods: Seven focus groups (five in English and two in Spanish) were conducted with self-identified Hispanic participants of the Healthy Oregon Project (HOP), a large population-based cohort of adults residing in Oregon.

Meta-analysis of the factor structure of the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS).

Introduction: The SAPS and SANS was designed to measure two broad factors, but the majority of factor analyses conducted have found substantially more dimensions. To investigate their structure a meta-analysis was conducted of SAPS and SANS factor analysis.

Method: A total of 42 articles reporting 55 factor analyses were retrieved from database searches (PubMed, PsychINFO) supplemented by searches of references.

Narrative Force: How Science and Storytelling Impact Parental Concussion Beliefs and Intentions Through Transportation and Trust.

Although news and entertainment coverage of sports concussions has increased in recent years, many parents of adolescent athletes remain indifferent to or unaware of practices that would mitigate concussion harm. This experiment with U.S.

Comparative Genomics of the World's Smallest Mammals Reveals Links to Echolocation, Metabolism, and Body Size Plasticity.

Originating 30 million years ago, shrews (Soricidae) have diversified into around 400 species worldwide. Shrews display a wide array of adaptations, with some species having developed distinctive traits such as echolocation, underwater diving, and venomous saliva. Accordingly, these tiny insectivores are ideal to study the genomic mechanisms of evolution and adaptation.

The skinny on skin: The role of skin-aware professionals in skin cancer surveillance.

Licensed nonmedical, skin-aware professionals (e.g., hairdressers, massage therapists, etc.

Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer: Clinical and translational results from a phase 2 trial.

Background: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood.

Methods: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.

Amplify Gait to Improve Locomotor Engagement in Spinal Cord Injury (AGILE SCI) trial: study protocol for an assessor blinded randomized controlled trial.

Background: Among ambulatory people with incomplete spinal cord injury (iSCI), balance deficits are a primary factor limiting participation in walking activities. There is broad recognition that effective interventions are needed to enhance walking balance following iSCI. Interventions that amplify self-generated movements (e.

IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.

Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.

Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant.

Island demographics and trait associations in white-tailed deer.

When a population is isolated and composed of few individuals, genetic drift is the paramount evolutionary force and results in the loss of genetic diversity. Inbreeding might also occur, resulting in genomic regions that are identical by descent, manifesting as runs of homozygosity (ROHs) and the expression of recessive traits. Likewise, the genes underlying traits of interest can be revealed by comparing fixed SNPs and divergent haplotypes between affected and unaffected individuals.

Epigenetic clocks, sex markers and age-class diagnostics in three harvested large mammals.

The development of epigenetic clocks, or the DNA methylation-based inference of age, is an emerging tool for ageing in free ranging populations. In this study, we developed epigenetic clocks for three species of large mammals that are the focus of extensive management throughout their range in North America: white-tailed deer, black bear and mountain goat. We quantified differential DNA methylation patterns at over 30,000 cytosine-guanine sites (CpGs) from tissue samples of all three species (black bear n = 49; white-tailed deer n = 47; mountain goat n = 45).

Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project.

Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system.

Genomic Analyses Capture the Human-Induced Demographic Collapse and Recovery in a Wide-Ranging Cervid.

The glacial cycles of the Quaternary heavily impacted species through successions of population contractions and expansions. Similarly, populations have been intensely shaped by human pressures such as unregulated hunting and land use changes. White-tailed and mule deer survived in different refugia through the Last Glacial Maximum, and their populations were severely reduced after the European colonization.

Prior uncertainty impedes discrete locomotor adaptation.

The impact of environmental uncertainty on locomotor adaptation remains unclear. Environmental uncertainty could either aid locomotor adaptation by prompting protective control strategies that stabilize movements to assist learning or impede adaptation by reducing error sensitivity and fostering hesitance to pursue corrective movements. To explore this, we investigated participants' adaptation to a consistent force field after experiencing environmental uncertainty in the form of unpredictable balance perturbations.

Evidence-Based Communication to Increase Melanoma Knowledge and Skin Checks.

Rates of melanoma-the deadliest form of skin cancer-have increased. Early detection can save lives, and patients have a critical role to play in checking their skin. We aim to identify health communication messages that best educate the public and increase intentions toward skin checks.

Robust fiber orientation distribution function estimation using deep constrained spherical deconvolution for diffusion-weighted magnetic resonance imaging.

Purpose: Diffusion-weighted magnetic resonance imaging (DW-MRI) is a critical imaging method for capturing and modeling tissue microarchitecture at a millimeter scale. A common practice to model the measured DW-MRI signal is via fiber orientation distribution function (fODF). This function is the essential first step for the downstream tractography and connectivity analyses.

Rectal Adenocarcinoma Presenting as a Cervical Mass: A Case Report.

BACKGROUND Invasive cervical tumors are often seen in clinical practice. However, there are multiple structures within the pelvis, and invasion of the cervix from another site must be included in the differential diagnosis. In such cases, a multidisciplinary approach is needed to define the organ of tumor origin.

Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer.

Background: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm.