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Hematopoietic stem cell transplantation (HSCT) is common practice today for life threatening malignant and non‐malignant diseases of the blood and immune systems. Umbilical cord blood (UCB) is rich in hematopoietic stem cells (HSCs) and is an attractive alternative to harvesting HSCs from bone marrow or when mobilized into peripheral blood. One of the most appealing attributes of UCB is that it can be banked for future use and hence provides an off‐the‐shelf solution for patients in urgent need of a transplantation. This has led to the establishment of publicly funded and private UCB banks, as seen by the rapid growth of the UCB industry in the early part of this century. However, from about 2010, the release of UCB units for treatment purposes plateaued and started to decrease year‐on‐year from 2013 to 2016. Our interest has been to investigate the factors contributing to these changes. Key drivers influencing the UCB industry include the emergence of haploidentical HSCT and the increasing use of UCB units for regenerative medicine purposes. Further influencing this dynamic is the high cost associated with UCB transplantation, the economic impact of sustaining public bank operations and an active private UCB banking sector. We foresee that these factors will continue in a tug‐of‐war fashion to shape and finally determine the fate of the UCB industry. Stem Cells Translational Medicine 2018 Stem Cells Translational Medicine 2018;7:643–650 Evolution and factors influencing the future growth of the umbilical cord (UCB) industry. Positive influencers will allow for a plateau or rise in UCB usage, while negative influencers will result in a further decline.

High-altitude (HA) affects sensory organ response, but its effects on the inner ear are not fully understood. The present scoping review aimed to collect the available evidence about HA effects on the inner ear with focus on auditory function. The scoping review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews. PubMed, Scopus, and Web of Science electronic databases were systematically searched to identify studies conducted in the last 20 years, which quantified in healthy subjects the effects of HA on auditory function. The systematic search identified 17 studies on a total population of 888 subjects (88.7% male, age: 27.8 ± 4.1 years; median sample size of 15 subjects). Nine studies were conducted in a simulated environment and eight during real expeditions at HA. To quantify auditory function, six studies performed pure tone audiometry, four studies measured otoacoustic emissions (OAE) and eight studies measured auditory evoked responses (AER). Study protocols presented heterogeneity in the spatio-temporal patterns of HA exposure, with highly varying maximal altitudes and exposure durations. Most studies reported a reduction of auditory function with HA in terms of either elevation of auditory thresholds, lengthening of AER latencies, reduction of distortion-product and transient-evoked OAEs. Future studies in larger populations, using standardized protocols and multi-technique auditory function evaluation, are needed to further characterize the spatio-temporal pattern of HA effects along the auditory pathways and clarify the pathophysiological implications and reversibility of the observed changes.

The D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutation facilitates transition towards an open state of the Spike protein. To explain the epidemiological success of D614G, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, the exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase, is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2. However, we did not observe a significant correlation between reported COVID-19 mortality in different countries and the prevalence of the Wuhan versus G/L variant. Nevertheless, when comparing the speed of emergence and the ultimate predominance in individual countries, it is clear that the G/L variant displays major epidemiological supremacy over the original variant.

Objective To survey perceived general and ear-nose-throat (ENT) symptoms of COVID-19 in relation to psychological impact, mental health, perception of information and demographic characteristics in quarantined subjects during a lockdown period in Italy. Methods Participants were 1380 respondents who completed an online survey. A logistic regression model was used to evaluate the association between the independent variables and perceived symptoms. Results Participants reported different prevalences of perceived ENT and general symptoms. Coryza, cough, sore throat and tinnitus were the most common symptoms, and there was a low prevalence of anxiety, depression and stress compared with the psychological impact of the symptom. Comparison of the two symptom groups demonstrated a common need for updates, their relationship with the media and correct information about the route of transmission. Conclusions The health information provided during a disease outbreak must be grounded in evidence. This would help to prevent adverse psychological reactions and somatization symptoms that can engulf healthcare systems, especially in clinical areas like ENT, which frequently treat airway problems.

