Abstract
Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in ...metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in
IL-10
-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction.
•Telemedicine contributes to improving Mother-to-Child transmission of HIV (PMTCT).•Telemedicine benefited early infant diagnosis (EID) in the sixth week.•Telemedicine improved the rate of exclusive ...breastfeeding and PMTCT retention.•Wider use of telemedicine may help to promote the balance of medical resources.
We aimed to estimate the effectiveness of telemedicine for the prevention of mother-to-child transmission (PMTCT) program of HIV in low- and middle-income countries (LMICs).
We did a systematic literature search of 15 databases for articles published from database inception to October 26, 2022, and performed meta-analyses to estimate the pooled risk ratio of intervention effect (RR) and its 95% confidence interval (CI). We used subgroup analyses and meta-regressions to explore variation in the RRs. Funnel plots and Egger regression tests were also performed to assess publication bias.
Seventeen studies were included in the systematic review, with a total sample size of 9118 participants. We found that telemedicine was beneficial for early infant diagnosis (EID) in the sixth week (RR 1.04 95% CI 1.00-1.09), exclusive breastfeeding (RR 1.12 95% CI 1.01-1.24) and PMTCT retention (RR 1.34 95% CI 1.16-1.55). However, we did not find a significant effect of telemedicine on infant prophylaxis, HIV transmission, and ART adherence. Besides, the heterogeneity of ART adherence was associated with enrollment time, while retention was related to ART initiation.
Our meta-analysis demonstrated the benefits of telemedicine in improving PMTCT, especially for EID, exclusive breastfeeding, and PMTCT retention.
Early detection is critical to achieving improved treatment outcomes for child patients with congenital heart diseases (CHDs). Therefore, developing effective CHD detection techniques using low-cost ...and non-invasive pediatric electrocardiogram are highly desirable. We propose a deep learning approach for CHD detection, CHDdECG, which automatically extracts features from pediatric electrocardiogram and wavelet transformation characteristics, and integrates them with key human-concept features. Developed on 65,869 cases, CHDdECG achieved ROC-AUC of 0.915 and specificity of 0.881 on a real-world test set covering 12,000 cases. Additionally, on two external test sets with 7137 and 8121 cases, the overall ROC-AUC were 0.917 and 0.907 while specificities were 0.937 and 0.907. Notably, CHDdECG surpassed cardiologists in CHD detection performance comparison, and feature importance scores suggested greater influence of automatically extracted electrocardiogram features on CHD detection compared with human-concept features, implying that CHDdECG may grasp some knowledge beyond human cognition. Our study directly impacts CHD detection with pediatric electrocardiogram and demonstrates the potential of pediatric electrocardiogram for broader benefits.
•A deep learning framework for identifying minimally conscious state (MCS) and cognitive motor dissociation (CMD) patients from rs-fMRIs.•Free of feature engineering.•Achieving better performance ...than counterparts.•Providing neuroimaging biomarkers indicative of consciousness for clinical reference.
Diagnosis of disorders of consciousness (DOC) remains a formidable challenge. Deep learning methods have been widely applied in general neurological and psychiatry disorders, while limited in DOC domain. Considering the successful use of resting-state functional MRI (rs-fMRI) for evaluating patients with DOC, this study seeks to explore the conjunction of deep learning techniques and rs-fMRI in precisely detecting awareness in DOC. We initiated our research with a benchmark dataset comprising 140 participants, including 76 unresponsive wakefulness syndrome (UWS), 25 minimally conscious state (MCS), and 39 Controls, from three independent sites. We developed a cascade 3D EfficientNet-B3-based deep learning framework tailored for discriminating MCS from UWS patients, referred to as “DeepDOC”, and compared its performance against five state-of-the-art machine learning models. We also included an independent dataset consists of 11 DOC patients to test whether our model could identify patients with cognitive motor dissociation (CMD), in which DOC patients were behaviorally diagnosed unconscious but could be detected conscious by brain computer interface (BCI) method. Our results demonstrate that DeepDOC outperforms the five machine learning models, achieving an area under curve (AUC) value of 0.927 and accuracy of 0.861 for distinguishing MCS from UWS patients. More importantly, DeepDOC excels in CMD identification, achieving an AUC of 1 and accuracy of 0.909. Using gradient-weighted class activation mapping algorithm, we found that the posterior cortex, encompassing the visual cortex, posterior middle temporal gyrus, posterior cingulate cortex, precuneus, and cerebellum, as making a more substantial contribution to classification compared to other brain regions. This research offers a convenient and accurate method for detecting covert awareness in patients with MCS and CMD using rs-fMRI data.
