bluuebunny/crossref_metadata_2025 huggingface dataset:
Hubungan Faktor-Faktor yang Mempengaruhi Kuat Tekan Beton
Authors: Amelia Rara , Suhendra Suhendra , Amalia Kiki Rizky
Published: October 2021

Penggunaan material sebagai bahan campuran beton dapat menjadi keuntungan dari perencanaan konstruksi, apabila komposisi campuran betonnya tepat. Kekuatan karakteristik beton menjadi perhatian penting bagi perencana dan pengendalian mutu, karena kekuatan beton biasanya memberikan gambaran kualitas beton secara keseluruhan. Kuat tekan beton dipengaruhi oleh banyak factor. Studi ini meneliti faktor yang mempengaruhi kuat tekan beton dari proporsi bahan-bahan penyusun beton saja.Adapun komponen-komponen yang mempengaruhi kuat tekan beton yang dikaji ialah Faktor Air-Semen, nilai abrasi, Faktor Agregat-Semen dan Faktor Luas Permukaan agregat. Kajian ini bertujuan untuk mengetahui hubungan pengaruh masing-masing komponen secara parsial dan kombinasi dua komponen atau lebih secara simultan terhadap kuat tekan beton dengan 15 hipotesis data yang ditelaah melalui program SPSS versi 22 dan Ms.Excel. Dari 100 data sekunder yang bersumber dari laporan perencanaan campuran beton pada Laboratorium Fakultas Teknik Universitas Batanghari diperoleh hasil Faktor Agregat-Semen memberikan pengaruh yang paling dominan secara parsial terhadap kuat tekan beton sebesar 63,8%. Pada kombinasi 2 komponen yakni Faktor Agregat-Semen dan nilai abrasi secara simultan memberikan pengaruh yang paling dominan terhadap kuat tekan beton sebesar 65,7%. Pada 3 kombinasi komponen yaitu Faktor Agregat-Semen, nilai abrasi dan Faktor Luas Permukaan secara simultan memberikan pengaruh yang paling dominan terhadap kuat tekan beton sebesar 71%. Pengaruh 4 kombinasi komponen ialah Faktor Air-Semen, Faktor Agregat-Semen, nilai abrasi dan Faktor Luas Permukaan secara simultan memberikan pengaruh sebesar 70,7% terhadap kuat tekan beton.
TRUCKS AS INSPIRATION FOR BABY BED CREATION
Authors: Triana Agus , Marwati Sri
Published: October 2021

Baby bed is one type of furniture which the existence is very necessary to meet the needs of the community, especially in family groups who have children / babies. The idea of creating the work is divided into two problem formulations, namely, how to design a baby bed in the form of a truck with decorative elements of Punakawan and how to visualize the design into works of art. The approach used is Dewitt H. Parker's aesthetic theory. The method of creation includes 3 stages, namely: the exploration stage, the design stage, and the embodiment stage. The baby bed produced in this artistic research is a work that has functional and aesthetic values with reference to the character of Punakawan. The symbolic value contains the exemplary teachings of Punakawan become a substance in this baby bed artwork. These baby beds are created creatively and innovatively for the renewal of baby bed shapes.
THE MOTION COMIC JAKA BEREK
Authors: - Sutikno - , Supriyanto Eko
Published: October 2021

In the past, people watched a theater called Ludruk on the mobile stage and on television. However, currently Ludruk's art is almost out of date. From this phenomenon, the researchers formulated the problem, namely how the local story artworks of Sawonggaling content can be transformed into a motion comic animated film using a three-act structure. The method of making comic motion animation for the legend of Jaka Berek uses two approaches, namely the method of making animation and the method of making comics. Both of them are done in 3 stages, namely pre-production, production and post-production. The results of the making of this motion comic animation show that the effort to bring back the legendary story that has long been drowned requires some appropriate medias that is easily understood by the current generation. The making of motion comics originating from legendary stories must be based on research and literature studies in order to give the spirit to the artwork that will be produced.
Implementasi Pembinaan Konsepsi Model Pembelajaran Up Grading untuk Meningkatkan Kualitas Mengajar Guru di Sekolah Dasar Binaan Segugus 05 Kopang Lombok Tengah
Authors: Ahmad Ahmad
Published: October 2021

The purpose of this research is to improve the teaching quality of teachers through the Up Grading learning model, especially in elementary schools assisted by the 05 Kopang cluster. This research method used action research with a qualitative approach. Data collection techniques using observation techniques (observation), field notes, and documentation. The data analysis technique in this study used qualitative data analysis techniques. The results showed that the implementation of the Up Grading learning model conception development was able to improve the quality of teacher teaching. The results of this study indicate that Up Grading Learning has a positive impact on improving teacher performance. This can be seen from the more stable students' understanding of the material presented by the teacher (learning mastery increases from cycles I, II, and III) which are 65.00%, 75.00%, and 85.00%, respectively. In cycle III, classical student learning completeness has been achieved. This research was successful because there was an increase with the research success criteria of 10% per cycle.
Detecting strong spatial and temporal variation in macrobenthic composition on an urban shelf using taxonomic surrogates
Authors: Kokesh BS , Kidwell SM , Tomašových A , Walther SM
Published: October 2021

