Publications by authors named "Han Yu"

1,207 Publications

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Therapeutic Potential of Cytokines in Demyelinating Lesions After Stroke.

J Mol Neurosci 2021 May 10. Epub 2021 May 10.

Department of Rehabilitation Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China.

White matter damage is a component of most human stroke and usually accounts for at least half of the lesion volume. Subcortical white matter stroke (WMS) accounts for 25% of all strokes and causes severe motor and cognitive dysfunction. The adult brain has a very limited ability to repair white matter damage. Pathological analysis shows that demyelination or myelin loss is the main feature of white matter injury and plays an important role in long-term sensorimotor and cognitive dysfunction. This suggests that demyelination is a major therapeutic target for ischemic stroke injury. An acute inflammatory reaction is triggered by brain ischemia, which is accompanied by cytokine production. The production of cytokines is an important factor affecting demyelination and myelin regeneration. Different cytokines have different effects on myelin damage and myelin regeneration. Exploring the role of cytokines in demyelination and remyelination after stroke and the underlying molecular mechanisms of demyelination and myelin regeneration after ischemic injury is very important for the development of rehabilitation treatment strategies. This review focuses on recent findings on the effects of cytokines on myelin damage and remyelination as well as the progress of research on the role of cytokines in ischemic stroke prognosis to provide a new treatment approach for amelioration of white matter damage after stroke.
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http://dx.doi.org/10.1007/s12031-021-01851-5DOI Listing
May 2021

Effects of preoperative nutrition on postoperative outcomes in esophageal cancer: a systematic review and meta-analysis.

Dis Esophagus 2021 May 10. Epub 2021 May 10.

Department of Thoracic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.

Postoperative enteral nutrition has been widely implemented in esophageal cancer, but the efficacy and safety of preoperative nutrition, particularly immune-enhancing nutrition (IEN), remain controversial. This meta-analysis aims to provide a quantitative synthesis of whether preoperative nutrition improves postoperative morbidity and mortality in patients with resectable esophageal cancer. A systematic search was conducted in Medline, Embase, Cochrane, and databases of clinical trials dated up to December 2019. Randomized controlled trials and observational studies comparing postoperative outcomes between esophageal cancer patients with and without preoperative nutritional support were included. Random-effects model was applied in the meta-analysis of primary outcomes (overall complication rate, in-hospital mortality) and secondary outcomes (infectious complication rate, anastomotic leak rate, length of postoperative hospital stay). Complications of feeding tube access and perioperative weight loss were evaluated by qualitative synthesis. Subgroup analyses were performed by stratifying immunonutrition and standard nutrition before surgery. Subgroup analysis of randomized controlled trials alone was also done. A total of 15 studies enrolling 1864 participants were included. The overall meta-analysis found that preoperative nutrition could reduce infectious complications (odds ratio [OR] = 0.51, 95% confidence interval [CI] [0.26, 0.98]; I2 = 48%) and length of hospital stay (mean difference = -2.10 day, 95% CI [-3.72, -0.47]; I2 = 78%) after esophagectomy, whereas no significant difference was revealed in the incidence of overall complications (OR = 0.76, 95% CI [0.52, 1.11]; I2 = 32%), in-hospital mortality (OR = 1.03, 95% CI [0.41, 2.61]; I2 = 12%), and anastomotic leak (OR = 1.05, 95% CI [0.69, 1.58]; I2 = 0%). Subgroup of preoperative immunonutrition showed more prominent benefits. The complication rate of feeding tube access was low (1.6-16%). In conclusion, preoperative nutrition is safe in esophageal cancer, but benefits are observed in infectious complication rate and length of stay on a limited scale. IEN holds more advantages over standard nutrition. Randomized trials in the context of nutritional support during neoadjuvant therapy are in demand.
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http://dx.doi.org/10.1093/dote/doab028DOI Listing
May 2021

Learning curve for robot-assisted Ivor Lewis esophagectomy.

Dis Esophagus 2021 May 10. Epub 2021 May 10.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

This study aimed to demonstrate the learning curve of robot-assisted minimally invasive esophagectomy (RAMIE). A retrospective analysis of the first 124 consecutive patients who underwent RAMIE with intrathoracic anastomosis (Ivor Lewis) by a single surgeon between May 2015 and August 2020 was performed. An risk-adjusted cumulative sum (RA-CUSUM) analysis was applied to generate a learning curve of RAMIE considering the major complication rate, which reflected the technical proficiency. The overall 30-day morbidity rate was 38.7%, while the major complication rate was 25.8%. The learning curve was divided into two phases based on the RA-CUSUM analysis: phase I, the initial learning phase (cases 1-51) and phase II, the proficiency phase (cases 52-124). As we compared the proficiency phase with the initial learning phase, significantly decreased trends were observed in relation to the major complication rate (37.3% vs. 18.7%, P = 0.017), total operation time (330.9 ± 55.6 vs. 267.3 ± 39.1 minutes, P < 0.001), and length of hospitalization (10 [IQR, 9-14] days vs. 9 [IQR, 8-11] days, P = 0.034). In conclusion, the learning curve of RAMIE consisted of two phases, and at least 51 cases were required to gain technical proficiency.
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http://dx.doi.org/10.1093/dote/doab026DOI Listing
May 2021

vgrG is separately transcribed from hcp in T6SS orphan clusters and is under the regulation of IHF and HapR.

