bluuebunny/crossref_metadata_2025 huggingface dataset:
PEMANFAATAN ABU KERTAS DAN SERBUK CANGKANG LOKAN PADA CAMPURAN BETON NORMAL DENGAN MENGGUNAKAN SIKACIM CONCRETE ADDITIVE
Authors: Mulyati Mulyati , Yulandi Wiki
Published: July 2021

This research uses paper ash, lokan shell powder, and sikacim concrete additivefor normal concrete mix. Paper ash is used as a cement additive, while lokan shell powder is used as a partial substitute for sand. To overcome the lack of water in the concrete mixture, Sikacim concrete additive is used. The purpose of this study was to determine the compressive strength of concrete resulting from the use of paper ash as an additive and lokan shell powder as a substitute for sand by adding sikacim concrete additive.The test object used a cube mold of 15 cm x 15 cm x 15 cm with a concrete compressive strength of K-250 design at the age of 28 days of testing. Variations of the specimens used paper ash 0.25% by weight of cement, and lokan shell powder 0%, 10%, 20%, 30% by weight of sand, and 0.7% additive from the volume of water. Based on the results of the compressive strength test of concrete, the compressive strength of concrete is obtained, for normal concrete it is 276.6 kg/cm2, from the use of 0.25% paper ash, 0% lokan shell and 0.7% additive of 362.6 kg/cm2, from the use of 0.25% paper ash, 10% lokan shell and 0.7% additive of 365.3 kg/cm2, from the use of 0.25% paper ash, 20% lokan shell and 0.7% additive of 300.53 kg /cm2, from the use of 0.25% paper ash, 30% lokan shell and 0.7% additive of 250.16 kg/cm2.
PERJANJIAN DENGAN JAMINAN FIDUSIA BERDASARKAN PERATURAN MENTERI KEUANGAN REPUBLIK INDONESIA NOMOR 130/PMK.010/2012
Authors: Harniwati Harniwati
Published: July 2021

The provision of fiduciary guarantees in banking transactions generally uses a notarial deed and has been clearly regulated, but how about the implementation of the fiduciary guarantee. Implementation of the Agreement with Fiduciary Guarantee Based on the Regulation of the Minister of Finance of the Republic of Indonesia Number 130/Pmk.010/2012”. The research method used in this research is mainly library research by examining secondary data, sourced from primary, secondary and research legal materials. This is done to obtain the necessary accurate data related to the problem under study. The registration of fiduciary guarantees has been determined by the Fiduciary Guarantee Law Number 42 of 1999, which is also confirmed in the Regulation of the Minister of Finance of the Republic of Indonesia Number 130/PMK.010/2012.
PELAKSANAAN ISBAD NIKAH DAN DISPENSASI NIKAH DI KOTA PADANG
Authors: Agustini Sri
Published: July 2021

Marriage is a marriage bond (contract) carried out in accordance with the provisions of Islamic law and teachings. Meanwhile, marriage is a marriage ceremony that is identified with the consent and kabul process. Literally, marriage is a sacred bond and is carried out by a combination of religious and state regulations. In order for the marriage bond to have legal certainty administratively, the marriage has been regulated in law. With the enactment of these rules, marriages that are not in accordance with the law cause their own problems in society. Especially about unregistered marriages and early marriage or marriages by minors.
C-PURE SUBMODULES AND C-FLAT MODULES
Authors: ALAGÖZ Yusuf
Published: July 2021

Let R be a ring. A right R-module A is said to be C-flat if the kernel of any epimorphism B → A is C-pure in B, i.e. the induced map Hom(C,B) → Hom(C,A) is surjective for any cyclic right R-module C. Projective modules are C-flat and C-flat modules are weakly-flat and neat-flat. In this article, it is discussed the connections between C-flat, weakly-flat, neat-flat and singly flat modules. It is shown that C-flat modules coincide with singly-projective modules over arbitrary rings. Next, several characterizations of certain classes of rings and modules via C-purity are considered. We prove that, every C-flat module is injective if and only if R is a QF ring. Moreover, we show that R is a CF ring if and only if every FP-injective right R-module is C-flat.
Our Experience of Using Soft Bifocal Contact Lenses in Children with Progressive Myopia
Authors: Slyshalova N. N. , Khvatova N. V.
Published: July 2021

Introduction. According to the studies, one out of three myopic patients with refraction greater than –6.00 D and an axial length greater than 26 mm is at high risk of facing low vision and loss of sight in the future. According to the results of medical examinations and screenings in carried out in Ivanovo, the prevalence of myopia in primary school children has increased three times during the past twenty years. Myopic children under 7 years old are six times more likely to have myopia progressed to higher degrees than children in which myopia onset took place later (at the age of 11–12 years). Optical interventions for myopia control such as orthokeratology and soft bifocal contact lenses have a strong body of evidence and are well accepted by ophthalmologists.

Purpose. The purpose of the present study was to investigate the effect of soft bifocal contact lenses on refraction, accommodation and axial length in children with progressive myopia.

Materials and methods. We observed 30 children aged 8–15 years with myopia progression rate of 0.82 D/year and accommodative weakness and instability. We prescribed OKVision PrimaBio Bi-focal design soft bifocal contact lenses (OKVision, Russia) that feature +4.00 D addition power on periphery. The effectiveness was estimated by monitoring refraction, accommodation and axial length every three months within a year.

