bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhance Ocean Carbon Observations: Successful Implementation of a Novel Autonomous Total Alkalinity Analyzer on a Ship of Opportunity
Authors: Seelmann Katharina , Steinhoff Tobias , Aßmann Steffen , Körtzinger Arne
Published: December 2020

Over recent decades, observations based on merchant vessels (Ships of Opportunity—SOOP) equipped with sensors measuring the CO2 partial pressure (pCO2) in the surface seawater formed the backbone of the global ocean carbon observation system. However, the restriction to pCO2 measurements alone is one severe shortcoming of the current SOOP observatory. Full insight into the marine inorganic carbon system requires the measurement of at least two of the four measurable variables which are pCO2, total alkalinity (TA), dissolved inorganic carbon (DIC), and pH. One workaround is to estimate TA values based on established temperature-salinity parameterizations, but this leads to higher uncertainties and the possibility of regional and/or seasonal biases. Therefore, autonomous SOOP-based TA measurements are of great interest. Our study describes the implementation of a novel autonomous analyzer for seawater TA, the CONTROS HydroFIAⓇ TA system (-4H-JENA engineering GmbH, Germany) for unattended routine TA measurements on a SOOP line operating in the North Atlantic. We present the installation in detail and address major issues encountered with autonomous measurements using this analyzer, e.g., automated cleaning and stabilization routines, and waste handling. Another issue during long-term deployments is the provision of reference seawater in large-volume containers for quality assurance measurements and drift correction. Hence, a stable large-volume seawater storage had to be found. We tested several container types with respect to their suitability to store seawater over a time period of 30 days without significant changes in TA. Only one gas sampling bag made of polyvinylidene fluoride (PVDF) satisfied the high stability requirement. In order to prove the performance of the entire setup, we compared the autonomous TA measurements with TA from discrete samples taken during the first two trans-Atlantic crossings. Although the measurement accuracy in unattended mode (about ± 5 μmol kg^-1) slightly deteriorated compared to our previous system characterization, its overall uncertainty fulfilled requirements for autonomous TA measurements on SOOP lines. A comparison with predicted TA values based on an established and often used parameterization pointed at regional and seasonal limitations of such TA predictions. Consequently, TA observations with better coverage of spatiotemporal variability are needed, which is now possible with the method described here.
Organic Matter Composition at Ocean Station Papa Affects Its Bioavailability, Bacterioplankton Growth Efficiency and the Responding Taxa
Authors: Stephens Brandon M. , Opalk Keri , Petras Daniel , Liu Shuting , Comstock Jacqueline , Aluwihare Lihini I. , Hansell Dennis A. , Carlson Craig A.
Published: December 2020

The bioavailability of organic matter (OM) to marine heterotrophic bacterioplankton is determined by both the chemical composition of OM and the microbial community composition. In the current study, changes in OM bioavailability were identified at Ocean Station Papa as part of the 2018 Export Processes in the Ocean from Remote Sensing (EXPORTS) field study. Removal rates of carbon (C) in controlled experiments were significantly correlated with the initial composition of total hydrolyzable amino acids, and C removal rates were high when the amino acid degradation index suggested a more labile composition. Carbon remineralization rates averaged 0.19 ± 0.08 μmol C L–1 d–1 over 6–10 days while bacterial growth efficiencies averaged 31 ± 7%. Amino acid composition and tandem mass spectrometry analysis of compound classes also revealed transformations to a more degraded OM composition during experiments. There was a log2-fold increase in the relative abundances of 16S rDNA-resolved bacterioplankton taxa in most experiments by members of the Methylophilaceae family (OM43 genus) and KI89A order. Additionally, when OM was more bioavailable, relative abundances increased by at least threefold for the classes Bacteroidetes (Flavobacteriaceae NS2b genus), Alphaproteobacteria (Rhodobacteraceae Sulfitobacter genus), and Gammaproteobacteria (Alteromonadales and Ectothiorhodospiraceae orders). Our data suggest that a diverse group of bacterioplankton was responsible for removing organic carbon and altering the OM composition to a more degraded state. Elevated community diversity, as inferred from the Shannon–Wiener H index, may have contributed to relatively high growth efficiencies by the bacterioplankton. The data presented here shed light on the interconnections between OM bioavailability and key bacterioplankton taxa for the degradation of marine OM.
Persistent Contaminants and Herpesvirus OtHV1 Are Positively Associated With Cancer in Wild California Sea Lions (Zalophus californianus)
Authors: Gulland Frances M. D. , Hall Ailsa J. , Ylitalo Gina M. , Colegrove Kathleen M. , Norris Tenaya , Duignan Pádraig J. , Halaska Barbie , Acevedo Whitehouse Karina , Lowenstine Linda J. , Deming Alissa C. , Rowles Teresa K.
Published: December 2020