Biochem Biophys Res Commun 2021 Apr 28;559:15-20. Epub 2021 Apr 28.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing, China. Electronic address:

V. cholerae, the causative agent of cholera epidemic, and V. fluvialis, the emerging foodborne pathogen, share highly homologous T6SS consisting of one large cluster and two small orphan or auxiliary clusters, and each of which was generally recognized as one operon. Here, we showed that the genes in each of the small clusters are organized into two transcriptional units. Specifically, the inner tube coding gene hcp/tssD is highly transcribed as one monocistron, while the tip component vgrG/tssI and its downstream effector and immunity genes are in one polycistron with very low transcriptional level. This conclusion is supported by qPCR analysis of mRNA abundance, reporter fusion analysis and transcriptional unit definition with RT-PCR analysis. Taking tssI2_a of V. fluvialis as an example, we further demonstrated that quorum sensing (QS) regulator HapR and global regulator IHF activate vgrG/tssI transcription by directly binding to its promoter region. Taken together, current studies deepen our understanding of T6SS system, highlighting its regulatory complexity during functional execution process.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.092DOI Listing
April 2021

Porcine and bovine aortic valve comparison for surgical optimization: A fluid-structure interaction modeling study.

Int J Cardiol 2021 Apr 28. Epub 2021 Apr 28.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Porcine aortic valve (PAV) and bovine aortic valve (BAV) are commonly used in aortic valve replacement (AVR) surgeries. A detailed comparison for their hemodynamic and structural stress/strain performances would help to better understand valve cardiac function and select valve type and size for AVR outcome optimizations.

Methods: Eight fluid-structure interaction models were constructed to compare hemodynamic and stress/strain behaviors of PAV and BAV with 4 sizes (19, 21, 23, and 25 mm). Blood flow velocity, systolic cross-valve pressure gradient (SCVPG), geometric orifice area (GOA), flow shear stresses (FSS), and stress/strain were obtained for comparison.

Results: Compared with PAV, BAV has better hemodynamic performance, with lower maximum flow velocity (7.17%) and pressure (9.82%), smaller pressure gradient (mean and peak SCVPG: 8.92% and 9.28%), larger GOA (9.56%) and lower FSS (6.61%). The averages of the mean and peak net pressure gradient values from 4 BAV models were 8.10% and 8.35% lower than that from PAV models. Larger valve sizes for both PAV and BAV had improved hemodynamic performance. Maximum flow velocity, pressure, mean SCVPG and maximum FSS from 25 mm BAV were 36.80%, 15.81%, 39.05% and 38.83% lower than those from 19 mm BAV. The GOA of PAV and BAV 25 mm Valve were 43.75% and 33.07% larger than 19 mm valves, respectively. BAV has lower stress on the leaflets than PAV.

Conclusions: BAV had better hemodynamic performance and lower leaflets stress than PAV. More patient studies are needed to validate our findings.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.051DOI Listing
April 2021

4-phenylbutyric acid promotes hepatocellular carcinoma via initiating cancer stem cells through activation of PPAR-α.

Clin Transl Med 2021 Apr;11(4):e379

National Center for Liver Cancer, Second Military Medical University, Shanghai, China.

Background And Aims: 4-phenylbutyric acid (4-PBA) is a low molecular weight fatty acid that is used in clinical practice to treat inherited urea cycle disorders. In previous reports, it acted as a chemical chaperone inhibiting endoplasmic reticulum (ER) stress and unfolded protein response signaling. A few studies have suggested its function against hepatic fibrosis in mice models. However, its role in hepatocarcinogenesis remained unknown.

Methods: 4-PBA was administered alone or in combination with diethylnitrosamine to investigate its long-term effect on liver tumorigenesis. The role of 4-PBA in oncogene-induced hepatocellular carcinoma (HCC) mice model using sleeping beauty system co-expressed with hMet and β-catenin point mutation (S45Y) was also observed. RNA-seq and PCR array were used to screen the pathways and genes involved. In vitro and in vivo studies were conducted to explore the effect of 4-PBA on liver and validate the underlying mechanism.

Results: 4-PBA alone didn't cause liver tumor in long term. However, it promoted liver tumorigenesis in HCC mice models via initiation of liver cancer stem cells (LCSCs) through Wnt5b-Fzd5 mediating β-catenin signaling. Peroxisome proliferator-activated receptors (PPAR)-α induced by 4-PBA was responsible for the activation of β-catenin signaling. Thus, intervention of PPAR-α reversed 4-PBA-induced initiation of LCSCs and HCC development in vivo. Further study revealed that 4-PBA could not only upregulate the expression of PPAR-α transcriptionally but also enhance its stabilization via protecting it from proteolysis. Moreover, high PPAR-α expression predicted poor prognosis in HCC patients.

Conclusions: 4-PBA could upregulate PPAR-α to initiate LCSCs by activating β-catenin signaling pathway, promoting HCC at early stage. Therefore, more discretion should be taken to monitor the potential tumor-promoting effect of 4-PBA under HCC-inducing environment.
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http://dx.doi.org/10.1002/ctm2.379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087947PMC
April 2021

Estimating dynamic population served by wastewater treatment plants using location-based services data.

Environ Geochem Health 2021 Apr 30. Epub 2021 Apr 30.

College of Environmental Science and Engineering, Dalian Maritime University, No. 1 Linghai Road, Dalian, 116026, China.