Surrogates of macrobenthic assemblages, intended to alleviate the effort and taxonomic expertise required for monitoring, can take many forms, such as using coarser taxonomic levels (‘sufficiency’) or only a subset of the whole fauna (‘subsetting’). Here, the power of both approaches to retain community-level patterns of spatial and temporal variation were evaluated using an exceptionally long (47 yr) infaunal dataset generated from monitoring wastewater impacts on an urban shelf in southern California, USA. Four taxonomic sets (whole infauna, polychaetes, bivalves, malacostracans) were evaluated at 5 resolutions (species, genus, family, order, functional guild) along a pollution gradient subdivided into 2 spatial bins based on proximity to the wastewater outfall (near-field vs. far-field) and 3 temporal bins based on wastewater treatment phases. All taxonomic sets detected weakening of the spatial gradient with improved wastewater treatment, i.e. communities became more similar in richness, evenness, and composition through time, and patterns were robust when coarsened to families or guilds. Polychaetes mirrored (‘proxied’) whole-fauna patterns most accurately, as expected since they constitute most of the individuals and species. However, bivalves outperformed all other sets in detecting (‘indicating’) the pollution gradient itself, owing to their breadth of feeding strategies. These results strengthen the consistently positive results from taxonomic coarsening emerging from tests elsewhere and the caveats for taxonomic subsetting: clade strengths serve different objectives. Comparable datasets should exist in environmental agency archives elsewhere, promoting the general surrogacy model. For monitoring programs still in their planning stages, regional insights could be acquired via analogous nested analyses of a single survey.
Pasture resilience reflects differences in root and shoot responses to defoliation, and water and nitrogen deficits
Authors: Moot Derrick , Black Alistair , Lyons Eric , Egan Lucy , Hofmann Rainer
Published: October 2021

The yield of a pasture is directly proportional to the amount of light plants intercept and allocate to different organs. When plants are carbon (C) limited, due to defoliation, they allocate more C preferentially to shoots to restore leaf area. In contrast, water and nitrogen (N) limitations lead to a greater allocation of C to roots. Changes in the root:shoot ratio therefore reflect changes in C and N partitioning and indicate their relative priority. A major factor that influences plant responses to stress is their ability to store and remobilise reserves to restore leaf area. Species with tap roots, like lucerne, have a large potential C and N storage capacity that is utilised seasonally for storage and remobilisation. This has been used to develop seasonally based grazing management rules. Similarly, recommendations to graze perennial ryegrass at the 2- or 3-leaf stage are based on the balance between maximizing growth rates and the need to replenish water-soluble carbohydrate reserves. However, perennial ryegrass has lower levels of perennial reserves than other grass species. This reduces its resilience to concurrent water deficits or N deficiency. Under these conditions maintaining the recommended 3-leaf grazing intervals and/or leaving higher post-grazing pasture masses are recommended to assist canopy recovery. Other grass species, such as cocksfoot and tall fescue, provide more resilience, particularly in response to water deficits.
HUKUK DEVLETİNİN KANUN DEVLETİNE ANAYASAL DEVLETİN ANAYASALI DEVLETE EVİRİLMESİ
Authors: KESKİNSOY Ömer , KAYA Semih Batur
Published: October 2021

Hukuk insan hak ve özgürlüklerini koruyan ve geliştiren bir ilkelerin toplamıdır. Bu ilkelerin en başat olanı ise hukuk devletidir. Biz hukuk devletini demokratik devleti de içine alacak şekilde düşünmekte ve genişletmekteyiz. Buradan karşımıza anayasal demokrasi çıkmaktadır. Anayasal demokrasi anayasal devlet ile demokratik devletin birleşimidir. Hukuksal bir birleşim olan anayasal demokrasi her iki olgunun, yani anayasal devlet ve demokratik devletin, ahlaki temellerini içermektedir. Anayasal devletin ahlaki temeli anayasacılıktır. Anayasacılık iktidarın sınırlandırması ve hak ve özgürlüklerin güvenceye bağlanmasıdır. Dolayısıyla anayasacılığın özü denge ve denetimdir. Demokratik devletin ahlaki temeli ise çoğulcu demokrasidir. Çoğulcu demokrasi sanıldığı gibi yönetime ilişkin bir irade daralması değildir; aksine çoğulcu demokrasi bir irade genişlemesidir. Zira çoğulcu demokraside çoğunluğun yönetim hakkı korunmakla birlikte azınlıkta kalanların hak ve özgürlükleri ve ileride çoğunluk haline gelme potansiyelleri göz ardı edilmemektedir. Şu hâlde anayasal demokrasi anayasal devlet ile demokratik devletin zoraki bir birleşimi değildir. Anayasal devlet ile demokratik devlet yönetime yönelik bir madalyonun iki yüzü gibidir. Biri olmadığı takdirde yönetim demokratik hukuk devleti niteliğini yitirir. Son olarak kanımızca anayasal demokrasi gerek ülkemizde gerek dünyada bir anlam ve uygulama aşınmasına uğramaktadır. Amacımız gelinen noktada hukukun evrensel ilkelerine yeniden dikkat çekmektir.
Dijital Peculium Kavramı
Authors: ÖZBAY Ümit Vefa
Published: October 2021

