Hyperspectral imaging (HSI) enables visualisation of morphological and biochemical information, which could improve disease diagnostic accuracy. Unfortunately, the wide range of image distortions ...that arise during flexible endoscopy in the clinic have made integration of HSI challenging. To address this challenge, we demonstrate a hyperspectral endoscope (HySE) that simultaneously records intrinsically co-registered hyperspectral and standard-of-care white light images, which allows image distortions to be compensated computationally and an accurate hyperspectral data cube to be reconstructed as the endoscope moves in the lumen. Evaluation of HySE performance shows excellent spatial, spectral and temporal resolution and high colour fidelity. Application of HySE enables: quantification of blood oxygenation levels in tissue mimicking phantoms; differentiation of spectral profiles from normal and pathological ex vivo human tissues; and recording of hyperspectral data under freehand motion within an intact ex vivo pig oesophagus model. HySE therefore shows potential for enabling HSI in clinical endoscopy.
Clonal hemopoiesis driven by leukemia-associated gene mutations can occur without evidence of a blood disorder. To investigate this phenomenon, we interrogated 15 mutation hot spots in blood DNA from ...4,219 individuals using ultra-deep sequencing. Using only the hot spots studied, we identified clonal hemopoiesis in 0.8% of individuals under 60, rising to 19.5% of those ≥90 years, thus predicting that clonal hemopoiesis is much more prevalent than previously realized. DNMT3A-R882 mutations were most common and, although their prevalence increased with age, were found in individuals as young as 25 years. By contrast, mutations affecting spliceosome genes SF3B1 and SRSF2, closely associated with the myelodysplastic syndromes, were identified only in those aged >70 years, with several individuals harboring more than one such mutation. This indicates that spliceosome gene mutations drive clonal expansion under selection pressures particular to the aging hemopoietic system and explains the high incidence of clonal disorders associated with these mutations in advanced old age.
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•Clonal hemopoiesis is an almost inevitable consequence of aging in humans•Spliceosome gene mutations drove clonal hemopoiesis only in persons aged ≥70 years•NPM1 mutations behave as gatekeepers for leukemogenesis
McKerrell et al. employ ultra-deep sequencing to show that age-related clonal hemopoiesis is much more common than previously realized. They find that clonal hemopoiesis, driven by mutations in spliceosome genes SF3B1 and SRSF2, was noted exclusively in individuals aged 70 years or older and that NPM1 mutations are not seen in association with this phenomenon, endorsing their close association with leukemogenesis.
Preterm birth (birth before 37 weeks of completed gestation) is the leading cause of neonatal death, and has an incidence of 5-13% which is believed to be on the rise. The objective of this study was ...to determine the rate of spontaneous preterm birth and investigate the relationship between preterm birth and cervical length in a pregnant Asian population.
A prospective observational study between September 2010 and November 2013 was performed at KK Women's and Children's Hospital, Singapore. 1013 women with single viable pregnancies were recruited at less than 14 weeks of gestation between September 2010 and November 2013, excluding those with multiple gestation, pre-existing autoimmune or renal disease or those with current pregnancies complicated by aneuploidy or fetal anomalies. Participant characteristics were obtained from an interviewer-administered questionnaire at the first recruitment visit. Cervical length was measured using ultrasound at each of the 4 antenatal visits (Visit 1: < 14 weeks, Visit 2: 18-22 weeks, Visit 3: 28-32 weeks and Visit 4: > 34 weeks) using the Fetal Medicine Foundation protocol. Data on pregnancy outcomes were obtained from obstetric case notes and records. The main outcome measure examined in this study was that of spontaneous preterm birth and its relationship to cervical length.
There was a significantly shorter cervical length both in the 2nd trimester (18 to 22 weeks) and the 3rd trimester (28 to 32 weeks) in the preterm birth group compared to the term birth group (p = 0.028 and p < 0.001 respectively). In the first trimester (11 to 14 weeks), there was no statistically significant difference in cervical length between the two groups (p = 0.425). ROC curve analysis for cervical length in the preterm birth group for 18 to 22 weeks and 28 to 32 weeks showed an AUC of 0.605 and 0.725 respectively. At 28 to 32 weeks of gestation, a cut-off level at 2.49 cm has a sensitivity of 54.8%, specificity of 82.5%, negative predictive value of 97.9% and positive predictive value of 11.1%.