The prevalence of cancer in wild California sea lions (Zalophus californianus) is one of the highest amongst mammals, with 18–23% of adult animals examined post-mortem over the past 40 years having urogenital carcinoma. To date, organochlorines, genotype and infection with Otarine herpesvirus-1 (OtHV-1) have been identified in separate studies using distinct animals as associated with this carcinoma. Multi-year studies using large sample sizes to investigate the relative importance of multiple factors on marine mammal health are rare due to logistical and ethical challenges. The objective of this study was to use a case control approach with samples from 394 animals collected over 20 years in a multifactorial analysis to explore the relative importance of distinct factors identified to date as associated with sea lion cancer in the likelihood of sea lion carcinoma. Stepwise regression indicated that the best model to explain carcinoma occurrence included herpesvirus status, contaminant exposure, and blubber depth, but not genotype at a single microsatellite locus, PV11. The odds of carcinoma was 43.57 times higher in sea lions infected with OtHV-1 (95% CI 14.61, 129.96, p < 0.001), and 1.48 times higher for every unit increase in the loge[contaminant concentrations], ng g–1 (an approximate tripling of concentration), in their blubber (95% CI 1.11, 1.97, p < 0.007), after controlling for the effect of blubber depth. These findings demonstrate the importance of contaminant exposure combined with OtHV1 infection, in the potential for cancer occurrence in wild sea lions.
A Case Study of Industrial Symbiosis to Reduce GHG Emissions: Performance Analysis and LCA of Asphalt Concretes Made With RAP Aggregates and Steel Slags
Authors: Bonoli Alessandra , Degli Esposti Anna , Magrini Chiara
Published: December 2020

The concept of sustainability in the road construction sector is a complex issue because of the various steps that contribute to the production and release of greenhouse gas (GHG) emissions. Addressing this issue, the European Commission has put various policy initiatives in place to encourage the construction industry to adopt circular economy (CE) and industrial symbiosis (IS) principles e.g., the use of recycled materials. Cooperativa Trasporti Imola (CTI), a company located in the Emilia-Romagna region (Italy), has been chosen for the current case study to examine practices, management, and the industrial symbiosis network among various companies in the road construction and rehabilitation sector. In this regard, the use of steel slags, obtained by an electric arc furnace (EAF), and reclaimed asphalt pavement (RAP), obtained by the deconstruction and milling of old asphalt pavement have been investigated. Two mixtures of recycled hot Mix Asphalt (HMA) i) were prepared incorporating different recycled material percentages for the wearing and binder course, respectively, ii) were characterized in terms of size distribution, strength modulus and volumetric properties, iii) and finally were compared to the performances of two mixtures entirely designed by virgin materials for the wearing and binder course, respectively. Therefore, the Life Cycle Assessment (LCA) tool was chosen to evaluate the environmental impacts that affect the designed road life cycle. The results show that recycling RAP and EAF slags in a CTI batch plant provides benefits by reducing the consumption of virgin bitumen and aggregates and by reducing CO2eq emissions. Finally, practical implications on the use of recycled materials in new asphalt mixtures from a life cycle and industrial symbiosis perspective are provided.
Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Study in the Chinese Population
Authors: Chen Yingying , Guo Xiaoxiao , Zhou Jiaxin , Li Jing , Wu Qingjun , Yang Hongxian , Zhang Shangzhu , Fei Yunyun , Zhang Wen , Zhao Yan , Zhang Fengchun , Zeng Xiaofeng
Published: December 2020

Introduction:Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) is associated with a poor prognosis and high mortality; however, few studies about cardiac involvement in EGPA in the Chinese population are available. We conducted this study to determine the clinical characteristics and overall outcomes of Chinese EGPA patients with cardiac involvement.

Materials and Methods:We retrospectively collected the clinical data of 83 patients diagnosed with EGPA and analyzed the differences between the patients with and without cardiac involvement.

Results:The prevalence of cardiac involvement in EGPA in this cohort was 27.7%. Compared with those without cardiac involvement, EGPA patients with cardiac involvement tended to have a younger age at onset (mean ± SD: 38.4 ± 10.5 vs. 42.1 ± 15.9 years, respectively,p= 0.039), higher eosinophil count (median [IQR]: 5810 [4020–11090] vs. 2880 [1530–6570] n/μL, respectively,p= 0.004), higher disease activity assessed using the Birmingham vasculitis activity score (BVAS) (median [IQR]: 20 [16–28] vs. 15 [12–18], respectively,p= 0.001), and poorer prognosis (Five Factor Score [FFS] ≥ 1: 100% vs. 38.3%, respectively,p= 0.001). In the cardiac involvement group, 43.5% of patients were asymptomatic, but cardiac abnormalities could be detected by cardiac examinations. With appropriate treatment, the overall outcomes of EGPA patients with cardiac involvement in our cohort were good, with only 3 (13.0%) patients dying in the acute phase and no patients dying during follow-up.

Conclusions:Cardiac involvement in EGPA was associated with a younger age at onset, higher eosinophil count, higher disease activity, and a poorer prognosis. Comprehensive cardiac examinations and appropriate treatment are essential to improve the prognosis of those with cardiac involvement.
NSs, the Silencing Suppressor of Tomato Spotted Wilt Orthotospovirus, Interferes With JA-Regulated Host Terpenoids Expression to Attract Frankliniella occidentalis
Authors: Du Jiao , Song Xiao-yu , Shi Xiao-bin , Tang Xin , Chen Jian-bin , Zhang Zhan-hong , Chen Gong , Zhang Zhuo , Zhou Xu-guo , Liu Yong , Zhang De-yong
Published: December 2020