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Important advances have been made regarding the diagnosis and management of polycystic kidney diseases. Care of patients with polycystic kidney diseases has moved beyond supportive care for ...complications and chronic kidney disease to new potentially disease-modifying therapies. Recently, the role of noncoding RNAs, in particular microRNAs, has been described in polycystic kidney diseases. microRNAs are involved in the regulation of gene expression, in which PKD1, PKD2, and other genes that contribute to the pathogenesis of polycystic kidney diseases are considerable participants. Seminal studies have highlighted the potential importance of microRNAs as new therapeutic targets and innovative diagnostic and/or prognostic biomarkers. Furthermore, an anti–miR-17 drug has advanced through preclinical autosomal dominant polycystic disease studies, and an anti–miR-21 drug has already cleared a phase 1 clinical trial. Most probably, new drugs in the microRNA research field will be yielded as a result of ongoing and planned therapeutic trials. To provide a foundation for understanding microRNA functions as a disease-modifying therapeutic drug in novel targeted therapies, in this narrative review we present an overview of the current knowledge of microRNAs in the pathogenesis of polycystic kidney diseases.
Abstract
Nephronophthisis (NPH) is the most prevalent monogenetic disorder leading to end-stage renal failure (ESRD) in childhood. Mutations in Nphp1, encoding a cilia-localized protein, account for ...the majority of NPH cases. Despite its identification many years ago, Nphp1 deletions targeting exon 4 or exon 20 have not reproduced the histological features of human NPH in murine models. In this study, we deleted exon 2–20 of Nphp1 by CRISPR/Cas9 gene editing to create a near-total knockout (KO) mouse model (Nphp1del2–20/del2–20). Nphp1del2–20/del2–20 mice faithfully reproduced the renal and extrarenal phenotypes associated with human NPH, including renal cyst development, tubular basement membrane thickening, retinal degeneration and abnormal spermatogenesis. Importantly, Nphp1 re-expression using an adenoviral-associated-virus-9 vector could partially rescue both renal and retinal phenotypes in Nphp1del2–20/del2–20 mice. Our results reported the first relevant Nphp1 mouse model with renal phenotypes for human disease. It will be a valuable model for future studies of Nphp1 function and to develop novel treatments for this common childhood disease.
Chillers are widely used in commercial buildings for air conditioning, and their energy consumption is the main contribution to the building’s carbon emissions. Currently, the COPs of small- and ...medium-capacity screw chillers are still generally lower than 6.5, whereas large-capacity commercial centrifugal chillers have achieved an ultra-high energy-efficiency level of COP ≥ 7.0. To achieve an ultra-high energy efficiency of COP ≥ 6.5 in medium-capacity chillers, the authors developed a 200 RT screw chiller by adopting the technologies of two-stage compression and interstage vapor injection. The whole development process, including the design, simulation, analysis, and experiment, is presented in this paper. It was found that the two-stage compression technology could effectively boost the performance of the chiller’s compressor to a maximum volumetric and adiabatic efficiency of 99% and 80%, respectively. With the interstage vapor injection technology, the chiller’s cooling capacity and COP were increased by more than 11% and 8%, respectively. When the use of these two technologies was combined, the maximum COP of the chiller reached 7.17. Additionally, under these working conditions, the COP and integrated part-load value (IPLV) were 6.74 and 10.04, respectively. In all, the combination use of vapor injection and two-stage compression technologies shows great potential to improve the performance of chillers. The work and conclusions described here might provide an effective reference for the future development of high-efficiency small- and medium-capacity screw chillers.