There is a significantly shorter cervical length in the 2nd and 3rd trimester in the preterm birth group. Cervical length is a moderate predictor of preterm birth with good negative predictive value and a relatively good specificity. Ultrasound cervical length screening for pregnant Asian women between 18 and 22 weeks of gestation with a cutoff of ≥ 2.48cm can help to identify a group of women who are at risk for preterm birth.
•We forecast the trend in the daily price of bitcoin with a hybrid Neuro-Fuzzy model.•The proposed methodology outperforms two other computational intelligence models.•The investment returns of the ...proposed model outperform a naive buy and hold strategy.
Cryptocurrencies, with Bitcoin being the most notable example, have attracted considerable attention in recent years, and they have experienced large fluctuations in their price. While a few studies employ conventional statistical and econometric approaches to reveal the driving factors of Bitcoin's prices, research on the development of forecasting models to be used as decision support tools in investment strategies is scarce. This study proposes a computational intelligence technique that uses a hybrid Neuro-Fuzzy controller, namely PATSOS, to forecast the direction in the change of the daily price of Bitcoin. The proposed methodology outperforms two other computational intelligence models, the first being developed with a simpler neuro-fuzzy approach, and the second being developed with artificial neural networks. Furthermore, the investment returns achieved by a trading simulation, based on the signals of the proposed model, are 71.21% higher than the ones achieved through a naive buy-and-hold strategy. The performance of the PATSOS system is robust to the use of other cryptocurrencies.
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Growth differentiation factor 15 (GDF-15) is a cytokine that is widely used as a biomarker for the severity of diverse disease states. It also has been shown to play a protective role after tissue ...injury and to promote a negative energy balance during obesity and diabetes. In addition to its metabolic effects, GDF-15 also regulates the host's immune responses to infectious and noninfectious diseases. GDF-15 can suppress a type 1 and, in contrast, promote a type 2 inflammatory response. In this brief review, we discuss how GDF-15 affects the effector function and recruitment of immune cells, the pathways that induce its expression, and the diverse mechanisms by which it is regulated during inflammation and infection. We further highlight outstanding questions that should be the focus of future investigations in this emerging field.
The importance of Zn ions (Zn) in regulating development and functions of the immune system is well established. However, recent years have witnessed a surge in our knowledge of how immune cells ...choreograph Zn regulatory mechanisms to combat the persistence of pathogenic microbes. Myeloid and lymphoid populations manipulate intracellular and extracellular Zn metabolism via Zn binding proteins and transporters in response to immunological signals and infection. Rapid as well as delayed changes in readily exchangeable Zn, also known as free Zn and the Zn proteome are crucial in determining activation of immune cells, cytokine responses, signaling and nutritional immunity. Recent studies have unearthed distinctive Zn modulatory mechanisms employed by specialized immune cells and necessitate an understanding of the Zn handling behavior in immune responses to infection. The focus of this review, therefore, stems from novel revelations of Zn intoxication, sequestration and signaling roles deployed by different immune cells, with an emphasis on innate immunity, to challenge microbial parasitization and cope with pathogen insult.
•Immunological orchestration of Zn homeostasis challenges microbial parasitization.•Specialized immune cells execute unique and overlapping Zn modulatory arsenals.•Zn intoxication, sequestration and signaling are three prime foci of host defenses.•Pathogens manipulate host Zn environment to battle immunological resistance.
Tumors often overcome the cytotoxic effects of chemotherapy through either acquired or environment-mediated drug resistance. In addition, signals from the microenvironment obfuscate the beneficial ...effects of chemotherapy and may facilitate progression and metastatic dissemination. Seminal mediators in chemotherapy-induced metastasis appear to be a wide range of hematopoietic, mesenchymal and immune progenitor cells, originating from the bone marrow. The actual purpose of these cells is to orchestrate the repair response to the cytotoxic damage of chemotherapy. However, these repair responses are exploited by tumor cells at every step of the metastatic cascade, ranging from tumor cell invasion, intravasation and hematogenous dissemination to extravasation and effective colonization at the metastatic site. A better understanding of the mechanistic underpinnings of chemotherapy-induced metastasis will allow us to better predict which patients are more likely to exhibit pro-metastatic responses to chemotherapy and will help develop new therapeutic strategies to neutralize chemotherapy-driven prometastatic changes.
