bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Recent Development of Renewable Diesel Production Using Bimetallic Catalysts
Authors: Chia Shir Reen , Nomanbhay Saifuddin , Ong Mei Yin , Chew Kit Wayne , Khoo Kuan Shiong , Karimi-Maleh Hassan , Show Pau Loke
Published: October 2021

Renewable diesel as a potential sustainable energy source in future requires catalysts to convert the feedstocks into end products. Among various type of catalysts, bimetallic catalysts are widely applied in the renewable diesel production due to their unique catalytic properties and enhanced catalytic activities, which differ from their parent monometallic catalysts. This mini review comprised of the brief introduction on technologies in producing renewable diesel and aims to discuss the underneath knowledge of synergistic interactions in bimetallic catalysts that synthesized through various techniques. The novelty of this review reveals the recent development of renewable diesel production, highlighting the mechanisms of bimetallic catalysts in the enhancement of the catalytic activity, and exploring their possibilities as practical solution in industrial production.
Impact of COVID-19 on Extremely Polluted Air Quality and Trend Forecast in Seven Provinces and Three Cities of China
Authors: Pan Xiaoying , Zhao Yonggang , Wang Meng
Published: October 2021

At the beginning of 2020, COVID-19 broke out. Because the virus is extremely contagious and the mortality rate after infection is extremely high, China and many countries in the world have imposed lockdowns. Air pollutants during the epidemic period have attracted the attention of many scholars. This research is to use predictive models to describe changes in extreme air pollutants. China is the first country in the world to enter the lockdown state. This study uses data from 2015-2020 to compare and predict the concentration of extreme pollutants before and after the lockdown. The results show that the lockdown of the epidemic will reduce the annual average concentration of PM2.5, and the annual average concentration of O3 will increase first and then decrease. Through analysis, it is concluded that there is a synergistic decrease trend between PM2.5 and O3. With the various blockade measures for epidemic prevention and control, the reduction of extreme air pollutant concentrations is sustainable. The assessment of China’s air quality in conjunction with the COVID-19 can provide scientific guidance for the Chinese government and other relevant departments to formulate policies.
Neutrophil Dynamics Affect Mycobacterium tuberculosis Granuloma Outcomes and Dissemination
Authors: Hult Caitlin , Mattila Joshua T. , Gideon Hannah P. , Linderman Jennifer J. , Kirschner Denise E.
Published: October 2021

Neutrophil infiltration into tuberculous granulomas is often associated with higher bacteria loads and severe disease but the basis for this relationship is not well understood. To better elucidate the connection between neutrophils and pathology in primate systems, we paired data from experimental studies with our next generation computational modelGranSimto identify neutrophil-related factors, including neutrophil recruitment, lifespan, and intracellular bacteria numbers, that drive granuloma-level outcomes. We predict mechanisms underlying spatial organization of neutrophils within granulomas and identify how neutrophils contribute to granuloma dissemination. We also performed virtual deletion and depletion of neutrophils within granulomas and found that neutrophils play a nuanced role in determining granuloma outcome, promoting uncontrolled bacterial growth in some and working to contain bacterial growth in others. Here, we present three key results: We show that neutrophils can facilitate local dissemination of granulomas and thereby enable the spread of infection. We suggest that neutrophils influence CFU burden during both innate and adaptive immune responses, implying that they may be targets for therapeutic interventions during later stages of infection. Further, through the use of uncertainty and sensitivity analyses, we predict which neutrophil processes drive granuloma severity and structure.
GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors
Authors: Calì Bianca , Agnellini Andrielly H. R. , Cioccarelli Chiara , Sanchez-Rodriguez Ricardo , Predonzani Andrea , Toffolo Giulia Ilaria , Viola Antonella , Bronte Vincenzo , Arrigoni Giorgio , Zonta Francesco , Albertoni Laura , Mescoli Claudia , Marigo Ilaria , Molon Barbara
Published: October 2021

Reactive oxygen species, including RNS, contribute to the control of multiple immune cell functions within the tumor microenvironment (TME). Tumor-infiltrating myeloid cells (TIMs) represent the archetype of tolerogenic cells that actively contribute to dismantle effective immunity against cancer. TIMs inhibit T cell functions and promote tumor progression by several mechanisms including the amplification of the oxidative/nitrosative stress within the TME. In tumors, TIM expansion and differentiation is regulated by the granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by cancer and immune cells. Nevertheless, the role of GM-CSF in tumors has not yet been fully elucidated. In this study, we show that GM-CSF activity is significantly affected by RNS-triggered post-translational modifications. The nitration of a single tryptophan residue in the sequence of GM-CSF nourishes the expansion of highly immunosuppressive myeloid subsets in tumor-bearing hosts. Importantly, tumors from colorectal cancer patients express higher levels of nitrated tryptophan compared to non-neoplastic tissues. Collectively, our data identify a novel and selective target that can be exploited to remodel the TME and foster protective immunity against cancer.
Glycinergic Signaling in Macrophages and Its Application in Macrophage-Associated Diseases
Authors: Gan Zhending , Zhang Meiyu , Xie Donghui , Wu Xiaoyan , Hong Changming , Fu Jian , Fan Lijuan , Wang Shengyi , Han Sufang
Published: October 2021

