Videos represent the primary source of information for surveillance applications. Video material is often available in large quantities but in most cases it contains little or no annotation for ...supervised learning. This article reviews the state-of-the-art deep learning based methods for video anomaly detection and categorizes them based on the type of model and criteria of detection. We also perform simple studies to understand the different approaches and provide the criteria of evaluation for spatio-temporal anomaly detection.
Pathogenic mutations in LAMIN A/C (LMNA) cause abnormal nuclear structure and laminopathies. These diseases have myriad tissue-specific phenotypes, including dilated cardiomyopathy (DCM), but how ...LMNA mutations result in tissue-restricted disease phenotypes remains unclear. We introduced LMNA mutations from individuals with DCM into human induced pluripotent stem cells (hiPSCs) and found that hiPSC-derived cardiomyocytes, in contrast to hepatocytes or adipocytes, exhibit aberrant nuclear morphology and specific disruptions in peripheral chromatin. Disrupted regions were enriched for transcriptionally active genes and regions with lower LAMIN B1 contact frequency. The lamina-chromatin interactions disrupted in mutant cardiomyocytes were enriched for genes associated with non-myocyte lineages and correlated with higher expression of those genes. Myocardium from individuals with LMNA variants similarly showed aberrant expression of non-myocyte pathways. We propose that the lamina network safeguards cellular identity and that pathogenic LMNA variants disrupt peripheral chromatin with specific epigenetic and molecular characteristics, causing misexpression of genes normally expressed in other cell types.
Display omitted
•Pathogenic LMNA variants disrupt peripheral chromatin in a cell-type-specific manner•Loss of lamina-bound chromatin occurs in regions with specific characteristics•Peripheral chromatin organization maintains silencing of alternative fate genes
Shah et al. demonstrate that pathogenic LMNA variants affect peripheral chromatin organization in a cell-type-specific manner. Their data suggest that lamina-chromatin interactions guard cellular identity. Pathogenic LMNA variants disrupt peripheral chromatin organization and abrogate normal silencing of alternative fate genes in cardiomyocytes.
Cardiovascular disease (CVD) complications have contributed significantly toward poor survival of cancer patients worldwide. These complications that result in myocardial and vascular damage lead to ...long-term multisystemic disorders. In some patient cohorts, the progression from acute to symptomatic CVD state may be accelerated due to exacerbation of underlying comorbidities such as obesity, diabetes and hypertension. In such situations, cardio-oncologists are often left with a clinical predicament in finding the optimal therapeutic balance to minimize cardiovascular risks and maximize the benefits in treating cancer. Hence, prognostically there is an urgent need for cost-effective, rapid, sensitive and patient-specific screening platform to allow risk-adapted decision making to prevent cancer therapy related cardiotoxicity. In recent years, momentous progress has been made toward the successful derivation of human cardiovascular cells from induced pluripotent stem cells (iPSCs). This technology has not only provided deeper mechanistic insights into basic cardiovascular biology but has also seamlessly integrated within the drug screening and discovery programs for early efficacy and safety evaluation. In this review, we discuss how iPSC-derived cardiovascular cells have been utilized for testing oncotherapeutics to pre-determine patient predisposition to cardiovascular toxicity. Lastly, we highlight the convergence of tissue engineering technologies and precision medicine that can enable patient-specific cardiotoxicity prognosis and treatment on a multi-organ level.
Suprachoroidal hemorrhage is a rare and potentially devastating clinical entity seen in individuals on anticoagulation presenting with severe unilateral eye pain, sudden vision loss, and elevated ...intraocular pressures. Herein, we report the first case of aseptic orbital cellulitis caused by recurrent spontaneous suprachoroidal hemorrhage. This case highlights an example of non-infectious orbital cellulitis arising from choroidal pathology in the setting of uncontrolled intraocular pressures and recurrent intraocular bleeding. Surgical intervention with blood drainage should be considered to prevent complications and preserve the globe.