Wastewater-based epidemiology is a useful approach to estimate population-level exposure to a wide range of substances (e.g., drugs, chemicals, biological agents) by wastewater analysis. An important uncertainty in population normalized loads generated is related to the size and variability of the actual population served by wastewater treatment plants (WWTPs). Here, we built a population model using location-based services (LBS) data to estimate dynamic consumption of illicit drugs. First, the LBS data from Tencent Location Big Data and resident population were used to train a linear population model for estimating population (r = 0.92). Then, the spatiotemporal accuracy of the population model was validated. In terms of temporal accuracy, we compared the model-based population with the time-aligned ammonia nitrogen (NH-N) population within the WWTP of SEG, showing a mean squared error of < 10%. In terms of spatial accuracy, we estimated the model-based population of 42 WWTPs in Dalian and compared it with the NH-N and design population, indicating good consistency overall (5% less than NH-N and 4% less than design). Furthermore, methamphetamine consumption and prevalence based on the model were calculated with an average of 111 mg/day/1000 inhabitants and 0.24%, respectively, and dynamically displayed on a visualization system for real-time monitoring. Our study provided a dynamic and accurate population for estimating the population-level use of illicit drugs, much improving the temporal and spatial trend analysis of drug use. Furthermore, accurate information on drug use could be used to assess population health risks in a community.
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http://dx.doi.org/10.1007/s10653-021-00954-7DOI Listing
April 2021

Classification of Prostate Transitional Zone Cancer and Hyperplasia Using Deep Transfer Learning From Disease-Related Images.

Cureus 2021 Mar 25;13(3):e14108. Epub 2021 Mar 25.

Department of Radiology, Fourth Military Medical University, Shaanxi, CHN.

Purpose The diagnosis of prostate transition zone cancer (PTZC) remains a clinical challenge due to their similarity to benign prostatic hyperplasia (BPH) on MRI. The Deep Convolutional Neural Networks (DCNNs) showed high efficacy in diagnosing PTZC on medical imaging but was limited by the small data size. A transfer learning (TL) method was combined with deep learning to overcome this challenge. Materials and methods A retrospective investigation was conducted on 217 patients enrolled from our hospital database (208 patients) and The Cancer Imaging Archive (nine patients). Using T2-weighted images (T2WIs) and apparent diffusion coefficient (ADC) maps, DCNN models were trained and compared between different TL databases (ImageNet vs. disease-related images) and protocols (from scratch, fine-tuning, or transductive transferring). Results PTZC and BPH can be classified through traditional DCNN. The efficacy of TL from natural images was limited but improved by transferring knowledge from the disease-related images. Furthermore, transductive TL from disease-related images had comparable efficacy to the fine-tuning method. Limitations include retrospective design and a relatively small sample size. Conclusion Deep TL from disease-related images is a powerful tool for an automated PTZC diagnostic system. In developing regions where only conventional MR scans are available, the accurate diagnosis of PTZC can be achieved via transductive deep TL from disease-related images.
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http://dx.doi.org/10.7759/cureus.14108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075764PMC
March 2021

F4/80 Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway.

Molecules 2021 Apr 13;26(8). Epub 2021 Apr 13.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80 KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80 KCs during the regenerative process. In RNA sequencing of isolated F4/80 KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80 KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80 KCs in the initiation and progression phases of liver regeneration. F4/80 KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80 KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80 KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.
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http://dx.doi.org/10.3390/molecules26082231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069260PMC
April 2021

Altered regional homogeneity and connectivity in cerebellum and visual-motor relevant cortex in Parkinson's disease with rapid eye movement sleep behavior disorder.

Sleep Med 2021 Apr 9;82:125-133. Epub 2021 Apr 9.

Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Objective: Rapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism underlying its occurrence is not clear. In this study, we explored whether there is abnormal spontaneous neuronal activities and connectivity maps in some brain areas under resting-state in PD patients with RBD.

Methods: We recruited 38 PD patients (19 PD with RBD and 19 PD without RBD), and 20 age- and gender-matched normal controls. We used resting-state functional magnetic resonance imaging (RS-fMRI) to analyze regional homogeneity (ReHo) and functional connectivity (FC), and further to reveal the neuronal activity in all subjects.

Results: Compared with the PD without RBD patients, the PD with RBD patients showed a significant increase in regional homogeneity in the left cerebellum, the right middle occipital region and the left middle temporal region, and decreased regional homogeneity in the left middle frontal region. The REM sleep behavioral disorders questionnaire scores were significantly positively correlated with the ReHo values of the left cerebellum. The functional connectivity analysis in which the four regions described above were used as regions of interest revealed increased functional activity between the left cerebellum and bilateral occipital regions, bilateral temporal regions and bilateral supplementary motor area.

Conclusion: The pathophysiological mechanism of PD with RBD may be related to abnormal spontaneous neuronal activity patterns with strong synchronization of cerebellar and visual-motor relevant cortex, and the increased connectivity of the cerebellum with the occipital and motor regions.
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http://dx.doi.org/10.1016/j.sleep.2021.03.041DOI Listing
April 2021

A Roadmap to Sorption-Based Atmospheric Water Harvesting: From Molecular Sorption Mechanism to Sorbent Design and System Optimization.

Environ Sci Technol 2021 Apr 29. Epub 2021 Apr 29.

Advanced Membranes and Porous Materials (AMPM) Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.

Sorption-based atmospheric water harvesting (SAWH), which uses sorbents to capture water vapor from the air and low-grade energy to produce fresh liquid water, has been recognized as a promising strategy for decentralized water supply in arid areas. This review aims to summarize the latest progress in this field and provide perspectives for the further development of SAWH, focusing on the design of sorbent materials and the optimization of the entire system. We first introduce the water sorption mechanisms on different sorbent materials. Next, we discuss the properties and performances of various sorbents developed for SAWH by categorizing them into specific groups: nanoporous solids, hygroscopic polymers, salt-based composites, and liquid sorbents; for each type of sorbent materials, we have analyzed its advantages and limitations, as well as design strategies. In addition, we discuss the influences of the mass and heat transport of the SAWH system on its overall performance in actual operations, and introduce different types of water harvesters developed for SAWH. In the last section, we outline the challenges in this field from fundamental research and practical application aspects, and describe roadmaps for the future development of this technology.
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http://dx.doi.org/10.1021/acs.est.1c00257DOI Listing
April 2021

Highly Active Heterogeneous Catalyst for Ethylene Dimerization Prepared by Selectively Doping Ni on the Surface of a Zeolitic Imidazolate Framework.