Accumulating evidences support that amino acids direct the fate decision of immune cells. Glycine is a simple structural amino acid acting as an inhibitory neurotransmitter. Besides, glycine receptors as well as glycine transporters are found in macrophages, indicating that glycine alters the functions of macrophages besides as an inhibitory neurotransmitter. Mechanistically, glycine shapes macrophage polarization via cellular signaling pathways (e.g., NF-κB, NRF2, and Akt) and microRNAs. Moreover, glycine has beneficial effects in preventing and/or treating macrophage-associated diseases such as colitis, NAFLD and ischemia-reperfusion injury. Collectively, this review highlights the conceivable role of glycinergic signaling for macrophage polarization and indicates the potential application of glycine supplementation as an adjuvant therapy in macrophage-associated diseases.
Vessel Strikes of Large Whales in the Eastern Tropical Pacific: A Case Study of Regional Underreporting
Authors: Ransome Nicola , Loneragan Neil R. , Medrano-González Luis , Félix Fernando , Smith Joshua N.
Published: October 2021

Vessel strike is recognized as a major modern threat to the recovery of large whale populations globally, but the issue is notoriously difficult to assess. Vessel strikes by large ships frequently go unnoticed, and those involving smaller vessels are rarely reported. Interpreting global patterns of vessel strikes is further hindered by underlying reporting biases caused by differences in countries’ research efforts, legislation, reporting structures and enforcement. This leaves global strike data “patchy” and typically scarce outside of developed countries, where resources are more limited. To explore this we investigated vessel strikes with large whales in the Eastern Tropical Pacific (ETP), a coastal region of ten developing countries where heavy shipping and high cetacean densities overlap. Although this is characteristic of vessel strike “hotspots” worldwide, only 11 ETP strike reports from just four countries (∼2% of total reports) existed in the International Whaling Commission’s Global Ship Strike Database (2010). This contrasts greatly with abundant reports from the neighboring state of California (United States), and the greater United States/Canadian west coast, making it a compelling case study for investigating underreporting. By reviewing online media databases and articles, peer review publications and requesting information from government agencies, scientists, and tourism companies, we compiled a regional ETP vessel strike database. We found over three times as many strike reports (n= 40), from twice as many countries (n= 8), identifying the geographic extent and severity of the threat, although likely still underestimating the true number of strikes. Reports were found from 1905 until 2017, showing that strikes are a regional, historic, and present threat to large whales. The humpback whale (Megaptera novaeangliae) was the most commonly hit species, and whale-watch industries involving small vessels in areas of high whale densities were recognized as a conservation and management concern. Industrial fishing fleets and shipping were suggested to be underrepresented sectors in the database, and are likely high-risk vessels for strikes with whales. We demonstrate the implications of known vessel strike reporting biases and conclude a more rapid assessment of global vessel strikes would substantially benefit from prioritized research efforts in developing regions, with known vessel strike “hotspot” characteristics, but few strike reports.
Spatial Planning Insights for Philippine Coral Reef Conservation Using Larval Connectivity Networks
Authors: Pata Patrick R. , Yñiguez Aletta T.
Published: October 2021

The marine habitats of the Philippines are recognized to be some of the most biodiverse systems globally yet only 1.7% of its seas are designated as marine protected areas (MPAs) with varying levels of implementation. Many of these MPAs were established based on local-scale conservation and fisheries objectives without considering larger-scale ecological connections. The connectivity of reefs through larval dispersal is important in the regional-scale resilience against anthropogenic disturbances and is considered a significant criterion in planning for MPAs. In this study, we provide insights into the delineation of ecologically connected MPA networks using larval dispersal modeling and network analysis. We characterized the network properties of the Philippine coral reefs, organized as 252 reef nodes, based on the larval connectivity networks of a branching coral, sea urchin, and grouper. We then evaluated the distribution of the existing 1,060 MPAs relative to the connectivity patterns. All reef nodes were found to be highly interconnected with a mean shortest path ranging from 1.96 to 4.06. Reef nodes were then ranked according to their relative importance in regional connectivity based on five connectivity indices. Despite the between-organism and between-index variability in rankings, there were reefs nodes, mostly located offshore and at major straits, which consistently ranked high. We found that the distribution of existing MPAs partially capture some of the regional connectivity functions but there is a spatial mismatch between the primarily coastal MPAs and the high-ranking reef nodes. Furthermore, network partitioning identified subnetworks and dispersal barriers. The existing MPAs were found to be disproportionately distributed to a few subnetworks and that the largest subnetworks do not contain the greatest number of MPAs. Considering these gaps, we suggest expanding the coverage of protected areas especially in underrepresented reef networks to meaningfully capture national-scale connectivity and meet global conservation objectives.
Maximizing Benefits From Punctual Ocean Infrastructure: An Ethical Perspective
Authors: Whoriskey Frederick , Barbier Michele , Mazur Mackenzie , Hahn Tobias , Kritzer Jacob , Vallee Richard
Published: October 2021