Results. After 12 months of wearing soft bifocal contact lenses, the annual myopia progression rate decreased 4.3 times on average. We were able to stabilize myopia in 50% of the children during the period of monitoring. The use of this intervention had a strong effect on accommodation resulting in an increase of its amplitude and reserve.

Conclusion. The use of soft bifocal contact lenses has been proven to have a strong inhibitory effect on myopia progression rate. Myopia stabilization manifested itself as the absence of increase in myopic refraction and axial length as well as normalization of accommodative function.
Проверка зрения у пациентов с аутизмом. Нарушение обработки информации мозгом – эффект Пульфриха
Authors: Абугова Т. Д.
Published: July 2021

Редакция продолжает публикацию книги основателя метода цветокоррекции Иана Джордана (Ian Jordan) «Руководство для родителей по проблемам зрения при заболеваниях аутистического спектра».
Fatiga y Calidad de vida en niños, niñas y adolescentes con cáncer hematológico
Authors: Espín Jordán Javier Andrés , Camacho Rodriguez Erick Andrés , Jurado Auria Stalin Augusto
Published: July 2021

Introducción: La fatiga es un problema relevante en pacientes con cáncer hematológico y puede ser un motivo de reducción importante de la calidad de vida. El objetivo del presente estudio fue realizar un estudio descriptivo de un grupo de niños y adolescentes portadores de neoplasias de origen hematológico en un centro único de referencia.

Metodología: El presente estudio observacional tiene un corte retrospectivo, en donde se incluyeron pacientes menores a 18 años con el diagnóstico de cáncer hematológico en quienes se revisó la historia clínica y se realizó un test de calidad de vida. Se realiza un análisis de correlación entre las variables usando estadística no paramétrica.

Resultados: ingresaron al estudio 64 pacientes. De sexo masculino (n=37) y femenino (n=27). El valor medio de fatiga fue (5.72 ± 0.53 y 5.85 ± 0.51), en actividad física y salud (1.49 ± 0.17 y 1.44 ± 0.13) en hombres y mujeres respectivamente. El valor medio de edad fue de 5.81 ± 2.46 en el rango de 2 a 10 años y 14.55 ±2.15 en el rango de 11 a 18 años. Según el rango etario existió más predominancia de fatiga en niños que en adolescentes y más en mujeres que en hombres.

Conclusión: No se encontró relación entre las variables de estudio. Sin embargo, los hallazgos expuestos indican una marcada sensación de fatiga siendo esta moderada pudiendo convertirse en seve-ra; de igual manera se obtuvo niveles bajos y medios de calidad de vida en las similares di-mensiones incluidas en las baterías de evaluación; sugiriendo futuras investigaciones inclu-yendo colaboración de abordaje multidisciplinaria para llegar a impartir las terapias adecuadas que beneficien a los pacientes con cáncer.
Recent Advances in the Synthetic Biology of Natural Drugs
Authors: Li Chun-Qiang , Lei Hong-Mei , Hu Qian-Yi , Li Guo-Hong , Zhao Pei-Ji
Published: July 2021

Natural drugs have been transformed and optimized during the long process of evolution. These compounds play a very important role in the protection of human health and treatment of human diseases. Sustainable approaches to the generation of raw materials for pharmaceutical products have been extensively investigated in drug research and development because chemical synthesis is costly and generates pollution. The present review provides an overview of the recent advances in the synthetic biology of natural drugs. Particular attention is paid to the investigations of drugs that may be mass-produced by the pharmaceutical industry after optimization of the corresponding synthetic systems. The present review describes the reconstruction and optimization of biosynthetic pathways for nine drugs, including seven drugs from plant sources and two drugs from microbial sources, suggesting a new strategy for the large-scale preparation of some rare natural plant metabolites and highly bioactive microbial compounds. Some of the suggested synthetic methods remain in a preliminary exploration stage; however, a number of these methods demonstrated considerable application potential. The authors also discuss the advantages and disadvantages of the application of synthetic biology and various expression systems for heterologous expression of natural drugs. Thus, the present review provides a useful perspective for researchers attempting to use synthetic biology to produce natural drugs.
Limitations of 16S rRNA Gene Sequencing to Characterize Lactobacillus Species in the Upper Genital Tract
Authors: O’Callaghan Jessica L. , Willner Dana , Buttini Melissa , Huygens Flavia , Pelzer Elise S.
Published: July 2021