Roma hukukunda köleler mal (res) statüsünde kabul ediliyordu. Mal gibi alınıp satılabiliyorlar, alacak veya borç konusu olabiliyorlardı. Ancak, köleler insan oldukları için düşünen ve irade sahibi canlı varlıklardı ve başkalarıyla birtakım hukuki ilişkilere girişmeleri kaçınılmaz bir şeydi. Kölelerin hukuki işlem yapabilmesinin önünü açmak ve onları ticaret hayatında aktif bir biçimde kullanabilmek adına Romalılar çeşitli düzenlemeler yaptılar. Bu düzenlemelerden en önemlisi aile babalarının kölelere (ve aile evlatlarına) aile mamelekinin belli bir kısmı üzerinde sınırlı yetki tanımasıydı. Söz konusu sermayeye peculium ismi verilmiştir. Sırtını Roma Hukuku’nun peculium kavramına dayayan dijital peculium kavramı ise günümüzde yapay zekâ tartışmalarında doktrinde kendisine yer bulmaktadır. Kavram bazı hukukçular tarafından yapay zekânın hukuki statüsü tatmin edici bir hal alana kadar, yapay zekâyı günlük hayata dâhil edebilme ve yapay zekâyı hesap verebilir bir hale getirme konusunda önerilmektedir. Çalışmamızda önce yapay zekâ ve robot kavramı kısaca tanımlanarak, yapay zekânın hukuki statüsüne yönelik fikirler değerlendirmeye alınacak, ardından Katz ve Pagallo’nun çalışmaları ile doktrindeki tartışmalarda kendisine yer bulmuş Dijital Peculium kavramı incelenecektir. Kavram incelenirken öncelikle Roma hukukundaki peculium kavramı tanıtılacak ve söz konusu kavrama dair düzenlemelerin çağdaş hukukumuzda, yapay zekâ düzenlemelerine ne gibi bir katkıda bulunabileceği tartışılacaktır.
APPROACH TO ANALYSIS OF INNOVATIVE DEVELOPMENT OF THE OIL AND GAS SECTOR OF RUSSIA: STRUCTURE OF PATENTS FOR INVENTIONS
Authors: Tokarev Anatoliy N.
Published: October 2021

The oil and gas sector plays a key role in the Russian economy. In the context of the growing complexity of the resource base, the emergence of the knowledge economy, its stability and competitiveness largely depend on innovative, technological development. Based on the analysis of data on patent activity in relation to inventions for oil and gas companies, the key actors in this segment of innovation were identified. These include Russian oil and gas producing companies (first of all, PJSC Tatneft and PJSC Gazprom), as well as foreign companies present on the Russian market, primarily large oil and gas field service companies.The existing structure of patenting activity for oil and gas companies of Russia determines significant risks in the face of sanctions pressure and the existing need for new technologies.
COMPARATIVE ANALYSIS OF THE BEHAVIOR OF RUSSIAN HIGH-TECH AND LOW-TECH MANUFACTURING COMPANIES
Authors: Goryushkin Anton A.
Published: October 2021

The high-tech sector is considered to be innovatively active, but its contribution to GDP does not change, despite the measures taken by the government. This may be due to the same behavior patterns of high- and low-tech companies. The analysis of the behavior of high- and low-tech companies was carried out according to the data of surveys of heads of domestic manufacturing enterprises. The approach for testing hypotheses about possible differences in the behavior of high- and low-tech companies in different economic conditions is based on a statistical comparison of the average values of indicators for companies in these sectors. It was found that the level of innovation activity among high-tech companies declines to a lesser extent than among low-tech companies during the crisis. In these conditions, high-tech companies are more actively using "internal reserves": they are working more to improve the skill level of staff and implementing innovation processes. During periods of high and low rates of economic growth, high-tech companies often buy new technology. The rest of the patterns of behavior of high- and low-tech companies do not differ.
FEATURES OF THE ORGANIZATION AND IMPLEMENTATION OF SPECIAL TREATMENT DURING THE IMPLEMENTATION OF DEGASSING IN EMERGENCY SITUATIONS WITH HAZARDOUS CHEMICALS OF GENERAL TOXIC ACTION
Authors: Vasendin Dmitry V. , Tatarenko Valery I.
Published: October 2021

Degassing is one of the most important measures taken in the event of emergency situations with hazardous chemicals of general toxic or general toxic action. This is a large group of toxic chemicals with various mechanisms of toxic action, as well as insufficiently studied mechanisms of action on living organisms. This explains the importance of proper organization and implementation of degassing measures. The purpose of the work was to summarize information about the features of the implementation of degassing as a component of special treatment in the event of emergency situations with hazardous chemicals of general toxic action.
AN APPROACH TO FORM A CONCEPT OF COMPLEX DEVELOPMENT OF ASIAN RUSSIA: FROM PROBLEMS THROUGH PROJECTS TO SCENARIOS
Authors: Kryukov Valerij A. , Suslov Nikita I. , Yagolnitser Miron A.
Published: October 2021

In the article both economic development problems of the Asian Russia, and their resource potential are discussed including mineral resources, forests, bio-resources, and geographic areas having strategic importance. Asignificant part of Asian Russia is situated in the permafrost and Arcticzones with sever climate, which both makes costlier local production and raises environmental risks. Poor development level and connectivity should be additionally mentioned which hinsumcreatesadem and to prepare and to use new approaches to projection of development of its socio-economic system. The theoretical basis for a methodological approach to the formation of scenarios for the development of Asian Russia based on the concept of the "big push", are substantiated. A methodology for assessing the multiplier effect of inter-industry interaction of the mineral resource sector on other sectors of the economy, based on the use of multivariate econometric models, is proposed. Using the proposed methodology, the multipliers of the impact of the mineral sector on GDP and employment were calculated.
THE ROLE OF MARKET POTENTIAL IN THE EVOLUTION OF THE RUSSIAN URBAN SYSTEM IN 1991-2020
Authors: Kolomak Evgeniya A.
Published: October 2021