J Am Chem Soc 2021 May 28;143(18):7144-7153. Epub 2021 Apr 28.

Advanced Membranes and Porous Materials Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.

The production of 1-butene by ethylene dimerization is an important chemical industrial process currently implemented using homogeneous catalysts. Here, we describe a highly active heterogeneous catalyst (Ni-ZIF-8) for ethylene dimerization, which consists of isolating Ni-active sites selectively located on the crystal surface of a zeolitic imidazolate framework. Ni-ZIF-8 can be easily prepared by a simple one-pot synthesis method in which site-specific anchoring of Ni is achieved spontaneously because of the incompatibility between the d electronic configuration of Ni and the three-dimensional framework of ZIF-8. The full exposure and square-planar coordination of the Ni sites accounts for the high catalytic activity of Ni-ZIF-8. It exhibits an average ethylene turnover frequency greater than 1 000 000 h (1-butene selectivity >85%) at 35 °C and 50 bar, far exceeding the activities of previously reported heterogeneous catalysts and many homogeneous catalysts under similar conditions. Moreover, compared to molecular Ni complexes used as homogeneous catalysts for ethylene dimerization, Ni-ZIF-8 has significantly higher stability and shows constant activity during 4 h of continuous reaction. Isotopic labeling experiments indicate that ethylene dimerization over Ni-ZIF-8 follows the Cossee-Arlman mechanism, and detailed characterizations combined with density functional theory calculations rationalize this observed high activity.
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http://dx.doi.org/10.1021/jacs.1c02272DOI Listing
May 2021

Photogenerated charge separation and recombination path modification in monocline LuWO lattice transition and Bi-O antibonding states.

Dalton Trans 2021 Apr 28. Epub 2021 Apr 28.

School of Physics, Beihang University, Beijing 100191, China.

Monoclinic Lu2WO6 undergoes diphase-to-perovskite BiLuWO6 transition via selective occupancy of Bi in three Lu sites. The transformation mechanism, process, and structure stabilities are revealed by variable cell nudged elastic band method, video, and phonon spectrum. Lattice transition brings about photogenerated charge separation in BiLuWO6. This is verified by indirect band gap transition, high electron migration rate, weak exciton binding energy, large photocurrent response, and small impedance. The electron-hole life time is elongated to produce abundant superoxide and hydroxyl radicals for the degradation of rhodamine B and phenol molecules. Bi-O antibonding states serve as immediate energy levels to change the recombination path, inducing 340 nm excitation band and 510 nm green light emission of Lu2WO6. Furthermore, multicolor emission of 1 at% Bi3+ + RE3+ (RE = Sm/Eu/Dy)-codoped Lu2WO6 is acquired via synergistic modification of the Bi-O antibonding state and RE3+ 4f states. Thus, the photogenerated charge motion in Lu2WO6 is tuned to expand application fields.
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http://dx.doi.org/10.1039/d1dt00700aDOI Listing
April 2021

Nano-Confinement Effects on Structural Development and Organic Solvent-Induced Swelling of Ultrathin Carbon Molecular Sieve Films.

ACS Appl Mater Interfaces 2021 May 28;13(18):21765-21774. Epub 2021 Apr 28.

Functional Polymer Membranes Group, Advanced Membranes and Porous Materials Center, Division of Physical Sciences and Engineering, King Abdullah University of Science and Technology, 23955 Thuwal, Saudi Arabia.

Successful implementation of carbon molecular sieve (CMS) membranes in large scale chemical processes inevitably relies on fabrication of high performance integrally skinned asymmetric or thin-film composite membranes. In principle, to maximize separation efficiency the selective CMS layer should be as thin as possible which requires its lateral confinement to a supporting structure. In this work, we studied pyrolysis-induced structural development as well as ethanol vapor-induced swelling of ultrathin CMS films made from a highly aromatic polyimide of an intrinsic microporosity (PIM-PI) precursor. Utilization of a light polarization-sensitive technique, spectroscopic ellipsometry, allowed for the identification of an internal orientation within the turbostratic amorphous CMS structure driven by the laterally constraining support. Our results indicated a significant thickness dependence both in the extent of pyrolytic collapse and response to organic vapor penetrant. Thinner, substrate-confined films (∼30 nm) collapsed more extensively leading to a reduction of microporosity in comparison to their thicker (∼300 nm) as well as self-supported (∼70 μm) counterparts. The reduced microporosity in the thinner films induced changes in the balance between penetrant-induced dilation (swelling) and filling of micropores. In comparison to thicker films, the initial lower microporosity of the thinner films was accompanied by slightly enhanced organic vapor-induced swelling. The presented results are anticipated to generate the fundamental knowledge necessary to design optimized ultrathin CMS membranes. In particular, our results reinforce previous findings that excessive reduction of the selective layer thickness in amorphous microporous materials (such as PIMs or CMS) beyond several hundred nanometers may not be optimal for maximizing their fluid transport performance.
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http://dx.doi.org/10.1021/acsami.1c03392DOI Listing
May 2021

Codon usage bias regulates gene expression and protein conformation in yeast expression system P. pastoris.

Microb Cell Fact 2021 Apr 26;20(1):91. Epub 2021 Apr 26.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Background: Protein synthesis is one of the extremely important anabolic pathways in the yeast expression system Pichia pastoris. Codon optimization is a commonly adopted strategy for improved protein expression, although unexpected failures did appear sometimes waiting for further exploration. Recently codon bias has been studied to regulate protein folding and activity in many other organisms.