The endometrial cavity is an upper genital tract site previously thought as sterile, however, advances in culture-independent, next-generation sequencing technology have revealed that this low-biomass site harbors a rich microbial community which includes multiple Lactobacillus species. These bacteria are considered to be the most abundant non-pathogenic genital tract commensals. Next-generation sequencing of the female lower genital tract has revealed significant variation amongst microbial community composition with respect to Lactobacillus sp. in samples collected from healthy women and women with urogenital conditions. The aim of this study was to evaluate our ability to characterize members of the genital tract microbial community to species-level taxonomy using variable regions of the 16S rRNA gene. Samples were interrogated for the presence of microbial DNA using next-generation sequencing technology that targets the V5–V8 regions of the 16S rRNA gene and compared to speciation using qPCR. We also performed re-analysis of published data using alternate variable regions of the 16S rRNA gene. In this analysis, we explore next-generation sequencing of clinical genital tract isolates as a method for high throughput identification to species-level of key Lactobacillus sp. Data revealed that characterization of genital tract taxa is hindered by a lack of a consensus protocol and 16S rRNA gene region target allowing comparison between studies.
CEACAM1 Activation by CbpF-Expressing E. coli
Authors: Shhadeh Amjad , Galaski Johanna , Alon-Maimon Tamar , Fahoum Jamal , Wiener Reuven , Slade Daniel J. , Mandelboim Ofer , Bachrach Gilad
Published: July 2021

Recent studies on the oral, anaerobic, gram-negative bacterium Fusobacterium nucleatum revealed its presence and involvement in colorectal, esophageal and breast cancer. We previously demonstrated that F. nucleatum binds and activates the human inhibitory receptors TIGIT and CEACAM1 leading to inhibition of T and NK cell anti-tumor immunity. CEACAM1 was found to be bound and activated by the fusobacterial trimeric autotransporter adhesin CbpF. Here we report the generation of a recombinant E. coli expressing full-length CbpF that efficiently binds and activates CEACAM1.
A Community Science Approach to Conservation Challenges Posed by Rebounding Marine Mammal Populations: Seal-Fishery Interactions in New England
Authors: Bogomolni Andrea , Nichols Owen C. , Allen Dee
Published: July 2021

Between 1880–1962, gray and harbor seals were targeted in legal seal bounty hunts across Maine and Massachusetts due to a perceived competition with commercial fisheries. Following their extirpation 50 years ago, legislative protections allowed seals to recolonize historical grounds along the New England coast. With this conservation success story, conflict has re-emerged as seen in the numerous media articles reflecting a temperament beckoning to the past century, with calls to cull the population and the spread of misinformation. The return of seals after decades of near-absence has created a new ecological and psychological baseline for New Englanders where for three generations, seals were rarely present. Although seals are statutorily protected species, unlike the tools and resources available for depleted, threatened or endangered species, the support needed to increase opportunities for coexistence of humans with rebounding pinnipeds, are comparatively lacking. Even as gray seals have the highest fisheries bycatch levels of any marine mammal in the U.S., resources to address these management challenges are minimal due to limitations and prioritization processes for committing available support. While seal conservation has been a success, the manner in which management is often separately applied to ecosystem elements (e.g., harvested species, protected species) contributes to knowledge gaps, and a disconnect between the goals of conservation to sustainably utilize natural resources while also protecting the intrinsic value of resources for ecosystem health. Solutions to such coexistence challenges could benefit from a more holistic ecosystem conservation approach. To address these disconnects, a two-day workshop was convened to understand seal-fishery interactions where we provided opportunities for community members to meet and learn from one another including, but not limited to, fishermen, natural resource managers, marine mammal stranding response personnel and scientists. A convening that might otherwise result in tumultuous and adversarial engagement, we used as a tool to engage. This community science approach led to long-term relationships that have allowed for successful applied, and community driven, solutions. Here we share the lessons learned and subsequent partnerships. Our intent is to share our approach to address other marine mammal conservation conflict challenges, allowing for collaborative pathways toward long-term coexistence.
Case Report: An Unusual Case of Biventricular Thrombosis in a COVID-19 Patient With Ischemic Dilated Cardiomyopathy: Assessment of Mass Mobility and Embolic Risk by Tissue Doppler Imaging
Authors: Sonaglioni Andrea , Albini Adriana , Nicolosi Gian Luigi , Rigamonti Elisabetta , Noonan Douglas M. , Lombardo Michele
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to angiotensin-converting enzyme 2 (ACE2) receptor on vascular cells. As a consequence, patients with COVID-19 have an increased incidence of thromboembolic complications of the SARS-CoV-2 infection and subsequent endothelial cell damage with consequence of development of systemic vasculitis and diffuse intravascular coagulation. The present case describes a COVID-19 female patient with ischemic dilated cardiomyopathy, who presented with congestive heart failure and echocardiographic evidence of biventricular apical thrombi. The peak antegrade longitudinal velocity (Va) of each thrombotic mass was measured by pulsed wave tissue Doppler imaging (PW-TDI). Both left ventricular and right ventricular apical thrombi were found with a TDI-derived mass peak Va < 10 cm/s. There was no clinical evidence of neither systemic nor pulmonary embolization, probably due to the hypomobility of both left and right ventricular masses.
Possible Environmental Influence on Eyewall Expansion During the Rapid Intensification of Hurricane Helene (2006)
Authors: Qin Nannan , Wu Liguang
Published: July 2021

