Publications by authors named "Ping Tan"

127 Publications

Patch-based Uncalibrated Photometric Stereo under Natural Illumination.

IEEE Trans Pattern Anal Mach Intell 2021 Sep 24;PP. Epub 2021 Sep 24.

This paper presents a photometric stereo method that works with unknown natural illumination without any calibration objects or initial guess of the target shape. To solve this challenging problem, we propose the use of an equivalent directional lighting model for small surface patches consisting of slowly varying normals, and solve each patch up to an arbitrary orthogonal ambiguity. We further build the patch connections by extracting consistent surface normal pairs via spatial overlaps among patches and intensity profiles. Guided by these connections, the local ambiguities are unified to a global orthogonal one through Markov Random Field optimization and rotation averaging. After applying the integrability constraint, our solution contains only a binary ambiguity, which could be easily removed. Experiments using both synthetic and real-world datasets show our method provides even comparable results to calibrated methods.
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http://dx.doi.org/10.1109/TPAMI.2021.3115229DOI Listing
September 2021

Interferon-β suppresses inflammatory pain through activating µ-opioid receptor.

Mol Pain 2021 Jan-Dec;17:17448069211045211

Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-β has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-β in reducing mechanical allodynia caused by Complete Freund's Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-β in naïve rats and the rats with CFA-induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-β in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-β antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-β is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-β at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-β produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-β injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/βR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-β is through µ-opioid receptors activation in spial cord.
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http://dx.doi.org/10.1177/17448069211045211DOI Listing
September 2021

Enhanced chemo-photodynamic therapy of an enzyme-responsive prodrug in bladder cancer patient-derived xenograft models.

Biomaterials 2021 Aug 27;277:121061. Epub 2021 Aug 27.

Department of Urology, Institute of Urology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Patient-derived xenograft (PDX) models are powerful tools for understanding cancer biology and drug discovery. In this study, a polymeric nano-sized drug delivery system poly (OEGMA)[email protected] ([email protected]) composed of a photosensitizer chlorin e6 (Ce6) and a cathepsin B-sensitive polymer-paclitaxel (PTX) prodrug was constructed. The photochemical internalization (PCI) effect and enhanced chemo-photodynamic therapy (PDT) were achieved via a two-stage light irradiation strategy. The results showed that the [email protected] had great tumor targeting and rapid cellular uptake induced by PCI, thereby producing excellent anti-tumor effects on human bladder cancer PDX models with tumor growth inhibition greater than 98%. Bioinformatics analysis revealed that the combination of PTX chemotherapy and PDT up-regulated oxidative phosphorylation and reactive oxygen species (ROS) generation, blocked cell cycle and proliferation, and down-regulated the pathways related to tumor progression, invasion and metastasis, including hypoxia, TGF-β signaling and TNF-α signaling pathways. Western blots analysis confirmed that proteins promoting apoptosis (Bax, Cleaved caspase-3, Cleaved PARP) and DNA damage (γH2A.X) were up-regulated, while those inhibiting apoptosis (Bcl-2) and mitosis (pan-actin and α/β-tubulin) were down-regulated after chemo-PDT treatment. Therefore, this stimuli-responsive polymer-PTX prodrug-based nanomedicine with combinational chemotherapy and PDT evaluated in the PDX models could be a potential candidate for bladder cancer therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121061DOI Listing
August 2021

SRT1720 inhibits the growth of bladder cancer in organoids and murine models through the SIRT1-HIF axis.

Oncogene 2021 Sep 1. Epub 2021 Sep 1.

Department of Urology, Institute of Urology, Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

There are unmet clinical needs for novel therapeutic targets and drugs for bladder cancer. Majority of previous work relied on limited bladder cancer cell lines, which could not well represent the tumor heterogeneity and pathology of this disease. Recently, it has been shown that cancer organoids can recapitulate pathological and molecular properties of bladder cancer. Here, we report, by our knowledge, the first bladder cancer organoid-based small molecule screening for epigenetic drugs. We found that SRT1720, a Sirtuin 1 (SIRT1) activator, significantly inhibits the growth of both mouse and human bladder cancer organoids. And it also restrains the development of mouse in situ bladder cancer and human PDX bladder cancer. Mutation of Sirt1 promotes the growth of cancer organoids and decreases their sensitivity to SRT1720, which validate Sirt1 as the target of SRT1720 in bladder cancer. Mechanistically, SRT1720 treatment represses the hypoxia pathway through deacetylating HIF1α by activating Sirt1. Genetic or pharmaceutic inhibitions of HIF mimic the anti-tumor effect of SRT1720. Furthermore, the SIRT1-repressed gene signature is associated with the hypoxia target gene signature and poor prognosis in human bladder cancers. Thus, our study demonstrates the power of cancer organoid-based drug discovery and, in principle, identifies SRT1720 as a new treatment for bladder cancer.
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http://dx.doi.org/10.1038/s41388-021-01999-9DOI Listing
September 2021

Palm oil supply chain factors impacting chlorinated precursors of 3-MCPD esters.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2021 Aug 18:1-14. Epub 2021 Aug 18.

Sime Darby Plantation Technology Centre Sdn Bhd, 1st Floor, Block B, UPM-MTDC Technology Centre III, Lebuh Silikon, Universiti Putra Malaysia, Serdang, Malaysia.