The paper studies the change in the proportions of the development of the Russian urban system over the period 1991-2020 and examines the influence of market potential on these processes. The methods of the analysis include descriptive statistics, empirical estimates of the density functions, maps, estimates of the Zipf’s equation parameters, and regression equations for the dependence of the city size on various types of market potential. The analysis showed that the urban system of modern Russia is undergoing structural changes, and there is an increase in heterogeneity in the development of cities due to the growth of large and the reduction of small cities. These changes are due to the size of external and internal markets, which include both urban and rural settlements. The market potential is unevenly distributed over the territory of the country, this resource is concentrated in the European part of the country, what will create a gap in the pace and quality of development of the urban system of Russia in the west-east dimension.
Yolcu Aracı Havalandırma Nozul Tasarımlarında Sızdırmazlık Problemlerine Hesaplamalı Akışkanlar Dinamiği ile Bir Mühendislik Çözümü
Authors: Altuncu Ekrem , Eker Cem , Kırmızıtepe Samet
Published: October 2021

Otobüslerde, geleneksel havalandırma sistemlerinde kullanılan nozul mekanizmasında tasarım kaynaklı, geometrik tolerans değerlerinden dolayı nozul mekanizması üzerinde hava kaçakları söz konusudur. Tolerans açıklıkları hem yolcu konforu açısından problem teşkil etmekte, hem de sınırlı ölçekte nozul çalışma debisine sebep olmaktadır. Bu durum sektörde tasarım nedenli bir mühendislik problemi olup, rekabet açısından kritik öneme sahiptir. Bu problemin çözümü için; ANSYS programının hesaplamalı akışkanlar dinamiği (CFD) modülü kullanılarak hava akış analizleri yapılmıştır. Bu şekilde nozul üzerinde olan açıklıklardan geçen hava debisi ve nozul içerisinde oluşan basınç değerleri için bilgisayar destekli benzeşim çalışmaları karşılaştırmalı olarak gerçekleştirilmiştir. Farklı toleranslar için tasarım değişiklikleri üzerinde deneysel çalışmalar hava sızdırmazlık testleri ile değerlendirilmiş ve doğrulanmıştır. PROVA Avm 07 marka anemometre kullanılarak nozuldan 10 cm mesafede ölçüm yapıldığında müşteri konforu için 0 m3/h’lik akışkan hızı hedefine ulaşılmıştır. Bu çalışma kapsamında tasarım kriterleri, ölçüm ve analizler karşılaştırmalı olarak analiz edilmiş ve tartışılmıştır.
Identification of an Autophagy-Related Risk Signature Correlates With Immunophenotype and Predicts Immune Checkpoint Blockade Efficacy of Neuroblastoma
Authors: Kang Wenjuan , Hu Jiajian , Zhao Qiang , Song Fengju
Published: October 2021

Neuroblastoma is one of the malignant solid tumors with the highest mortality in childhood. Targeted immunotherapy still cannot achieve satisfactory results due to heterogeneity and tolerance. Exploring markers related to prognosis and evaluating the immune microenvironment remain the major obstacles. Herein, we constructed an autophagy-related gene (ATG) risk model by multivariate Cox regression and least absolute shrinkage and selection operator regression, and identified four prognostic ATGs (BIRC5, GRID2, HK2, and RNASEL) in the training cohort, then verified the signature in the internal and external validation cohorts. BIRC5 and HK2 showed higher expression in MYCN amplified cell lines and tumor tissues consistently, whereas GRID2 and RNASEL showed the opposite trends. The correlation between the signature and clinicopathological parameters was further analyzed and showing consistency. A prognostic nomogram using risk score, International Neuroblastoma Staging System stage, age, and MYCN status was built subsequently, and the area under curves, net reclassification improvement, and integrated discrimination improvement showed more satisfactory prognostic predicting performance. The ATG prognostic signature itself can significantly divide patients with neuroblastoma into high- and low-risk groups; differentially expressed genes between the two groups were enriched in autophagy-related behaviors and immune cell reactions in gene set enrichment analysis (false discovery rate q -value < 0.05). Furthermore, we evaluated the relationship of the signature risk score with immune cell infiltration and the cancer-immunity cycle. The low-risk group was characterized by more abundant expression of chemokines and higher immune checkpoints (PDL1, PD1, CTLA-4, and IDO1). The risk score was significantly correlated with the proportions of CD8+ T cells, CD4+ memory resting T cells, follicular helper T cells, memory B cells, plasma cells, and M2 macrophages in tumor tissues. In conclusion, we developed and validated an autophagy-related signature that can accurately predict the prognosis, which might be meaningful to understand the immune microenvironment and guide immune checkpoint blockade.
DNA Methylation Patterns in CD8+ T Cells Discern Psoriasis From Psoriatic Arthritis and Correlate With Cutaneous Disease Activity
Authors: Charras Amandine , Garau Jessica , Hofmann Sigrun R. , Carlsson Emil , Cereda Cristina , Russ Susanne , Abraham Susanne , Hedrich Christian M.
Published: October 2021

Background: Psoriasis is a T cell-mediated chronic autoimmune/inflammatory disease. While some patients experience disease limited to the skin (skin psoriasis), others develop joint involvement (psoriatic arthritis; PsA). In the absence of disease- and/or outcome-specific biomarkers, and as arthritis can precede skin manifestations, diagnostic and therapeutic delays are common and contribute to disease burden and damage accrual.