In this paper, a novel organic flash Rankine cycle (OFRC) system for low‐temperature heat recovery is analyzed and optimized using the 3E (energy, exergy, and economic) analysis method and particle ...swarm optimization algorithm, respectively. Five environmentally friendly organic fluids and three typical heat source conditions are simultaneously discussed during the parametric analysis and optimization process, to obtain a comprehensive understanding of the thermo‐economic characteristics of this novel system. The main analysis results show that the biggest exergy loss of the OFRC system is caused by the condenser, followed by the evaporator. About 70% of the specific power cost is caused by the capital investment of the system, and more than 60% of the capital investment is spent on purchasing the high‐pressure and low‐pressure expanders. Under the same operating conditions, the working fluids with high critical temperatures can achieve higher cycle thermal efficiency and lower specific power costs than those with low critical temperatures. The optimization results show that the OFRC system is able to achieve a better thermodynamic performance than the organic Rankine cycle (ORC) and organic flash cycle (OFC) systems, and when the heat source's inlet temperature is set to 100°C, 120°C, and 140°C, R245fa, R290, and R152a are, respectively, recommended as the best working fluid for the OFRC system. Besides this, it is found that the OFC system has the worst thermo‐economic performance, and the ORC system can achieve the lowest specific power cost. A new finding is that, for all three systems, the higher the critical temperature of the working fluid, the lower the specific power cost of the system.
A novel organic flash Rankine cycle (OFRC) system was analyzed and optimized. Five potential organic fluids and three typical heat source conditions were investigated. The OFRC system could achieve the best thermodynamic performance.
Top tensioned risers (TTRs) and steel catenary risers (SCRs) have been widely used in the field of marine engineering. They are commonly used to transport fluids from subsea wells to surface ...platforms. Under the action of ocean currents, these risers are often subjected to vortex-induced vibrations (VIVs), which might lead to serious fatigue damage. In this study, VIV around TTR and SCR were numerically simulated using the computational fluid dynamics software FLUENT when the Reynolds number was 4000. In the calculations, the full hexahedron grid and large eddy simulation were used to ensure calculation accuracy from the boundary conditions, as well as solution control. The shape, frequency, and amplitude of VIV produced by TTRs and SCRs at different times and depths were simulated.
Objective
This study systematically evaluated the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions, providing evidence for future research.
Methods
We systematically ...searched the literature in 10 databases from inception to February 18, 2021. Studies on the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions were included. Then, we calculated the overall incidence rates of four outcomes, for which we used the risk ratio (RR) and 95% confidence interval (95% CI) to describe the effects of high-grade squamous intraepithelial lesions (HSILs) on recurrence.
Results
A total of 39 studies were included, all reported in English, published from 1989 to 2021 in 16 countries. The studies covered 22,865 women aged 15–65 years, with a total of 5,794 vaccinated, and 21 vaccines were divided into six types. Meta-analysis showed that the overall incidence rate of HSIL regression in vaccine therapies was 62.48% 95% CI (42.80, 80.41), with the highest rate being 72.32% for viral vector vaccines 95% CI (29.33, 99.51). Similarly, the overall incidence rates of HPV and HPV16/18 clearance by vaccines were 48.59% 95% CI (32.68, 64.64) and 47.37% 95% CI (38.00, 56.81), respectively, with the highest rates being 68.18% 95% CI (45.13, 86.14) for bacterial vector vaccines and 55.14% 95% CI (42.31, 67.66) for DNA-based vaccines. In addition, a comprehensive analysis indicated that virus-like particle vaccines after conization reduced the risk of HSIL recurrence with statistical significance compared to conization alone RR = 0.46; 95% CI (0.29, 0.74). Regarding safety, only four studies reported a few severe adverse events, indicating that vaccines for precancerous cervical lesions are generally safe.
Conclusion
Virus-like particle vaccines as an adjuvant immunotherapy for conization can significantly reduce the risk of HSIL recurrence. Most therapeutic vaccines have direct therapeutic effects on precancerous lesions, and the effectiveness in HSIL regression, clearance of HPV, and clearance of HPV16/18 is great with good safety. That is, therapeutic vaccines have good development potential and are worthy of further research.
Systematic Review Registration
PROSPERO
https://www.crd.york.ac.uk/PROSPERO/
, CRD42021275452.
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