Chlorinated compounds such as sphingolipid-based organochlorine compounds are precursors for the formation of 3-monochlororopanediol (3-MCPD) esters in palm oil. This study evaluates the effects of several factors within the palm oil supply chain on the levels of sphingolipid-based organochlorine, which in turn may influence the formation of 3-MCPD esters during refining. These factors include application of inorganic chlorinated fertiliser in the oil palm plantation, bruising and degradation of oil palm fruits after harvest, recycling of steriliser condensate as water for dilution of crude oil during oil palm milling, water washing of palm oil and different refining conditions. It was observed that bruised and degraded oil palm fruits showed higher content of sphingolipid-based organochlorine than control. In addition, recycling steriliser condensate during milling resulted in elevated content of sphingolipid-based organochlorine in palm oil. However, the content of sphingolipid-based organochlorine compounds was reduced by neutralisation, degumming and bleaching steps during refining. Although water washing of crude palm oils (CPO) prior to refining did not reduce the content of sphingolipid-based organochlorine, it did reduce the formation of 3-MCPD esters through the removal of water-soluble chlorinated compounds. It was found that the use of inorganic chlorinated fertiliser in plantations did not increase the content of chlorinated compounds in oil palm fruits and extracted oil, and hence chlorinated fertiliser does not seem to play a role in the formation of 3-MCPD esters in palm oil. Overall, this study concluded that lack of freshness and damage to the fruits during transport to mills, combined with water and oil recycling in mills are the major contributors of chlorinated precursor for 3-MCPD esters formation in palm oil.
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http://dx.doi.org/10.1080/19440049.2021.1960430DOI Listing
August 2021

Gaussian fitting algorithm with multi-geometric parameters for rotated elliptical beam profiling using pixel ion chamber.

Med Phys 2021 Sep 11;48(9):4799-4811. Epub 2021 Aug 11.

State Key Laboratory of Advanced Electromagnetic Engineering and Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Hubei, China.

Purpose: A high-precision rotated elliptical beam profiling method based on pixel ion chamber is proposed in this paper. This method aims to improve the accuracy by modeling the transverse profile of rotated beam as an ellipse with additional correlation coefficient and eliminating the fitting error due to the volume averaging effect of pixel ion chamber.

Methods: In pencil beam scanning (PBS) proton therapy systems, the transverse beam profile model is generally represented as a standard Gaussian distribution. Considering the elliptical spots, two-dimensional (2D) joint Gaussian distribution characterized with the correlation coefficient ρ is adopted in this study. Gaussian-type particle distribution with white noise was generated and processed in MATLAB to simulate the secondary particle collection in the pixel ion chamber. The simulated pixel ion chamber is a commercially available ion chamber which consists of 12 × 12 small square pixels (3.75 × 3.75 mm ) with a 0.05 mm interval. The simulated signals were preprocessed by filtering with the noise threshold and extracting the maximum simply connected domain (MSCD) of the signal. Then, five geometric parameters that identify the transverse beam profiles were fitted under different signal-to-noise ratio (SNR) conditions: the center of the beam (x , y ), the spot size (σ , σ ), and the rotation angle θ formed between the major axes of elliptical spot and the x axes of the ion chamber. First, the simulated signals were preprocessed by filtering with the noise threshold and extracting the MSCD of the signal. Second, a rectification curve of systematic error in fitted spot size versus the prescribed spot size was used to predict the systematic error due to the volume averaging effect. Finally, the effects of fitting errors on therapeutic dose were evaluated in terms of gamma index and relative dose difference.

Results: When the SNR is not less than 20 dB, the relative fitting error of spot size and the absolute fitting error of angle θ are less than 1% and 6.1°, respectively. The fitting error of beam center increases with spot size and will not exceed 0.22 mm when spot size reaches up to 12 mm. At a SNR equal to 20 dB, neither cold nor hot spots were presented in dose distribution calculated with the fitted spot parameters.

Conclusion: The improved Gaussian fitting algorithm performs well when SNR is not less than 20 dB. This method can effectively distinguish the nominal beam and rotated elliptical beam. An ideal systematic error curve can be predicted and used to correct the fitted spot size, thus eliminating the systematic error due to the volume averaging effect of the pixel ion chamber. The fitting error of spot size cannot be fully corrected, but it is negligible and shows little effect on the overall therapeutic dose.
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http://dx.doi.org/10.1002/mp.15140DOI Listing
September 2021

Dual-Mode Plasmonic Coupling-Enhanced Color Conversion of Inorganic CsPbBr Perovskite Quantum Dot Films.

ACS Appl Mater Interfaces 2021 Jul 12;13(28):32856-32864. Epub 2021 Jul 12.

Collaborative Innovation Center for Optoelectronic Semiconductors and Efficient Devices, Jiujiang Research Institute, Department of Physics / Pen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, Xiamen, Fujian 361005, China.

Plasmonic coupling has been demonstrated to be an effective manipulation strategy for emission enhancement in low-dimensional semiconductor materials. Here, dual-mode plasmonic resonances based on a metal dimer structure were proposed to simultaneously enhance the absorption under short-wavelength excitation and excitons' emission at longer wavelengths for CsPbBr perovskite quantum dots (QDs). Large-area metal nanodimer arrays with well-controlled local surface plasmon resonance were facilely fabricated by a simple method combined with metal angular deposition and nanosphere lithography. With the addition of an optimized polymethyl methacrylate spacer, the effective plasmonic coupling and interfacial passivation of QDs were successfully achieved in the hybrid system. As a result, the QD films exhibited a significant and approximately 3.95-fold overall fluorescence enhancement when using blue light excitation, showing the novel advantages of dual-mode plasmonic coupling of semiconductor quantum structures for color conversion applications.
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http://dx.doi.org/10.1021/acsami.1c02801DOI Listing
July 2021

Structure-Aware Motion Deblurring Using Multi-Adversarial Optimized CycleGAN.