Tropical cyclone (TC) rapid intensification (RI) is usually accompanied by a rapid eyewall contraction, followed by a slow contraction, and then a nearly steady eyewall. However, this study shows that Hurricane Helene (2006) exhibited an eyewall expansion during its 30-h rapid intensification period. The possible environmental influence on the eyewall expansion during the RI of Helene is examined. It is found that the synoptic-scale circulations led to additional low-level inflows and upper-level outflows that may play an important role in the eyewall expansion during the RI of Helene. Examination of the divergence of the absolute angular momentum flux (AAMF) associated with the environmental circulation suggests that the synoptic-scale atmospheric circulation played an important role in the eyewall expansion during the RI of Helene. In the lower and middle troposphere, the synoptic-scale cross-equatorial flow, which was enhanced by the Helene-induced wave train, led to the horizontal convergence of absolute angular momentum flux, while the TC-trough interaction and the related outflow in the upper troposphere resulted in the divergence of AAMF. The environment-induced low-level convergence and upper-level divergence of AAMF were superimposed on the secondary circulation of Helene and may be important to the eyewall expansion during the RI by accelerating the tangential wind outside of the eyewall. This study suggests that RI can occur with an eyewall expansion.
Market Power, Intertemporal Permits Trading, and Economic Efficiency
Authors: Jiang Minxing , Feng Xingliang , Li Liang
Published: July 2021

The banking and borrowing (BB) system has been developed gradually in the tradable permits market to perform a role as an environmental management tool. One question naturally arises as to how it will impact the behaviors of firms and the efficiency in presence of market power in the permits market. This paper considers market power in two cases: with and without the BB system. The equilibrium behaviors of the firms are identified in two cases. The findings show that the producing and discharging behaviors of firms depend on the permits price elasticity of output price without BB system, while they only depend on the growth rate of the output price in the BB system. Although both cases fail to obtain efficient solutions, the market with a BB system is capable of alleviating the inefficiency arising from market power compared with that without a BB system. The path of permits price satisfies the Hotelling rule in the case of the BB system, while it is closely related to the path of output price and output price elasticity of permits price in the case without the BB system.
Multi-Energy Flow Calculation Considering the Convexification Network Constraints for the Integrated Energy System
Authors: Chen Danlei , Bai Xiaoqing
Published: July 2021

To alleviate environmental pollution and improve the energy efficiency of end-user utilization, the integrated energy systems (IESs) have become an important direction of energy structure adjustment over the world. The widespread application of the coupling units, such as gas-fired generators, gas-fired boilers, and combined heat and power (CHP), increases the connection among electrical, natural gas, and heating systems in IESs. This study proposes a mixed-integer nonlinear programming (MINLP) model combining electrical, natural gas, and heating systems, as well as the coupling components, such as CHP and gas-fired generators. The proposed model is applicable for either the radial multi-energy network or the meshed multi-energy network. Since the proposed MINLP model is difficult to be solved, the second-order cone and linearized techniques are used to transform the non-convex fundamental matrix formulation of multi-energy network equations to a mixed-integer convex multi-energy flow model, which can improve the computational efficiency significantly. Moreover, the potential convergence problem of the original model can also be avoided. A simulation of IEEE 14-node electrical system, 6-node natural gas system, and 23-node heating system are studied to verify the accuracy and computational rapidity of the proposed method.
Deep Learning-Based Prediction of Wind Power for Multi-turbines in a Wind Farm
Authors: Chen Xiaojiao , Zhang Xiuqing , Dong Mi , Huang Liansheng , Guo Yan , He Shiying
Published: July 2021

The prediction of wind power plays an indispensable role in maintaining the stability of the entire power grid. In this paper, a deep learning approach is proposed for the power prediction of multiple wind turbines. Starting from the time series of wind power, it is present a two-stage modeling strategy, in which a deep neural network combines spatiotemporal correlation to simultaneously predict the power of multiple wind turbines. Specifically, the network is a joint model composed of Long Short-Term Memory Network (LSTM) and Convolutional Neural Network (CNN). Herein, the LSTM captures the temporal dependence of the historical power sequence, while the CNN extracts the spatial features among the data, thereby achieving the power prediction for multiple wind turbines. The proposed approach is validated by using the wind power data from an offshore wind farm in China, and the results in comparison with other approaches shows the high prediction preciseness achieved by the proposed approach.
Patterns of Pelagic Fish Diversity in Floodplain Lakes of Whitewater and Blackwater Drainage Systems Within the Central Amazon River Basin of Brazil
Authors: Siqueira-Souza Flávia K. , Hurd Lawrence E. , Yamamoto Kedma C. , Soares Maria Gercilia M. , Cooper Gregory J. , Kahn James R. , Freitas Carlos E. C.
Published: July 2021

The Amazon River Basin, one of the world’s most threatened ecosystems, has an enormous diversity of fish species, a result of temporally and spatially complex habitat containing biogeochemically different river systems. The annual hydrologic cycle results in floodplain lakes during low water and inundates forests during high water, exposing fish to different resources and environmental conditions. The two principal river systems in the central Brazilian Amazon are blackwater, with nutrient-poor acidic water, and nutrient-rich whitewater. Although species-rich, the Amazon Basin is data-poor in terms of comparative studies on a regional scale. We analyzed data sets from independent sampling studies of pelagic fish in 16 floodplain lakes, nine whitewater (Rio Solimões) and seven blackwater (Rio Negro), in the central Amazon Basin of Brazil. Our findings suggest striking similarities in pelagic fish diversity patterns. Species richness was virtually equal (165 in whitewater and 168 in blackwater). Both species richness, and number of migratory species, per lake increased toward the confluence of the rivers in both systems in our study. The proportion of unique species was also similar in whitewater lakes and blackwater (41 and 43%, respectively), boosting total regional richness to 237 species. However, species composition in whitewater lakes was more homogenous (lower β diversity), and species composition was associated with conductivity and pH in whitewater, but with dissolved oxygen and transparency in blackwater. Therefore, regional fish diversity cannot be represented by sampling one lake or even one drainage system, but must include multiple lakes from both systems. These two systems may differ in sensitivity to anthropogenic stressors such as damming and deforestation.
The First Age of Reptiles? Comparing Reptile and Synapsid Diversity, and the Influence of Lagerstätten, During the Carboniferous and Early Permian
Authors: Brocklehurst Neil
Published: July 2021

