Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.
View Article and Find Full Text PDFLipids are an important component of food and oral drug formulations. Upon release into gastrointestinal fluids, triglycerides, common components of foods and drug delivery systems, form emulsions and are digested into simpler amphiphilic lipids (e.g.
View Article and Find Full Text PDFDisability acceptance has been conceptualized as an internalization of oneself as a person experiencing disability and associated with better coping and motivation for rehabilitation. This is particularly pertinent to individuals experiencing stroke because many are initially not fully aware of their stroke-related impairments, which affects the acceptance process. This qualitative metasynthesis aimed to synthesize qualitative findings regarding disability acceptance in stroke and identify barriers and facilitators associated with it.
View Article and Find Full Text PDFMultiple myeloma is a plasma cell malignancy that is currently incurable with conventional therapies. Following the success of CD19-targeted chimeric antigen receptor (CAR) T cells in leukemia and lymphoma, CAR T cells targeting B-cell maturation antigen (BCMA) more recently demonstrated impressive activity in relapsed and refractory myeloma patients. However, BCMA-directed therapy can fail due to weak expression of BCMA on myeloma cells, suggesting that novel approaches to better address this antigen-low disease may improve patient outcomes.
View Article and Find Full Text PDFAcademic Abstract: In the wake of the replication crisis, social and personality psychologists have increased attention to power analysis and the adequacy of sample sizes. In this article, we analyze current controversies in this area, including choosing effect sizes, why and whether power analyses should be conducted on already-collected data, how to mitigate the negative effects of sample size criteria on specific kinds of research, and which power criterion to use. For novel research questions, we advocate that researchers base sample sizes on effects that are likely to be cost-effective for other people to implement (in applied settings) or to study (in basic research settings), given the limitations of interest-based minimums or field-wide effect sizes.
View Article and Find Full Text PDFBackground: Evidence for the association between acceptance of disability (AOD) and positive rehabilitation outcomes, as well as for the use of AOD measurements in stroke rehabilitation practice, has increased in the international literature in the last decade. However, measurement tools for AOD are heterogenous and there has not been a systematic review summarizing the current evidence on the use of AOD measures and factors associated with AOD.
Objective: This study aimed to summarize current evidence on measurement tools used, present existing AOD scores in people with stroke and identify risk factors for and protective factors against poor AOD in people with stroke.
Pain invalidation involves the dismissal or lack of understanding of another's pain, undermining their subjective experience. Frequent exposure to invalidation negatively impacts mental and physical health as well as pain-related behaviors, potentially leading people to conceal their pain from others in the future and/or withdraw from potential sources of support. It is therefore possible that experiencing pain invalidation may also impact pain-reporting behavior in clinical settings.
View Article and Find Full Text PDFTwenty-seven methods of estimating vertical ground reaction force first peak, loading rate, second peak, average, and/or time series from a single wearable accelerometer worn on the shank or approximate center of mass during running were compared. Force estimation errors were quantified for 74 participants across different running surfaces, speeds, and foot strike angles and biases, repeatability coefficients, and limits of agreement were modeled with linear mixed effects to quantify the accuracy, reliability, and precision. Several methods accurately and reliably estimated the first peak and loading rate, however, none could do so precisely (the limits of agreement exceeded ±65% of target values).
View Article and Find Full Text PDFIntroduction: The accuracy of detecting myocardial infarction (MI) has greatly improved with the advent of more sensitive assays, and this has led to etiologic subtyping. Distinguishing between type 1 and type 2 non-ST-segment elevation myocardial infarction (NSTEMI) early in the clinical course allows for the most appropriate advanced diagnostic procedures and most efficacious treatments. The purpose of this study was to investigate the predictive effect of demographic and clinical variables on predicting NSTEMI subtypes in patients presenting with ischemic symptoms.
View Article and Find Full Text PDFWide-spread cultural beliefs influence personal experiences and clinical treatment of pain, yet are often unexamined and unchallenged in the pain literature. The common cultural belief that people generally over-report or exaggerate pain is familiar, reflected in discordant patient-provider pain assessments, and compounded in the context of disparities in pain treatment. However, no studies have directly measured the prevalence of this belief among the general population, nor challenged the validity of this assumption by assessing normative pain reporting in clinical settings.
View Article and Find Full Text PDFSupraphysiologic androgen (SPA) inhibits cell proliferation in prostate cancer (PCa) cells by transcriptional repression of DNA replication and cell-cycle genes. In this study, quantitative glycoprotein profiling identified androgen-regulated glycoprotein networks associated with SPA-mediated inhibition of PCa cell proliferation, and androgen-regulated glycoproteins in clinical prostate tissues. SPA-regulated glycoprotein networks were enriched for translation factors and ribosomal proteins, proteins that are known to be O-GlcNAcylated in response to various cellular stresses.
View Article and Find Full Text PDFComplex factors influence how people report and interpret numerical pain ratings. Such variability can introduce noise and systematic bias into clinical pain assessment. Identification of factors that influence self-rated pain and its interpretation by others may bolster utility of these scales.
View Article and Find Full Text PDFIntroduction: The aim of this study was to increase student empathy towards hemodialysis patients through an educational intervention that simulates a hemodialysis patient experience.
Methods: Second-year pharmacy students (n = 83) in a required therapeutic module were asked to follow key lifestyle modifications of a hemodialysis patient for two weeks. Students' self-perceived empathy level was assessed using the Kiersma-Chen Empathy Scale (KCES) pre- and post-intervention and post-reflection questions captured students' perceptions of the experience.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFPurpose: A new type of diazonium-based adhesive has been recently developed by our team to bind dental alloys (Titanium, stainless steel, and cobalt chromium) to dental polymers. Here, we explored the endurance of the resulting adhesive after thermal-cycling and autoclave aging.
Materials And Methods: Polished samples of titanium (Ti), stainless steel (SS) and cobalt chromium (Co-Cr) were coated with a diazonium-based adhesive.
Traditional electrodiagnostic (EDX) criteria for Guillain-Barré Syndrome (GBS), e.g. those delineated by Ho et al.
View Article and Find Full Text PDFJ Peripher Nerv Syst
September 2018
Although individuals with Zika virus (ZIKV) antibodies were reported in Malaya in mid-1950s, entomological and human surveillance in Singapore did not identify autochthonous transmission until the outbreak of August-November, 2016. A total of 455 cases from 15 separate clusters were identified. We asked if this ZIKV outbreak increased the incidence of Guillain-Barré syndrome (GBS) and aimed to characterize these cases.
View Article and Find Full Text PDFImmunotherapy has a great potential in advancing cancer treatment, especially in light of recent discoveries and therapeutic interventions that lead to complete response in specific subgroups of melanoma patients. By using the body's own immune system, it is possible not only to specifically target and eliminate cancer cells while leaving healthy cells unharmed but also to elicit long-term protective response. Despite the promise, current immunotherapy is limited and fails in addressing all tumor types.
View Article and Find Full Text PDFHematological malignancies are a group of diseases characterized by clonal proliferation of blood-forming cells. Malignant blood cells are classified as myeloid or lymphoid cells depending on their stem cell origin. Lymphoid malignancies are characterized by lymphocyte accumulation in the blood stream, in the bone marrow, or in lymphatic nodes and organs.
View Article and Find Full Text PDFAberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the "AR-interactome." Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined.
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