Objective: Altered epigenetic marks, including DNA methylation, contribute to effector T cell phenotypes and altered cytokine expression in autoimmune/inflammatory diseases. This project aimed at the identification of disease-/outcome-specific DNA methylation signatures in CD8+ T cells from patients with psoriasis and PsA as compared to healthy controls.

Method: Peripheral blood CD8+ T cells from nine healthy controls, 10 psoriasis, and seven PsA patients were collected to analyze DNA methylation marks using Illumina Human Methylation EPIC BeadChips (>850,000 CpGs per sample). Bioinformatic analysis was performed using R (minfi, limma, ChAMP, and DMRcate packages).

Results: DNA methylation profiles in CD8+ T cells differentiate healthy controls from psoriasis patients [397 Differentially Methylated Positions (DMPs); 9 Differentially Methylated Regions (DMRs) when ≥CpGs per DMR were considered; 2 DMRs for ≥10 CpGs]. Furthermore, patients with skin psoriasis can be discriminated from PsA patients [1,861 DMPs, 20 DMRs (≥5 CpGs per region), 4 DMRs (≥10 CpGs per region)]. Gene ontology (GO) analyses considering genes with ≥1 DMP in their promoter delivered methylation defects in skin psoriasis and PsA primarily affecting the BMP signaling pathway and endopeptidase regulator activity, respectively. GO analysis of genes associated with DMRs between skin psoriasis and PsA demonstrated an enrichment of GABAergic neuron and cortex neuron development pathways. Treatment with cytokine blockers associated with DNA methylation changes [2,372 DMPs; 1,907 DMPs within promoters, 7 DMRs (≥5 CpG per regions)] affecting transforming growth factor beta receptor and transmembrane receptor protein serine/threonine kinase signaling pathways. Lastly, a methylation score including TNF and IL-17 pathway associated DMPs inverse correlates with skin disease activity scores (PASI).

Conclusion: Patients with skin psoriasis exhibit DNA methylation patterns in CD8+ T cells that allow differentiation from PsA patients and healthy individuals, and reflect clinical activity of skin disease. Thus, DNA methylation profiling promises potential as diagnostic and prognostic tool to be used for molecular patient stratification toward individualized treatment.
Titin Mutation Is Associated With Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Squamous Cell Carcinoma
Authors: Xie Xiaona , Tang Yemeng , Sheng Jueqi , Shu Pingping , Zhu Xiayan , Cai Xueding , Zhao Chengguang , Wang Liangxing , Huang Xiaoying
Published: October 2021

Lung squamous cell carcinoma (LUSC) is a leading cause of mobidity and mortality worldwide. Recently, there was a shift in the treatment pattern of immune therapy in LUSC patients; merely a small number of patients with non-small cell lung cancer (NSCLC) at advanced stages respond well to immune checkpoint blockade (ICB) therapy, and tumor mutation burden (TMB) is a valuable independent indicator of response to immune therapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immunocytes in LUSC are still unclear. In the present paper, our team analyzed the somatically mutated genes from the ICGC (International Cancer Genome Consortium) and TCGA (The Cancer Genome Atlas) datasets and discovered that 15 frequent gene mutations occurred in both cohorts, including ZFHX4, MUC16, FLG, TP53, LRP1B, TTN, SYNE1, RYR2, CSMD3, USH2A, MUC17, DNAH5, FAM135B, COL11A1, and RYR3. Interestingly, only mutated TTN was related to higher TMB and prognostic outcomes among the 15 mutated genes. Moreover, according to the CIBERSORT algorithm, we revealed that TTN mutation enhanced the antitumor immune response. In conclusion, TTN may have important clinical implications for relevant immune therapy of lung squamous carcinoma.
Co-Ni Basic Carbonate Nanowire/Carbon Nanotube Network With High Electrochemical Capacitive Performance via Electrochemical Conversion
Authors: Tan Furui , Chen Hongyuan , Yuan Ronghua , Zhang Xuming , Chen Deliang
Published: October 2021

In this work, the Co-Ni basic carbonate nanowires were in-situ grown on carbon nanotube (CNT) network through a facile chemical bath deposition method, which could be further converted into active hydroxide via cyclic voltammetry strategy. A series of carbonate nanowire/nanotube with different Co/Ni ratio revealed the different growth status of the nanowires on CNT network. The nanostructures of the as-synthesized samples were examined via powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) techniques. The Co/Ni ratio of the carbonate largely affected the size of the nanowires, that the low Co/Ni ratio was beneficial for thin nanowire formation and the nanowires loading on CNT network. Subsequently, the electrochemical performance of the Co-Ni basic hydroxides was studied in a three-electrode test system. The nanowires with low Co/Ni ratio 1/2 can form nanowire array on individual CNTs, which exhibited better electrochemical capacitive performance than the composite network with high Co/Ni ratio nanowires after electrochemical activation. The addition of Co enhanced the rate performance of the hydroxide/CNT, especially improved the long cycle stability largely compared to the rate performance of pure Ni converted hydroxide/CNT composite film reported by our previous research. This result is valuable for the design of inorganic electrochemical active composites based on conductive networks for energy conversion/storage applications.
Nanozymes Regulate Redox Homeostasis in ROS-Related Inflammation
Authors: Li Qing , Liu Ying , Dai Xianglin , Jiang Wei , Zhao Huan
Published: October 2021