Ethics are becoming a component of best practices in ocean science and observing systems, with the research community facing a duty to society to maximize the efficient use and benefits that stem from investments in ocean science/monitoring. Sustained ocean observing systems on issues of global importance are coordinated, internationally sanctioned and making the most out of the resources accorded to them and consequently fulfilling their duty to society. However, globally huge investments are made annually in establishing infrastructure for shorter-term, punctual studies that address targeted as opposed to broad science needs. More could be done to maximize the benefits and impacts of these punctual efforts. Given punctual infrastructure’s small and frequently transient nature, connections to enable sharing will probably be done locally, and both potential additional users and owners of the infrastructure will need to be energetic, receptive and flexible. The accommodation of new uses will have to be balanced against any costs of these additional activities, which could pose an ethical dilemma in themselves if they compromise the infrastructure’s ability to meet its original intent. However, such adaptive infrastructures may be the most efficient way to provide the resources needed to identify and monitor emerging or new ocean stressors.
Mining of a Clinical Database: The Interpretation of Intense Serial Procalcitonin in the Prediction for Bloodstream Infection
Authors: Jiang Zhiyi , Liu Ning , Wang Luhao , Wu Jianfeng , Guan Xiangdong
Published: October 2021

Background: Procalcitonin (PCT) is a promising biomarker for predicting infection. Bloodstream infection (BSI) is usually a deteriorating stage of sepsis. The purpose of this study was to explore the predictive value of intense serial PCT assays for BSI in the intensive care unit (ICU).

Methods: This study was a retrospective study based on a clinical database. We analyzed the data of critically ill patients from February 2016 to May 2020. The patients who received PCT assays and blood cultures (BCs) were classified into four groups according to the BCs: (i) BC negative, (ii) bacteria positive, (iii) fungi-positive, and (iv) combined-positive, and the patients with bacteremia were further subdivided into Gram+ and Gram– bacteremia.

Results: The database included 11,219 patients. There were 3,593 patients who met the criteria for the analysis. The PCT concentration differed significantly across BC groups (p < 0.0001). The fluctuation of PCT significantly increased in the BC positive groups (p < 0.0001). According to the receiver operating characteristic (ROC), the optimum cutoff of the fluctuation of PCT was around 8 ng/ml for predicting BSI.

Conclusion: Our study indicated that the fluctuation of PCT could be an indicator for screening BSI, but less accurate for Gram-positive infections. With a fluctuation of PCT less than 8 ng/ml, BSI should not be a rational cause for sepsis exacerbating.
EASE: Clinical Implementation of Automated Tumor Segmentation and Volume Quantification for Adult Low-Grade Glioma
Authors: van Garderen Karin A. , van der Voort Sebastian R. , Versteeg Adriaan , Koek Marcel , Gutierrez Andrea , van Straten Marcel , Rentmeester Mart , Klein Stefan , Smits Marion
Published: October 2021

The growth rate of non-enhancing low-grade glioma has prognostic value for both malignant progression and survival, but quantification of growth is difficult due to the irregular shape of the tumor. Volumetric assessment could provide a reliable quantification of tumor growth, but is only feasible if fully automated. Recent advances in automated tumor segmentation have made such a volume quantification possible, and this work describes the clinical implementation of automated volume quantification in an application named EASE: Erasmus Automated SEgmentation. The visual quality control of segmentations by the radiologist is an important step in this process, as errors in the segmentation are still possible. Additionally, to ensure patient safety and quality of care, protocols were established for the usage of volume measurements in clinical diagnosis and for future updates to the algorithm. Upon the introduction of EASE into clinical practice, we evaluated the individual segmentation success rate and impact on diagnosis. In its first 3 months of usage, it was applied to a total of 55 patients, and in 36 of those the radiologist was able to make a volume-based diagnosis using three successful consecutive measurements from EASE. In all cases the volume-based diagnosis was in line with the conventional visual diagnosis. This first cautious introduction of EASE in our clinic is a valuable step in the translation of automatic segmentation methods to clinical practice.
Hypoxia-Inducible Factors as Key Players in the Pathogenesis of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis
Authors: Holzner Lorenz M. W. , Murray Andrew J.
Published: October 2021

Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) are a major public health concern with high and increasing global prevalence, and a significant disease burden owing to its progression to more severe forms of liver disease and the associated risk of cardiovascular disease. Treatment options, however, remain scarce, and a better understanding of the pathological and physiological processes involved could enable the development of new therapeutic strategies. One process implicated in the pathology of NAFLD and NASH is cellular oxygen sensing, coordinated largely by the hypoxia-inducible factor (HIF) family of transcription factors. Activation of HIFs has been demonstrated in patients and mouse models of NAFLD and NASH and studies of activation and inhibition of HIFs using pharmacological and genetic tools point toward important roles for these transcription factors in modulating central aspects of the disease. HIFs appear to act in several cell types in the liver to worsen steatosis, inflammation, and fibrosis, but may nevertheless improve insulin sensitivity. Moreover, in liver and other tissues, HIF activation alters mitochondrial respiratory function and metabolism, having an impact on energetic and redox homeostasis. This article aims to provide an overview of current understanding of the roles of HIFs in NAFLD, highlighting areas where further research is needed.
Iron-Rich Conditions Induce OmpA and Virulence Changes of Acinetobacter baumannii
Authors: Liu Hui , Cao Chun yuan , Qiu Fu lan , Huang Hao Nan , Xie Hongyan , Dong Renkang , Shi Yu Zhen , Hu Xiu Nian
Published: October 2021

Background: Iron ions affect the expression of outer membrane protein A (OmpA), a major pathogenic protein in Acinetobacter baumannii.

