Almost all biomedical research to date has relied upon mean measurements from cell populations, however it is well established that what it is observed at this macroscopic level can be the result of many interactions of several different single cells. Thus, the observable macroscopic ‘average’ cannot outright be used as representative of the ‘average cell’. Rather, it is the resulting emerging behaviour of the actions and interactions of many different cells. Single‐cell RNA sequencing (scRNA‐Seq) enables the comparison of the transcriptomes (...) of individual cells. This provides high‐resolution maps of the dynamic cellular programmes allowing us to answer fundamental biological questions on their function and evolution. It also allows to address medical questions such as the role of rare cell populations contributing to disease progression and therapeutic resistance. Furthermore, it provides an understanding of context‐specific dependencies, namely the behaviour and function that a cell has in a specific context, which can be crucial to understand some complex diseases, such as diabetes, cardiovascular disease and cancer. Here, we provide an overview of scRNA‐Seq, including a comparative review of emerging technologies and computational pipelines. We discuss the current and emerging applications and focus on tumour heterogeneity a clear example of how scRNA‐Seq can provide new understanding of a complex disease. Additionally, we review the limitations and highlight the need of powerful computational pipelines and reproducible protocols for the broader acceptance of this technique in basic and clinical research. (shrink)

An important issue in the management of knowledge-based systems is the handling of inconsistency. This problem has recently been attracting a lot of attention from Artificial Intelligence community. When inconsistency occurs in a knowledge base, there are mainly two ways to deal with it; we either resolve it or accept inconsistency and cope with it. This paper tackles the problem of evaluating the amount of contradiction in propositional knowledge bases, and provides a new measure of conflict based on deductive argumentation (...) theory. Measuring the degree of conflict of a knowledge base can help us to deal with inconsistencies. Several semantic- and syntax-based approaches have been proposed separately. Given the pivotal role of argumentation in representing and handling inconsistency, in this paper, we use logical argumentation as a way to compute the inconsistency measure for propositional formulae. We show using the complete argumentation tree that our family of inconsistency measures is able to... (shrink)

Drawing out literal and metaphorical meanings of 'foreignness' this wide-ranging volume offers much to scholars of postcolonial, gender, and cultural studies seeking new approaches to the study of alterity.

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Maternal opioid use during pregnancy is a growing national problem and can lead to newborns developing neonatal opioid withdrawal syndrome soon after birth. Recent data demonstrates that nearly every 15 min a baby is born in the United States suffering from NOWS. The primary treatment for NOWS is opioid replacement therapy, commonly oral morphine, which has neurotoxic effects on the developing brain. There is an urgent need for non-opioid treatments for NOWS. Transcutaneous auricular neurostimulation, a novel and non-invasive form of (...) electrostimulation, may serve as a promising alternative to morphine. tAN is delivered via a multichannel earpiece electrode worn on and around the left ear, targeting two cranial nerves—the vagus and trigeminal nerves. Prior research suggests that auricular neurostimulation exerts an anxiolytic effect on the body by releasing endogenous opioids and reduces withdrawal symptoms in adults actively withdrawing from opioids. In this first-in-human prospective, open-label trial, we investigated tAN as an adjuvant to morphine therapy in eight infants >33 weeks gestational age suffering from NOWS and receiving oral morphine treatment. Infants received tAN for 30 min 1 h before receiving a morphine dose. tAN was delivered at 0.1 mA below perception intensity at two different nerve targets on the ear: Region 1, the auricular branch of the vagus nerve; and Region 2, the auriculotemporal nerve. tAN was delivered up to four times daily for a maximum of 12 days. The primary outcome measures were safety [heart rate monitoring, Neonatal Infant Pain Scale, and skin irritation] and morphine length of treatment. tAN was well-tolerated and resulted in no unanticipated adverse events. Comparing to the national average of 23 days, the average oral morphine LOT was 13.3 days and the average LOT after tAN initiation was 7 days. These preliminary data suggest that tAN is safe and may serve as a promising alternative adjuvant for treating NOWS and reducing the amount of time an infant receives oral morphine. (shrink)

BackgroundOrgan donation has become one of the most effective ways to save lives and improve the quality of life for patients with end-stage organ failure. No previous studies have investigated the preferences for the different consenting options for organ donation in Egypt. This study aims to assess Egyptians’ preferences regarding consenting options for posthumous organ donation, and measure their awareness and acceptance of the Egyptian law articles regulating organ donation.MethodsA cross sectional study was conducted among 2743 participants over two years. (...) Each participant was required to rank eleven consenting options from 1 to 11, and to report his awareness and acceptance of the seven articles of the Egyptian law of organ donation.Results47% of the participants expressed willingness to donate their organs after death. This percentage increased to 78% when consenting options were explained to participants. “Informed consent by donor only” was the most preferred type of consent for one third of respondents. Awareness of the law articles regulating organ donation was relatively low ranging from 56% to 23%.ConclusionCurrently, around half of the Egyptian population agree to posthumous organ donation. This percentage could be increased significantly by raising the awareness about how the process of donation could be regulated and how the patient’s right of decision could be protected. (shrink)