Reactive oxygen species (ROS), in moderate amounts, play an essential role in regulating different physiological functions in organisms. However, increased amounts of ROS may cause oxidative stress and damage to biomolecules, leading to a variety of diseases including inflammation and even cancer. Therefore, ROS scavenging reagents are needed to maintain healthy levels of ROS. With considerable advances in nanotechnology, nanozymes possess SOD or CAT-like activities with outstanding free radical scavenging activity, facile synthesis conditions, and excellent biocompatibility. Based on these extraordinary properties, nanozymes has been used to modulate the redox homeostasis and relieve the ROS-related injury. This has led to the emergence of nanozyme-based therapies. In the current review, we presented recently developed applications of nanozymes to treat ROS-dependent disorders with an emphasis on inflammatory and brain diseases.
Alterations in Faecal Metagenomics and Serum Metabolomics Indicate Management Strategies for Patients With Budd-Chiari Syndrome
Authors: Lu Qinwei , Xu Hao , Zhou Lin , Zhang Ruifang , Li Zhen , Xu Peng , Bai Tao , Wang Zhiwei , Wu Gang , Ren Jianzhuang , Jiao Dechao , Song Yan , Zhu Rongtao , Li Jian , Wang Weijie , Liang Ruopeng , Li Lin , Ma Xiuxian , Zu Maoheng , Sun Yuling
Published: October 2021

We investigated the effects of gut microbiota and serum metabolite levels in patients with Budd-Chiari syndrome (B-CS) and their importance for guiding clinical management strategies. In total, 214 B-CS patients (93 untreated and 121 treated) and 41 healthy controls were enrolled. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography-mass spectrometry. The gut microbiota of the patients showed abundance of Campylobacter and low levels of Saccharomyces, Deinococcus, and Thiomonas (P < 0.05). Thirty metabolites, including taurocholate and (R)-3-hydroxybutyric acid, were identified in the patients (VIP > 1, P < 0.05 and FC > 1.2 or FC < 0.83). Random forest (RF) models showed that serum metabolome could effectively identify B-CS from healthy controls and RF-metabolomics exhibited perfect discrimination (AUC = 100%, 95% CI: 100% – 100%), which was significantly higher than that achieved by RF-metagenomics (AUC = 58.48%, 95% CI: 38.46% – 78.5%). Campylobacter concisus and taurocholate showed significant positive correlation in patients with clinical manifestations (P < 0.05). Actinobacteria levels were significantly higher in untreated patients than in treated patients (P < 0.05). Campylobacter and Veillonella levels were significantly higher in treated patients than in healthy controls (P < 0.05). We identified major alterations in the gut microbiota and serum metabolome of patients with B-CS. Faecal metagenomics- and serum metabolomics-guided management strategies are required for patients with B-CS.
Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients
Authors: Shrivastava Shubham , Chelluboina Shweta , Jedge Prashant , Doke Purwa , Palkar Sonali , Mishra Akhilesh Chandra , Arankalle Vidya A.
Published: October 2021

Understanding of the basis for severity and fatal outcome of SARS-CoV-2 infection is of paramount importance for developing therapeutic options and identification of prognostic markers. So far, accumulation of neutrophils and increased levels of pro-inflammatory cytokines are associated with disease severity in COVID-19 patients. In this study, we aimed to compare circulatory levels of neutrophil secretory proteins, alpha-defensins (DEFA1), calprotectin (S100A8/A9), and myeloperoxidase (MPO) in COVID-19 patients with different clinical presentations. We studied 19 healthy subjects, 63 COVID-19 patients with mild (n=32) and severe (n=31) disease, 23 asymptomatic individuals identified through contact tracing programme and 23 recovering patients (1-4 months post-disease). At the time of disease presentation, serum levels of DEFA1 were significantly higher in patients with mild (mean230 ± 17, p<0.0001) and severe (mean452 ± 46, p<0.0001) disease respectively in comparison to healthy subjects (mean113 ± 11). S100A8/A9 proteins were significantly higher in COVID-19 patients (p<0.0001) irrespective of disease severity. The levels of DEFA1, S100A8/A9 and MPO reduced to normal in recovering patients and comparable to healthy subjects. Surprisingly, DEFA1 levels were higher in severe than mild patients in first week of onset of disease (p=0.004). Odds-ratio analysis showed that DEFA1 could act as potential biomarker in predicting disease severity (OR=11.34). In addition, levels of DEFA1 and S100A8/A9 were significantly higher in patients with fatal outcome (p=0.004 and p=0.03) respectively. The rise in DEFA1 levels was independent of secondary infections. In conclusion, our data suggest that induction of elevated levels of alpha-defensins and S100A8/A9 is associated with poor disease outcome in COVID-19 patients.
Ethnic and Sociocultural Differences in Ovarian Reserve: Age-Specific Anti-Müllerian Hormone Values and Antral Follicle Count for Women of the Arabian Peninsula
Authors: Melado Laura , Vitorino Raquel , Coughlan Carol , Bixio Leyla Depret , Arnanz Ana , Elkhatib Ibrahim , De Munck Neelke , Fatemi Human M. , Lawrenz Barbara
Published: October 2021

Background

Anti-Müllerian hormone (AMH) and antral follicle count (AFC) age-specific reference values form the basis of infertility treatments, yet they were based upon studies performed primarily on Caucasian populations. However, they may vary across different age-matched ethnic populations. This study aimed to describe age-specific serum AMH and AFC for women native to the Arabian Peninsula.