IEEE Trans Image Process 2021 9;30:6142-6155. Epub 2021 Jul 9.

Recently, Convolutional Neural Networks (CNNs) have achieved great improvements in blind image motion deblurring. However, most existing image deblurring methods require a large amount of paired training data and fail to maintain satisfactory structural information, which greatly limits their application scope. In this paper, we present an unsupervised image deblurring method based on a multi-adversarial optimized cycle-consistent generative adversarial network (CycleGAN). Although original CycleGAN can handle unpaired training data well, the generated high-resolution images are probable to lose content and structure information. To solve this problem, we utilize a multi-adversarial mechanism based on CycleGAN for blind motion deblurring to generate high-resolution images iteratively. In this multi-adversarial manner, the hidden layers of the generator are gradually supervised, and the implicit refinement is carried out to generate high-resolution images continuously. Meanwhile, we also introduce the structure-aware mechanism to enhance the structure and detail retention ability of the multi-adversarial network for deblurring by taking the edge map as guidance information and adding multi-scale edge constraint functions. Our approach not only avoids the strict need for paired training data and the errors caused by blur kernel estimation, but also maintains the structural information better with multi-adversarial learning and structure-aware mechanism. Comprehensive experiments on several benchmarks have shown that our approach prevails the state-of-the-art methods for blind image motion deblurring.
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http://dx.doi.org/10.1109/TIP.2021.3092814DOI Listing
July 2021

Inflammatory cytokines TNF-α and IL-17 enhance the efficacy of cystic fibrosis transmembrane conductance regulator modulators.

J Clin Invest 2021 Aug;131(16)

Department of Internal Medicine and Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine and.

Without cystic fibrosis transmembrane conductance regulator-mediated (CFTR-mediated) HCO3- secretion, airway epithelia of newborns with cystic fibrosis (CF) produce an abnormally acidic airway surface liquid (ASL), and the decreased pH impairs respiratory host defenses. However, within a few months of birth, ASL pH increases to match that in non-CF airways. Although the physiological basis for the increase is unknown, this time course matches the development of inflammation in CF airways. To learn whether inflammation alters CF ASL pH, we treated CF epithelia with TNF-α and IL-17 (TNF-α+IL-17), 2 inflammatory cytokines that are elevated in CF airways. TNF-α+IL-17 markedly increased ASL pH by upregulating pendrin, an apical Cl-/HCO3- exchanger. Moreover, when CF epithelia were exposed to TNF-α+IL-17, clinically approved CFTR modulators further alkalinized ASL pH. As predicted by these results, in vivo data revealed a positive correlation between airway inflammation and CFTR modulator-induced improvement in lung function. These findings suggest that inflammation is a key regulator of HCO3- secretion in CF airways. Thus, they explain earlier observations that ASL pH increases after birth and indicate that, for similar levels of inflammation, the pH of CF ASL is abnormally acidic. These results also suggest that a non-cell-autonomous mechanism, airway inflammation, is an important determinant of the response to CFTR modulators.
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http://dx.doi.org/10.1172/JCI150398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363270PMC
August 2021

Regional lymph nodes distribution pattern in central area of right-sided colon cancer: in-vivo detection and the update on the clinical exploration.

Am J Cancer Res 2021 15;11(5):2095-2105. Epub 2021 May 15.

Department of Colorectal (Tumor) Surgery, Guangdong Province Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine No. 111, Dade Rd, Yuexiu, Guangzhou 510120, Guangdong, China.

Distribution of regional lymph nodes (LNs) is decisive for the lymphadenectomy boundary in radical resection of right-sided colon cancer (RCC). Currently, the data of LNs in central area remains ambiguous and scarce. Herein we aim to provide a more detailed anatomical research on LNs surrounding the superior mesenteric vessels for RCC and investigated the metastasis rate. In this study, Carbon Nanoparticles (CNs) and Indocyanine Green (ICG) were used for regional LNs mapping by preoperative colonoscopic tattooing (PCT) and we laparoscopically observed the stained LNs distribution pattern. Lastly, 143 RCC patients who received a "superior mesenteric artery (SMA)-oriented" hemicolectomy were included to calculate the probability of LNs metastasis in our target area. 27 patients diagnosed as RCC (mean age 58.04 years, 17 male) were included. 14 patients underwent CNs injection and 13 patients consented to the ICG, while 4 cases suffered from imaging failure. The unequal number of the regional LNs located between SMV and SMA was detected in 22 cases (81.48%), posterior to SMV area in 6 cases (22.22%), and anterior to SMA in 16 cases (59.26%), respectively. The presence of LNs posterior to SMV was associated with the crossing pattern of ileocolic artery (χ = 4.24, ). The probability of LNs metastasis in the above areas (target areas) was 2.10% (3/143). In conclusion, right-hemi colon-draining lymphatic vessels anteriorly/posteriorly traversed the SMV and arrived at the surface of SMA near the middle colonic artery (MCA) level, which highlights the potential need of removing mesenteric tissue in our target area on lymphatic resection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167669PMC
May 2021

Comprehensive analysis of the long non-coding RNA expression profile and functional roles in a contrast-induced acute kidney injury rat model.

Exp Ther Med 2021 Jul 9;22(1):739. Epub 2021 May 9.

Department of Cardiology, 900 Hospital of The Joint Logistics Team, Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.