Objective: To analyze the effect of iron ions on the expression of the OmpA protein of A. baumannii and explore its association with the virulence of OmpA.

Methods: Site-directed mutagenesis was used to construct ompA gene deletion strains and gene repair strains. The OmpA protein expression of A. baumannii under culture with different contents of iron ions was detected. The virulence of A. baumannii with different OmpA protein expression levels were evaluated in macrophages and mice.

Results: OmpA protein levels of the three strains were enhanced under iron-rich conditions. They were reduced in the presence of the iron-chelating agent 2,2′-bipyridine. A. baumannii wild type and + ompA had a remarkable toxic effect on RAW246.7 macrophages (P < 0.05). In contrast, the ΔompA had a significantly reduced toxic effect on RAW246.7 macrophages (P < 0.05). The levels of the inflammatory factors IL-1β, IL-6, IL-8, and TNFα in the mice spleen were significantly increased in the + ompA strain treatment group compared with the ΔompA strain group (all P < 0.05). In addition, the levels were higher in the presence of iron ions than in the presence of the chelating agent.

Conclusion: Iron-rich conditions increase the OmpA protein expression of A. baumannii. Strains with high OmpA protein expression were more invasive, which may be a key determinant of A. baumannii infection and pathogenicity. Iron control strategies might be used for the management of A. baumannii.
The Clinical Efficacy Analysis of Treatment With a Willis Covered Stent in Traumatic Pseudoaneurysm of the Internal Carotid Artery
Authors: Zhao Yueyuan , Liu Zhiwen , Sun Ronghui , Pan Li , Yang Ming , Song Jian , Ma Lianting
Published: October 2021

Objective: To investigate the safety and efficacy of Willis covered stents (WCS) in the treatment of traumatic pseudoaneurysm of the cranial internal carotid artery (CICA).

Methods: Fifteen patients with traumatic pseudoaneurysm of the intracranial segment of the ICA treated with the WCS system at our institution from 2013 to 2019 were analyzed retrospectively. Follow-up observation and digital subtraction angiography (DSA) examination were conducted ~6 months after the treatment.

Results: DSA performed immediately after stent deployment revealed that complete occlusion of the lesion was achieved in 13 patients and that endoleak occurred in two patients. In 12 patients, postoperative DSA examination indicated that the lesions were completely occluded. In two patients who had a second stent implantation at the break of the ICA, traumatic ICA rupture was essentially completely obstructed in 1 patient. The endoleak remained in one patient with carotid cavernous sinus fistula because the placement of the second stent system was difficult with his ICA tortuosity. No recurrence of aneurysms, hemorrhage, or other lesions was observed, and the patients' parent arteries were patent without stenosis. No procedure-related complications or ischemic strokes occurred during the follow-up period of ~6 months.

Conclusions: For treatment of traumatic pseudoaneurysm of the CICA, Willis covered stent implantation in some appropriate cases, is safe and effective. However, large-sample controlled studies and multicenter studies are needed for further confirmation.
The Effect of Task-Irrelevant Emotional Valence on Limited Attentional Resources During Deception: An ERPs Study
Authors: Liang Jing , Ruan Qian-Nan , Fu Ke-Ke , Chen Yu-Hsin , Yan Wen-Jing
Published: October 2021

Deception is a complex and cognitively draining dyadic process that simultaneously involves cognitive and emotional processes, both of which demand/capture attentional resources. However, few studies have investigated the allocation of attentional resources between cognitive and emotional processes during deception. The current study presented facial expressions of different valences to 36 participants. While an electroencephalogram was recording, they were asked to make either truthful or deceptive gender judgments according to preceding cues. The results showed that deceptive responses induced smaller P300 amplitudes than did truthful responses. Task-irrelevant negative emotional information (TiN) elicited larger P300 amplitudes than did task-irrelevant positive emotional information (TiP). Furthermore, the results showed that TiN elicited larger LPP amplitudes than did TiP in deceptive responses, but not in truthful ones. The results suggested that attentional resources were directed away to deception-related cognitive processes and TiN, but not TiP, was consistently able to compete for and obtain attentional resources during deception. The results indicated that TiN could disrupt with deception and may facilitate deception detection.
Yttrium-90 TOF-PET-Based EUD Predicts Response Post Liver Radioembolizations Using Recommended Manufacturer FDG Reconstruction Parameters
Authors: Hesse Michel , d’Abadie Philipe , Lhommel Renaud , Jamar Francois , Walrand Stephan
Published: October 2021

Purpose

Explaining why 90Y TOF-PET based equivalent uniform dose (EUD) using recommended manufacturer FDG reconstruction parameters has been shown to predict response.