Methods

A retrospective large-scale study was performed including 2,495 women, aged 19 to 50 years, native to the Arabian Peninsula. AMH and AFC were measured as part of their fertility assessment at tertiary-care fertility centres. Age-specific values and nomograms were calculated.

Results

2,495 women were evaluated. Mean, standard deviation and median values were calculated for AMH and AFC by 1-year and 5-years intervals. Median age was 34.81 years, median AMH was 1.76ng/ml and median AFC was 11. From the total group, 40.60% presented with AMH levels below 1.3ng/mL. For women <45 years old, the decrease in AFC was between -0.6/-0.8 per year. Up to 36 years old, the decrease of AMH was 0.1ng/ml. However, from 36 to 40 years old, an accelerated decline of 0.23ng/ml yearly was noted. In keeping with local customs, 71.23% of women wore the hijab and 25.76% the niqab. AMH and AFC were significantly lower for niqab group compared with hijab group (p=0.02 and p=0.04, respectively).

Conclusion

This is to-date the largest data set on age-specific AMH and AFC values in women from the Arabian Peninsula aiming to increase clinical awareness of the ovarian reserve in this population.
Cancer Stemness-Based Prognostic Immune-Related Gene Signatures in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
Authors: Li Na , Li Yalin , Zheng Peixian , Zhan Xianquan
Published: October 2021

Background

Cancer stem cells (CSCs) refer to cells with self-renewal capability in tumors. CSCs play important roles in proliferation, metastasis, recurrence, and tumor heterogeneity. This study aimed to identify immune-related gene-prognostic models based on stemness index (mRNAsi) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively.

Methods

X-tile software was used to determine the best cutoff value of survival data in LUAD and LUSC based on mRNAsi. Tumor purity and the scores of infiltrating stromal and immune cells in lung cancer tissues were predicted with ESTIMATE R package. Differentially expressed immune-related genes (DEIRGs) between higher- and lower-mRNAsi subtypes were used to construct prognostic models.

Results

mRNAsi was negatively associated with StromalScore, ImmuneScore, and ESTIMATEScore, and was positively associated with tumor purity. LUAD and LUSC samples were divided into higher- and lower-mRNAsi groups with X-title software. The distribution of immune cells was significantly different between higher- and lower-mRNAsi groups in LUAD and LUSC. DEIRGs between those two groups in LUAD and LUSC were enriched in multiple cancer- or immune-related pathways. The network between transcriptional factors (TFs) and DEIRGs revealed potential mechanisms of DEIRGs in LUAD and LUSC. The eight-gene-signature prognostic model (ANGPTL5, CD1B, CD1E, CNTFR, CTSG, EDN3, IL12B, and IL2)-based high- and low-risk groups were significantly related to overall survival (OS), tumor microenvironment (TME) immune cells, and clinical characteristics in LUAD. The five-gene-signature prognostic model (CCL1, KLRC3, KLRC4, CCL23, and KLRC1)-based high- and low-risk groups were significantly related to OS, TME immune cells, and clinical characteristics in LUSC. These two prognostic models were tested as good ones with principal components analysis (PCA) and univariate and multivariate analyses. Tumor T stage, pathological stage, or metastasis status were significantly correlated with DEIRGs contained in prognostic models of LUAD and LUSC.

Conclusion

Cancer stemness was not only an important biological process in cancer progression but also might affect TME immune cell infiltration in LUAD and LUSC. The mRNAsi-related immune genes could be potential biomarkers of LUAD and LUSC. Evaluation of integrative characterization of multiple immune-related genes and pathways could help to understand the association between cancer stemness and tumor microenvironment in lung cancer.
Effects of Heat Stress on Mating Behavior and Colony Development in Bombus terrestris (Hymenoptera: Apidae)
Authors: Przybyla Kimberly , Michez Denis , Zambra Ella , Anselmo Abigaël , Hennebert Elise , Rasmont Pierre , Martinet Baptiste
Published: October 2021

Climate change is related to an increase in the frequency and intensity of extreme events such as heatwaves. In insect pollinators, heat exposure is associated with direct physiological perturbations, and in several species, could lead to a decrease of fitness related to a decrease in fertility. Here we developed a new experimental protocol in controlled conditions to assess if the exposure to high temperatures could modify the attractiveness and fertility of Bombus terrestris males. Our results show that virgin queens of B. terrestris do not have preferences between the pheromonal secretions of heat-exposed and control males. Moreover, mating with a heat-exposed male has no impact on the copulation behavior and the development of the nest (brood composition). We advise to extend trials to cover a range of wild and heat-sensitive species on multiple generations to better understand the impact of heat waves on the bumblebee communities.
A Ferroptosis-Related Gene Signature for Predicting the Prognosis and Drug Sensitivity of Head and Neck Squamous Cell Carcinoma
Authors: Lu Wei , Wu Yihua , Huang Shengyun , Zhang Dongsheng
Published: October 2021