Tomato spotted wilt orthotospovirus (TSWV) causes serious crop losses worldwide and is transmitted by Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). NSs protein is the silencing suppressor of TSWV and plays an important role in virus infection, cycling, and transmission process. In this research, we investigated the influences of NSs protein on the interaction of TSWV, plants, and F. occidentalis with the transgenic Arabidopsis thaliana. Compared with the wild-type Col-0 plant, F. occidentalis showed an increased number and induced feeding behavior on transgenic Arabidopsis thaliana expressing exogenous NSs. Further analysis showed that NSs reduced the expression of terpenoids synthesis-related genes and the content of monoterpene volatiles in Arabidopsis. These monoterpene volatiles played a repellent role in respect to F. occidentalis. In addition, the expression level of plant immune-related genes and the content of the plant resistance hormone jasmonic acid (JA) in transgenic Arabidopsis were reduced. The silencing suppressor of TSWV NSs alters the emission of plant volatiles and reduces the JA-regulated plant defenses, resulting in enhanced attractiveness of plants to F. occidentalis and may increase the transmission probability of TSWV.
Microbial Diversity of Pinnacle and Conical Microbial Mats in the Perennially Ice-Covered Lake Untersee, East Antarctica
Authors: Greco Carla , Andersen Dale T. , Hawes Ian , Bowles Alexander M. C. , Yallop Marian L. , Barker Gary , Jungblut Anne D.
Published: December 2020

Antarctic perennially ice-covered lakes provide a stable low-disturbance environment where complex microbially mediated structures can grow. Lake Untersee, an ultra-oligotrophic lake in East Antarctica, has the lake floor covered in benthic microbial mat communities, where laminated organo-sedimentary structures form with three distinct, sympatric morphologies: small, elongated cuspate pinnacles, large complex cones and flat mats. We examined the diversity of prokaryotes and eukaryotes in pinnacles, cones and flat microbial mats using high-throughput sequencing of 16S and 18S rRNA genes and assessed how microbial composition may underpin the formation of these distinct macroscopic mat morphologies under the same environmental conditions. Our analysis identified distinct clustering of microbial communities according to mat morphology. The prokaryotic communities were dominated by Cyanobacteria, Proteobacteria, Verrucomicrobia, Planctomycetes, and Actinobacteria. While filamentous Tychonema cyanobacteria were common in all mat types, Leptolyngbya showed an increased relative abundance in the pinnacle structures only. Our study provides the first report of the eukaryotic community structure of Lake Untersee benthic mats, which was dominated by Ciliophora, Chlorophyta, Fungi, Cercozoa, and Discicristata. The eukaryote richness was lower than for prokaryote assemblages and no distinct clustering was observed between mat morphologies. These findings suggest that cyanobacterial assemblages and potentially other bacteria and eukaryotes may influence structure morphogenesis, allowing distinct structures to form across a small spatial scale.
Proteomics of Colorectal Cancer: Tumors, Organoids, and Cell Cultures—A Minireview
Authors: Lindhorst Philip H. , Hummon Amanda B.
Published: December 2020

Proteomics, the study of the complete protein composition of a sample, is an important field for cancer research. Changes in the proteome can serve as a biomarker of cancer or lead to the development of a targeted therapy. This minireview will focus on mass spectrometry-based proteomics studies applied specifically to colorectal cancer, particularly the variety of cancer model systems used, including tumor samples, two-dimensional (2D) and three-dimensional (3D) cell cultures such as spheroids and organoids. A thorough discussion of the application of these systems will accompany the review of the literature, as each provides distinct advantages and disadvantages for colorectal cancer research. Finally, we provide conclusions and future perspectives for the application of these model systems to cancer research as a whole.
Identification and Validation of the N6-Methyladenosine RNA Methylation Regulator YTHDF1 as a Novel Prognostic Marker and Potential Target for Hepatocellular Carcinoma
Authors: Bian Saiyan , Ni Wenkai , Zhu Mengqi , Song Qianqian , Zhang Jianping , Ni Runzhou , Zheng Wenjie
Published: December 2020

Purpose: N6-methyladenosine (m6A) RNA methylation has been implicated in various malignancies. This study aimed to identify the m6A methylation regulator-based prognostic signature for hepatocellular carcinoma (HCC) as well as provide candidate targets for HCC treatment.

Methods: The least absolute shrinkage and selection operator (LASSO) analyses were performed to identify a risk signature in The Cancer Genome Atlas (TCGA) datasets. The risk signature was further validated in International Cancer Genome Consortium (ICGC) and Pan-Cancer Analysis of Whole Genomes (PCAWG) datasets. Following transfection of short hairpin RNA (shRNA) targeting YTHDF1, the biological activities of HCC cells were evaluated by Cell Counting Kit-8 (CCK-8), wound-healing, Transwell, flow cytometry, and xenograft tumor assays, respectively. The potential mechanisms mediated by YTHDF1 were predicted by overrepresentation enrichment analysis (ORA)/gene set enrichment analysis (GSEA) and validated by Western blotting.

Results: Overexpression of m6A RNA methylation regulators was correlated with malignant clinicopathological characteristics of HCC patients. The Cox regression and LASSO analyses identified a risk signature with five m6A methylation regulators (KIAA1429, ZC3H13, YTHDF1, YTHDF2, and METTL3). In accordance with HCC cases in TCGA, the prognostic value of risk signature was also determined in ICGC and PCAWG datasets. Following analyzing the expression and clinical implications in TCGA and Gene Expression Omnibus (GEO), YTHDF1 was chosen for further experimental validation. Knockdown of YTHDF1 significantly inhibited the proliferation, migration, and invasion of HCC cells, as well as enhanced the apoptosis in vitro. Moreover, silencing YTHDF1 repressed the growth of xenograft tumors in vivo. Mechanism investigation indicated that YTHDF1 might promote the aggressive phenotypes by facilitating epithelial–mesenchymal transition (EMT) and activating AKT/glycogen synthase kinase (GSK)-3β/β-catenin signaling.