Methods

The hot rods insert of a Jaszczak deluxe phantom was partially filled with a 2.65 GBq 90Y - 300ml DTPA water solution resulting in a 100 Gy mean absorbed dose in the 6 sectors. A two bed 20min/position acquisition was performed on a 550ps- and on a 320ps- TOF-PET/CT and reconstructed with recommended manufacturer FDG reconstruction parameters, without and with additional filtering. The whole procedure was repeated on both PET after adding 300ml of water (50Gy setup). The phantom was acquired again after decay by a factor of 10 (5Gy setup), but with 200min per bed position. For comparison, the phantom was also acquired with 18F activity corresponding to a clinical FDG whole body acquisition.

Results

The 100Gy-setup provided a hot rod sectors image almost as good as the 18F phantom. However, despite acquisition time compensation, the 5Gy-setup provides much lower quality imaging. TOF-PET based sectors EUDs for the three large rod sectors agreed with the actual EUDs computed with a radiosensitivity of 0.021Gy-1 well in the range observed in external beam radiotherapy (EBRT), i.e. 0.01-0.04Gy-1. This agreement explains the reunification of the dose-response relationships of the glass and resin spheres in HCC using the TOF-PET based EUD. Additional filtering reduced the EUDs agreement quality.

Conclusions

Recommended manufacturer FDG reconstruction parameters are suitable in TOF-PET post 90Y liver radioembolization for accurate tumour EUD computation. The present results rule out the use of low specific activity phantom studies to optimize reconstruction parameters.
Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study
Authors: Xue Ruiqi , Chen Meiwei , Cai Jinhua , Deng Zhenhong , Pan Dong , Liu Xiaohuan , Li Yi , Rong Xiaoming , Li Honghong , Xu Yongteng , Shen Qingyu , Tang Yamei
Published: October 2021

Background

Blood–brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective study, BBB repair by bevacizumab and corticosteroid and the correlation between BBB permeability and treatment response and relapse were evaluated by dynamic contrast-enhanced MRI (DCE-MRI).

Methods

Forty-one patients with RN after radiotherapy for nasopharyngeal carcinoma (NPC) (28 treated with bevacizumab and 13 with corticosteroid), 12 patients with no RN after NPC radiotherapy, and 12 patients with no radiotherapy history were included as RN, non-RN, and normal groups, respectively. DCE-MRI assessed BBB permeability in white matter of bilateral temporal lobe. DCE parameters were compared at baseline among the three groups. DCE parameters after treatment were compared and correlated with RN volume decrease, neurological improvement, and relapse.

Results

The extent of BBB leakage at baseline increased from the normal group and non-RN group and to RN necrosis lesions, especially Ktrans (Kruskal–Wallis test, P < 0.001). In the RN group, bevacizumab-induced Ktrans and ve decrease in radiation necrosis lesions (both P < 0.001), while corticosteroid showed no obvious effect on BBB. The treatment response rate of bevacizumab was significantly higher than that of corticosteroid [30/34 (88.2%) vs. 10/22 (45.4%), P < 0.001]. Spearman analysis showed baseline Ktrans, Kep, and vp positively correlated with RN volume decrease and improvement of cognition and quality of life in bevacizumab treatment. After a 6-month follow-up for treatment response cases, the relapse rate of bevacizumab and corticosteroid was 10/30 (33.3%) and 2/9 (22.2%), respectively, with no statistical difference. Post-bevacizumab Ktrans level predicted relapse in 6 months with AUC 0.745 (P < 0.05, 95% CI 0.546–0.943, sensitivity = 0.800, specificity = 0.631).

Conclusions

Bevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.
Arsenic Trioxide Promotes Tumor Progression by Inducing the Formation of PGCCs and Embryonic Hemoglobin in Colon Cancer Cells
Authors: Li Zugui , Zheng Minying , Zhang Hao , Yang Xiaohui , Fan Linlin , Fu Fangmei , Fu Junjie , Niu Rui , Yan Man , Zhang Shiwu
Published: October 2021

