Personalized bone organoid using iPSC-derived cells for clinically relevant applications.

Patient-specific induced pluripotent stem cells (iPSCs)-based modeling potentially recapitulates the pathology and mechanisms more faithfully than cell line models and general animal models. Utilizing iPSC-derived cells for personalized bone formation research offers a powerful tool to better understand the role of individual differences in bone health and disease and provide more precise information for personalized bone regeneration therapies. Here we generated iPSC-derived mesenchymal progenitor cells (iMPCs), endothelial cells (iECs), and macrophages (iMØ), from different donors.

Loss of reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes.

There are multiple independent genetic signals at the () locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss remains unknown.

Approach to Bone Health in the Patient With Breast Cancer.

Treatment for breast cancer, including endocrine therapies, can contribute to bone loss and increase the risk of osteoporosis and fractures. Management of bone health in patients with cancer is often coordinated between oncologists, endocrinologists, and primary care physicians. In this article, we discuss the approach to screening for fracture risk among patients initiating treatments for breast cancer and recommendations for lifestyle modifications to optimize bone health.

Pudgy mouse rib deformities emanate from abnormal paravertebral longitudinal cartilage/bone accumulations.

The pudgy (pu/pu) mouse, caused by a recessive mutation in the Notch family Delta like-3 gene (Dll3), has severe rib, vertebral body and intervertebral disc abnormalities. Using whole-mount preparations and serial histologic sections we demonstrate: 1) localized paravertebral longitudinal cartilage/bone accumulations (PVLC/BAs) invariably associated with branched, fused and asymmetrically spaced ribs that emanate from it laterally; 2) abnormal rib formation immediately adjacent to abnormal vertebral body and intervertebral disc formation in asymmetric right/left fashion; and 3) patterns of rib deformation that differ in each mouse. Normal BALB/c embryo and age-matched non-affected pu/+ mice assessments allow for pu/pu comparisons.

Multimodal Pediatric Lymphoma Detection using PET and MRI.

Lymphoma is one of the most common types of cancer for children (ages 0 to 19). Due to the reduced radiation exposure, PET/MR systems that allow simultaneous PET and MR imaging have become the standard of care for diagnosing cancers and monitoring tumor response to therapy in the pediatric population. In this work, we developed a multimodal deep learning algorithm for automatic pediatric lymphoma detection using PET and MRI.

The role of vesicle trafficking genes in osteoblast differentiation and function.

Using Col2.3GFP transgenic mice expressing GFP in maturing osteoblasts, we isolated Col2.3GFP enriched osteoblasts from 3 sources.

Spatially patterned 3D model mimics key features of cancer metastasis to bone.

Bone is the most common target of metastasis in breast cancer and prostate cancer, leading to significant mortality due to lack of effective treatments. The discovery of novel therapies has been hampered by a lack of physiologically relevant in vitro models that can mimic key clinical features of bone metastases. To fill this critical gap, here we report spatially patterned, tissue engineered 3D models of breast cancer and prostate cancer bone metastasis which mimic bone-specific invasion, cancer aggressiveness, cancer-induced dysregulation of bone remodeling, and in vivo drug response.

Parathyroid hormone 1 receptor signaling mediates breast cancer metastasis to bone in mice.

Bone metastases are a common complication of breast cancer. We have demonstrated that intermittent administration of parathyroid hormone (PTH[1-34]) reduces the incidence of bone metastases in murine models of breast cancer by acting on osteoblasts to alter the bone microenvironment. Here, we examined the role of signaling mediated by PTH 1 receptor (PTH1R) in both osteoblasts and breast cancer cells in influencing bone metastases.

Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline.

Background: Hypercalcemia of malignancy (HCM) is the most common metabolic complication of malignancies, but its incidence may be declining due to potent chemotherapeutic agents. The high mortality associated with HCM has declined markedly due to the introduction of increasingly effective chemotherapeutic drugs. Despite the widespread availability of efficacious medications to treat HCM, evidence-based recommendations to manage this debilitating condition are lacking.

Sex-Specific Differences in Gα-Mediated Signaling Downstream of PTH1R Activation by Abaloparatide in Bone.

Teriparatide, recombinant parathyroid hormone (PTH[1-34]), and abaloparatide, an analogue of PTH related-peptide (PTHrP[1-34]), are both anabolic medications for osteoporosis that target the PTH receptor PTH1R. PTH1R is a G protein-coupled receptor, and the stimulatory Gs protein is an important mediator of the anabolic actions of PTH1R activation in bone. We have published that mice lacking the α subunit of Gs in osteoprogenitors do not increase bone mass in response to PTH(1-34).

Osteoblast Lineage Support of Hematopoiesis in Health and Disease.

