Deep-learning optical flow for measuring velocity fields from experimental data.

Deep learning-based optical flow (DLOF) extracts features in adjacent video frames with deep convolutional neural networks. It uses those features to estimate the inter-frame motions of objects. We evaluate the ability of optical flow to quantify the spontaneous flows of microtubule (MT)-based active nematics under different labeling conditions, and compare its performance to particle image velocimetry (PIV).

A machine learning approach to robustly determine director fields and analyze defects in active nematics.

Active nematics are dense systems of rodlike particles that consume energy to drive motion at the level of the individual particles. They exist in natural systems like biological tissues and artificial materials such as suspensions of self-propelled colloidal particles or synthetic microswimmers. Active nematics have attracted significant attention in recent years due to their spectacular nonequilibrium collective spatiotemporal dynamics, which may enable applications in fields such as robotics, drug delivery, and materials science.

Experimental factors that impact CaV1.2 channel pharmacology-Effects of recording temperature, charge carrier, and quantification of drug effects on the step and ramp currents elicited by the "step-step-ramp" voltage protocol.

Background And Purpose: CaV1.2 channels contribute to action potential upstroke in pacemaker cells, plateau potential in working myocytes, and initiate excitation-contraction coupling. Understanding drug action on CaV1.

Bending stiffness characterization of Bacillus subtilis' flagellar filament.

The filament of a bacterial flagellum is a tube-like organelle made of a single protein-flagellin-and assembled into multiple polymorphic forms. The filament can be further discretized into four subunit domains (D0, D1, D2, and D3) along the radial direction. However, it remains unclear which subunit domain plays an important role in regulating the rigidity of the filament.

Mechanisms of QT prolongation by buprenorphine cannot be explained by direct hERG channel block.

Buprenorphine is a μ-opioid receptor (MOR) partial agonist used to manage pain and addiction. QTC prolongation that crosses the 10 msec threshold of regulatory concern was observed at a supratherapeutic dose in two thorough QT studies for the transdermal buprenorphine product BUTRANS®. Because QTC prolongation can be associated with Torsades de Pointes (TdP), a rare but potentially fatal ventricular arrhythmia, these results have led to further investigation of the electrophysiological effects of buprenorphine.

Catheter-related right atrial thrombosis.

Introduction: Catheter-related right atrial thrombosis is an under-recognized complication of central venous catheter placement. We performed a retrospective review, characterizing clinical aspects of catheter-related right atrial thrombosis (CRAT).

Methods: To identify cases, a literature search was conducted in PubMed and additional items selected by review of related items and bibliography review.

Drug potency on inhibiting late Na current is sensitive to gating modifier and current region where drug effects were measured.

Introduction: Cardiac late Na current (I) contributes to ventricular action potential duration. Pathological increase in I is arrhythmogenic, and inhibition of I offers protection against ventricular repolarization disturbance. Recently, two I datasets generated by different laboratories that assessed current inhibition by a panel of clinical drugs as a part of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative were published.

Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative.

The International Council on Harmonization (ICH) S7B and E14 regulatory guidelines are sensitive but not specific for predicting which drugs are pro-arrhythmic. In response, the Comprehensive In Vitro Proarrhythmia Assay (CiPA) was proposed that integrates multi-ion channel pharmacology data in vitro into a human cardiomyocyte model in silico for proarrhythmia risk assessment. Previously, we reported the model optimization and proarrhythmia metric selection based on CiPA training drugs.

Cobalamin deficiency presenting with thrombotic microangiopathy (TMA) features: A systematic review.

Introduction: Cobalamin deficiency may result in hematologic characteristics similar to thrombotic microangiopathy (TMA). To facilitate diagnosis, we reviewed reported cases of acquired cobalamin deficiency presenting with TMA features (c.def-TMA).

Corrigendum: Optimization of an Cardiac Cell Model for Proarrhythmia Risk Assessment.

[This corrects the article on p. 616 in vol. 8, PMID: 28878692.

Uncertainty Quantification Reveals the Importance of Data Variability and Experimental Design Considerations for Proarrhythmia Risk Assessment.

The Comprehensive Proarrhythmia Assay (CiPA) is a global initiative intended to improve drug proarrhythmia risk assessment using a new paradigm of mechanistic assays. Under the CiPA paradigm, the relative risk of drug-induced Torsade de Pointes (TdP) is assessed using an model of the human ventricular action potential (AP) that integrates pharmacology data from multiple ion channels. Thus, modeling predictions of cardiac risk liability will depend critically on the variability in pharmacology data, and uncertainty quantification (UQ) must comprise an essential component of the assay.

The impact of gender, race, socioeconomic status, and treatment on outcomes in esophageal cancer: A population-based analysis.

Background: African Americans and Hispanics are reported to have higher mortality from esophageal cancer (EC) than Caucasians. In this study, we analyzed the independent effects of race, gender, treatment, and socioeconomic status (SES) on overall survival (OS).

Methods: Data for all EC cases between 2004 and 2010 with follow-up through 2012 were obtained from the California Cancer Registry.

Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion.