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and has a high mortality. Ferroptosis, an iron-dependent form of programmed cell death, plays a crucial role in tumor suppression and chemotherapy resistance in cancer. However, the prognostic and clinical values of ferroptosis-related genes (FRGs) in HNSCC remain to be further explored. In the current study, we constructed a ferroptosis-related prognostic model based on the Cancer Genome Atlas database and then explored its prognostic and clinical values in HNSCC via a series of bioinformatics analyses. As a result, we built a four-gene prognostic signature, including FTH1, BNIP3, TRIB3, and SLC2A3. Survival analysis showed that the high-risk group presented significantly poorer overall survival than the low-risk group. Moreover, the ferroptosis-related signature was found to be an independent prognostic predictor with high accuracy in survival prediction for HNSCC. According to immunity analyses, we found that the low-risk group had higher anti-tumor immune infiltration cells and higher expression of immune checkpoint molecules and meanwhile corelated more closely with some anti-tumor immune functions. Meanwhile, all the above results were validated in the independent HSNCC cohort GSE65858. Besides, the signature was found to be remarkably correlated with sensitivity of common chemotherapy drugs for HNSCC patients and the expression levels of signature genes were also significantly associated with drug sensitivity to cancer cells. Overall, we built an effective ferroptosis-related prognostic signature, which could predict the prognosis and help clinicians to perform individualized treatment strategy for HNSCC patients.
Recognition of DNA Methylation Molecular Features for Diagnosis and Prognosis in Gastric Cancer
Authors: Liu Donghui , Li Long , Wang Liru , Wang Chao , Hu Xiaowei , Jiang Qingxin , Wang Xuyao , Xue Guiqin , Liu Yu , Xue Dongbo
Published: October 2021

Background: The management of gastric cancer (GC) still lacks tumor markers with high specificity and sensitivity. The goal of current research is to find effective diagnostic and prognostic markers and to clarify their related mechanisms.

Methods: In this study, we integrated GC DNA methylation data from publicly available datasets obtained from TCGA and GEO databases, and applied random forest and LASSO analysis methods to screen reliable differential methylation sites (DMSs) for GC diagnosis. We constructed a diagnostic model of GC by logistic analysis and conducted verification and clinical correlation analysis. We screened credible prognostic DMSs through univariate Cox and LASSO analyses and verified a prognostic model of GC by multivariate Cox analysis. Independent prognostic and biological function analyses were performed for the prognostic risk score. We performed TP53 correlation analysis, mutation and prognosis analysis on eleven-DNA methylation driver gene (DMG), and constructed a multifactor regulatory network of key genes.

Results: The five-DMS diagnostic model distinguished GC from normal samples, and diagnostic risk value was significantly correlated with grade and tumor location. The prediction accuracy of the eleven-DMS prognostic model was verified in both the training and validation datasets, indicating its certain potential for GC survival prediction. The survival rate of the high-risk group was significantly lower than that of the low-risk group. The prognostic risk score was an independent risk factor for the prognosis of GC, which was significantly correlated with N stage and tumor location, positively correlated with the VIM gene, and negatively correlated with the CDH1 gene. The expression of CHRNB2 decreased significantly in the TP53 mutation group of gastric cancer patients, and there were significant differences in CCDC69, RASSF2, CHRNB2, ARMC9, and RPN1 between the TP53 mutation group and the TP53 non-mutation group of gastric cancer patients. In addition, CEP290, UBXN8, KDM4A, RPN1 had high frequency mutations and the function of eleven-DMG mutation related genes in GC patients is widely enriched in multiple pathways.

Conclusion: Combined, the five-DMS diagnostic and eleven-DMS prognostic GC models are important tools for accurate and individualized treatment. The study provides direction for exploring potential markers of GC.
Early Initiation of Tocilizumab Treatment Against Moderate-to-Severe Myelitis in Neuromyelitis Optica Spectrum Disorder
Authors: Du Chen , Zeng Pei , Han Jin-Rui , Zhang Tian-Xiang , Jia Dongmei , Shi Fu-Dong , Zhang Chao
Published: October 2021

Background

Interleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive.

Objective

We investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis.

Methods

Nineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS).

Results

Improved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06–0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013).

Conclusion

Early initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.
Deep Parallel Characterization of AAV Tropism and AAV-Mediated Transcriptional Changes via Single-Cell RNA Sequencing
Authors: Brown David , Altermatt Michael , Dobreva Tatyana , Chen Sisi , Wang Alexander , Thomson Matt , Gradinaru Viviana
Published: October 2021

Engineered variants of recombinant adeno-associated viruses (rAAVs) are being developed rapidly to meet the need for gene-therapy delivery vehicles with particular cell-type and tissue tropisms. While high-throughput AAV engineering and selection methods have generated numerous variants, subsequent tropism and response characterization have remained low throughput and lack resolution across the many relevant cell and tissue types. To fully leverage the output of these large screening paradigms across multiple targets, we have developed an experimental and computational single-cell RNA sequencing (scRNA-seq) pipeline for in vivo characterization of barcoded rAAV pools at high resolution. Using this platform, we have both corroborated previously reported viral tropisms and discovered unidentified AAV capsid targeting biases. As expected, we observed that the tropism profile of AAV.CAP-B10 in mice was shifted toward neurons and away from astrocytes when compared with AAV-PHP.eB. Transcriptomic analysis revealed that this neuronal bias is due mainly to increased targeting efficiency for glutamatergic neurons, which we confirmed by RNA fluorescence in situ hybridization. We further uncovered cell subtype tropisms of AAV variants in vascular and glial cells, such as low transduction of pericytes and Myoc+ astrocytes. Additionally, we have observed cell-type-specific transitory responses to systemic AAV-PHP.eB administration, such as upregulation of genes involved in p53 signaling in endothelial cells three days post-injection, which return to control levels by day twenty-five. The presented experimental and computational approaches for parallel characterization of AAV tropism will facilitate the advancement of safe and precise gene delivery vehicles, and showcase the power of understanding responses to gene therapies at the single-cell level.