Terrestrial ecosystems during the Pennsylvanian (late Carboniferous) and Cisuralian (early Permian) are usually described in the literature as being dominated by synapsids, the mammal-line amniotes. The pelycosaurs (a paraphyletic grouping of synapsid families) have been considered more speciose, abundant, and ecologically diverse than contemporary reptile-line amniotes. However, this dominance has never been subjected to quantitative testing accounting for sampling bias. Moreover, in recent years the amniote phylogeny has undergone numerous revisions, with suggestions that varanopids and recumbirostran microsaurs fall within reptiles, and that diadectomorphs may be pelycosaurian-grade synapsids. An examination of local species richness (alpha diversity) of synapsids and reptiles during the Pennsylvanian and Cisuralian at different spatial scales shows that these taxonomic revisions have substantial impacts on relative diversity patterns of synapsids and reptiles. Synapsids are only found to be consistently more diverse through the early Permian when using the “traditional” taxonomy. The recent taxonomic updates produce diversity estimates where reptile diversity is consistent with, or in some cases higher than that of synapsids. Moreover, biases in preservation may affect patterns. Where preservation favors smaller vertebrates, e.g., Richards Spur, South Grandfield, reptiles overwhelmingly dominate. If smaller vertebrates are expected to make up the bulk of amniote diversity, as they do in the present day, such lagerstätten may be more representative of true diversity patterns. Therefore, the dominance of pelycosaurs during this interval should be reconsidered, and this interval may be considered the First Age of Reptiles.
Immunomodulatory Role and Therapeutic Potential of Non-Coding RNAs Mediated by Dendritic Cells in Autoimmune and Immune Tolerance-Related Diseases
Authors: Liu Yifeng , Wang Xiaoze , Yang Fan , Zheng Yanyi , Ye Tinghong , Yang Li
Published: July 2021

Dendritic cells (DCs) are professional antigen-presenting cells that act as a bridge between innate immunity and adaptive immunity. After activation, DCs differentiate into subtypes with different functions, at which point they upregulate co-stimulatory molecules and produce various cytokines and chemokines. Activated DCs also process antigens for presentation to T cells and regulate the differentiation and function of T cells to modulate the immune state of the body. Non-coding RNAs, RNA transcripts that are unable to encode proteins, not only participate in the pathological mechanisms of autoimmune-related diseases but also regulate the function of immune cells in these diseases. Accumulating evidence suggests that dysregulation of non-coding RNAs contributes to DC differentiation, functions, and so on, consequently producing effects in various autoimmune diseases. In this review, we summarize the main non-coding RNAs (miRNAs, lncRNAs, circRNAs) that regulate DCs in pathological mechanisms and have tremendous potential to give rise to novel therapeutic targets and strategies for multiple autoimmune diseases and immune tolerance-related diseases.
The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer
Authors: Guo Qiang , Li Dan , Luo Xiangyu , Yuan Ye , Li Tian , Liu Huasong , Wang Xinju
Published: July 2021

Background

The occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis.

Methods

The expression and clinical significance of LINC00973 in NSCLC tissues were analyzed via the The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), lnCAR, and clinical samples in Taihe Hospital. The biological functions and signaling pathways involved in target genes of ceRNA network were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis, univariate and multivariate Cox regression analysis were used for prognostic-related mRNA.

Results

Expression of LINC00973 was increased in NSCLC tissues. High expression of LINC00973 was associated with poor prognosis of NSCLC patients. There were 15 miRNA and 238 differential mRNA in the INC00973-miRNA-mRNA ceRNA network, involving cell migration, endothelial cell proliferation, tumor growth factor (TGF)-β, cellular senescence, phosphatidylinositol 3-hydroxy kinase (PI3K)-Akt, Hippo, Rap1, mitogen-activated protein kinase (MAPK), cell cycle signaling pathway, etc. The expression levels of RTKN2, NFIX, PTX3, BMP2 and LOXL2 were independent risk factors for the poor prognosis of NSCLC patients.