Long non-coding RNAs (lncRNAs) have been identified as a class of regulatory RNAs that participate in both physiological and pathological conditions, including acute kidney injury. However, the roles of lncRNA dysregulation in the pathogenesis of contrast-induced acute kidney injury (CI-AKI) are largely unknown. In the present study, the expression profiles of lncRNAs in kidney tissue were compared between rats with CI-AKI and controls using high-throughput RNA sequencing. In total, 910 differentially expressed (DE) lncRNAs (DElncRNAs), including 415 downregulated and 495 upregulated lncRNAs, were identified at 12 h after intra-arterial iodinated contrast medium injection (fold change ≥2; P<0.05). Eight DElncRNAs were further selected and validated using reverse transcription-quantitative polymerase chain reaction. A previous study defined microRNA (miRNA) and mRNA expression changes in the same CI-AKI model. In the present study, a lncRNA-mRNA co-expression network comprising 349 DElncRNAs and 202 DEmRNAs was constructed. The function of these DElncRNAs was mainly associated with oxidative stress and inflammation. Additionally, lncRNA-associated competing endogenous RNA (ceRNA) analysis revealed a network comprising 40 DElncRNA nodes, 5 DEmiRNA nodes and 59 DEmRNA nodes. Among which, the carnosine dipeptidase 1-specific and the transmembrane protein 184B-specific networks were likely to be associated with CI-AKI. The results of the present study revealed the expression profile and potential roles of lncRNAs in CI-AKI, and provide a framework for further mechanistic studies.
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http://dx.doi.org/10.3892/etm.2021.10171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138274PMC
July 2021

A Novel Homozygous Splice-Site Mutation Causing the Skipping of Exon 38 in a Chinese Family With Cohen Syndrome.

Front Pediatr 2021 20;9:651621. Epub 2021 Apr 20.

Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China.

Cohen syndrome (CS) is a clinically heterogeneous disorder characterized by extensive phenotypic variation with autosomal recessive inheritance. was identified to be the disease-causing gene for CS. The objectives of the present study were to screen likely pathogenic mutations of the patient with developmental delay and mental retardation, and to determinate the effect of this splice-site mutation by reverse transcription analysis. Whole exome sequencing (WES) in combination with Sanger sequencing were performed to identify the causative mutations of this CS family. Subsequently, the impact of the intronic variant on splicing was analyzed by reverse transcription and the construction of expression vector. A novel homozygous splice-site mutation (c.6940+1G>T) in the VPS13B gene was identified in this proband. Sanger sequencing analysis of the cDNA demonstrated that the c.6940+1G>T variant could cause the skipping of entire exon 38, resulting in the loss of 208 nucleotides and further give rise to the generation of a premature in-frame stop codon at code 2,247. The homozygous splicing variant c.6940+1G>T was co-segregated with the CS phenotypes in this family and was identified to be the cause of CS after comprehensive consideration of the clinical manifestations, genetic analysis and cDNA sequencing result.
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http://dx.doi.org/10.3389/fped.2021.651621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093766PMC
April 2021

Effect of adjuvant therapy on the prognosis in stage I/II uterine carcinosarcoma: A meta-analysis.

J Obstet Gynaecol Res 2021 Jul 28;47(7):2473-2480. Epub 2021 Apr 28.

Department of Gynecology and Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China.

Introduction: To assess the efficacy of adjuvant chemotherapy, radiotherapy, or both following the primary surgery on the progression-free survival and 5-year overall survival in patients with stage I/II uterine carcinosarcoma.

Methods: A preliminary investigation was conducted using PubMed and Embase databases to identify relevant studies published up to March, 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Revman 5.3 software to analysis outcomes.

Results: Six retrospective cohort studies were involved in the analysis, including 1516 patients in observation group, 956 patients in chemotherapy group, 750 patients in radiotherapy group, and 1082 patients in raidochemotherapy group. The results indicated that chemotherapy alone (HR = 0.59, 95% CI = 0.38-0.91, p < 0.05) and radiochemotherapy (HR = 0.35, 95% CI: 0.24-0.53, p < 0.001) were associated with improved progression-free survival in patients. Similarly, pooled results suggested chemotherapy (HR = 0.49, 95% CI = 0.34-0.71, p < 0.001) and radiochemotherapy (HR = 0.46, 95% CI = 0.29-0.72, p < 0.001) promoted the 5-year overall survival compared with observation. However, radiotherapy alone had no statistical significance in improving progression-free survival (HR = 0.80, 95% CI = 0.49-1.29, p = 0.36) and 5-year overall survival (HR = 0.65, 95% CI = 0.38-1.12, p = 0.12).

Discussion: Chemotherapy and radiochemotherapy appeared to be prognostic beneficial to early-stage uterine carcinosarcoma.
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http://dx.doi.org/10.1111/jog.14800DOI Listing
July 2021

Hand Pose Understanding With Large-Scale Photo-Realistic Rendering Dataset.

IEEE Trans Image Process 2021 14;30:4275-4290. Epub 2021 Apr 14.

Hand pose understanding is essential to applications such as human computer interaction and augmented reality. Recently, deep learning based methods achieve great progress in this problem. However, the lack of high-quality and large-scale dataset prevents the further improvement of hand pose related tasks such as 2D/3D hand pose from color and depth from color. In this paper, we develop a large-scale and high-quality synthetic dataset, PBRHand. The dataset contains millions of photo-realistic rendered hand images and various ground truths including pose, semantic segmentation, and depth. Based on the dataset, we firstly investigate the effect of rendering methods and used databases on the performance of three hand pose related tasks: 2D/3D hand pose from color, depth from color and 3D hand pose from depth. This study provides insights that photo-realistic rendering dataset is worthy of synthesizing and shows that our new dataset can improve the performance of the state-of-the-art on these tasks. This synthetic data also enables us to explore multi-task learning, while it is expensive to have all the ground truth available on real data. Evaluations show that our approach can achieve state-of-the-art or competitive performance on several public datasets.
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http://dx.doi.org/10.1109/TIP.2021.3070439DOI Listing
September 2021

Development of novel quality control material based on CRISPR/Cas9 editing and xenografts for MLH1 protein deficiency testing.