Arsenic trioxide (ATO) has been used to treat acute promyelocytic leukemia. However, it is not effective in treating solid tumors such as colorectal cancer. We have previously reported that polyploid giant cancer cells (PGCCs) exhibiting the characteristics of cancer stem cells can be generated by various inducers. In this study, ATO was used to induce the formation of PGCCs in LoVo and Hct116 colon cancer cell lines. The migration, invasion, and proliferation abilities of colon cancer cells with and without ATO treatment were assessed by wound-healing, transwell, and plate colony formation assays. The expression of epithelial to mesenchymal transition-related proteins and erythroid differentiation-related proteins in colon cancer cells was further evaluated by western blot and immunocytochemical assays. LoVo and Hct116 cells were transfected with a eukaryotic expression vector for green fluorescent protein (GFP), red fluorescent protein (RFP), H2B-GFP, and H2B-mCherry to study PGCCs formation via cell fusion. WB and ICC assays were performed to assess the expression of cell fusion-related proteins. MG132, small interfering RNA-glial cell missing 1 (GCM1), and chromatin immunoprecipitation-polymerase chain reaction assays were performed to study the role of GCM1/syncytin-1-mediated cell fusion. Clinically, the significance of cell fusion-related proteins and erythroid differentiation-related proteins expression in human colorectal cancer tissues was evaluated. Results of our study showed that ATO induced the formation of PGCCs, and the daughter cells derived from PGCCs gained a mesenchymal phenotype and exhibited strong migration, invasion, and proliferation abilities. PGCCs also produced embryonic hemoglobin-delta and -zeta with strong oxygen-binding ability and erythroid differentiation-related proteins after ATO treatment. In addition, cell fusion was observed during the formation of PGCCs, indicated by the presence of yellow fluorescence via the GCM1/syncytin-1 signaling pathway. Clinically, the expression of cell fusion-related and erythroid differentiation-related proteins gradually increased with the progression of human colorectal cancer tissues. In conclusion, ATO can promote tumor progression by inducing the formation of PGCCs via GCM1/syncytin-1-mediated cell fusion. PGCCs can produce daughter cells with high invasion and migration abilities and embryonic hemoglobin with strong oxygen binding ability, promoting survival of tumor cells in a hypoxic microenvironment.
Long-Term Response to Gemcitabine, Cisplatin, and Nab-Paclitaxel Followed by Maintenance Therapy for Advanced Gallbladder Cancer: A Case Report and Literature Review
Authors: Liu Ting , Li Qing , Zhang Wenjie , Zhu Qing
Published: October 2021

Background

Gallbladder cancer (GBC) is the most common and devastating tumor type of biliary tract cancer (BTC) with poor outcomes. A new combined regimen of gemcitabine, cisplatin, plus nab-paclitaxel is currently considered an effective option for patients with advanced BTC following the results of a phase II trial. In addition, maintenance therapy after first-line treatment has been shown to improve disease control rate of various solid tumors but has not been evaluated for GBC patients. The scenario we report herein is of a metastatic GBC patient treated with the triple-drug regimen followed by maintenance therapy with capecitabine or S-1, who achieved a long-term survival benefit.

Case Presentation

A 68-year-old man was diagnosed with gallbladder adenocarcinoma with liver, supra-diaphragmatic, and abdominal lymph node metastases (cT3N2M1, stage IVB). Partial response (PR) was achieved after five cycles of gemcitabine and cisplatin chemotherapy. A further three cycles of nab-paclitaxel plus gemcitabine-cisplatin regimen yielded a complete response of all tumor lesions. Subsequent administration of maintenance therapy with capecitabine followed by S-1 achieved a disease-free survival of 15 months for the patient. Moreover, the patient remained responsive to this triple-drug regimen when the disease progressed, achieving PR after two cycles of chemotherapy. Overall, the treatment regimens were well tolerated with no grade 3 or higher adverse effects occurring. Notably, the serum carbohydrate antigen 199 (CA199) levels were closely related to the treatment response and increased before the lesions were found on PET-CT during follow-up.

Conclusion

Our findings suggested that adding nab-paclitaxel into gemcitabine-cisplatin regimen may result in a favorable efficacy in patients with advanced GBC. Further maintenance therapy with capecitabine or S-1 after first-line therapy appeared to be a reasonable option for these patients, and it is valuable to monitor CA199 levels during treatment and follow-up.
Detection of HPV and Human Chromosome Sites by Dual-Color Fluorescence In Situ Hybridization Reveals Recurrent HPV Integration Sites and Heterogeneity in Cervical Cancer
Authors: Xiong Jinfeng , Cheng Jing , Shen Hui , Ren Ci , Wang Liming , Gao Chun , Zhu Tong , Li Xiaomin , Ding Wencheng , Zhu Da , Wang Hui
Published: October 2021

Human papillomavirus (HPV) integration in the human genome is suggested to be an important cause of cervical cancer. With the development of sequencing technologies, an increasing number of integration “hotspots” have been identified. However, this HPV integration information was derived from analysis of whole cervical cancer tissue, and we know very little about the integration in different cancer cell subgroups or individual cancer cells. This study optimized the preparation of probes and provided a dual-color fluorescence in situ hybridization (FISH) method to detect HPV integration sites in paraffin-embedded cervical cancer samples. We used both HPV probes and site-specific probes: 3p14 (FHIT), 8q24 (MYC), 13q22 (KLF5/KLF12), 3q28 (TP63), and 5p15 (TERT). We detected HPV signals in 75 of the 96 cases of cervical cancer; 62 cases showed punctate signals, and 13 cases showed diffuse punctate signals. We identified 3p14 as a high-frequency HPV integration site in 4 cervical cancer cases. HPV integration at 8p14 occurred in 2 cases of cervical cancer. In the same cervical cancer tissue of sample No.1321, two distinct subgroups of cells were observed based on the HPV probe but showed no difference in cell and nucleus morphology. Our study provides a new method to investigate the frequent HPV integration sites in cervical cancer and reports the heterogeneity within cervical cancer from the perspective of HPV integration.
Dynamic 18F-FDopa PET Imaging for Newly Diagnosed Gliomas: Is a Semiquantitative Model Sufficient?
Authors: Zaragori Timothée , Doyen Matthieu , Rech Fabien , Blonski Marie , Taillandier Luc , Imbert Laëtitia , Verger Antoine
Published: October 2021

Purpose

Dynamic amino acid positron emission tomography (PET) has become essential in neuro-oncology, most notably for its prognostic value in the noninvasive prediction of isocitrate dehydrogenase (IDH) mutations in newly diagnosed gliomas. The 6-[18F]fluoro-l-DOPA (18F-FDOPA) kinetic model has an underlying complexity, while previous studies have predominantly used a semiquantitative dynamic analysis. Our study addresses whether a semiquantitative analysis can capture all the relevant information contained in time–activity curves for predicting the presence of IDH mutations compared to the more sophisticated graphical and compartmental models.