Results: Here the codon bias profile of P. pastoris genome was examined first and a direct correlation between codon translation efficiency and usage frequency was identified. By manipulating the codon choices of both endogenous and heterologous signal peptides, secretion abilities of N-terminal signal peptides were shown to be tolerant towards codon changes. Then two gene candidates with different levels of structural disorder were studied, and full-length codon optimization was found to affect their expression profiles differentially. Finally, more evidences were provided to support possible protein conformation change brought by codon optimization in structurally disordered proteins.

Conclusion: Our results suggest that codon bias regulates gene expression by modulating several factors including transcription and translation efficiency, protein folding and activity. Because of sequences difference, the extent of affection may be gene specific. For some genes, special codon optimization strategy should be adopted to ensure appropriate expression and conformation.
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http://dx.doi.org/10.1186/s12934-021-01580-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077831PMC
April 2021

The formation and evolution of carbonate species in CO oxidation over mono-dispersed Fe on graphene.

Phys Chem Chem Phys 2021 May;23(17):10509-10517

State Key Laboratory of Fine Chemicals, Department of Chemistry, Dalian University of Technology, Dalian, 116024, P. R. China.

Fe is not only the most abundant metal on the planet but is also the key component of many enzymes in organisms that are capable of catalyzing many chemical conversions. Mono-dispersed Fe atoms on carbonaceous materials are single atom catalysts (SACs) that function like enzymes. To take advantage of the outstanding catalytic performance of Fe-based SACs, we extended a CO oxidation reaction network over mono-dispersed Fe atoms on graphene (FeGR) by first-principles based calculations. FeGR-catalyzed CO oxidation is initiated with a revised Langmuir-Hinshelwood pathway through a CO-assisted scission of the O-O bond in peroxide species (OCOO). We showed that carbonate species (CO3), which were previously generally considered as a persistent species blocking reaction sites, may form from CO2 and negatively charged O species. This pathway competes with desorption of CO2 and reduction of the Fe center with gaseous CO, and it is exothermic and inevitable, especially at low temperatures and with high CO2 content. Although direct dissociation of CO3 is demanding on FeGR, further adsorption of CO on Fe in CO3 is plausible and takes place spontaneously. We then showed that adsorbed CO may react with CO3, forming a cyclic-carbonate-like species that dissociates easily to CO2. These findings highlight the reaction condition-dependent formation and evolution of CO3 as well as its contribution to CO conversion, and it may extend the understanding of the performance of SACs in low temperature CO oxidation.
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http://dx.doi.org/10.1039/d1cp00814eDOI Listing
May 2021

Associations of Serum Cytokine Levels and Interleukin-6-572C/G Polymorphism with Myelin Damage in Chinese Children with Autism Spectrum Disorder.

Neuroscience 2021 Apr 22. Epub 2021 Apr 22.

Department of Maternal, Child & Adolescence Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China. Electronic address:

Increasing evidence suggests that immunological disturbances and abnormalities in axonal myelination are involved in the pathophysiology of autism spectrum disorder (ASD). The present study aimed to determine the role of cytokines in myelin damage in Chinese children with ASD and the role of cytokine dysregulation, myelin damage, and cytokine polymorphisms in ASD in Chinese children. The present case-control study included 98 ASD subjects and 252 typically developing (TD) controls; the levels of serum cytokines and myelin basic protein (MBP) were determined using enzyme-linked immunosorbent assay. Cytokine polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Autistic clinical manifestations were assessed by the Childhood Autism Rating Scale (CARS). The results showed that serum levels of interleukin (IL)-1β, IL-2R, IL-6, IL-8, and MBP were higher in children with ASD compared with those in TD children. In individuals with ASD, serum MBP level was significantly positively associated with the CARS total score, and serum levels of IL-1β, IL-2R, IL-6, and MBP demonstrated positive correlations. The data identified IL-6*MBP as a factor that influenced the risk of ASD, and IL-2R*MBP was identified as a factor that influenced symptom severity, which influenced auxiliary diagnosis of ASD. The presence of the interleukin-6-572CC genotype was associated with significantly higher serum levels of IL-6 and MBP but did not influence the risk and symptom severity of ASD. Therefore, the results suggested inflammatory responses and myelin damage in Chinese children with ASD. Cytokine dysregulation influenced myelin damage in ASD; moreover, the interactions of the cytokines and myelin damage influenced the risk and symptom severity of ASD. The IL-6-572C/G genotypes may be associated with myelin damage in ASD by influencing the circulating level of IL-6.
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http://dx.doi.org/10.1016/j.neuroscience.2021.04.006DOI Listing
April 2021

Design, synthesis and biological evaluation of selective histone deacetylase 6 (HDAC6) inhibitors bearing benzoindazole or pyrazoloindazole scaffold as surface recognition motif.

Bioorg Chem 2021 Apr 20;111:104910. Epub 2021 Apr 20.

Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

A series of compounds were designed and synthesized based on the compound 11i bearing phenylpyrazole scaffold with histone deacetylase 6 (HDAC6) inhibitory activity. Most of the compounds showed considerable inhibitory activity against HDAC6 and compound A16 with good inhibitory activity was found therein. We further found that A16 had an inhibitory effect on inflammatory mediators (NO, TNF-α, IL-6) involved in inflammatory response and neuroendocrine regulation. In addition, A16 has a certain neuroprotective effect on PC12 cells injured by hydrogen peroxide. Acute toxicity assay showed that the LD of A16 was 274.47 mg/kg in mouse model. Furthermore, A16 displayed good stability properties in microsomes and plasma.
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http://dx.doi.org/10.1016/j.bioorg.2021.104910DOI Listing
April 2021

Prognostic biomarkers and therapeutic targets in oral squamous cell carcinoma: a study based on cross-database analysis.

Hereditas 2021 Apr 23;158(1):15. Epub 2021 Apr 23.