Cell therapy of the degenerated intervertebral disc is limited by the lack of appropriate cell sources, thus new strategies for the differentiation of stem cells towards a nucleus pulposus (NP)‐like ...phenotype need investigation. In the current study, it is hypothesized that spherical niche‐like structures composed of type II collagen and hyaluronan (HA) mimic the NP microenvironment and promote the differentiation of adipose‐derived stem cells (ADSCs) towards an NP‐like phenotype. ADSCs are embedded in microgels of different concentrations of collagen II/HA. Cells' response to the different environments is studied by characterizing differences in cells' viability, morphology, and gene expression. After 21 days of culture, ADSCs maintain ±80% viability in all the conditions tested. Moreover, microgels with higher concentration of collagen are stable and maintain cells in a rounder shape. In presence of differentiation media, cells are able to differentiate in all the conditions tested, but in a more pronounced manner in the microgel with a higher concentration of collagen. By tuning microgels' properties, it is possible to influence ADSCs' phenotype and ability to differentiate. Indeed, when cultured in high concentrations of collagen, ADSCs expresses high levels of collagen II, aggrecan, SOX9, and low levels of collagen I.
Type II collagen/hyaluronan microgels as a 3D platform to mimic the microenvironment of the nucleus pulposus (NP). By tuning the composition of the microgels, it is possible to influence the phenotype of the embedded adipose‐derived stem cells (ADSCs). High concentrations of type II collagen and hyaluronan can prime ADSCs to differentiate towards an NP‐like phenotype.
Stem-cell derived in vitro cardiac models have provided profound insights into mechanisms in cardiac development and disease. Efficient differentiation of specific cardiac cell types from human ...pluripotent stem cells using a three-step Wnt signaling modulation has been one of the major discoveries that has enabled personalized cardiovascular disease modeling approaches. Generation of cardiac cell types follow key development stages during embryogenesis, they intuitively are excellent models to study cardiac tissue patterning in primitive cardiac structures. Here, we provide a brief overview of protocols that have laid the foundation for derivation of stem-cell derived three-dimensional cardiac models. Further this article highlights features and utility of the models to distinguish the advantages and trade-offs in modeling embryonic development and disease processes. Finally, we discuss the challenges in improving robustness in the current models and utilizing developmental principles to bring higher physiological relevance. In vitro human cardiac models are complimentary tools that allow mechanistic interrogation in a reductionist way. The unique advantage of utilizing patient specific stem cells and continued improvements in generating reliable organoid mimics of the heart will boost predictive power of these tools in basic and translational research.
Excessive iron accumulation in the heart causes iron overload cardiomyopathy (IOC), which initially presents as diastolic dysfunction and arrhythmia but progresses to systolic dysfunction and ...end-stage heart failure when left untreated. However, the mechanisms of iron-related cardiac injury and how iron accumulates in human cardiomyocytes are not well understood. Herein, using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we model IOC and screen for drugs to rescue the iron overload phenotypes. Human iPSC-CMs under excess iron exposure recapitulate early-stage IOC, including oxidative stress, arrhythmia, and contractile dysfunction. We find that iron-induced changes in calcium kinetics play a critical role in dysregulation of CM functions. We identify that ebselen, a selective divalent metal transporter 1 (DMT1) inhibitor and antioxidant, could prevent the observed iron overload phenotypes, supporting the role of DMT1 in iron uptake into the human myocardium. These results suggest that ebselen may be a potential preventive and therapeutic agent for treating patients with secondary iron overload.
Display omitted
•Human iPSC-CMs recapitulate clinical features of iron overload cardiomyopathy•Iron overload impairs calcium kinetics leading to iPSC-CM contractile dysfunction•Ebselen, a selective DMT1 inhibitor, can prevent iron overload phenotypes
Rhee et al. model iron overload cardiomyopathy in a dish using human iPSC-CMs. They find significantly altered calcium kinetics mediating contractile dysfunction and arrhythmia. Ebselen, a selective DMT1 inhibitor and antioxidant, effectively prevents the observed iron overload phenotypes and therefore may provide a promising therapeutic solution for iron overload cardiomyopathy.
Ipilimumab is a monoclonal antibody to cytotoxic T-lymphocyte antigen-4, a negative regulator of T-cell-mediated immune response. Ipilimumab is approved by the US Food and Drug Administration for the ...treatment of advanced melanoma. However, its use frequently has been associated with immune-related side effects, which can be explained by its mechanism of action. More common adverse effects include dermatitis, colitis, hepatitis, and endocrinopathies, but many less common immune-related adverse effects that involve various tissues and organ systems have been reported with more widespread use of ipilimumab since its approval in 2011. A case of bilateral orbital inflammatory syndrome secondary to ipilimumab, in a patient undergoing adjuvant treatment for metastatic melanoma, is reported.
PDF
