COSMOS: a platform for real-time morphology-based, label-free cell sorting using deep learning.

Cells are the singular building blocks of life, and a comprehensive understanding of morphology, among other properties, is crucial to the assessment of underlying heterogeneity. We developed Computational Sorting and Mapping of Single Cells (COSMOS), a platform based on Artificial Intelligence (AI) and microfluidics to characterize and sort single cells based on real-time deep learning interpretation of high-resolution brightfield images. Supervised deep learning models were applied to characterize and sort cell lines and dissociated primary tissue based on high-dimensional embedding vectors of morphology without the need for biomarker labels and stains/dyes.

Primary care family physicians' experiences with clinical integration in qualitative and mixed reviews: a systematic review protocol.

Introduction: Clinical (service) integration in primary care settings describes how comprehensive care is coordinated by family physicians (FPs) over time across healthcare contexts to meet patient care needs. To improve care integration and healthcare service planning, a systematic approach to understanding its numerous influencing factors is paramount. The objective of this study is to generate a comprehensive map of FP-perceived factors influencing clinical integration across diseases and patient demographics.

Routine Elective Gastrojejunostomy Tube Changes Are Associated With Reduced Tube Complications and Radiation Exposure.

Gastrojejunostomy tubes (GJTs) can be a long-term solution for patients with intragastric feeding intolerance. Our retrospective study of 101 patients correlates the frequency of routine and urgent GJT changes, as well as complications and radiation exposure. Over a 2.

Residual CIS after neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer: Implications for neoadjuvant trials.

Purpose: To better define surrogate endpoints for neoadjuvant chemotherapy (NAC) trials in patients with muscle-invasive bladder cancer. We compared survival in patients with carcinoma in-situ (CIS) only vs. complete response following NAC and radical cystectomy (RC).

Adeno-Associated Virus (AAV) Vectors: Rational Design Strategies for Capsid Engineering.

Adeno-associated virus (AAV) consists of a simple genome, infects mammalian cells, displays nonpathogenicity in humans, and spans an array of serotypes and variants bearing distinct tissue tropisms. These attributes lend AAV tremendous promise as a gene delivery vector, further substantiated by its extensive testing in human clinical trials. Rational design approaches to capsid engineering leverage current scientific knowledge of AAV to further modulate, enhance and optimize the performance of the vectors.

Reverse transduction can improve efficiency of AAV vectors in transduction-resistant cells.

Reverse transduction, also known as substrate-mediated gene delivery, is a strategy in which viral vectors are first coated onto a surface that subsequently comes into contact with mammalian cells. The cells internalize the surface-attached vectors, resulting in transgene expression. We hypothesized that forcing the interaction between cells and adeno-associated virus (AAV) vectors through a reverse transduction format would increase in vitro gene delivery efficiencies of the vectors in transduction-resistant cells.

A stochastic and dynamical view of pluripotency in mouse embryonic stem cells.

Pluripotent embryonic stem cells are of paramount importance for biomedical sciences because of their innate ability for self-renewal and differentiation into all major cell lines. The fateful decision to exit or remain in the pluripotent state is regulated by complex genetic regulatory networks. The rapid growth of single-cell sequencing data has greatly stimulated applications of statistical and machine learning methods for inferring topologies of pluripotency regulating genetic networks.

Application of Materials as Medical Devices with Localized Drug Delivery Capabilities for Enhanced Wound Repair.

The plentiful assortment of natural and synthetic materials can be leveraged to accommodate diverse wound types, as well as different stages of the healing process. An ideal material is envisioned to promote tissue repair with minimal inconvenience for patients. Traditional materials employed in the clinical setting often invoke secondary complications, such as infection, pain, foreign body reaction, and chronic inflammation.

Honing Cell and Tissue Culture Conditions for Bone and Cartilage Tissue Engineering.