Conclusion: The current study identified a robust risk signature consisting of m6A RNA methylation regulators for HCC prognosis. In addition, YTHDF1 was a potential molecular target for HCC treatment.
Prevalence and Risk Factors for Malnutrition in Patients With Parkinson's Disease
Authors: Yang Tianting , Zhan Zhen , Zhang Liang , Zhu Jun , Liu Yi , Zhang Lili , Ge Jianchao , Zhao Ying , Zhang Li , Dong Jingde
Published: December 2020

Objectives: This study aimed to investigate the relationship between nutritional status and Parkinson's disease (PD) features.

Methods: The cohort was composed of 556 Parkinson's patients who were admitted to the hospital. Patients were categorized as normal nutrition or at risk of malnutrition/already malnourished. Questionnaires, physical examinations, and biochemical tests were conducted. The relationship between nutrition status and PD was analyzed using t-tests, χ2-tests, and logistic regression models.

Results: The prevalence of malnutrition [defined as a Mini Nutritional Assessment (MNA) score <17] was 39.2%, and 30.3% of patients were at risk of malnutrition (17 ≤ MNA score ≤ 23.5). There was no difference in gender and age between the different nutrition groups (P < 0.05). Patients at risk of malnutrition and those who were malnourished had a longer course of disease, more severe motor symptoms, a higher stage of PD according to the Hoehn and Yahr (H-Y) classification, a lower body mass index (BMI) index, a lower cognitive score, higher levels of depression and anxiety, and more serious non-motor symptoms (P < 0.05) than patients with normal nutrition. There were differences in adenosine deaminase, albumin, phosphorus, chlorine, total protein, and uric acid between the two groups (P < 0.05). High Unified PD Rating Scale (UPDRS-III) scores, high H-Y stages, and dyskinesia were risk factors for malnutrition in PD patients, while high levels of total protein, uric acid, and chlorine were protective factors that led to good nutrition (P < 0.05).

Conclusions: Our results showed that dyskinesia, disease severity, total protein levels, uric acid levels, and chlorine levels were associated with nutritional status among Chinese PD patients. The findings of this study indicate the significance of the early detection and prevention of malnutrition to improve the quality of life of PD patients.
Comparison of Novel Oral Anticoagulants and Vitamin K Antagonists in Patients With Cerebral Venous Sinus Thrombosis on Efficacy and Safety: A Systematic Review
Authors: Li Hongjie , Yao Meiling , Liao Songjie , Chen Jingyan , Yu Jian
Published: December 2020

Vitamin K antagonists (VKAs) are guideline-suggested subacute anticoagulants for cerebral venous sinus thrombosis (CVST), although there is potential hemorrhage risk in clinical use. In the last decade, novel oral anticoagulants (NOACs) have been applied as an alternative to VKAs in some kinds of thromboembolic diseases. Whether NOACs could replace VKAs in CVST treatment remains unclear. We conducted a comparison between the two types of medicines on efficacy and safety for the treatment of CVST based on the present clinical evidence from a literature search. Six studies [four retrospective studies, one prospective study, and 1 randomized clinical trial (RCT)] including 398 patients were included. Data suggested no significant difference between NOACs and VKAs in terms of recurrence of venous thrombotic events (VTEs) or death [risk ratio (RR) = 0.34, 95% confidence interval (CI) 0.06–1.98], partial recanalization (RR = 0.97, 95% CI 0.93–1.14), and overall hemorrhage events (RR = 0.86, 95% CI 0.47–1.58). In conclusion, the application of NOACs for CVST is similar to that of VKAs in terms of efficacy and safety.
Optical Coherence Tomography Angiography (OCTA) in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
Authors: Kleerekooper Iris , Houston Sarah , Dubis Adam M. , Trip S. Anand , Petzold Axel
Published: December 2020

Vascular changes are increasingly recognized as important factors in the pathophysiology of neuroinflammatory disease, especially in multiple sclerosis (MS). The relatively novel technology of optical coherence tomography angiography (OCTA) images the retinal and choroidal vasculature non-invasively and in a depth-resolved manner. OCTA provides an alternative quantitative measure of retinal damage, by measuring vascular density instead of structural atrophy. Preliminary results suggest OCTA is sensitive to retinal damage in early disease stages, while also having less of a “floor-effect” compared with commonly used OCT metrics, meaning it can pick up further damage in a severely atrophied retina in later stages of disease. Furthermore, it may serve as a surrogate marker for vascular pathology in the central nervous system. Data to date consistently reveal lower densities of the retinal microvasculature in both MS and neuromyelitis optica spectrum disorder (NMOSD) compared with healthy controls, even in the absence of prior optic neuritis. Exploring the timing of vascular changes relative to structural atrophy may help answer important questions about the role of hypoperfusion in the pathophysiology of neuroinflammatory disease. Finally, qualitative characteristics of retinal microvasculature may help discriminate between different neuroinflammatory disorders. There are however still issues regarding image quality and development of standardized analysis methods before OCTA can be fully incorporated into clinical practice.
Sural Nerve Perfusion in Mice
Authors: Dudele Anete , Rasmussen Peter Mondrup , Østergaard Leif
Published: December 2020