PurposeMultiple chemical sensitivity (MCS) also known as idiopathic environmental intolerance/illness (IEI) encompasses a cohort of subjective symptoms characterized by susceptibility to a wide spectrum of environmental compounds, causing symptoms involving various organs and a decrease in quality of life. The aim of this systematic review is to summarize evidence about MCS, with focus on indexed studies analyzing sensory pathway-related disorders.MethodsMedical databases were searched for English language articles related to the topic, published between 1965 and 2017 in academic, peer-reviewed journals. Particular focus was concentrated on articles depicting disturbances involving sensory organs. References of the relevant articles were examined to identify additional significant documents.ResultsFifty-eight studies were eligible for full text review. Of these, 34 studies met the selection criteria and were included in this analysis. Many variables, such as different diagnostic criteria, lack of homogeneous symptom questionnaires and the general incidence of personality traits in control subjects, biased studies as confounding factors. However, moderate evidences show that sensory pathways are somewhat altered, especially with respect to information processing in the limbic system and related cortical areas. Recent studies suggested the presence, in MCS cohorts, of attention bias, sensitization and limbic kindling, as well as recently revealed subclinical organic alterations along sensory pathways.ConclusionsEvidences are consistent with MCS/IEI to be the result of a neural altered processing of sensorial ascending pathways, which combined with peculiar personality traits constitutes the underpinning of a multisensory condition needing multidisciplinary clinical approach.

Background/Objectives: Due to conflicting results about hypertension and the involvement of associated risk factors in the presentation of idiopathic benign paroxysmal positional vertigo recurrence (R-BPPV), this study aimed to explore possible associations between the resolution rate (RR) and recurrence onset (RO) of R-BPPV, as well as hypertension classification and stages and demographic characteristics. Methods: A total of 1201 medical records from patients collected over a 6-year span who first presented with R-BPPV were retrospectively evaluated regarding blood pressure (BP) presentation and associated risk factors. R-BPPV included patients treated with necessary canalith repositioning procedures (CRPs) and followed up with for 12 months. The RO and RR were evaluated when comparing patients sub-grouped by current classification and staging. The association between the RO and RR and many prognostic factors, including the presence of cardio- and neuro-vascular risks, was examined via multiple regression analysis. Results: Among the 857 included patients with R-BPPV, 211 presented with an optimal/normal BP, 210 were found to have a high–normal BP, 222 were classified with Grade 1 hypertension, and 214 were found to have Grade 2 hypertension. Significant (p < 0.05) progressive earlier presentations and increases in needed CRPs were found with the respective increase in BP subgroups. For the RO, the correlation was statistically significant for age and gender, while for the RR, the correlation was statistically significant for age and hypertension stage. Conclusions: This study demonstrates for the first time that clinical consequences of R-BPPV are strongly associated with cardio-, neuro-vascular, and socio-demographic risk factors, which are commonly involved in R-BPPV occurrence.

The airfoil is the prime component of flying vehicles. For low-speed flights, low Reynolds number airfoils are used. The characteristic of low Reynolds number airfoils is a laminar separation bubble and an associated drag rise. This paper presents a framework for the design of a low Reynolds number airfoil. The contributions of the proposed research are twofold. First, a convolutional neural network (CNN) is designed for the aerodynamic coefficient prediction of low Reynolds number airfoils. Data generation is discussed in detail and XFOIL is selected to obtain aerodynamic coefficients. The performance of the CNN is evaluated using different learning rate schedulers and adaptive learning rate optimizers. The trained model can predict the aerodynamic coefficients with high accuracy. Second, the trained model is used with a non-dominated sorting genetic algorithm (NSGA-II) for multi-objective optimization of the low Reynolds number airfoil at a specific angle of attack. A similar optimization is performed using NSGA-II directly calling XFOIL, to obtain the aerodynamic coefficients. The Pareto fronts of both optimizations are compared, and it is concluded that the proposed CNN can replicate the actual Pareto in considerably less time.