An avenue of tremendous interest and need in health care encompasses the regeneration of bone and cartilage. Over the years, numerous tissue engineering strategies have contributed substantial progress toward the realization of clinically relevant therapies. Cell and tissue culture protocols, however, show many variations that make experimental results among different publications challenging to compare.

Effects of Local Antibiotic Delivery from Porous Space Maintainers on Infection Clearance and Induction of an Osteogenic Membrane in an Infected Bone Defect.

Reconstruction of large bone defects can be complicated by the presence of both infection and local antibiotic administration. This can be addressed through a two-stage reconstructive approach, called the Masquelet technique, that involves the generation of an induced osteogenic membrane over a temporary poly(methyl methacrylate) (PMMA) space maintainer, followed by definitive reconstruction after the induced membrane is formed. Given that infection and antibiotic delivery each have independent effects on local tissue response, the objective of this study is to evaluate the interaction between local clindamycin release and bacterial contamination with regards to infection prevention and the restoration of pro-osteogenic gene expression in the induced membrane.

Data describing the swelling behavior and cytocompatibility of biodegradable polyelectrolyte hydrogels incorporating poly(L-lysine) for applications in cartilage tissue engineering.

This data article presents data associated with the research article entitled "Evaluation of cell-laden polyelectrolyte hydrogels incorporating poly(L-lysine) for applications in cartilage tissue engineering" (Lam et al., 2016) [1]. Synthetic hydrogel composites fabricated using oligo(poly(ethylene glycol) fumarate) (OPF) macromers were utilized as vehicles for the incorporation of poly(L-lysine) (PLL) as well as the encapsulation of mesenchymal stem cells (MSCs).

Evaluation of Gelatin Microparticles as Adherent-Substrates for Mesenchymal Stem Cells in a Hydrogel Composite.

Due to the lack of cell-adhesive moieties in traditional synthetic hydrogels, the present work investigated the use of degradable gelatin microparticles (GMPs) as temporary adherent substrates for anchorage-dependent mesenchymal stem cells (MSCs). MSCs were seeded onto GMPs of varying crosslinking densities and sizes to investigate their role on influencing MSC differentiation and aggregation. The MSC-seeded GMPs were then encapsulated in poly(ethylene glycol)-based hydrogels and cultured in serum-free, growth factor-free osteochondral medium.

Evaluation of cell-laden polyelectrolyte hydrogels incorporating poly(L-Lysine) for applications in cartilage tissue engineering.

To address the lack of reliable long-term solutions for cartilage injuries, strategies in tissue engineering are beginning to leverage developmental processes to spur tissue regeneration. This study focuses on the use of poly(L-lysine) (PLL), previously shown to up-regulate mesenchymal condensation during developmental skeletogenesis in vitro, as an early chondrogenic stimulant of mesenchymal stem cells (MSCs). We characterized the effect of PLL incorporation on the swelling and degradation of oligo(poly(ethylene) glycol) fumarate) (OPF)-based hydrogels as functions of PLL molecular weight and dosage.

Identification of Whole Mitochondrial Genomes from Venezuela and Implications on Regional Phylogenies in South America.

Recent studies have expanded and refined the founding haplogroups of the Americas using whole mitochondrial (mtDNA) genome analysis. In addition to pan-American lineages, specific variants have been identified in a number of studies that show higher frequencies in restricted geographical areas. To further characterize Native American maternal lineages and specifically examine local patterns within South America, we analyzed 12 maternally unrelated Yekuana whole mtDNA genomes from one village (Sharamaña) that include the four major Native American haplogroups A2, B2, C1, and D1.

Materials from Mussel-Inspired Chemistry for Cell and Tissue Engineering Applications.

Current advances in biomaterial fabrication techniques have broadened their application in different realms of biomedical engineering, spanning from drug delivery to tissue engineering. The success of biomaterials depends highly on the ability to modulate cell and tissue responses, including cell adhesion, as well as induction of repair and immune processes. Thus, most recent approaches in the field have concentrated on functionalizing biomaterials with different biomolecules intended to evoke cell- and tissue-specific reactions.

Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites.

The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and bone repair, respectively, at 6 and 12 weeks. Correlation analysis revealed significant associations between specific cartilage indices and subchondral bone parameters that varied with location in the defect (cortical vs.

Ancient DNA analysis of the oldest canid species from the Siberian Arctic and genetic contribution to the domestic dog.

Modern Arctic Siberia provides a wealth of resources for archaeological, geological, and paleontological research to investigate the population dynamics of faunal communities from the Pleistocene, particularly as the faunal material coming from permafrost has proven suitable for genetic studies. In order to examine the history of the Canid species in the Siberian Arctic, we carried out genetic analysis of fourteen canid remains from various sites, including the well-documented Upper Paleolithic Yana RHS and Early Holocene Zhokhov Island sites. Estimated age of samples range from as recent as 1,700 years before present (YBP) to at least 360,000 YBP for the remains of the extinct wolf, Canis cf.

The impact of pioglitazone on bladder cancer and cardiovascular events.

Type 2 diabetes mellitus (T2DM) is a chronic condition with increasing prevalence and severe complications. Thiazolidinediones have been marketed since 1997 and are effective glucose-lowering drugs, but individual drugs within the class have been linked to serious adverse effects that resulted in the removal of troglitazone from the market, restrictions to rosiglitazone's use, and a warning added to pioglitazone's label. In 2007, a meta-analysis linked rosiglitazone to myocardial infarction (MI).

Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair.

The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formulations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers.

Synthetic biodegradable hydrogel delivery of demineralized bone matrix for bone augmentation in a rat model.

There exists a strong clinical need for a more capable and robust method to achieve bone augmentation, and a system with fine-tuned delivery of demineralized bone matrix (DBM) has the potential to meet that need. As such, the objective of the present study was to investigate a synthetic biodegradable hydrogel for the delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol) fumarate) (OPF) constructs were designed and fabricated by varying the content of rat-derived DBM particles (either 1:3, 1:1 or 3:1 DBM:OPF weight ratio on a dry basis) and using two DBM particle size ranges (50-150 or 150-250 μm).

Human umbilical cord mesenchymal stromal cells exhibit immature nucleus pulposus cell phenotype in a laminin-rich pseudo-three-dimensional culture system.

Introduction: Cell supplementation to the herniated or degenerated intervertebral disc (IVD) is a potential strategy to promote tissue regeneration and slow disc pathology. Human umbilical cord mesenchymal stromal cells (HUCMSCs) - originating from the Wharton's jelly - remain an attractive candidate for such endeavors with their ability to differentiate into multiple lineages. Previously, mesenchymal stem cells (MSCs) have been studied as a potential source for disc tissue regeneration.

Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus pulposus-like cells in vitro.

A large percentage of the population may be expected to experience painful symptoms or disability associated with intervertebral disc (IVD) degeneration - a condition characterized by diminished integrity of tissue components. Great interest exists in the use of autologous or allogeneic cells delivered to the degenerated IVD to promote matrix regeneration. Induced pluripotent stem cells (iPSCs), derived from a patient's own somatic cells, have demonstrated their capacity to differentiate into various cell types although their potential to differentiate into an IVD cell has not yet been demonstrated.

Biomaterials for tissue engineering.

Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties.

The effect of obesity on the relationship between serum parathyroid hormone and 25-hydroxyvitamin D in women.

Context: Obesity is associated with lower serum concentrations of 25-hydroxyvitamin D (25OHD) and higher intact PTH. The threshold of 25OHD needed to maximally suppress intact PTH has been suggested as a marker of optimal vitamin D status.

Objective: In this study, we hypothesized that whereas the obese have a higher serum PTH and lower 25OHD, suppression of serum PTH by 25OHD would be independent of body weight.