Quantitative mapping of proteasome interactomes and substrates using ProteasomeID.

Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite the relevance for human disease and drug development, no method currently exists to monitor proteasome composition and interactions in vivo in animal models.

Melanoma risk prediction based on a polygenic risk score and clinical risk factors.

Melanoma is one of the most commonly diagnosed cancers in the Western world: third in Australia, fifth in the USA and sixth in the European Union. Predicting an individual's personal risk of developing melanoma may aid them in undertaking effective risk reduction measures. The objective of this study was to use the UK Biobank to predict the 10-year risk of melanoma using a newly developed polygenic risk score (PRS) and an existing clinical risk model.

A combined clinical and genetic model for predicting risk of ovarian cancer.

Objective: Women with a family history of ovarian cancer or a pathogenic or likely pathogenic gene variant are at high risk of the disease, but very few women have these risk factors. We assessed whether a combined polygenic and clinical risk score could predict risk of ovarian cancer in population-based women who would otherwise be considered as being at average risk.

Methods: We used the UK Biobank to conduct a prospective cohort study assessing the performance of 10-year ovarian cancer risks based on a polygenic risk score, a clinical risk score and a combined risk score.

Validation of a clinical and genetic model for predicting severe COVID-19.

Using nested case–control data from the Lifelines COVID-19 cohort, we undertook a validation study of a clinical and genetic model to predict the risk of severe COVID-19 in people with confirmed COVID-19 and in people with confirmed or self-reported COVID-19. The model performed well in terms of discrimination of cases and controls for all ages (area under the receiver operating characteristic curve (AUC) = 0.680 for confirmed COVID-19 and AUC = 0.

Lights, camera, active! appreciation of active learning predicts positive attitudes towards lecture capture.

Much has been written about instructor attitudes towards lecture capture, particularly concerning political issues such as opt-out policies and the use of recordings by management. Additionally, the pedagogical concerns of lecturers have been extensively described and focus on the belief that recording lectures will impact on attendance and will reduce interactivity and active learning activities in lectures. However, little work has looked at the relationship between attitudes towards lecture capture and broader conceptions of learning and teaching.

A streamlined model for use in clinical breast cancer risk assessment maintains predictive power and is further improved with inclusion of a polygenic risk score.

Five-year absolute breast cancer risk prediction models are required to comply with national guidelines regarding risk reduction regimens. Models including the Gail model are under-utilized in the general population for various reasons, including difficulty in accurately completing some clinical fields. The purpose of this study was to determine if a streamlined risk model could be designed without substantial loss in performance.

Virtual reality as an analgesic for acute and chronic pain in adults: a systematic review and meta-analysis.

Previous studies have shown that virtual reality (VR) is effective in reducing acute and chronic pain both in adults and in children. Given the emergence of new VR technology, and the growing body of research surrounding VR and pain management, an updated systematic review is warranted. The purpose of this systematic review is to compare the effectiveness of VR in reducing acute and chronic pain in adults.

Bridging the Data Gap in Breast Cancer Risk Assessment to Enable Widespread Clinical Implementation across the Multiethnic Landscape of the US.

Breast cancer remains the second leading cause of cancer death among women and is the most commonly diagnosed cancer in women. Breast cancer risk assessment has been clinically available for nearly 30 years yet is under-utilized in practice for multiple reasons. Incorporation of polygenic risk as well as breast density measurements, promise to increase the accuracy of risk assessment.

Establishment of a normative database and evaluation of the test-retest repeatability of the Spaeth/Richman contrast sensitivity test.

Purpose: To evaluate the test-retest repeatability of a computer-based contrast sensitivity (CS) test, the Spaeth/Richman contrast sensitivity (SPARCS) test, and to determine the effects of age and lens status on CS in normal eyes.

Study Design: Prospective cross-sectional study.

Methods: The participants were assessed by use of the SPARCS test in each eye 3 times.

Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction.

Mounting clinical and preclinical evidence supports a key role for sustained adrenergic signaling in the tumor microenvironment as a driver of tumor growth and progression. However, the mechanisms by which adrenergic neurotransmitters are delivered to the tumor microenvironment are not well understood. Here we present evidence for a feed-forward loop whereby adrenergic signaling leads to increased tumoral innervation.

Epistemic injustice in dementia and autism patient organizations: An empirical analysis.

Patient organizations (POs) represent patient collectives in health care policy. The inclusion of people with a 'neuro-psychiatric' condition poses a particular challenge for the organizational processes and political representation of such collectives. In recent years, new POs (POs of) have been established in the field of autism spectrum disorder and dementia that advocate a different agenda and have a different organizational structure than traditional POs (POs for).

SPARCS and Pelli-Robson contrast sensitivity testing in normal controls and patients with cataract.