J Clin Lab Anal 2021 May 7;35(5):e23746. Epub 2021 Apr 7.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Background: Mismatch repair deficiency (dMMR) status induced by MLH1 protein deficiency plays a pivotal role in therapeutic decision-making for cancer patients. Appropriate quality control (QC) materials are necessary for monitoring the accuracy of MLH1 protein deficiency assays used in clinical laboratories.

Methods: CRISPR/Cas9 technology was used to edit the MLH1 gene of GM12878Cas9 cells to establish MLH1 protein-deficient cell lines. The positive cell lines were screened and validated by Sanger sequencing, Western blot (WB), and next-generation sequencing (NGS) and were then used to prepare formalin-fixed, paraffin-embedded (FFPE) samples through xenografting. These FFPE samples were tested by hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for suitability as novel QC materials for MLH1 protein deficiency testing.

Results: We successfully cultured 358 monoclonal cells, with a survival rate of 37.3% (358/960) of the sorted monoclonal cells. Through Sanger sequencing, cell lines with MLH1 gene mutation were identified. Subsequently, two cell lines with MLH1 protein deficiency were identified by WB and named as GM12878Cas9_6 and GM12878Cas9_10. The NGS results further confirmed that the MLH1 gene mutation in these two cell lines would cause the formation of stop codons and terminate the expression of the MLH1 protein. The H&E staining and IHC results also verified the deficiency of the MLH1 protein, and FFPE samples from xenografts proved their similarity and consistency with clinical samples.

Conclusions: We successfully established MLH1 protein-deficient cell lines. Followed by xenografting, we developed novel FFPE QC materials with homogenous, sustainable, and typical histological structures advantages that are suitable for the standardization of clinical IHC methods.
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http://dx.doi.org/10.1002/jcla.23746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128289PMC
May 2021

Correction: A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

Chem Commun (Camb) 2021 Feb;57(8):1054

Department of Urology, Institute of Urology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China.

Correction for 'A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma' by Ping Tan et al., Chem. Commun., 2021, DOI: 10.1039/d0cc07336a.
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http://dx.doi.org/10.1039/d1cc90021hDOI Listing
February 2021

A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

Chem Commun (Camb) 2021 Jan 7;57(8):1046-1049. Epub 2021 Jan 7.

Department of Urology, Institute of Urology, Huaxi MR Research Center (HMRRC), State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610064, P. R. China.

A one-step synthesized LD specific fluorescent probe TTIE with high specificity, good photostability and great capacity in generating cytotoxic reactive oxygen species (ROS) under low powered white light irradiation is designed and synthesized for LD specific image-guided photodynamic therapy (PDT) in human clear cell renal cell carcinoma (ccRCC) primary cells and tissues.
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http://dx.doi.org/10.1039/d0cc07336aDOI Listing
January 2021

Reliable assessment of BRCA1 and BRCA2 germline variants by next-generation sequencing: a multicenter study.

Breast Cancer 2021 May 5;28(3):672-683. Epub 2021 Jan 5.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: BRCA1/2 gene mutation testing, based on next-generation sequencing (NGS), has been gradually applied in the clinic to serve as preventive early screening for predisposed individuals or to provide treatment options for patients with hereditary breast or ovarian cancers. Here, we evaluated the accuracy of NGS-based mutation detection in BRCA1/2 and the consistency in variant interpretation among clinical laboratories to find the possible reasons underlying inaccurate results and discrepant variant interpretation.

Methods: Laboratories were asked to use their routine procedures to detect six mimetic DNA samples with different BRCA1/2 germline variants. The results of variant detection were required to be submitted via a web-based evaluation system and were automatically scored, according to predefined criteria. The variant interpretation report, including the detailed clinical evidence, was summarized and analyzed for reasons underlying inconsistent results.

Results: Overall, only 55.2% (16/29) of laboratories, whose detection score was higher than 90 points, was found to be an acceptable detection capability level. 82.9% (29/35) of the errors were genotype errors. The variant classification results were generally consistent, and 77.8% (7/9) of the variants were given the consistent classification answer. Only two single nucleotide variants (SNVs) had a discrepant classification opinion across laboratories.

Conclusions: The BRCA1/2 variant detection performance should be further improved, especially in reporting the correct genome coordinates. Inconsistent variant classification may be a result of the different clinical pieces of evidence collected by the laboratories. However, discordant clinical evidence also appeared within the same classification results. Therefore, our study provided clear clinical evidence assessment strategies for BRCA1/2 variants, which was aimed at obtaining a consistent variant classification strategy for providing accurate clinical reports to the clinicians.
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http://dx.doi.org/10.1007/s12282-020-01204-xDOI Listing
May 2021

Cloning and Functional Determination of Ammonium Transporter PpeAMT3;4 in Peach.

Biomed Res Int 2020 3;2020:2147367. Epub 2020 Dec 3.

Key Laboratory of Molecular Module-Based Breeding of High Yield and Abiotic Resistant Plants in Universities of Shandong (Ludong University), Yantai 264025, China.