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No.127, Changle West Road, Xi'an, 710032, Shaanxi Province, China.

Background: Oral squamous cell carcinoma (OSCC) is a malignant cancer, the survival rate of patients is disappointing. Therefore, it is necessary to identify the driven-genes and prognostic biomarkers in OSCC.

Methods: Four Gene Expression Omnibus (GEO) datasets were integratedly analyzed using bioinformatics approaches, including identification of differentially expressed genes (DEGs), GO and KEGG analysis, construction of protein-protein interaction (PPI) network, selection of hub genes, analysis of prognostic information and genetic alterations of hub genes. ONCOMINE, The Cancer Genome Atlas (TCGA) and Human Protein Atlas databases were used to evaluate the expression and prognostic value of hub genes. Tumor immunity was assessed to investigate the functions of hub genes. Finally, Cox regression model was performed to construct a multiple-gene prognostic signature.

Results: Totally 261 genes were found to be dysregulated. 10 genes were considered to be the hub genes. The Kaplan-Meier analysis showed that upregulated SPP1, FN1, CXCL8, BIRC5, PLAUR, and AURKA were related to poor outcomes in OSCC patients. FOXM1 and TPX2 were considered as the potential immunotherapeutic targets with future clinical significance. Moreover, we constructed a nine-gene signature (TEX101, DSG2, SCG5, ADA, BOC, SCARA5, FST, SOCS1, and STC2), which can be utilized to predict prognosis of OSCC patients effectively.

Conclusion: These findings may provide new clues for exploring the molecular mechanisms and targeted therapy in OSCC. The hub genes and risk gene signature are helpful to the personalized treatment and prognostic judgement.
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http://dx.doi.org/10.1186/s41065-021-00181-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066950PMC
April 2021

Molecular Scalpel to Chemically Cleave Metal-Organic Frameworks for Induced Phase Transition.

J Am Chem Soc 2021 May 23;143(17):6681-6690. Epub 2021 Apr 23.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, South Australia 5005, Australia.

A bottom-up chemical synthesis of metal-organic frameworks (MOFs) permits significant structural diversity because of various combinations of metal centers and different organic linkers. However, fabrication generally complies with the classic hard and soft acids and bases (HSAB) theory. This restricts direct synthesis of desired MOFs with converse Lewis type of metal ions and ligands. Here we present a top-down strategy to break this limitation via the structural cleavage of MOFs to trigger a phase transition using a novel "molecular scalpel". A conventional CuBDC MOF (BDC = 1,4-benzenedicarboxylate) prepared from a hard acid (Cu) metal and a hard base ligand was chemically cleaved by l-ascorbic acid acting as chemical scalpel to fabricate a new CuBDC structure composed of a soft acid (Cu) and a hard base (BDC). Controlled phase transition was achieved by a series of redox steps to regulate the chemical state and coordination number of Cu ions, resulting in a significant change in chemical composition and catalytic activity. Mechanistic insights into structural cleavage and rearrangement are elaborated in detail. We show this novel strategy can be extended to general Cu-based MOFs and supramolecules for nanoscopic casting of unique architectures from existing ones.
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http://dx.doi.org/10.1021/jacs.1c02379DOI Listing
May 2021

Cisplatin resistance reversal in lung cancer by tumor acidity-activable vesicular nanoreactors via tumor oxidative stress amplification.

J Mater Chem B 2021 Apr 22;9(13):3055-3067. Epub 2021 Mar 22.

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, China.

Drug resistance of cisplatin significantly limits its therapeutic efficacy in clinical applications against different cancers. Herein, we develop a novel strategy to overcome cisplatin drug resistance through sensitizing cisplatin-resistant human lung cancer cells (A549R) under amplified oxidative stress using a vesicular nanoreactor for simultaneous cisplatin delivery and HO generation. We engineer the nanoreactor by the self-assembly of the amphiphilic diblock copolymers to co-deliver glucose oxidase (GOD) and cisplatin (Cis) (Cis/GOD@Bz-V). Cis/GOD@Bz-V was rationally designed to stay impermeable during blood circulation while mild acidity (pH 6.5-6.8) can activate its molecular-weight selective membrane permeability and release cisplatin locally. Diffusion of small molecules such as oxygen and glucose across the membranes can induce the in situ generation of superfluous HO to promote cellular oxidative stress and sensitize A549R cells via activation of pro-apoptotic pathways. Cis/GOD@Bz-V nanoreactors could effectively kill A549R at pH 6.8 in the presence of glucose by the combination of HO generation and cisplatin release. Growth of A549R xenograft tumors can be inhibited efficiently without the obvious toxic side effects via the systemic administration of Cis/GOD@Bz-V. Accordingly, the tumor acidity-activable cisplatin-loaded nanoreactors show great potential to enhance the therapeutic efficacy against cisplatin-resistant cancers.
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http://dx.doi.org/10.1039/d0tb02876bDOI Listing
April 2021

A single-molecule van der Waals compass.

Nature 2021 04 21;592(7855):541-544. Epub 2021 Apr 21.

Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology, Department of Chemical Engineering, Tsinghua University, Beijing, China.

Single-molecule imaging is challenging but highly beneficial for investigating intermolecular interactions at the molecular level. Van der Waals interactions at the sub-nanometre scale strongly influence various molecular behaviours under confinement conditions. Inspired by the traditional compass, here we use a para-xylene molecule as a rotating pointer to detect the host-guest van der Waals interactions in the straight channel of the MFI-type zeolite framework. We use integrated differential phase contrast scanning transmission electron microscopy to achieve real-space imaging of a single para-xylene molecule in each channel. A good correlation between the orientation of the single-molecule pointer and the atomic structure of the channel is established by combining the results of calculations and imaging studies. The orientations of para-xylene help us to identify changes in the van der Waals interactions, which are related to the channel geometry in both spatial and temporal dimensions. This work not only provides a visible and sensitive means to investigate host-guest van der Waals interactions in porous materials at the molecular level, but also encourages the further study of other single-molecule behaviours using electron microscopy techniques.
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http://dx.doi.org/10.1038/s41586-021-03429-yDOI Listing
April 2021

TAVR in a Patient With Quadricuspid Aortic Stenosis: The Role of Patient-Specific Computer Simulation in Treatment Planning and Outcome Prediction.