The dramatic increase in fungal diseases in recent years can be attributed to the increased aggressiveness of medical therapy and other human activities. Immunosuppressed patients are at risk of ...contracting fungal diseases in healthcare settings and from natural environments. Increased prescribing of antifungals has led to the emergence of resistant fungi, resulting in treatment challenges. These concerns, together with the elucidation of the mechanisms of protective immunity against fungal diseases, have renewed interest in the development of vaccines against the mycoses. Most research has used murine models of human disease and, as we review in this article, the knowledge gained from these studies has advanced to the point where the development of vaccines targeting human fungal pathogens is now a realistic and achievable goal.
Several novel cuffless wearable devices and smartphone applications claiming that they can measure blood pressure (BP) are appearing on the market. These technologies are very attractive and ...promising, with increasing interest among health care professionals for their potential use. Moreover, they are becoming popular among patients with hypertension and healthy people. However, at the present time, there are serious issues about BP measurement accuracy of cuffless devices and the 2021 European Society of Hypertension Guidelines on BP measurement do not recommend them for clinical use. Cuffless devices have special validation issues, which have been recently recognized. It is important to note that the 2018 Universal Standard for the validation of automated BP measurement devices developed by the American Association for the Advancement of Medical Instrumentation, the European Society of Hypertension, and the International Organization for Standardization is inappropriate for the validation of cuffless devices. Unfortunately, there is an increasing number of publications presenting data on the accuracy of novel cuffless BP measurement devices, with inadequate methodology and potentially misleading conclusions. The objective of this review is to facilitate understanding of the capabilities and limitations of emerging cuffless BP measurement devices. First, the potential and the types of these devices are described. Then, the unique challenges in evaluating the BP measurement accuracy of cuffless devices are explained. Studies from the literature and computer simulations are employed to illustrate these challenges. Finally, proposals are given on how to evaluate cuffless devices including presenting and interpreting relevant study results.
Night-time ambulatory blood pressure (nABP) is the most important aspect of the blood pressure profile in terms of prognosis. Novel low-cost home monitors allow automated night-time blood pressure ...monitoring (nHBP). This study reviewed the evidence on the association of nHBP with nABP and preclinical organ damage.
Systematic review and meta-analysis.
Analysis of six studies (n = 1404) showed pooled difference between nHBP and nABP (SBP/DBP) at 1.4, 95% confidence interval (CI) 0.3, 2.6/-0.2, 95% CI -0.9, 0.6 mmHg, whereas the pooled correlation coefficient between nHBP and nABP (SBP/DBP) was r = 0.70, 95% CI 0.59, 0.81/r = 0.72, 95% CI 0.67, 0.77, respectively. Two studies (n = 212) investigated the agreement between nHBP and nABP in detecting nondippers with weighted agreement 77.3% (pooled kappa 0.27, 95% CI 0.08, 0.45). Three studies (n = 954) reported on the association of left ventricular mass index with systolic nHBP and nABP (pooled correlation coefficient r = 0.36, 95% CI 0.23, 0.50 and r = 0.32, 95% CI 0.10, 0.54, respectively, P = NS for comparison). Two studies (n = 950) reported on the association of urinary albumin excretion with systolic nHBP and nABP (pooled r = 0.39, 95% CI 0.21, 0.58 and r = 0.30, 95% CI 0.06, 0.55, respectively, P < 0.01 for comparison). Two studies (n = 350) reported on the association of common carotid intima-media thickness with systolic nHBP and nABP (pooled r = 0.31, 95% CI 0.16, 0.46 and r = 0.35, 95% CI 0.17, 0.53, respectively, P = NS for comparison).
The available evidence suggests that nHBP and nABP present similar values and comparable relationship with target-organ damage. Studies on the prognostic value of nHBP are needed.
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