Conclusions

LINC00973-miRNA-mRNA ceRNA network might be the basis for determining pivotal post-translational regulatory mechanisms in the progression of NSCLC. BMP2, LOXL2, NFIX, PTX3 and RTKN2 might be valuable prognostic markers and potential therapeutic targets.
Clinical Significance and Inflammatory Landscape of aNovel Recurrence-Associated Immune Signature in Stage II/III Colorectal Cancer
Authors: Liu Zaoqu , Lu Taoyuan , Li Jing , Wang Libo , Xu Kaihao , Dang Qin , Liu Long , Guo Chunguang , Jiao Dechao , Sun Zhenqiang , Han Xinwei
Published: July 2021

Background

A considerable number of patients with stage II/III colorectal cancer (CRC) will relapse within 5 years after surgery, which is a leading cause of death in early-stage CRC. The current TNM stage system is limited due to the heterogeneous clinical outcomes displayed in patients of same stage. Therefore, searching for a novel tool to identify patients at high recurrence-risk for improving post-operative individual management is an urgent need.

Methods

Using four independent public cohorts and qRT-PCR data from 66 tissues, we developed and validated a recurrence-associated immune signature (RAIS) based on global immune genes. The clinical and molecular features, tumor immune microenvironment landscape, and immune checkpoints profiles of RAIS were also investigated.

Results

In five independent cohorts, this novel scoring system was proven to be an independent recurrent factor and displayed excellent discrimination and calibration in predicting the recurrence-risk at 1~5 years. Further analysis revealed that the high-risk group displayed high mutation rate of TP53, while the low-risk group had more abundance of activated CD4+/CD8+ T cells and high expression of PD-1/PD-L1.

Conclusions

The RAIS model is highly predictive of recurrence in patients with stage II/III CRC, which might serve as a powerful tool to further optimize decision-making in adjuvant chemotherapy and immunotherapy, as well as tailor surveillance protocol for individual patients.
The Norwegian Sea Gyre – A Regulator of Iceland-Scotland Ridge Exchanges
Authors: Hátún Hjálmar , Chafik Léon , Larsen Karin Margretha Húsgarð
Published: July 2021

The Norwegian Sea gyre (NSG) is a large body of Arctic intermediate water and deep dense overflow waters, which circulate counterclockwise within the Norwegian Sea. Argo float trajectories presented in this study suggest that the NSG attains its strongest and most focused flow downstream of a confluence of subarctic waters from the Iceland Sea and the Jan Mayen Ridge at steep bathymetry north of the Faroe slope. Based on hydrographic data from a meridional standard section across this flow (1988 to present), the first baroclinic estimate of the NSG circulation strength is provided. We, furthermore, show that the NSG circulation regulates key aspects of both the poleward Atlantic Water (AW) currents and the equatorward near-bottom and mid-depth flows in the Norwegian Sea – the main arteries of the Meridional Overturning Circulation. More specifically, we demonstrate close links between the NSG circulation and (i) the observed Faroe Bank Channel Overflow (FBCO) transport, (ii) variable depth of the main thermocline separating AW from the underlying colder and denser subarctic water masses, and (iii) satellite-derived sea-surface heights (SSHs) in the southern Nordic Seas. In general, a strong NSG and weak FBCO transport are associated with an uplifted thermocline and depressed SSH. Along a narrow band near the Norwegian and Shetland slopes, a strong NSG – oppositely – links to a depressed interface. Daily records of the FBCO transport, and satellite altimetry in a sensitive region north of the Iceland-Faroe Ridge, complement our hydrographic monitoring of the NSG strength. Together these records constitute valuable indicators for aspects of the Norwegian Sea physical oceanography, which likely have an impact on regional climate, ecology and biological productivity.
Defining Nature-Based Solutions Within the Blue Economy: The Example of Aquaculture
Authors: Hughes Adam D.
Published: July 2021

The concepts of Nature-based Solutions (NbS) and the Blue Economy (BE) are two prominent sustainability frameworks at the forefront of policy dialogues. However, investment within the BE has been slowed by the lack of a sufficiently robust operational definition. This lack of definition reduces investor confidence and impacts adoption by policy makers and practitioners. By considering the overlap between the two sustainability frameworks it is possible to identify specific sectors and activities within the BE that also fit the operationalised criteria for NbS. Undertaking this process for one sector of the BE (aquaculture) has provided evidence that aquaculture activities, if planned and operated within the criteria, would qualify as NbS and as such may unlock financing for the provision of ecosystem services.
Desaturation-Distance Ratio During Submaximal and Maximal Exercise Tests and Its Association With Lung Function Parameters in Patients With Lymphangioleiomyomatosis
Authors: Queiroz Douglas Silva , da Silva Cibele Cristine Berto Marques , Amaral Alexandre Franco , Oliveira Martina Rodrigues , Moriya Henrique Takachi , Carvalho Carlos Roberto Ribeiro , Baldi Bruno Guedes , Carvalho Celso R. F.
Published: July 2021

Background: The desaturation–distance ratio (DDR), the ratio of the desaturation area to the distance walked, is a promising, reliable, and simple physiologic tool for functional evaluation in subjects with interstitial lung diseases. Lymphangioleiomyomatosis (LAM) is a rare neoplastic condition frequently associated with exercise impairment. However, DDR has rarely been evaluated in patients with LAM.

Objectives: To assess DDR during maximal and submaximal exercises and evaluate whether DDR can be predicted using lung function parameters.

Methods: A cross-sectional study was conducted in a cohort of women with LAM. The 6-min walking test (6MWT) and the incremental shuttle walking test (ISWT) were performed, and DDR was obtained from both tests. The functional parameters were assessed at rest using spirometry and body plethysmography. The pulmonary function variables predictive of DDR were also assessed.

