Pharmacogenetic and microRNA mechanisms of beta blocker use on bone.

Motivated by studies showing an association between beta blocker (BB) use and positive bone outcomes, a pilot randomized control trial (RCT) was performed at the Mayo Clinic which randomized postmenopausal women to placebo, propranolol (40 or 80 mg twice daily), atenolol (50 mg/day), or nebivolol (5 mg/day) to determine changes in bone turnover markers (BTMs) and in bone mineral density (BMD) over 20 weeks. Pharmacogenetic effects and microRNA-mediated mechanisms involving beta adrenergic receptor and related genes have previously been found. We sought to validate these effects and discover new candidates in an ancillary study to the pilot clinical trial.

NOISe: Nuclei-Aware Osteoclast Instance Segmentation for Mouse-to-Human Domain Transfer.

Osteoclast cell image analysis plays a key role in osteoporosis research, but it typically involves extensive manual image processing and hand annotations by a trained expert. In the last few years, a handful of machine learning approaches for osteoclast image analysis have been developed, but none have addressed the full instance segmentation task required to produce the same output as that of the human expert led process. Furthermore, none of the prior, fully automated algorithms have publicly available code, pretrained models, or annotated datasets, inhibiting reproduction and extension of their work.

Longitudinal Case-Control Study of Active and Passive Dense Mammographic Breast Tissue.

Mammography is used as secondary prevention for breast cancer. Computer-aided detection and image-based short-term risk estimation were developed to improve the accuracy of mammography. However, most approaches inherently lack the ability to connect observations at the mammography level to observations of cancer onset and progression seen at a smaller scale, which can occur years before imageable cancer and lead to primary prevention.

A pilot study evaluating the use of sirolimus in children and young adults with desmoid-type fibromatosis.

Deregulation of the mTOR pathway may play an important role in tumor biology when the APC/β-catenin pathway is disrupted in desmoid-type fibromatosis (DT). A pilot study was conducted to determine whether sirolimus can block the mTOR pathway (primary aim) as well as determine whether it can safely be given in the preoperative setting, decrease tumor size/recurrence, and decrease tumor-associated pain in children and young adults (secondary aims) with DT. Nine subjects ages 5-28 years were enrolled from 2014 to 2017 across four centers.

Social isolation through single housing negatively affects trabecular and cortical bone in adult male, but not female, C57BL/6J mice.

Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising "epidemic" of loneliness. Isolation is associated with an increased risk for many physical and mental health disorders and increased overall mortality risk.

Gaps in Cystic Fibrosis Care Are Associated with Reduced Lung Function in the U.S. Cystic Fibrosis Foundation Patient Registry.

Cystic fibrosis (CF) is a genetic disease leading to progressive lung function loss and early mortality. Many clinical and demographic variables are associated with lung function decline, but little is known about the effects of prolonged periods of missed care. To determine if missed care in the Cystic Fibrosis Foundation Patient Registry (CFFPR) is associated with decreased lung function at follow-up visits.

Social Isolation Causes Cortical and Trabecular Bone Loss in Adult Male, but not Female, C57BL/6J Mice.

Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising "epidemic" of loneliness. Isolation is associated with an increased risk for many physical and mental health disorders and increased overall mortality risk.

Targeting the secreted RGDKGE collagen fragment reduces PD‑L1 by a proteasome‑dependent mechanism and inhibits tumor growth.

Structural alterations of collagen impact signaling that helps control tumor progression and the responses to therapeutic intervention. Integrins represent a class of receptors that include members that mediate collagen signaling. However, a strategy of directly targeting integrins to control tumor growth has demonstrated limited activity in the clinical setting.

In silico discovery of blood cell macromolecular associations.

Background: Physical molecular interactions are the basis of intracellular signalling and gene regulatory networks, and comprehensive, accessible databases are needed for their discovery. Highly correlated transcripts may reflect important functional associations, but identification of such associations from primary data are cumbersome. We have constructed and adapted a user-friendly web application to discover and identify putative macromolecular associations in human peripheral blood based on significant correlations at the transcriptional level.

Does tamsulosin decrease postoperative urinary retention in spine surgery? A double-blind, randomized controlled trial.

Objective: The authors' objective was to determine whether preoperative administration of tamsulosin decreases postoperative urinary retention after spine surgery.

Methods: In this randomized, double-blind, placebo-controlled clinical trial performed at a single institution between 2016 and 2019, eligible males aged 50 to 85 years were administered tamsulosin or placebo for 5 days prior to elective spine surgery. Patients were excluded if they were taking alpha adrenergic blocking drugs; were allergic to tamsulosin, lactose, or sulfa drugs; had a preexisting indwelling urinary catheter, orthostatic hypotension, history of urological surgery, or renal failure; or were scheduled for cataract surgery within 2 weeks.