JACC Cardiovasc Interv 2021 May 14;14(9):e93-e95. Epub 2021 Apr 14.

Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, Zhengzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.jcin.2021.01.014DOI Listing
May 2021

The toxic impacts of microplastics (MPs) and polycyclic aromatic hydrocarbons (PAHs) on haematic parameters in a marine bivalve species and their potential mechanisms of action.

Sci Total Environ 2021 Apr 9;783:147003. Epub 2021 Apr 9.

College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China. Electronic address:

Microplastics (MPs) and polycyclic aromatic hydrocarbons (PAHs) are universally detected in the marine ecosystem and may exert adverse impacts on marine species. Although under realistic pollution scenarios, PAH pollution usually occurs as a mixture of different PAH compounds, the toxic impacts of PAH mixtures on marine organisms remain largely unknown to date, including their interactions with other emergent pollutants such as MPs. In this study, the single and combined toxic impacts of polystyrene MPs and a mixture of PAHs (standard mix of 16 representative PAHs) on haematic parameters were evaluated in the blood clam Tegillarca granosa. Our data demonstrated that blood clams treated with the pollutants examined led to decreased total haemocyte count (THC), changed haematic composition, and inhibited phagocytosis of haemocytes. Further analyses indicated that MPs and a mixture of PAHs may exert toxic impacts on haematic parameters by elevating the intracellular contents of reactive oxygen species (ROS), giving rise to lipid peroxidation (LPO) and DNA damage, reducing the viability of haemocytes, and disrupting important molecular signalling pathways (indicated by significantly altered expressions of key genes). In addition, compared to clams treated with a single type of pollutant, coexposure to MPs and a mixture of PAHs exerted more severe adverse impacts on all the parameters investigated, indicating a significant synergistic effect of MPs and PAHs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147003DOI Listing
April 2021

Nonlinear elasticity of biological basement membrane revealed by rapid inflation and deflation.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;

Basement membrane (BM) is a thin layer of extracellular matrix that surrounds most animal tissues, serving as a physical barrier while allowing nutrient exchange. Although they have important roles in tissue structural integrity, physical properties of BMs remain largely uncharacterized, which limits our understanding of their mechanical functions. Here, we perform pressure-controlled inflation and deflation to directly measure the nonlinear mechanics of BMs in situ. We show that the BMs behave as a permeable, hyperelastic material whose mechanical properties and permeability can be measured in a model-independent manner. Furthermore, we find that BMs exhibit a remarkable nonlinear stiffening behavior, in contrast to the reconstituted Matrigel. This nonlinear stiffening behavior helps the BMs to avoid the snap-through instability (or structural softening) widely observed during the inflation of most elastomeric balloons and thus maintain sufficient confining stress to the enclosed tissues during their growth.
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http://dx.doi.org/10.1073/pnas.2022422118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980462PMC
March 2021

The protective effect of hydrogen-rich water on rats with type 2 diabetes mellitus.

Mol Cell Biochem 2021 Apr 8. Epub 2021 Apr 8.

Key Laboratory of Advanced Technology for Materials of the Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.

The hydrogen-rich water (HW) has been reported to possess a beneficial role in patients with diabetes. However, a systemic evaluation with an appropriate animal model is necessary to reveal its mechanisms and efficacy. Herein, the protective effects of drinking HW on lipid and glucose metabolism, oxidative stress, and inflammation in type 2 diabetes mellitus (T2DM) rats were investigated. The well-modeled T2DM rats (induced by high-fat diet combined with low-dose streptozotocin (STZ) injection) were divided into two groups (n ≥ 15 of each): fed a high-fat diet and drinking distilled water or HW at a constant concentration above 1.0 ppm; normal rats were used as control group (n ≥ 10): fed a regular diet and drinking distilled water. Several biomarkers of lipid and glucose metabolism, oxidative stress ,and inflammation were evaluated after drinking distilled water or HW for 3 weeks. The effect of HW on liver, kidney, and spleen of T2DM rats was also analyzed by HE and Oil Red O staining. The results showed that drinking HW suppressed the increase in glucose, total cholesterol, oxidative stress, and inflammation. Moreover, HW also ameliorates hyperglycemia-induced liver, kidney, and spleen dysfunction. Overall, this study indicates that patients with T2DM may be able to improve their condition by supplementing HW as daily drinking water.
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http://dx.doi.org/10.1007/s11010-021-04145-xDOI Listing
April 2021

Cloning, characterization, and transcriptional activity of β-actin promoter of African catfish (Clarias gariepinus).

Mol Biol Rep 2021 Mar 7;48(3):2561-2571. Epub 2021 Apr 7.

College of Animal Sciences, Zhejiang University, Hangzhou, 310058, PR China.