Peripheral nerve function is metabolically demanding and nerve energy failure has been implicated in the onset and development of diabetic peripheral neuropathy and neuropathic pain conditions. Distal peripheral nerve oxygen supply relies on the distribution of red blood cells (RBCs) in just a few, nearby capillary-sized vessels and is therefore technically challenging to characterize. We developed an approach to characterize distal sural nerve hemodynamics in anesthetized, adult male mice using in vivo two-photon laser scanning microscopy. Our results show that RBC velocities in mouse sural nerve vessels are higher than those previously measured in mouse brain, and are sensitive to hindlimb temperatures. Nerve blood flow, measured as RBC flux, however, was similar to that of mouse brain and unaffected by local temperature. Power spectral density analysis of fluctuations in RBC velocities over short time intervals suggest that the technique is sufficiently sensitive and robust to detect subtle flow oscillations over time scales from 0.1 to tens of seconds. We conclude that in vivo two-photon laser scanning microscopy provides a suitable approach to study peripheral nerve hemodynamics in mice, and that local temperature control is important during such measurements.
Qualitative and Quantitative Wall Enhancement Analyses in Unruptured Aneurysms Are Associated With an Increased Risk of Aneurysm Instability
Authors: Zhang Yi , Fu Qichang , Wang Yuting , Cheng Jingliang , Ren Cuiping , Guan Sheng , Zhu Chengcheng
Published: December 2020

Objective

Intracranial aneurysm wall enhancement (AWE) is independently associated with unstable aneurysms. However, a quantitative analysis of wall enhancement is lacking. This study aims to investigate the relationship between qualitative and quantitative wall enhancement indices (WEIs), traditional risk factors for aneurysms, and clinical ELAPSS/PHASES scores in a large cohort of intracranial saccular aneurysms.

Materials and Methods

In this cross-sectional study, a total of 174 patients (mean age 60.4 ± 9.5 years; 53% women) with 248 asymptomatic unruptured intracranial aneurysms underwent pre- and post-contrast black-blood magnetic resonance imaging (MRI). The extent of AWE was defined as non-AWE (pattern 0), focal AWE (pattern 1), or circumferential AWE (pattern 2). WEI was calculated using wall signal intensities on pre- and post-contrast images. Predicted 3- and 5-year growth risk and 5-year rupture risk were obtained from ELAPSS and PHASES scores, respectively. Uni- and multivariate analyses were conducted to explore the relationship between AWE characteristics, risk-related factors, and aneurysm instability.

Results

Aneurysm size [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.2–1.4; P < 0.001], non-internal carotid artery/middle cerebral artery location (OR, 1.9; 95% CI, 1.0–3.6; P = 0.045), and irregular shape (OR, 2.4; 95% CI, 1.2–4.5; P = 0.009) were independently associated with AWE. For aneurysms with AWE, the estimated 3- and 5-year growth risk (25.3 ± 13.0% and 38.0 ± 17.4%) and the 5-year rupture risk (3.9 ± 5.2%) were 1.9–3.3 times higher than those for aneurysms without AWE (12.8 ± 9.1%, 20.3 ± 13.0%, and 1.2 ± 1.6%, respectively; all P < 0.001). Larger areas and higher WEIs of enhancement positively correlated with aneurysm size (r = 0.43 and 0.38, respectively), 3- and 5-year growth risk, and 5-year rupture risk (r = 0.49 and 0.40, r = 0.49 and 0.40, r = 0.36 and 0.24, respectively; all P < 0.001). In sum, a larger aneurysm size, non-internal carotid artery/middle cerebral artery location, and irregular shape were independently associated with AWE. Larger areas and higher WEIs were associated with an increased risk of aneurysm growth and rupture. These findings suggest that quantitative AWE metrics should be considered in future large-scale longitudinal studies to evaluate their value in aneurysm risk management.
Interactions Between Phytochemicals and Minerals in Terminalia ferdinandiana and Implications for Mineral Bioavailability
Authors: Akter Saleha , Netzel Michael , Tinggi Ujang , Fletcher Mary , Osborne Simone , Sultanbawa Yasmina
Published: December 2020

Oxalic and phytic acid are phytochemicals considered to be anti-nutritional factors as they are predominantly found as oxalates and phytates bound to minerals like calcium and potassium. Studies have associated excessive oxalate consumption with increased urinary excretion of oxalate (hyperoxaluria) and calcium oxalate kidney stone formation, and excessive phytate consumption with decreased bioaccessibility and bioavailability of certain minerals and reduced utilization of dietary protein. However, other studies suggest that dietary consumption of phytate may be beneficial and inhibit formation of calcium oxalate kidney stones. In light of these conflicting reports, dietary intake of oxalate and phytate enriched plants should be considered in relation to potential health outcomes following consumption. Terminalia ferdinandiana is one such plant and is investigated here with respect to oxalate, phytate, and mineral contents. Assessment of oxalate and phytate contents in T. ferdinandiana fruit, leaf, and seedcoat tissues through hydrolysis into acid forms revealed oxalic acid contents ranging from 327 to 1,420 mg/100 g on a dry weight (DW) basis whilst phytic acid contents ranged from 8.44 to 121.72 mg/100 g DW. Calcium content in the different tissues ranged from 131 to 1,343 mg/100 g. There was no correlation between oxalic acid and calcium, however a significant, positive correlation was observed between phytic acid and calcium (r = 0.9917; p < 0.001), indicating that tissues rich in phytic acid also contain higher levels of calcium. The high content of phytic acid in comparison to oxalic acid in T. ferdinandiana fruit found in this study and the dietary significance of this in terms of calcium bioavailability, needs to be investigated further.
Stereotactic Body Radiation Therapy: A Versatile, Well-Tolerated, and Effective Treatment Option for Extracranial Metastases From Primary Ovarian and Uterine Cancer
Authors: Aghdam Nima , Repka Michael C. , McGunigal Mary , Pepin Abby , Paydar Ima , Rudra Sonali , Paudel Nitika , Pernia Marin Monica , Suy Simeng , Collins Sean P. , Barnes Willard , Collins Brian T.
Published: December 2020

Purpose

Single extracranial metastases from ovarian and uterine malignancies have historically been treated with surgery or conventional radiation. We report mature local control (LC), overall survival (OS), progression free survival (PFS), and toxicity for patients who completed 5-fraction stereotactic body radiation therapy (SBRT).

