Identifying and mapping steroids in tissues can provide opportunities for biomarker discovery, the interrogation of disease progression, and new therapeutics. Although separation coupled to mass ...spectrometry (MS) has emerged as a powerful tool for studying steroids, imaging and annotating steroid isomers remains challenging. Herein, we present a new method based on the fragmentation of silver-cationized steroids in tandem MS, which produces distinctive and consistent fragmentation patterns conferring confidence in steroid annotation at the regioisomeric level without using prior derivatization, separation, or instrumental modification. In addition to predicting the structure of the steroid with isomeric specificity, the method is simple, flexible, and inexpensive, suggesting that the wider community will easily adapt to it. We demonstrate the utility of our approach by visualizing steroids and steroid isomer distributions in mouse brain tissue using silver-doped pneumatically assisted nanospray desorption electrospray ionization mass spectrometry imaging.
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Single-cell metabolomics with mass spectrometry enables a large variety of metabolites to be simultaneously detected from individual cells, without any preselection or labelling, to ...map phenotypes on the single cell level. Although the field is relatively young, it is steadily progressing with an increasing number of active research groups, techniques for cell sampling and ionization, tools for data analysis, and applications to answer important biomedical and environmental questions. In addition, the community shows great creativity in overcoming challenges associated with low sample volumes, a wide range of metabolite species, and large datasets. Here, we briefly discuss publications since 2019 and aim to provide the unfamiliar reader with an insight into the field and the expert reader with an update on the current status of the field.
In aortic root surgery, valve-sparing aortic root replacement is an attractive alternative by mitigating the risks inherent to prosthetic valves; however, little is known about the variables that ...impact its durability. We review our mid- to long-term outcomes after valve-sparing aortic root replacement and describe factors that impact survival and valve reintervention and insufficiency.
A retrospective review of 284 consecutive patients undergoing valve-sparing aortic root replacement between November 1999 and January 2022 at Austin Health, Melbourne, Australia, was undertaken, with a median follow-up of 6.43 ± 4.83 years, but up to 22.0 years. Freedom from mortality, aortic reintervention, and insufficiency was analyzed using Kaplan-Meier methods, Cox proportional hazard models, and Fine-Gray analysis.
The median age of patients at intervention was 60.0 years (interquartile range, 48.0-67.0), of whom 68 (23.9%) had bicuspid aortic valve disease, 27 (9.5%) had Marfan syndrome, 119 (41.9%) had severe aortic root dilation (>50 mm), and 155 had (54.6%) severe aortic insufficiency at the time of intervention. The 30-day mortality was 1.8%, with freedom from mortality of 96.0% (95% CI, 92.6-97.8) at 5 years and 88.2% (95% CI, 81.4-92.6) at 10 years. Freedom from aortic reintervention was 92.2% (95% CI, 87.7-95.2) at 5 years and 79.8% (95% CI, 71.8-85.8) at 10 years. Factors associated with reintervention were concomitant leaflet repair (hazard ratio, 8.13, 95% CI, 1.07-61.7) and bicuspid valvulopathy (hazard ratio, 2.23, 95% CI, 1.07-4.68), with reintervention in the bicuspid aortic valve being more likely due to aortic stenosis and in the tricuspid aortic valve due to aortic insufficiency (chi-square P = .05). The freedom from aortic insufficiency was 89.1% (95% CI, 83.5-92.9), 84.9% (95% CI, 77.8-89.9) at 5 and 10 years, respectively, and 80.7% (95% CI, 71.0-87.4).
Valve-sparing aortic root replacement has excellent long-term outcomes, with low mortality and reintervention rates. Concomitant leaflet repair and bicuspid valve disease are the only long-term factors associated with reintervention.
The Internet of things (IoT) extends the Internet space by allowing smart things to sense and/or interact with the physical environment and communicate with other physical objects (or things) around ...us. In IoT, sensors, actuators, smart devices, cameras, protocols, and cloud services are used to support many intelligent applications such as environmental monitoring, traffic monitoring, remote monitoring of patients, security surveillance, and smart home automation. To optimize the usage of an IoT network, certain challenges must be addressed such as energy constraints, scalability, reliability, heterogeneity, security, privacy, routing, quality of service (QoS), and congestion. To avoid congestion in IoT, efficient load balancing (LB) is needed for distributing traffic loads among different routes. To this end, this survey presents the IoT architectures and the networking paradigms (i.e., edge–fog–cloud paradigms) adopted in these architectures. Then, it analyzes and compares previous related surveys on LB in the IoT. It reviews and classifies dynamic LB techniques in the IoT for cloud and edge/fog networks. Lastly, it presents some lessons learned and open research issues.
•Meta-analysis of randomised controlled trials only, comparing operative rib fixation to non operative management.•Outcomes included in hospital outcomes and quality of life at 6 months.•Benefit ...demonstrated for rib fixation with fewer complications and shorter intensive care unit stay.•No benefit of rib fixation demonstrated in quality of life at six months.
Rib fixation for ventilator dependent flail chest patients has become a mainstay of management in major trauma centres. However, the expansion of rib fixation for fractured ribs beyond this remains largely in the hands of enthusiasts with the benefits in non ventilator dependent groups largely unproven. Previous meta-analyses have largely included non-randomised and retrospective data, much of which is now more than two decades out of date. We wanted to perform an updated meta-analysis including only rigorous prospective trials which were randomised. Further we wanted to include quality of life outcomes which have not been previously examined in published meta-analyses.
This meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomised controlled trials only, of rib fixation compared to non-operative management in adult patients.