Ammonium (NH ) plays key roles in plant growth, development, fruit quality, and yield. In plants, NH uptake and transport are facilitated by NH transporters (AMT). However, molecular mechanisms and physiological functions of type-II AMT (AMT2) transporters in fruit trees are still unclear, especially in peach. In this study, we cloned and characterized an AMT2 family gene from peach, , and determined its function in yeast mutant. Expression analysis showed that was majorly expressed in peach roots and significantly decreased by NH excess but had no response to NH deficiency. Functional determination and nitrogen-labeled NH uptake assay in yeast cells implied that PpeAMT3;4 was a typical high-affinity transporter, with a value of 86.3 M, that can uptake external NH in yeast cells. This study provides gene resources to uncover the biological function of AMT2 transporters and reveals molecular basis for NH uptake and nitrogen (N) nutrition mechanisms in fruit trees.
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http://dx.doi.org/10.1155/2020/2147367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732375PMC
June 2021

High-Flow Nasal Cannula vs. Continuous Positive Airway Pressure Therapy for the Treatment of Children <2 Years With Mild to Moderate Respiratory Failure Due to Pneumonia.

Front Pediatr 2020 13;8:590906. Epub 2020 Nov 13.

National Clinical Research Center for Child Health and Disorders, Chongqing Medical University, Chongqing, China.

The aim of this prospective randomized controlled study was to further compare the clinical benefits and adverse reactions of HFNC with CPAP in the treatment of mild to moderate respiratory failure due to pneumonia in children below 2 years old. Using a prospective randomized controlled study method, 84 patients with pneumonia and mild to moderate respiratory failure admitted to the Children's Hospital Affiliated to Chongqing Medical University from January 2018 to December 2019 were randomly divided into the HFNC group and the CPAP group. It was registered as a clinical trial at clinical trials.gov, registration number: ChiCTR2000030463. The analyses included 84 patients. No differences were observed between the two groups in baseline demographic or physiological characteristics. Treatment failure necessitating intubation and transfer to the PICU was noted in six of 43 infants (14%) in the HFNC group, as compared with four of 41 infants (10%) in the CPAP group ( > 0.05). There were no significant differences between the two groups in the duration of hospital stay, the duration of non-invasive respiratory support, and mortality. The 10 infants who experienced treatment failure had more severe hypoxemia with lower PaO2/FiO2 (HFNC 182 ± 11.5 and CPAP 172 ± 8.6). We found that both the HFNC group and the CPAP group showed significantly improved oxygenation and relief of respiratory distress after treatment. No differences were observed between the two groups in the development improvement of RR, PaO2, PaCO2, SpO2, and PH. Assessment of the occurrence of adverse events showed that the HFNC group had a lower level of nasal injury, a lower risk of abdominal distension, a lower intensity and frequency of sedation, and better tolerance. HFNC is an effective and safe initial respiratory support treatment in children <2 years with mild to moderate respiratory failure due to pneumonia, and the incidence of intubation and death is very low; concurrently, the comfort and tolerance of HFNC are better. To some extent, HFNC is a well-tolerated alternative to CPAP.
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http://dx.doi.org/10.3389/fped.2020.590906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693448PMC
November 2020

Learning Guided Convolutional Network for Depth Completion.

IEEE Trans Image Process 2021 15;30:1116-1129. Epub 2020 Dec 15.

Dense depth perception is critical for autonomous driving and other robotics applications. However, modern LiDAR sensors only provide sparse depth measurement. It is thus necessary to complete the sparse LiDAR data, where a synchronized guidance RGB image is often used to facilitate this completion. Many neural networks have been designed for this task. However, they often naïvely fuse the LiDAR data and RGB image information by performing feature concatenation or element-wise addition. Inspired by the guided image filtering, we design a novel guided network to predict kernel weights from the guidance image. These predicted kernels are then applied to extract the depth image features. In this way, our network generates content-dependent and spatially-variant kernels for multi-modal feature fusion. Dynamically generated spatially-variant kernels could lead to prohibitive GPU memory consumption and computation overhead. We further design a convolution factorization to reduce computation and memory consumption. The GPU memory reduction makes it possible for feature fusion to work in multi-stage scheme. We conduct comprehensive experiments to verify our method on real-world outdoor, indoor and synthetic datasets. Our method produces strong results. It outperforms state-of-the-art methods on the NYUv2 dataset and ranks 1st on the KITTI depth completion benchmark at the time of submission. It also presents strong generalization capability under different 3D point densities, various lighting and weather conditions as well as cross-dataset evaluations. The code will be released for reproduction.
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http://dx.doi.org/10.1109/TIP.2020.3040528DOI Listing
December 2020

Prevalence of Toxoplasma gondii Antibodies in Stray Dogs from Various Locations in West and East Malaysia.

Korean J Parasitol 2020 Oct 22;58(5):487-492. Epub 2020 Oct 22.

Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.

Toxoplasmosis is caused by an obligate intracellular protozoan parasite; Toxoplasma gondii, which is one of the most important zoonotic parasite worldwide. In dogs, the sexual reproductive cycle of T. gondii is lacking, and the animals are not widely consumed as food, but they are vital in the mechanical transmission of the parasite. However, there is no present data on the exposure of stray dogs to T. gondii in Malaysia. The objective of this serological survey was to determine the prevalence of T. gondii antibodies (IgG) and associated factors in stray dogs in East and West Malaysia. Antibodies to T. gondii were determined in serum samples from 222 stray dogs from 6 different states in East and West Malaysia (Peninsular Malaysia) using an Indirect ELISA. The seroprevalence for T. gondii was 23.4% (Confidence interval: CI 17.8-29.2%). Stray dogs from Selangor and Kuala Lumpur had the highest seroprevalence (32.4%; CI 13.2-45.5%) and lowest in those from Penang and Kedah (12.5%; CI 1.3-23.5%). Gender and breed were not associated with T. gondii seropositivity. However, adult dogs were more likely to be seropositive for T. gondii (OR=2.89; CI 1.1-7.7) compared with younger dogs. These results revealed that T. gondii is prevalent in stray dogs in the studied areas in Malaysia, and indicative of the level of environmental contamination of this parasite especially in urban areas.
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http://dx.doi.org/10.3347/kjp.2020.58.5.487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672237PMC
October 2020

Weakly Supervised Learning for Single Depth-Based Hand Shape Recovery.