In mammals, hematopoiesis migrates to the bone marrow during embryogenesis coincident with the appearance of mineralized bone, where hematopoietic stem cells (HSCs) and their progeny are maintained by the surrounding microenvironment or niche, and sustain the entirety of the hematopoietic system. Genetic manipulation of niche factors and advances in cell lineage tracing techniques have implicated cells of both hematopoietic and nonhematopoietic origin as important regulators of hematopoiesis in health and disease. Among them, cells of the osteoblast lineage, from stromal skeletal stem cells to matrix-embedded osteocytes, are vital niche residents with varying capacities for hematopoietic support depending on stage of differentiation.

Developing and Validating Multi-Modal Models for Mortality Prediction in COVID-19 Patients: a Multi-center Retrospective Study.

The unprecedented global crisis brought about by the COVID-19 pandemic has sparked numerous efforts to create predictive models for the detection and prognostication of SARS-CoV-2 infections with the goal of helping health systems allocate resources. Machine learning models, in particular, hold promise for their ability to leverage patient clinical information and medical images for prediction. However, most of the published COVID-19 prediction models thus far have little clinical utility due to methodological flaws and lack of appropriate validation.

Loss of Parathyroid Hormone Receptor Signaling in Osteoprogenitors Is Associated With Accumulation of Multiple Hematopoietic Lineages in the Bone Marrow.

Osteoblasts and their progenitors play an important role in the support of hematopoiesis within the bone marrow (BM) microenvironment. We have previously reported that parathyroid hormone receptor (PTH1R) signaling in osteoprogenitors is required for normal B cell precursor differentiation, and for trafficking of maturing B cells out of the BM. Cells of the osteoblast lineage have been implicated in the regulation of several other hematopoietic cell populations, but the effects of PTH1R signaling in osteoprogenitors on other maturing hematopoietic populations have not been investigated.

Semantic Expansion of Clinician Generated Data Preferences for Automatic Patient Data Summarization.

Patient Electronic Health Records (EHRs) typically contain a substantial amount of data, which can lead to information overload for clinicians, especially in high-throughput fields like radiology. Thus, it would be beneficial to have a mechanism for summarizing the most clinically relevant patient information pertinent to the needs of clinicians. This study presents a novel approach for the curation of clinician EHR data preference information towards the ultimate goal of providing robust EHR summarization.

Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model.

Background: Despite the high incidence of fractures and pseudoarthrosis in the aged population, a potential role for the use of mesenchymal stem cells (MSCs) in the treatment of bone defects in elderly patients has not been elucidated. Inflammation and the innate immune system, including macrophages, play crucial roles in the differentiation and activation of MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages to an M2 phenotype to promote bone healing in an established young murine critical size bone defect model.

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update.

Purpose: To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline.

Methods: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data.

Results: Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations.

Curation of the CANDID-PTX Dataset with Free-Text Reports.

Conventional Radiography, Thorax, Trauma, Ribs, Catheters, Segmentation, Diagnosis, Classification, Supervised Learning, Machine Learning © RSNA, 2021.

Sex Differences in Mesenchymal Stem Cell Therapy With Gelatin-Based Microribbon Hydrogels in a Murine Long Bone Critical-Size Defect Model.

Mesenchymal stem cell (MSC)-based therapy and novel biomaterials are promising strategies for healing of long bone critical size defects. Interleukin-4 (IL-4) over-expressing MSCs within a gelatin microribbon (µRB) scaffold was previously shown to enhance the bridging of bone within a critical size femoral bone defect in male Balb/c mice. Whether sex differences affect the healing of this bone defect in conjunction with different treatments is unknown.

AI Accelerated Human-in-the-loop Structuring of Radiology Reports.

Rule-based Natural Language Processing (NLP) pipelines depend on robust domain knowledge. Given the long tail of important terminology in radiology reports, it is not uncommon for standard approaches to miss items critical for understanding the image. AI techniques can accelerate the concept expansion and phrasal grouping tasks to efficiently create a domain specific lexicon ontology for structuring reports.

Extracting and Learning Fine-Grained Labels from Chest Radiographs.

Chest radiographs are the most common diagnostic exam in emergency rooms and intensive care units today. Recently, a number of researchers have begun working on large chest X-ray datasets to develop deep learning models for recognition of a handful of coarse finding classes such as opacities, masses and nodules. In this paper, we focus on extracting and learning fine-grained labels for chest X-ray images.

Combining Deep Learning and Knowledge-driven Reasoning for Chest X-Ray Findings Detection.

The application of deep learning algorithms in medical imaging analysis is a steadily growing research area. While deep learning methods are thriving in the medical domain, they seldom utilize the rich knowledge associated with connected radiology reports. The knowledge derived from these reports can be utilized to enhance the performance of deep learning models.