Methods

Patients with biopsy-proven, single extracranial metastases from primary ovarian and uterine malignancies treated with 5-fraction SBRT were included. Patients were stratified based on tumor volume (small < 50 cc or large ≥ 50 cc) and dose (low dose < 35 Gy or high ≥ 35 Gy). Kaplan–Meier method was used to estimate LC, OS, and PFS.

Results

Between July 2007 and July 2012, 20 patients underwent SBRT to a single extracranial metastasis. Primary site was divided evenly between ovarian and uterine (n = 10 each). Metastases involved the liver (30%), abdominal lymph nodes (25%), lung (20%), pelvic lymph nodes (10%), spine (10%), and extremity (5%). The median gross tumor volume (GTV) was 42.5 cc (range, 5–273 cc) and the median dose to the GTV was 35 Gy (range, 30–50 Gy). At a median follow-up of 56 months, the 5-year LC and OS estimates were 73 and 46%. When stratified by tumor volume, the 5-year LC and OS for small tumors were significantly better at 100% (p < 0.01) and 65% (p < 0.02). When stratified by dose, the 5-year LC was 87.5% with high dose and 53.6% with low dose (p = 0.035). The 5-year PFS for the entire cohort was 20%. Four patients with small metastases who had complete response remained disease free at study completion and were considered cured (median PFS > 10 years). Treatment was generally well tolerated, and only one patient experienced a late grade III musculoskeletal SBRT related toxicity.

Conclusions

SBRT is a versatile, well-tolerated, and effective treatment option for single extracranial metastases from ovarian and uterine primary tumors. 35 Gy in five fractions appears to be a practical minimum effective dose. Four patients with small metastases were disease free at the study completion and considered cured. However, patients with larger metastases (≥50 cc) may require higher SBRT dosing or alternative treatments.
Systemic Inflammation Response Index Is a Predictor of Poor Survival in Locally Advanced Nasopharyngeal Carcinoma: A Propensity Score Matching Study
Authors: Feng Yuhua , Zhang Na , Wang Sisi , Zou Wen , He Yan , Ma Jin-an , Liu Ping , Liu Xianling , Hu Chunhong , Hou Tao
Published: December 2020

Introduction

Nasopharyngeal carcinoma (NPC) is a common malignancy in China and known prognostic factors are limited. In this study, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) were evaluated as prognostic factors in locally advanced NPC patients.

Materials and Methods

NPC patients who received curative radiation or chemoradiation between January 2012 and December 2015 at the Second Xiangya Hospital were retrospectively reviewed, and a total of 516 patients were shortlisted. After propensity score matching (PSM), 417 patients were eventually enrolled. Laboratory and clinical data were collected from the patients’ records. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value. Survival curves were analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic variables.

Results

After PSM, all basic characteristics between patients in the high SIRI group and low SIRI group were balanced except for sex (p=0.001) and clinical stage (p=0.036). Univariate analysis showed that NLR (p=0.001), PLR (p=0.008), SII (p=0.001), and SIRI(p<0.001) were prognostic factors for progression-free survival (PFS) and overall survival (OS). However, further multivariate Cox regression analysis showed that only SIRI was an independent predictor of PFS and OS (hazard ratio (HR):2.83; 95% confidence interval (CI): 1.561-5.131;p=0.001, HR: 5.19; 95% CI: 2.588-10.406;p<0.001), respectively.

Conclusion

Our findings indicate that SIRI might be a promising predictive indicator of locally advanced NPC patients.
Macrophages in Osteosarcoma Immune Microenvironment: Implications for Immunotherapy
Authors: Luo Zhong-Wei , Liu Pan-Pan , Wang Zhen-Xing , Chen Chun-Yuan , Xie Hui
Published: December 2020

Osteosarcoma is a malignant primary bone tumor commonly occurring in children and adolescents. The treatment of local osteosarcoma is mainly based on surgical resection and chemotherapy, whereas the improvement of overall survival remains stagnant, especially in recurrent or metastatic cases. Tumor microenvironment (TME) is closely related to the occurrence and development of tumors, and macrophages are among the most abundant immune cells in the TME. Due to their vital roles in tumor progression, macrophages have gained increasing attention as the new target of tumor immunotherapy. In this review, we present a brief overview of macrophages in the TME and highlight the clinical significance of macrophages and their roles in the initiation and progression of osteosarcoma. Finally, we summarize the therapeutic approaches targeting macrophage, which represent a promising strategy in osteosarcoma therapies.
Integrative Analysis of Multi-Omics Identified the Prognostic Biomarkers in Acute Myelogenous Leukemia
Authors: Zheng Jiafeng , Zhang Tongqiang , Guo Wei , Zhou Caili , Cui Xiaojian , Gao Long , Cai Chunquan , Xu Yongsheng
Published: December 2020

Background

Acute myelogenous leukemia (AML) is a common pediatric malignancy in children younger than 15 years old. Although the overall survival (OS) has been improved in recent years, the mechanisms of AML remain largely unknown. Hence, the purpose of this study is to explore the differentially methylated genes and to investigate the underlying mechanism in AML initiation and progression based on the bioinformatic analysis.