Eight studies comprising 752 patients of whom 372 had been randomised to receive rib fixation were included. Benefits of rib fixation were identified with significant reductions in mechanical ventilation and lengths of stay (both ICU and hospital) as well as rates of pneumonia and tracheostomy. No significant benefit in quality of life at 6 months was identified.
Operative intervention for rib fractures leads to significantly lower rates of pneumonia, lengths of intensive care stay and time on mechanical ventilation compared to non-operative intervention. Further study is needed to investigate quality of life improvements after rib fractures as operative rib fixation expands to non-ventilator dependent groups.
Advancements in mass spectrometry‐based proteomics have enabled experiments encompassing hundreds of samples. While these large sample sets deliver much‐needed statistical power, handling them ...introduces technical variability known as batch effects. Here, we present a step‐by‐step protocol for the assessment, normalization, and batch correction of proteomic data. We review established methodologies from related fields and describe solutions specific to proteomic challenges, such as ion intensity drift and missing values in quantitative feature matrices. Finally, we compile a set of techniques that enable control of batch effect adjustment quality. We provide an R package, "proBatch", containing functions required for each step of the protocol. We demonstrate the utility of this methodology on five proteomic datasets each encompassing hundreds of samples and consisting of multiple experimental designs. In conclusion, we provide guidelines and tools to make the extraction of true biological signal from large proteomic studies more robust and transparent, ultimately facilitating reliable and reproducible research in clinical proteomics and systems biology.
In mass spectrometry‐based proteomics, handling large sample sets introduces technical variability known as batch effects. This tutorial provides guidelines and tools for the assessment, normalization, and batch correction of proteomics data.
Histopathology is the gold standard for diagnosing fibrosis, but its routine use is constrained by the need for additional stains, time, personnel and resources. Vibrational spectroscopy is a novel ...technique that offers an alternative atraumatic approach, with short scan times, while providing metabolic and morphological data. This review evaluates vibrational spectroscopy for the assessment of fibrosis, with a focus on point-of-care capabilities. OVID Medline, Embase and Cochrane databases were systematically searched using PRISMA guidelines for search terms including vibrational spectroscopy, human tissue and fibrosis. Studies were stratified based on imaging modality and tissue type. Outcomes recorded included tissue type, machine learning technique, metrics for accuracy and author conclusions. Systematic review yielded 420 articles, of which 14 were relevant. Ten of these articles considered mid-infrared spectroscopy, three dealt with Raman spectroscopy and one with near-infrared spectroscopy. The metrics for detecting fibrosis were Pearson correlation coefficients ranging from 0.65–0.98; sensitivity from 76–100%; specificity from 90–99%; area under receiver operator curves from 0.83–0.98; and accuracy of 86–99%. Vibrational spectroscopy identified fibrosis in myeloproliferative neoplasms in bone, cirrhotic and hepatocellular carcinoma in liver, end-stage heart failure in cardiac tissue and following laser ablation for acne in skin. It also identified interstitial fibrosis as a predictor of early renal transplant rejection in renal tissue. Vibrational spectroscopic techniques can therefore accurately identify fibrosis in a range of human tissues. Emerging data show that it can be used to quantify, classify and provide data about the nature of fibrosis with a high degree of accuracy with potential scope for point-of-care use.
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•A non-invasive, wearable biosensor has been developed for in situ monitoring of biological analytes in sweat.•Various morphological, compositional, physiochemical, and photophysical ...properties of nanosensors have been studied.•The LOD and LOQ values within pH 4.5 to 7.5 were found to be 25.25 to 36.13 μg/dL and 84.16–120.44 μg/dL, respectively.•The disposable and biodegradable nature of the nanosensor probe was also investigated.
The promise of non-invasive health monitoring has fuelled the development of wearable biosensors for in situ detection of biological analytes in sweat. This paper presents a new fluorescent nanosensor probe based on boric acid functionalized and heteroatom doped carbon quantum dots (CQDs) embedded in paper-based analytical devices and integrated with a hydrophilic cotton thread-based microfluidic channel for the development of a flexible, wearable, biocompatible, and biodegradable sweat sensor for real-time measurement of sweat glucose concentration via smartphone readout. The morphological, physiochemical, compositional, crystallinity, and optical properties of nanosensors were extensively investigated. CQD particle sizes were found to be widely dispersed, ranging from 2.6 to 7.1 nm, with an average diameter of 4.38 nm. A dual response via fluorescence and colorimetric change was demonstrated for on-site sweat glucose monitoring using a smartphone camera to capture images in RGB (red, green, and blue) format and analyse them simultaneously by a customized android app, with quantitative results displayed on the smartphone. The limit of detection value for in situ measurement of sweat glucose concentration was 1.40 to 2.00 μM (25.25 to 36.13 μg/dL) and the limit of quantification value was 4.67 to 6.69 μM (84.16–120.44 μg/dL) in the pH range of 4.5 to 7.5. The developed sensor's performance metrics were validated using a standard clinical technique, which indicates strong correlation between two methods with Pearson correlation coefficient values of 0.83 and 0.80 for non-diabetic and type- II diabetes patients, respectively. Besides, interference, spike, and recovery studies were carried out with recovery rates ranging from 96.5 to 105.8 %, demonstrating good repeatability and reproducibility. Furthermore, feasible fluorescence quenching processes have been explored. In addition, the disposable and biodegradable nature of the nanosensor probe was studied by throwing it into the soil in the natural environment, where it dissolves almost spontaneously after three weeks.
We herein describe our technique of “branch first continuous perfusion arch repair (BF-CPAR)” which does away with both cerebral circulatory arrest and the need for deep hypothermia. We use this ...technique for all aortic surgeries including for type A acute aortic dissections.
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