PurposeTo determine the ability of the newly developed internet-based Spaeth/Richman Contrast Sensitivity (SPARCS) test to assess contrast sensitivity centrally and peripherally in cataract subjects and controls, in comparison with the Pelli-Robson (PR) test.MethodsIn this prospective cross-sectional study, cataract subjects and age-matched normal controls were evaluated using the SPARCS and PR tests. Contrast sensitivity testing was performed in each eye twice in a standardized testing environment in randomized order.

Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.

Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF.

The SPARCS: a novel assessment of contrast sensitivity and its reliability in patients with corrected refractive error.

Purpose: To explore the reliability of the Spaeth/Richman Contrast Sensitivity (SPARCS) test and to assess the contrast sensitivity (CS) distribution among subjects with various refractive errors.

Methods: Cross-sectional study. Ninety-three individuals (182 eyes) with varying amounts of refractive error were included in this study and divided into six groups according to their spherical equivalent.

EVALUATING CONTRAST SENSITIVITY IN AGE-RELATED MACULAR DEGENERATION USING A NOVEL COMPUTER-BASED TEST, THE SPAETH/RICHMAN CONTRAST SENSITIVITY TEST.

Background: Contrast sensitivity (CS) is a valuable measure of visual function in patients with age-related macular degeneration (AMD). The authors aimed to compare a novel computer-based test (the Spaeth/Richman Contrast Sensitivity test) with Pelli-Robson test for evaluating CS in patients with AMD.

Methods: In this prospective cross-sectional study, CS was evaluated in patients with various stages of AMD and healthy controls using Spaeth/Richman Contrast Sensitivity test and Pelli-Robson test.

Disproportionate pupillary involvement in diabetic autonomic neuropathy.

Objective: To study the degree of pupillary impairment in diabetic and non-diabetic autonomic neuropathy.

Methods: We retrospectively sampled from all patients who underwent comprehensive autonomic testing and infrared pupillometry at UT Southwestern Medical Center. Composite autonomic severity score (CASS) and pupillary indices from the average of at least three pupillary response curves were recorded.

The Spaeth/Richman contrast sensitivity test (SPARCS): design, reproducibility and ability to identify patients with glaucoma.

Aims: (1) To determine the ability of a novel, internet-based contrast sensitivity test titled the Spaeth/Richman Contrast Sensitivity Test (SPARCS) to identify patients with glaucoma. (2) To determine the test-retest reliability of SPARCS.

Methods: A prospective, cross-sectional study of patients with glaucoma and controls was performed.

Reciprocal leukemia-stroma VCAM-1/VLA-4-dependent activation of NF-κB mediates chemoresistance.

Leukemia cells are protected from chemotherapy-induced apoptosis by their interactions with bone marrow mesenchymal stromal cells (BM-MSCs). Yet the underlying mechanisms associated with this protective effect remain unclear. Genome-wide gene expression profiling of BM-MSCs revealed that coculture with leukemia cells upregulated the transcription of genes associated with nuclear factor (NF)-κB signaling.

Quantitative multispectral analysis following fluorescent tissue transplant for visualization of cell origins, types, and interactions.

With the desire to understand the contributions of multiple cellular elements to the development of a complex tissue; such as the numerous cell types that participate in regenerating tissue, tumor formation, or vasculogenesis, we devised a multi-colored cellular transplant model of tumor development in which cell populations originate from different fluorescently colored reporter gene mice and are transplanted, engrafted or injected in and around a developing tumor. These colored cells are then recruited and incorporated into the tumor stroma. In order to quantitatively assess bone marrow derived tumor stromal cells, we transplanted GFP expressing transgenic whole bone marrow into lethally irradiated RFP expressing mice as approved by IACUC.

Dynamic pupillometry as an autonomic testing tool.

Objective: To determine normal values for pupillometry indices in healthy control subjects and to examine these indices in patients with autonomic dysfunction and healthy controls.

Methods: Infrared video pupillometry was used to investigate the pupil response to a brief light flash in 79 healthy controls, 28 patients with normal autonomic function (composite autonomic severity score, CASS < 2), and 26 patients with moderate to severe autonomic failure (CASS > 4) seen in our autonomic laboratory from January 2008 to June 2011. In six subjects, we examined the effects of varying light stimulus intensity and light stimulus duration.

Mesenchymal CD44 expression contributes to the acquisition of an activated fibroblast phenotype via TWIST activation in the tumor microenvironment.

Tumor-stroma interactions play a crucial role in cancer progression by eliciting factors that promote proliferative, angiogenic, and invasive supports to the tumor microenvironment. Mesenchymal stromal/stem cells (MSC) contribute to stroma in part as cancer-associated fibroblasts (CAF), but a complete understanding of how MSC contribute to the tumor stroma is lacking. In this study, we show how CAF phenotypes rely upon MSC expression of the multifunctional cell surface glycoprotein CD44, a putative stem cell marker.