Methods

Thirty-seven tumour time–activity curves from 18F-FDOPA PET dynamic acquisitions of newly diagnosed gliomas (median age = 58.3 years, range = 20.3–79.9 years, 16 women, 16 IDH-wild type) were analyzed with a semiquantitative model based on classical parameters, with (SQ) or without (Ref SQ) a reference region, or on parameters of a fit function (SQ Fit), a graphical Logan model with input function (Logan) or reference region (Ref Logan), and a two-tissue compartmental model previously reported for 18F-FDOPA PET imaging of gliomas (2TCM). The overall predictive performance of each model was assessed with an area under the curve (AUC) comparison using multivariate analysis of all the parameters included in the model. Moreover, each extracted parameter was assessed in a univariate analysis by a receiver operating characteristic curve analysis.

Results

The SQ model with an AUC of 0.733 for predicting IDH mutations showed comparable performance to the other models with AUCs of 0.752, 0.814, 0.693, 0.786, and 0.863, respectively corresponding to SQ Fit, Ref SQ, Logan, Ref Logan, and 2TCM (p ≥ 0.10 for the pairwise comparisons with other models). In the univariate analysis, the SQ time-to-peak parameter had the best diagnostic performance (75.7% accuracy) compared to all other individual parameters considered.

Conclusions

The SQ model circumvents the complexities of the 18F-FDOPA kinetic model and yields similar performance in predicting IDH mutations when compared to the other models, most notably the compartmental model. Our study provides supportive evidence for the routine clinical application of the SQ model for the dynamic analysis of 18F-FDOPA PET images in newly diagnosed gliomas.
A Nomogram for Predicting Pathological Complete Response to Neoadjuvant Chemoradiotherapy Using Semiquantitative Parameters Derived From Sequential PET/CT in Locally Advanced Rectal Cancer
Authors: Pyo Dae Hee , Choi Joon Young , Lee Woo Yong , Yun Seong Hyeon , Kim Hee Cheol , Huh Jung Wook , Park Yoon Ah , Shin Jung Kyong , Cho Yong Beom
Published: October 2021

We evaluated the predictive value of semiquantitative volumetric parameters derived from sequential PET/CT and developed a nomogram to predict pathological complete response (pCR) in patients with rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). From April 2008 to December 2013, among the patients who underwent nCRT, those who were taken sequential PET/CT before and after nCRT were included. MRI-based staging and semiquantitative parameters of PET/CT including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated before and after nCRT. Multivariable analysis was performed to select significant predictors to construct a nomogram. Sensitivity, specificity, accuracy, and area under the receiver operating characteristics curve (AUC) of the model were evaluated to determine its performance. Among 137 eligible patients, 17 (12.4%) had pCR. All post-PET/CT parameters showed significant differences between pCR and non-pCR groups. Patients were randomly assigned to a training group (91 patients) and a validation group (46 patients). In multivariable analysis with the training group, post-CEA, post-MRI T staging, post-SUVmax, and post-MTV were significantly associated with pCR. There was no significant pre-nCRT variable for predicting pCR. Using significant predictors, a nomogram was developed. Sensitivity, specificity, accuracy, and AUC of the nomogram were 0.882, 0.808, 0.848, and 0.884 with the training group and 0.857, 0.781, 0.783, and 0.828 with the validation group, respectively. This model showed the better performance than other predictive models that did not contain PET/CT parameters. A nomogram containing semiquantitative post-PET/CT could effectively select candidates for organ-sparing strategies.
Physical Activity, Screen-Based Sedentary Behavior and Physical Fitness in Chinese Adolescents: A Cross-Sectional Study
Authors: Dong Xiaosheng , Ding Lijie , Zhang Rui , Ding Meng , Wang Baozhen , Yi Xiangren
Published: October 2021

Purpose: The aim of this study is to explore the relationship between screen-based sedentary behavior, physical activity and physical fitness among Chinese adolescents.

Methods: This study randomly selected adolescents from 10 administrative districts in Shandong, China. The data gathering tools for demographic and other characteristics (gender, age, body mass index and socioeconomic status), PA (PAQ-A) and screen-based sedentary behavior (YRBSS) and physical fitness (NSPFH 2014) were utilized in this study. Statistical analysis was performed by T-test, chi-square test and multiple linear regression.