Results: Forty patients were included in this study. The mean age was 46 ± 10 years. Airway obstruction, reduced DLCO, and air trapping were found in 60, 57, and 15% of patients, respectively. The distance walked and the DDR for the 6MWT and ISWT were, respectively, 517 ± 65 and 443 ± 127 m; and 6.6 (3.8–10.9) and 8.3 (6.2–12.7). FEV1 (airway obstruction) and reduced DLCO and RV/TLC (air trapping) were independent variables predictive of DDR during exercises field tests [DDR6MWT = 18.66–(0.06 × FEV1%pred)–(0.10 × DLCO%pred) + (1.54 × air trapping), Radjust2 = 0.43] and maximal [DDRISWT = 18.84–(0.09 × FEV1%pred)–(0.05 × DLCO%pred) + (3.10 × air trapping), Radjust2 = 0.33].

Conclusion: Our results demonstrated that DDR is a useful tool for functional evaluation during maximal and submaximal exercises in patients with LAM, and it can be predicted using airway obstruction, reduced DLCO, and air trapping.
Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept
Authors: Macioszek Szymon , Wawrzyniak Renata , Kranz Anna , Kordalewska Marta , Struck-Lewicka Wiktoria , Dudzik Danuta , Biesemans Margot , Maternik Michał , Żurowska Aleksandra M. , Markuszewski Michał J.
Published: July 2021

Renal dysplasia is a severe congenital abnormality of the kidney parenchyma, which is an important cause of end-stage renal failure in childhood and early adulthood. The diagnosis of renal dysplasia relies on prenatal or postnatal ultrasounds as children show no specific clinical symptoms before chronic kidney disease develops. Prompt diagnosis is important in terms of early introduction of nephroprotection therapy and improved long-term prognosis. Metabolomics was applied to study children with renal dysplasia to provide insight into the changes in biochemical pathways underlying its pathology and in search of early indicators for facilitated diagnosis. The studied cohort consisted of 72 children, 39 with dysplastic kidneys and 33 healthy controls. All subjects underwent comprehensive urine metabolic profiling with the use of gas chromatography and liquid chromatography coupled to mass spectrometry, with two complementary separation modes of the latter. Univariate and multivariate statistical calculations identified a total of nineteen metabolites, differentiating the compared cohorts, independent of their estimated glomerular filtration rate. Seven acylcarnitines, xanthine, and glutamine were downregulated in the urine of renal dysplasia patients. Conversely, renal dysplasia was associated with higher urinary levels of dimethylguanosine, threonic acid or glyceric acid. This is the first metabolomic study of subjects with renal dysplasia. The authors define a characteristic urine metabolic signature in children with dysplastic kidneys, irrespective of renal function, linking the condition with altered fatty acid oxidation, amino acid and purine metabolisms.
Tailoring Human Milk Oligosaccharides to Prevent Necrotising Enterocolitis Among Preterm Infants
Authors: Abbas Safiyyah , Keir Amy K. , Makrides Maria , Klein Laura D. , Grzeskowiak Luke E. , McPhee Andrew J. , Rumbold Alice R.
Published: July 2021

Necrotising enterocolitis (NEC) is a devastating disease affecting preterm infants, with little improvement in mortality rates and treatment strategies in the last 30 years. Human milk oligosaccharides (HMOs) are emerging as a potential preventive therapy, with multiple protective functions postulated. Our aim is to summarise the evidence concerning the role of HMOs in NEC development and emerging strategies to tailor the delivery of HMOs to preterm infants. Most research efforts to date have focused on supplementing preterm infants with simple oligosaccharides, which are structurally different to HMOs and derived mainly from plants. Clinical trials demonstrate limited benefits for NEC prevention arising from the use of these supplements. Alternative strategies under investigation include optimising HMOs for infants receiving donor human milk, concentrating oligosaccharides from donor human milk and from animal milks, as well as more sophisticated synthetic oligosaccharide production strategies. Critically, high quality evidence to support implementation of any of these approaches in the neonatal unit is lacking. Whether it is a specific HMO alone or a combination of HMOs that exert protective effects remains to be elucidated. Further challenges include how best to manufacture and administer oligosaccharides whilst retaining bioactivity and safety, including evaluation of the long-term effects of altering the balance of HMOs and gut microbiota in preterm infants. While several human clinical trials are underway, further research is needed to understand whether a tailored approach to oligosaccharide supplementation is beneficial for preterm infants.
The Evolving Role of 18F-FDG PET/CT in Diagnosis and Prognosis Prediction in Progressive Prostate Cancer
Authors: Shen Kai , Liu Bo , Zhou Xiang , Ji Yiyi , Chen Lei , Wang Qi , Xue Wei
Published: July 2021