The aim of the present scoping review was to evaluate the impact of experimental meal loads or observational diet changes/habits on taste tests in both healthy subjects and patients. A systematic search performed in PubMed, Scopus, and Institute for Scientific Information (ISI) Web of Science electronic databases retrieved, respectively 2981, 6258, and 7555 articles from January 2000 to December 2020. A total of 17 articles were included for full-text review. Literature results were stratified according to the observational/interventional approach, the involvement of healthy subjects or patients, the taste test, and the meal/dietary changes. The present scoping review reinforced the notions postulating that certain taste tests (for example focusing on fatty acid, salt, or sugar) might be specifically influenced by the nutritional intervention and that other ones might be susceptible to a wide span of changes beyond the extent of tastant included in the specific food changes. This could also depend on the inhomogeneity of literature trend: The short duration of the intervention or the random type of meal load, unsuitability of the taste test chosen, and the presence of underlying disorders. Future studies for a better comprehension of taste tests reliability in relation to specific food changes are thus to be fostered.

Multiplex gene-edited chimeric antigen receptor (CAR) T-cell therapies face significant challenges, including potential oncogenic risks associated with double-strand DNA breaks. Targeted microRNAs (miRNAs) may provide a safer, functional, and tunable alternative for gene silencing without the need for DNA editing. As a proof of concept for multiplex gene silencing, we employed an optimized miRNA backbone and gene architecture to silence T-cell receptor (TCR) and major histocompatibility complex class I (MHC-I) in mesothelin-directed CAR (M5CAR) T cells. The efficacy of this approach was compared to CD3ζ and β2-microglobulin (β2M) CRISPR/Cas9 knockout (KO) cells. miRNA-expressing cassettes were incorporated into M5CAR lentiviral vectors, enabling combined gene silencing and CAR expression. Antitumor activity was evaluated using assays and pancreatic ductal adenocarcinoma models. Silenced (S) M5CAR T cells retained antitumor functionality comparable to, and in some cases exceeding, that of KO cells. , S M5CAR T cells achieved tumor control with higher persistence and superior metastasis prevention. assays demonstrated enhanced resistance to alloreactive natural killer (NK) cells and peripheral blood mononuclear cells (PBMCs). Titratable multiplex gene silencing via targeted miRNAs offers an alternative to gene editing for CAR T cells, with potential advantages in potency, persistence, metastasis prevention, and immune evasion for allogeneic products. This strategy may overcome tumor-induced immunosuppression while avoiding the risks associated with DNA double-strand breaks.

Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting from loss of function mutations in the reactive oxygen species generating phagocyte NADPH oxidase (NOX2). CGD patients are prone to infection, but also have an increased susceptibility to autoimmune diseases. The aim of this study was to investigate the role of NOX2 in the regulation of specific immunity. In both CGD patients and NOX2-deficient mice, we observed an alteration in the basal proportions of IgG subtypes. Upon immunization with curdlan-a dectin 1 agonist-NOX2-deficient mice showed increased production of IgG2c compared to controls, and restimulation of lymph node-derived cells led to increased production of IFNγ, but not IL-5, indicative hallmark of an enhanced Th1 response. T cell activation was increased in NOX2-deficient mice and a similar trend was observed when T cells were co-cultured with NOX2-deficient bone marrow-derived cells. In contrast, no difference in T cell activation was observed when NOX2-deficient T cells were co-cultured with wild-type BMDC. Following stimulation of NOX2-deficient dendritic cells (DCs), no difference in costimulatory molecules was observed, while there was an increase in the release of Th1-driving cytokines. In summary, both CGD patients and CGD mice have an altered IgG subtype distribution, which is associated with an increased IFNγ production. Thus, NOX2 within DCs appears to be an important regulator at the interface of innate and specific immunity, especially after activation of the dectin 1 pathway, limiting immune activation and the development of autoimmunity.