Methods

Methylation array data and gene expression data were obtained from TARGET Data Matrix. The consensus clustering analysis was performed using ConsensusClusterPlus R package. The global DNA methylation was analyzed using methylationArrayAnalysis R package and differentially methylated genes (DMGs), and differentially expressed genes (DEGs) were identified using Limma R package. Besides, the biological function was analyzed using clusterProfiler R package. The correlation between DMGs and DEGs was determined using psych R package. Moreover, the correlation between DMGs and AML was assessed using varElect online tool. And the overall survival and progression-free survival were analyzed using survival R package.

Results

All AML samples in this study were divided into three clusters at k = 3. Based on consensus clustering, we identified 1,146 CpGs, including 40 hypermethylated and 1,106 hypomethylated CpGs in AML. Besides, a total 529 DEGs were identified, including 270 upregulated and 259 downregulated DEGs in AML. The function analysis showed that DEGs significantly enriched in AML related biological process. Moreover, the correlation between DMGs and DEGs indicated that seven DMGs directly interacted with AML. CD34, HOXA7, and CD96 showed the strongest correlation with AML. Further, we explored three CpG sites cg03583857, cg26511321, cg04039397 of CD34, HOXA7, and CD96 which acted as the clinical prognostic biomarkers.

Conclusion

Our study identified three novel methylated genes in AML and also explored the mechanism of methylated genes in AML. Our finding may provide novel potential prognostic markers for AML.
Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers
Authors: Xu Jiabin , Koval Alexey , Katanaev Vladimir L.
Published: December 2020

Wnt signaling plays key roles in oncogenic transformation and progression in a number of cancer types, including tumors in the breast, colon, ovaries, liver, and other tissues. Despite this importance, no therapy targeting the Wnt pathway currently exists. We have previously shown that the anti-mycobacterium drug clofazimine is a specific inhibitor of Wnt signaling and cell proliferation in triple-negative breast cancer (TNBC). Here, we expand the applicability of clofazimine to a set of other Wnt-dependent cancers. Using a panel of cell lines from hepatocellular carcinoma, glioblastoma, as well as colorectal and ovarian cancer, we show that the efficacy of clofazimine against a given cancer type correlates with the basal levels of Wnt pathway activation and the ability of the drug to inhibit Wnt signaling in it, being further influenced by the cancer mutational spectrum. Our study establishes the basis for patient stratification in the future clinical trials of clofazimine and may ultimately contribute to the establishment of the Wnt pathway-targeted therapy against a diverse set of cancer types relying on the oncogenic Wnt signaling.
Repurposing Cationic Amphiphilic Drugs and Derivatives to Engage Lysosomal Cell Death in Cancer Treatment
Authors: Hu Michelle , Carraway Kermit L.
Published: December 2020

A major confounding issue in the successful treatment of cancer is the existence of tumor cell populations that resist therapeutic agents and regimens. While tremendous effort has gone into understanding the biochemical mechanisms underlying resistance to each traditional and targeted therapeutic, a broader approach to the problem may emerge from the recognition that existing anti-cancer agents elicit their cytotoxic effects almost exclusively through apoptosis. Considering the myriad mechanisms cancer cells employ to subvert apoptotic death, an attractive alternative approach would leverage programmed necrotic mechanisms to side-step therapeutic resistance to apoptosis-inducing agents. Lysosomal cell death (LCD) is a programmed necrotic cell death mechanism that is engaged upon the compromise of the limiting membrane of the lysosome, a process called lysosomal membrane permeabilization (LMP). The release of lysosomal components into the cytosol upon LMP triggers biochemical cascades that lead to plasma membrane rupture and necrotic cell death. Interestingly, the process of cellular transformation appears to render the limiting lysosomal membranes of tumor cells more fragile than non-transformed cells, offering a potential therapeutic window for drug development. Here we outline the concepts of LMP and LCD, and discuss strategies for the development of agents to engage these processes. Importantly, the potential exists for existing cationic amphiphilic drugs such as antidepressants, antibiotics, antiarrhythmics, and diuretics to be repurposed to engage LCD within therapy-resistant tumor cell populations.
Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma
Authors: Qian Jie , Chen Rongrong , Zhao Ruiying , Han Yuchen , Yu Yongfeng
Published: December 2020

Background

This study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors.

Methods

We retrospectively identified 204 surgically resected LUSC patients in Shanghai Chest Hospital who underwent capture-based targeted next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes from September 2017 to January 2019. NGS was used to profile comprehensive molecular characterizations.

Results

Of 204 cases, 114 (55.9%) were keratinizing squamous cell carcinoma (KSCC), 77 (37.7%) were non-keratinizing squamous cell carcinoma (NKSCC), 13 (6.4%) were basaloid squamous cell carcinoma (BSCC), respectively. All subtypes presented similarly high proportions of mutations, including TP53, CDKN2A, and NOTCH1. A comparable prevalence of FGFR1 amplifications was identified between KSCC and NKSCC (11.4 versus 26.9%, p = 0.007). Compared with NKSCC, IGF1R amplifications were more frequent in BSCC (0 versus 15.4%, p = 0.019). We found cases with TP53 alterations had less EGFR alterations in KSCC (P = 0.013, OR = 0.158). Compared with TCGA cohorts, our Chinese cohorts exhibited statistic differences in both somatic mutations and signaling pathways. We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with LUSC.