Community oncologists' perceptions and utilization of large-panel genomic tumor testing.

Purpose: Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists' perceptions and use of GTT, but little is known about community oncologists' perceptions of GTT and how perceptions relate to clinicians' intentions to use GTT.

Methods: Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs.

Pharmacogenomic Effects of β-Blocker Use on Femoral Neck Bone Mineral Density.

Context: Recent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects.

Objective: To investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study's (FHS) Offspring Cohort.

Communicating Scientific Uncertainty About the COVID-19 Pandemic: Online Experimental Study of an Uncertainty-Normalizing Strategy.

Background: Communicating scientific uncertainty about public health threats such as COVID-19 is an ethically desirable task endorsed by expert guidelines on crisis communication. However, the communication of scientific uncertainty is challenging because of its potential to promote ambiguity aversion-a well-described syndrome of negative psychological responses consisting of heightened risk perceptions, emotional distress, and decision avoidance. Communication strategies that can inform the public about scientific uncertainty while mitigating ambiguity aversion are a critical unmet need.

FOXD1 regulates cell division in clear cell renal cell carcinoma.

Background: Forkhead transcription factors control cell growth in multiple cancer types. Foxd1 is essential for kidney development and mitochondrial metabolism, but its significance in renal cell carcinoma (ccRCC) has not been reported.

Methods: Transcriptome data from the TCGA database was used to correlate FOXD1 expression with patient survival.

An RGDKGE-Containing Cryptic Collagen Fragment Regulates Phosphorylation of Large Tumor Suppressor Kinase-1 and Controls Ovarian Tumor Growth by a Yes-Associated Protein-Dependent Mechanism.

The growth and spread of malignant tumors, such as ovarian carcinomas, are governed in part by complex interconnected signaling cascades occurring between stromal and tumor cells. These reciprocal cross-talk signaling networks operating within the local tissue microenvironment may enhance malignant tumor progression. Understanding how novel bioactive molecules generated within the tumor microenvironment regulate signaling pathways in distinct cellular compartments is critical for the development of more effective treatment paradigms.

Myeloma-Modified Adipocytes Exhibit Metabolic Dysfunction and a Senescence-Associated Secretory Phenotype.

Bone marrow adipocytes (BMAd) have recently been implicated in accelerating bone metastatic cancers, such as acute myelogenous leukemia and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity, two key risk factors in multiple myeloma disease prevalence, suggesting that BMAds may influence and be influenced by myeloma cells in the marrow. Here, we provide evidence that reciprocal interactions and cross-regulation of myeloma cells and BMAds play a role in multiple myeloma pathogenesis and treatment response.

Association of Beta Blocker Use With Bone Mineral Density in the Framingham Osteoporosis Study: A Cross-Sectional Study.

Some, but not all, prior observational studies have shown that beta blocker (BB) use is associated with lower fracture risk and higher bone mineral density (BMD). Rodent studies show the mechanism to involve the reduction in the effects of beta-adrenergic signaling on bone remodeling. Because previous studies did not have detailed information on dose, duration, and beta-1 selectivity, we examined these in a cross-sectional analysis of the association between BB use and hip and spine BMD using DXA with the Offspring Cohort of the Framingham Heart Study.

Reproducibility of a prediabetes classification in a contemporary population.

Aims: To assess whether meeting both fasting plasma glucose (FPG) and HbA1c criteria for prediabetes in people at high risk indicates with near certainty the presence of dysglycemia on repeat testing.

Methods: Observational study using data from Vitamin D and Type 2 Diabetes (D2d) study. HbA1c, FPG were measured at screening visit 1; FPG, HbA1c and 2 h plasma glucose (2hPG) measured at screening visit 2 (a median of 21 days later); participants classified as having normal glucose regulation (all 3 tests in normal range), prediabetes or diabetes (at least 1 of 3 tests in diabetes range).

miRNA Mechanisms Underlying the Association of Beta Blocker Use and Bone Mineral Density.

Osteoporosis is a debilitating and costly disease that causes fractures in 33% of women and 20% of men over the age of 50 years. Recent studies have shown that beta blocker (BB) users have higher bone mineral density (BMD) and decreased risk of fracture compared with non-users. The mechanism underlying this association is thought to be due to suppression of adrenergic signaling in osteoblasts, which leads to increased BMD in rodent models; however, the mechanism in humans is unknown.