IEEE Trans Image Process 2021 24;30:532-545. Epub 2020 Nov 24.

Recent emerging technologies such AR/VR and HCI are drawing high demand on more comprehensive hand shape understanding, requiring not only 3D hand skeleton pose but also hand shape geometry. In this paper, we propose a deep learning framework to produce 3D hand shape from a single depth image. To address the challenge that capturing ground truth 3D hand shape in the training dataset is non-trivial, we leverage synthetic data to construct a statistical hand shape model and adopt weak supervision from widely accessible hand skeleton pose annotation. To bridge the gap due to the different hand skeleton definitions in the existing public datasets, we propose a joint regression network for hand pose adaptation. To reconstruct the hand shape, we use Chamfer loss between the predicted hand shape and the point cloud from the input depth to learn the shape reconstruction model in a weakly-supervised manner. Experiments demonstrate that our model adapts well to the real data and produces accurate hand shapes that outperform the state-of-the-art methods both qualitatively and quantitatively.
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http://dx.doi.org/10.1109/TIP.2020.3037479DOI Listing
November 2020

Quality evaluation of molecular diagnostic tests for astrovirus, sapovirus and poliovirus: A multicenter study.

Clin Chim Acta 2021 Jan 9;512:172-178. Epub 2020 Nov 9.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, PR China. Electronic address:

Background: Astrovirus (AstV), Sapovirus (SaV) and Poliovirus (PV) are important pathogens that cause infections in children under five years of age. It is a very important task to systematically monitor and evaluate the diagnostic performance of these viruses in clinical laboratories.

Methods: In our study, we performed a multicenter evaluation study among 21 laboratories across China using simulated stool samples spiked with self-designed AstV, SaV and PV pseudoviral particles.

Results: The testing capability of 80.0% (16/20, AstV), 52.6% (10/19, SaV), and 25.0% (2/8, PV) of the participating laboratories were found to be "competent" in reporting correct results for all samples. The main type of errors were false negatives. None of the laboratories identified the subtypes of AstV and SaV, and six laboratories specifically identified the subtypes of PV. Lacking of well-trained personnel and adequate funding were the main challenges. From the questionnaire results, 55.6% laboratories (10/18) believe that training personnel could improve the laboratory testing performance.

Conclusions: The laboratories showed a competent diagnostic performance for AstV, but inferior diagnostic performances for SaV and PV. Sensitivity of detection and the ability for virus typing should be improved clinically. Professional and standardized personnel training is urgently needed to further improve laboratory performance.
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http://dx.doi.org/10.1016/j.cca.2020.11.006DOI Listing
January 2021

Multicenter assessment of microbial community profiling using 16S rRNA gene sequencing and shotgun metagenomic sequencing.

J Adv Res 2020 Nov 21;26:111-121. Epub 2020 Jul 21.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, 100005, PR China.

Introduction: Microbiome research based on high-throughput sequencing has grown exponentially in recent years, but methodological variations can easily undermine the reproducibility across studies.

Objectives: To systematically evaluate the comparability of sequencing results of 16S rRNA gene sequencing (16Ss)- and shotgun metagenomic sequencing (SMs)-based microbial community profiling in laboratories under routine conditions.

Methods: We designed a multicenter study across 35 participating laboratories in China using designed mock communities and homogenized fecal samples.

Results: A wide range of practices and approaches was reported by the participating laboratories. The observed microbial compositions of the mock communities in 46.2% (12/26) of the 16Ss and 82.6% (19/23) of the SMs laboratories had significant correlations with the expected result (Spearman r>0.59, <0.05). The results from laboratories with near-identical protocols showed slight interlaboratory deviations. However, a high degree of interlaboratory deviation was found in the observed abundances of specific taxa, such as Bacteroides spp. (range: 0.3%-53.5%), Enterococci spp. (range: 0.8%-43.9%) and Fusobacterium spp. (range: 0.1%-39.8%). SMs performed better than 16Ss in detecting low-abundance bacteria (B. bifidum). The differences in DNA extraction methods, amplified regions and bioinformatics analysis tools (taxonomic classifiers and database) were important factors causing interlaboratory deviations. Addressing laboratory contamination is an urgent task because various sources of unexpected microbes were found in negative control samples.

Conclusions: Well-defined control samples, such as the mock communities in this study, should be routinely used in microbiome research for monitoring potential biases. The findings in this study will provide guidance in the choice of more reasonable operating procedures to minimize potential methodological biases in revealing human microbiota composition.
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http://dx.doi.org/10.1016/j.jare.2020.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584675PMC
November 2020

The primary treatment of prostate cancer with high-intensity focused ultrasound: A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Oct;99(41):e22610

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu.

Background: We systematically evaluated the evidences on oncological and functional outcomes of high-intensity focused ultrasound (HIFU) as the primary treatment for localized prostate cancer (PCa).