Despite the risk of cyanide toxicity and lack of efficacy, amygdalin is still used as alternative cancer treatment. Due to the highly lethal nature of cyanide toxicity, many patients die before getting medical care. Herein, we describe the case of a 73-year-old female with metastatic pancreatic cancer who developed cyanide toxicity from taking amygdalin.

Optimization of an Cardiac Cell Model for Proarrhythmia Risk Assessment.

Drug-induced Torsade-de-Pointes (TdP) has been responsible for the withdrawal of many drugs from the market and is therefore of major concern to global regulatory agencies and the pharmaceutical industry. The Comprehensive Proarrhythmia Assay (CiPA) was proposed to improve prediction of TdP risk, using models and multi-channel pharmacology data as integral parts of this initiative. Previously, we reported that combining dynamic interactions between drugs and the rapid delayed rectifier potassium current (IKr) with multi-channel pharmacology is important for TdP risk classification, and we modified the original O'Hara Rudy ventricular cell mathematical model to include a Markov model of IKr to represent dynamic drug-IKr interactions (IKr-dynamic ORd model).

Characterization of loperamide-mediated block of hERG channels at physiological temperature and its proarrhythmia propensity.

Background: Loperamide (Immodium®) is indicated for symptomatic control of diarrhea. It is a μ-opioid receptor agonist, and recently has been associated with misuse and abuse. At therapeutic doses loperamide has not been associated with cardiotoxicity.

PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence.

Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and mortality, and new therapeutic approaches are needed. Despite the improved outcomes with monoclonal antibodies targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor receptor 2, durable responses are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have led to improved survival across several tumor types, frequently characterized by prolonged benefit in responding patients.

The safety of Bruton's tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia.

The approval of ibrutinib has revolutionized the therapeutic landscape of chronic lymphocytic leukemia (CLL). Currently ibrutinib is indicated for patients that are both treatment naïve as well as those with relapsed CLL. Ibrutinib is generally well-tolerated with durable responses that improve over time in most patients.

Cytarabine Induced Acute Cerebellar Syndrome during Hyper-CVAD Treatment for B-Cell Acute Lymphoblastic Leukemia.

Acute cerebellar syndrome can be caused by high doses of cytarabine, but it has not been described in patients with acute lymphoblastic leukemia (ALL) who received hyper-CVAD chemotherapy. Herein, we report two cases with histories of positive Philadelphia chromosome B-cell ALL who developed acute cerebellar syndrome after the exposure to relatively low doses of cytarabine in the second cycle of hyper-CVAD regimen. The cerebellar symptoms were attenuated by cytarabine discontinuation and administration of steroids.

Emerging Role of Direct Oral Anticoagulants in the Management of Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) are rare but potentially limb- and life-threatening complications of heparin therapy. Continuation of heparin or low-molecular-weight heparin is contraindicated due to platelet activation in the presence of (heparin-dependent) HIT antibodies. Primary treatment options currently include argatroban, fondaparinux, or bivalirudin.

Profile of rociletinib and its potential in the treatment of non-small-cell lung cancer.

Patients with non-small-cell lung cancer (NSCLC) harboring activating mutations in benefit from treatment with EGFR small-molecule tyrosine-kinase inhibitors. However, the development of acquired resistance to EGFR inhibitors is universal and limits treatment efficacy. Over half of patients receiving first-generation EGFR inhibitors (erlotinib and gefitinib) develop resistance via the gatekeeper T790M () mutation, and therapies able to overcome T790M-mediated resistance have been an unmet need in NSCLC.

Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel-Drug Binding Kinetics and Multichannel Pharmacology.

Background: The current proarrhythmia safety testing paradigm, although highly efficient in preventing new torsadogenic drugs from entering the market, has important limitations that can restrict the development and use of valuable new therapeutics. The CiPA (Comprehensive in vitro Proarrhythmia Assay) proposes to overcome these limitations by evaluating drug effects on multiple cardiac ion channels in vitro and using these data in a predictive in silico model of the adult human ventricular myocyte. A set of drugs with known clinical torsade de pointes risk was selected to develop and calibrate the in silico model.

Focus on Alectinib and Competitor Compounds for Second-Line Therapy in -Rearranged NSCLC.

The management of anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) exemplifies the potential of a precision medicine approach to cancer care. The ALK inhibitor crizotinib has led to improved outcomes in the first- and second-line setting; however, toxicities, intracranial activity, and acquired resistance necessitated the advent of later generation ALK inhibitors. A large portion of acquired resistance to ALK inhibitors is caused by secondary mutations in the ALK kinase domain.

Dramatic Response to Carboplatin, Paclitaxel, and Radiation in a Patient With Malignant Myoepithelioma of the Breast.

Malignant myoepithelioma of the breast (MMB) is extremely rare and often presents as a diagnostic challenge. This article reports on a rare case of aggressive MMB in a 52-year-old woman who experienced a dramatic response to carboplatin, paclitaxel, and radiation.

A temperature-dependent in silico model of the human ether-à-go-go-related (hERG) gene channel.

Introduction: Current regulatory guidelines for assessing the risk of QT prolongation include in vitro assays assessing drug effects on the human ether-à-go-go-related (hERG; also known as Kv11.1) channel expressed in cell lines. These assays are typically conducted at room temperature to promote the ease and stability of recording hERG currents.