Conclusions

Significant differences exist among three subtypes of LUSC in molecular characterizations.
A Novel, Portable MESH Nebulizer—An Alternative to Metered Dose Inhaler: Efficacy and Usability in Preschool Wheezers
Authors: Ullmann Nicola , Di Marco Antonio , Columbu Fabiana , Negro Valentina , Chiarini Testa Maria Beatrice , Panetta Valentina , Tripodi Salvatore , Potapova Ekaterina , Allegorico Annalisa , Matricardi Paolo Maria , Cutrera Renato
Published: December 2020

Introduction and Objectives: Wheezing episodes are the first causes of doctor's consultation in preschool age. Treatment is usually administered with a metered dose inhaler (MDI) spacer. At variance, many parents and doctors prefer to use a compressor nebulizer, which cannot be easily carried. The study is aimed at testing whether a pocket mesh nebulizer has similar efficacy and acceptability than a standard MDI device.

Materials and Methods: The IPAC study was a randomized, controlled, non-inferiority trial (number: 1616/2018, Ospedale Pediatrico Bambino Gesu'—IRCCS). The study had two arms: cases, using MicroAIR U100, and controls, using MDI+spacer device. Both devices were adopted for long-term treatment and for exacerbations. Follow-up was organized with clinical visits and a daily e-diary connected to an application for mobile phone.

Results: One hundred patients were enrolled. The frequency of asthmatic symptoms showed a non-inferiority for MicroAIR U100 group vs. MDI. Accordingly, no significant difference was found in the average % of days with cough, wheezing, breathlessness after exercise, days lost at school, and not-programmed visits. Considering only patients with >1 day with symptoms, no significant sdifferences were found in the number of exacerbations nor in the cumulative days with symptoms. The acceptance and usability of both devices have been favorable. However, the MDI+AeroChamber® device showed better acceptability.

Conclusions: Our study shows that MicroAIR U-100, a mesh nebulizer, has similar clinical efficacy but lower acceptance and usability than an MDI plus Aerochamber® in delivering therapy in preschool wheezers. Therefore, MicroAIR U-100 might be a valuable second choice, when the delivery of medication with an MDI plus Aerochamber® is not accepted, or wrongly used by the parents.
Socio-Demographic Factors Affect the Prevalence of Hematuria and Proteinuria Among School Children in Hualien, Taiwan: A Longitudinal Localization-Based Cohort Study
Authors: Chen Ming-Chun , Wang Jen-Hung , Chen Jui-Shia , Chang Yung-Chieh , Jan Rong-Hwa , Yang Shang-Hsien , Chu Shao-Yin , Lai Pei-Chun , Chu Chia-Hsiang , Cheng Ching-Feng , Chang Yu-Hsun
Published: December 2020

Objective:Child hematuria/proteinuria is a risk factor for chronic kidney disease (CKD) in later life, and mass urinary screening could detect asymptomatic glomerulonephritis at an early stage. This study aimed to evaluate the longitudinal prevalence of hematuria/proteinuria and its association with socio-demographic factors among school children in Hualien, Taiwan.

Methods:The study cohort consisted of first and fourth graders enrolled from 2008 to 2015 in Hualien. We combined the data from two consecutive health examinations to ensure the validity of the body mass index (BMI), urbanization, proteinuria, and hematuria grouping. Prevalence and health status differences between sex, age, BMI, and urbanization level were examined.

Results:A total of 16,990 students within the same BMI and urbanization categories were included during the study interval. The prevalence of persistent hematuria was 1.0%. Fourth graders (odds ratio OR: 1.68,p= 0.002), girls (OR: 1.48,p= 0.014), and students from suburban/rural areas (OR: 1.99, and OR: 4.93, respectively; bothp< 0.001) demonstrated higher hematuria risk. The prevalence of proteinuria was 0.2%. Fourth graders (OR: 4.44,p< 0.001) and students in suburban areas (OR: 0.27,p= 0.031) were associated with persistent proteinuria. After stratifying by age, the significant association remained. A higher risk of proteinuria was noted in underweight subjects (OR: 2.52,p= 0.023) among the fourth-grade students.

Conclusion:The prevalence of hematuria/proteinuria in Hualien was higher than the average reported for Taiwan. Hematuria/proteinuria was significantly associated with sex, age, BMI, and urbanization. Our longitudinal results can provide information for future pediatric CKD prevention in Taiwan.
Impact of COVID-19 Pandemic on Pediatrics and Pediatric Transplantation Programs
Authors: Lobritto Steven , Danziger-Isakov Lara , Michaels Marian G. , Mazariegos George V.
Published: December 2020

COVID-19 has dramatically altered the health care landscape and disrupted global health and world economics in ways that are still being measured. Its impact on children with chronic conditions or those undergoing transplantation is evolving. The organ specific manifestations in children will be reviewed and treatment strategies outlined. The impact on pediatric transplantation in the United States over the initial 6 months of the pandemic has shown significant regional variation and lags persist in resumption of normal transplant activity, particularly for living related transplantation. Finally, guidelines regarding return to school will be discussed.