Methods: A systematic review was used Medline, Embase, and the Cochrane Library from the inception of each database. The review analyzed the oncological and functional outcomes of HIFU in the treatment of PCa. The RevMan 5.3 software was used for quantity analysis incidence of complications.

Results: Twenty-seven articles were included for analysis with a total of 7393 patients. Eighteen studies investigated the whole-gland HIFU, and the duration of follow-up ranged from 2 to 168 months. After whole-gland HIFU, the mean prostate-specific antigen (PSA) nadir was found to be 0.4 to 1.95 ng/mL and the mean time to PSA nadir was 2.4 to 5.4 months. The rate of positive biopsy after HIFU was 4.5% to 91.1%. Meta-analysis revealed the incidences of urinary incontinence, impotence, urinary obstruction, retention, and infection was 10%, 44%, 15%, 11%, 7%, respectively. Nine studies investigated partial-gland HIFU, and the duration of follow-up was 1 to 131 months. After partial-gland HIFU, the mean PSA nadir was 1.9 to 2.7 ng/mL and the mean time to PSA nadir 5.7 to 7.3 months. The rate of positive biopsy after HIFU in the treatment area was 14% to 37.5%. Meta-analysis revealed the incidences of urinary incontinence, impotence, urinary obstruction, retention, and infection was 2%, 21%, 2%, 9%, 11%, respectively.

Conclusions: Early evidence suggested the partial-gland HIFU was safer than whole-gland HIFU, and they had similar oncological outcomes. More prospective randomized controlled trials of whole-gland and partial-gland HIFU for PCa was needed.
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http://dx.doi.org/10.1097/MD.0000000000022610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544371PMC
October 2020

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract.

EBioMedicine 2020 Oct 21;60:102976. Epub 2020 Sep 21.

Departments of Pathology, University of Iowa College of Medicine, University of Iowa, Iowa City, IA, USA. Electronic address:

Background: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors.

Materials And Methods: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19.

Findings: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19.

Interpretation: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.
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http://dx.doi.org/10.1016/j.ebiom.2020.102976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505653PMC
October 2020

Choosing tumor mutational burden wisely for immunotherapy: A hard road to explore.

Biochim Biophys Acta Rev Cancer 2020 12 21;1874(2):188420. Epub 2020 Aug 21.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, PR China. Electronic address:

Immunotherapy has revolutionized the treatment of cancer due to its remarkable efficacy and extensive survival benefit in multiple tumor types. However, predictive biomarkers are required to identify patients who are likely to respond to immunotherapy. Recently, tumor mutational burden (TMB) has been shown to be associated with clinical outcomes in diverse cancers, such as melanoma, non-small-cell lung cancer and colorectal cancer. Several studies have demonstrated that high TMB can effectively predict the objective response rate and progression-free survival, but the ability of TMB to predict overall survival is limited. Thus, the clinical utility of TMB as a predictive and prognostic biomarker in immunotherapy is currently controversial. Importantly, multiple factors can affect the accurate assessment of TMB and further interfere with its prediction of clinical outcomes. These factors include preanalytical factors such as sample status, analytical factors such as differences in platforms and methods for determining TMB and variability of cutoff values, and postanalytical factors such as inconsistent interpretation and reporting of results. In addition, the optimal definition and quantification of TMB are unclear and require harmonization and standardization for reliable clinical application. This review elaborates on the factors affecting TMB status in primary tumors, summarizes the clinical utility of TMB as a biomarker in immunotherapy, and evaluates the impact of each analysis stage on the accurate estimation of TMB, especially its quantification, aiming to facilitate TMB assessment in routine clinical settings.
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http://dx.doi.org/10.1016/j.bbcan.2020.188420DOI Listing
December 2020

Fabrication of Concentrated Palm Olein-Based Diacylglycerol Oil-Soybean Oil Blend Oil-In-Water Emulsion: In-Depth Study of the Rheological Properties and Storage Stability.

Foods 2020 Jul 3;9(7). Epub 2020 Jul 3.

Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.

The present study focused on investigating the storage stability of oil-in-water (O/W) emulsions with high oil volume fractions prepared with palm olein-based diacylglycerol oil (POL-DAG)/soybean oil (SBO) blends at 25 °C. The incorporation of different ratios of oil blends significantly influenced ( < 0.05) the texture, color, droplet size distribution, and rheological parameters of the emulsions. Only emulsions incorporated with 10% to 20% POL-DAG in oil phase exhibited pseudoplastic behavior that fitted the Power Law model well. Furthermore, the O/W emulsions prepared with POL-DAG/SBO blends exhibited elastic properties, with higher than . During storage, the emulsion was found to be less solid-like with the increase in tan δ values. All emulsions produced with POL-DAG/SBO blends also showed thixotropic behavior. Optical microscopy revealed that the POL-DAG incorporation above 40% caused aggregated droplets to coalesce and flocculate and, thus, larger droplet sizes were observed. The current results demonstrated that the 20% POL-DAG substituted emulsion was more stable than the control emulsion. The valuable insights gained from this study would be able to generate a lot more possible applications using POL-DAG, which could further sustain the competitiveness of the palm oil industry.
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http://dx.doi.org/10.3390/foods9070877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404400PMC
July 2020

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract.

bioRxiv 2020 Aug 13. Epub 2020 Aug 13.

Pathology, University of Iowa College of Medicine, University of Iowa, Iowa City, IA USA.

Background: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors.

Materials And Methods: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19.

Findings: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19.

Interpretation: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.
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http://dx.doi.org/10.1101/2020.04.22.056127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302220PMC
August 2020
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