Positron emission tomography/computed tomography (PET/CT) is widely used in prostate cancer to evaluate the localized tumor burden and detect symptomatic metastatic lesions early. 18F-FDG is the most used tracer for oncologic imaging, but it has limitations in detecting early-stage prostate cancer. 68Ga-PSMA is a new tracer that has high specificity and sensibility in detecting local and metastatic tumors. But with the progression of prostate cancer, the enhancement of glucose metabolism in progressive prostate cancer provides a chance for 18F-FDG. This review focuses on PET/CT in the detection and prognosis of prostate cancer, summarizing the literature on 18F-FDG and 68Ga-PSMA in prostate cancer and highlighting that 18F-FDG has advantages in detecting local recurrence, visceral and lymph node metastases compared to 68Ga-PSMA in partial progressive prostate cancer and castration-resistant prostate cancer patients. We emphasize 18F-FDG PET/CT can compensate for the weakness of 68Ga-PSMA PET/CT in progressive prostate cancer.
Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic In Vitro-Conditions
Authors: Adrian Gabriel , Konradsson Elise , Beyer Sarah , Wittrup Anders , Butterworth Karl T. , McMahon Stephen J. , Ghita Mihaela , Petersson Kristoffer , Ceberg Crister
Published: July 2021

Background

Irradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several in vivo studies. Few cell lines have been investigated in vitro, and previous results are inconsistent. Assuming that oxygen depletion accounts for the FLASH sparing effect, no sparing should appear for cells irradiated with low doses in normoxia.

Methods

Seven cancer cell lines (MDA-MB-231, MCF7, WiDr, LU-HNSCC4, HeLa [early passage and subclone]) and normal lung fibroblasts (MRC-5) were irradiated with doses ranging from 0 to 12 Gy using FLASH (≥800 Gy/s) or conventional dose rates (CONV, 14 Gy/min), with a 10 MeV electron beam from a clinical linear accelerator. Surviving fraction (SF) was determined with clonogenic assays. Three cell lines were further studied for radiation-induced DNA-damage foci using a 53BP1-marker and for cell cycle synchronization after irradiation.

Results

A tendency of increased survival following FLASH compared with CONV was suggested for all cell lines, with significant differences for 4/7 cell lines. The magnitude of the FLASH-sparing expressed as a dose-modifying factor at SF=0.1 was around 1.1 for 6/7 cell lines and around 1.3 for the HeLasubclone. Similar cell cycle distributions and 53BP1-foci numbers were found comparing FLASH to CONV.

Conclusion

We have found a FLASH effect appearing at low doses under normoxic conditions for several cell lines in vitro. The magnitude of the FLASH effect differed between the cell lines, suggesting inherited biological susceptibilities for FLASH irradiation.
CDK4: A Novel Therapeutic Target for Extramammary Paget’s Disease
Authors: Hashimoto Hiroki , Kaku-Ito Yumiko , Oda Yoshinao , Ito Takamichi
Published: July 2021

Background

The outcome of extramammary Paget’s disease (EMPD) is poor when it progresses to metastasis because of the lack of effective systemic therapies. Recently, CDK4-targeted therapy has attracted attention as a potential therapeutic target for some cancers. The aim of this study was to analyze the impact of CDK4 expression on the survival of patients with EMPD.

Methods

We retrospectively reviewed 110 patients with EMPD. We conducted immunohistochemical analysis of CDK4 and cyclin D1 expression, and assessed the association between their expression and survival.

Results

Most EMPD lesions (108/110, 98.2%) were positive for CDK4 staining and there was a positive correlation between CDK4 expression and cyclin D1 expression (r = 0.54,p< 0.001). Tumor thickness (p= 0.0003) and the presence of regional lymph node metastasis (p= 0.015) were significantly associated with high CDK4 expression. Regarding invasive EMPD, the multivariate analysis did not show the correlation between the expression of CDK4/cyclin D1 and survival outcomes (HR: 3.14,p= 0.14).

Conclusion

The overexpression of CDK4 was identified as a major risk factor for disease progression. CDK4-targeted therapy could thus be a novel treatment option for unresectable EMPD.
Digital Pathology Scoring of Immunohistochemical Staining Reliably Identifies Prognostic Markers and Anatomical Associations in a Large Cohort of Oral Cancers
Authors: Moratin Julius , Mock Andreas , Obradovic Sonja , Metzger Karl , Flechtenmacher Christa , Zaoui Karim , Fröhling Stefan , Jäger Dirk , Krauss Jürgen , Hoffmann Jürgen , Freier Kolja , Horn Dominik , Hess Jochen , Freudlsperger Christian
Published: July 2021

Utilizing digital pathology algorithms for the objective quantification of immunohistochemical staining, this study aimed to identify robust prognostic biomarkers for oral cancer. Tissue microarrays with specimens of a large cohort of oral squamous cell carcinoma (n=222) were immunohistochemically stained to determine the expression of PD-L1, EGFR, and COX-2 and the amount of infiltrating NK cells and CD8-positive T cells. Immunoreactivity scores were assessed using both a classical manual scoring procedure and a digital semi-automatic approach using QuPath. Digital scoring was successful in quantifying the expression levels of different prognostic biomarkers (CD8: p<0.001; NK cells: p=0.002, PD-L1: p=0.026) and high levels of concordance with manual scoring results were observed. A combined score integrating EGFR expression, neck node status and immune cell signatures with a significant impact on overall and progression-free survival was identified (p<0.001). These data may contribute to the ongoing research on the identification of reliable and clinically relevant biomarkers for the individualization of primary and adjuvant treatment in oral cancer.