Results: 10,002 adolescents (14.39 years ± 1.79) participated in the study. The results demonstrated that BMI and high TV viewing time had a significant negative correlation with physical fitness, but there was no association between the amount of time spent playing computer/video games and physical fitness among adolescents. High SES and physical activity in leisure time five or more times per week were significantly associated with most dimensions of physical fitness.

Conclusions: the results suggest that we not only need to focus on adolescent risk behavior associated with low socioeconomic status and obesity, but also enforce physical activity and reduce sedentary television-watching behavior, which will be crucial pathways and strategies to improve the physical fitness of Chinese adolescents.
A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study Cohort at Baseline
Authors: Palmer Clare E. , Sheth Chandni , Marshall Andrew T. , Adise Shana , Baker Fiona C. , Chang Linda , Clark Duncan B. , Coronado Clarisa , Dagher Rada K. , Diaz Vanessa , Dowling Gayathri J. , Gonzalez Marybel R. , Haist Frank , Herting Megan M. , Huber Rebekah S. , Jernigan Terry L. , LeBlanc Kimberly , Lee Karen , Lisdahl Krista M. , Neigh Gretchen , Patterson Megan W. , Renshaw Perry , Rhee Kyung E. , Tapert Susan , Thompson Wesley K. , Uban Kristina , Sowell Elizabeth R. , Yurgelun-Todd Deborah
Published: October 2021

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development StudySM (ABCD study®), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9–10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index. Further this summary will describe how physical health measures collected from the ABCD cohort compare with current normative data and clinical guidelines. We propose this data set has the potential to facilitate clinical recommendations and inform national standards of physical health in this age group. This manuscript will also provide important information for ABCD users and help guide analyses investigating physical health including new avenues for health disparity research as it pertains to adolescent and young adult development.
Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis
Authors: Zhong Ping , Zeng Hai , Huang Miaochun , He Guoxin , Chen Zhixia
Published: October 2021

Background: This meta-analysis aimed to combine the data available from clinical trials to assess the effects of subcutaneous and oral semaglutide administration on glycemic control, weight management, and safety outcomes in patients with type 2 diabetes (T2D).

Methods: We systematically searched for phase 3 randomized controlled trials (RCTs) that compared semaglutide with placebo or other anti-diabetic drugs in T2D patients. The primary outcome was the change from baseline in glycated hemoglobin (HbA1c) levels. Secondary efficacy endpoints included the change from baseline in body weight, achievement of HbA1c targets, and clinically significant weight loss. Key safety outcomes were also assessed.

Results: In this meta-analysis, 24 trials with a total of 22185 patients were included. Subcutaneous semaglutide administration reduced HbA1c levels (weighted mean difference [WMD]: −1.14% and −1.37%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: −2.73 kg and −4.09 kg, for 0.5 mg and 1 mg, respectively) when compared with placebo; its efficacy was also superior to other anti-diabetic drugs in reducing HbA1c levels (WMD: −0.71% and −0.86%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: −2.65 kg and −3.78 kg, for 0.5 mg and 1 mg, respectively). Oral semaglutide administration was superior to placebo in decreasing HbA1c levels (WMD: −0.96% and −1.02%, for 7 mg and 14 mg, respectively). Moreover, oral administration of 14 mg of semaglutide also showed a significant reduction in HbA1c levels (WMD: −0.36%) compared with other anti-diabetic drugs. Furthermore, oral semaglutide administration resulted in substantial weight loss compared with other anti-diabetic drugs (WMD: −1.53 kg and −1.73 kg, for 7 mg and 14 mg, respectively). Notably, subcutaneous and oral semaglutide administration also resulted in higher numbers of patients achieving the targets of HbA1c levels and weight loss than placebo and other anti-diabetic drugs. Overall, we noted no clear evidence of detrimental effects on safety endpoints due to semaglutide treatment, except for some gastrointestinal adverse events.

Conclusion: Both subcutaneous and oral semaglutide administration could enable the achievement of sufficient glycemic control and weight management without increasing the risk of hypoglycemia, which were effective and safe for the treatment of T2D.
The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases
Authors: Chen Wen-jian , Yu Xiao , Yuan Xin-Rong , Chen Bang-jie , Cai Na , Zeng Shuo , Sun Yuan-song , Li Hai-wen
Published: October 2021

A member of the interleukin (IL)-1 superfamily was IL-36, which contained IL-36α, IL-36β, IL-36γ, and IL-36Ra. Heterotrimer complexes, consisting of heterodimeric receptor complexes and IL-36 agonist, gave signals through intracellular functional domains, so as to bind to downstream proteins and induce inflammatory response. IL-36 agonists upregulated mature-associated CD80, CD86, MHCII, and inductively produced several pro-inflammatory cytokines through the IL-36R-dependent manner in dendritic cells (DCs). Besides, DCs had the ability to initiate the differentiation of helper T (Th) cells. Up to date, the role of IL-36 in immunity, inflammation and other diseases is of great importance. Additionally, autoimmune diseases were characterized by excessive immune response, resulting in damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases were related to inflammatory response. In this review, we will conclude the recent research advances of IL-36 in the occurrence and development of autoimmune diseases, which may provide new insight for the future research and the treatment of these diseases.