Selection of suitable promoters is crucial for the efficient expression of exogenous genes in transgenic animals. Although one of the most effective promoters, the β-actin promoter, has been widely studied in fish species, it still remains unknown in the economical important African catfish (Clarias gariepinus). In this study, the β-actin promoter of African catfish (cgβ-actinP) was cloned and characterized. In addition, recombinant plasmid pcgβ-actinP-EGFP with enhanced green fluorescent protein (GFP) gene as the reporter gene was constructed to verify the transcriptional activity. We obtained a cgβ-actinP fragment length of 1405 bp, consisting 104 bp of the 5' proximal promoter, 96 bp of the first exon, and 1205 bp of the first intron. Similar to those of other fish species, cgβ-actinP contains three key transcription regulatory elements (CAAT box, CArG motif, and TATA box). GFP-specific fluorescent signals were detected in chicken embryonic fibroblasts cells (DF-1 cells) transfected with pcgβ-actinP-EGFP, which was approximately 1.11 times of the positive control. In addition, GFP was effectively expressed in zebrafish larvae microinjected with linearized cgβ-actinP-EGFP, with expression rate reaching approximately 49.84%. Our data indicate that cgβ-actinP could be a potential candidate promoter in the practice of constructing "all fish" transgenic fish.
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http://dx.doi.org/10.1007/s11033-021-06306-zDOI Listing
March 2021

NPI-GNN: Predicting ncRNA-protein interactions with deep graph neural networks.

Brief Bioinform 2021 Apr 5. Epub 2021 Apr 5.

College of Intelligence and Computing, Tianjin University, Tianjin 300350, China.

Noncoding RNAs (ncRNAs) play crucial roles in many biological processes. Experimental methods for identifying ncRNA-protein interactions (NPIs) are always costly and time-consuming. Many computational approaches have been developed as alternative ways. In this work, we collected five benchmarking datasets for predicting NPIs. Based on these datasets, we evaluated and compared the prediction performances of existing machine-learning based methods. Graph neural network (GNN) is a recently developed deep learning algorithm for link predictions on complex networks, which has never been applied in predicting NPIs. We constructed a GNN-based method, which is called Noncoding RNA-Protein Interaction prediction using Graph Neural Networks (NPI-GNN), to predict NPIs. The NPI-GNN method achieved comparable performance with state-of-the-art methods in a 5-fold cross-validation. In addition, it is capable of predicting novel interactions based on network information and sequence information. We also found that insufficient sequence information does not affect the NPI-GNN prediction performance much, which makes NPI-GNN more robust than other methods. As far as we can tell, NPI-GNN is the first end-to-end GNN predictor for predicting NPIs. All benchmarking datasets in this work and all source codes of the NPI-GNN method have been deposited with documents in a GitHub repo (https://github.com/AshuiRUA/NPI-GNN).
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http://dx.doi.org/10.1093/bib/bbab051DOI Listing
April 2021

An Improved UNet++ Model for Congestive Heart Failure Diagnosis Using Short-Term RR Intervals.

Diagnostics (Basel) 2021 Mar 16;11(3). Epub 2021 Mar 16.

School of Computer Science and Engineering (SCSE), Nanyang Technological University (NTU), Singapore 639798, Singapore.

Congestive heart failure (CHF), a progressive and complex syndrome caused by ventricular dysfunction, is difficult to detect at an early stage. Heart rate variability (HRV) was proposed as a prognostic indicator for CHF. Inspired by the success of 2-D UNet++ in medical image segmentation, in this paper, we introduce an end-to-end encoder-decoder model to detect CHF using HRV signals. The developed model enhances the UNet++ model with Squeeze-and-Excitation (SE) residual blocks to extract deep features hierarchically and distinguish CHF patients from normal subjects. Two open-source databases are utilized for evaluating the proposed method, and three segment lengths of intervals between successive R-peaks are employed in comparison with state-of-the-art methods. The proposed method achieves an accuracy of 85.64%, 86.65% and 88.79% when 500, 1000 and 2000 RR intervals are utilized, respectively. It demonstrates that HRV evaluation based on deep learning can be an important tool for early detection of CHF, and may assist clinicians in achieving timely and accurate diagnoses.
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http://dx.doi.org/10.3390/diagnostics11030534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002263PMC
March 2021

A Principal Component of Quality of Life Measures Is Associated with Survival for Head and Neck Cancer Patients Treated with Radiation Therapy.

Cancers (Basel) 2021 Mar 8;13(5). Epub 2021 Mar 8.

Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY 14203, USA.

Background: Health-related quality of life (HRQOL) metrics can be associated with survival in head and neck cancer (HNC); however, the impact of HRQOL recovery and the relevant HRQOL domains regarding outcome are unclear.

Methods: Using a single-institution database, we retrospectively reviewed HNC patients treated with definitive or postoperative radiation therapy between 2013 and 2018. The recovery of individual HRQOL domains were determined by the ratio of the post-treatment to baseline scores. Univariate and Multivariate Cox regression were used to analyze survival outcomes. Principal component analysis was used to adjust for multicollinearity of HRQOL domains.

Results: In 218 HNC patients who received radiation therapy, median follow-up was 24.8 months (interquartile range (IQR) 14.5-32.0). Principal component analysis evaluating the recovery of HRQOL domains revealed two independent principal components (PC), PC1 and PC2. PC1, which received contributions from the functional domains; physical (PF), role (RF), emotional (EF), cognitive (CF), and global health status (GQOL) was significantly associated with disease-free (HR = 0.77, 95% CI 0.61-0.98, = 0.034) and overall survival (HR = 0.76, 95% CI 0.65-0.91, = 0.004) on multivariate analysis and PC2, had no correlation with outcome and was mainly represented by social functioning. Unplanned hospitalization was significantly associated with lower PC1 scores (β = -0.997, Std. Error = 0.244, < 0.001).

Conclusion: Our study provides evidence that post-treatment recovery of HRQOL domains were associated with overall survival (OS) in HNC. PC1 is an attractive clinical tool to assess the recovery across multiple different HRQOL and the relationship with survival. Future prospective studies may identify patients who could benefit from additional rehabilitation based on PC1 score.
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http://dx.doi.org/10.3390/cancers13051155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962523PMC
March 2021