bluuebunny/crossref_metadata_2025 huggingface dataset:
ATATÜRK VE İNÖNÜ DÖNEMİ KÜLTÜR POLİTİKALARININ KARŞILAŞTIRMASINA YÖNELİK BİR İNCELEME
Authors: BOLAT Bengül , GÖK Hacı Veli
Published: March 2021

Osmanlı Devleti farklı kıtalarda uzun yıllar hakimiyet kurmuştur. Ancak zamanla değişen
dünya düzenine ayak uyduramamak ve uzun süren savaşlar nedeniyle gücü sarsılmaya
başlamıştır. Bu sancılı süreç 20. yy'a gelindiğinde devletin ömrünü tamamlaması ile sona
ermiştir. Osmanlı Devleti'nin tarih sahnesinden çekilmesinin ardından Türkiye'de cumhuriyetin
ilan edilmesi ile birlikte birçok alanda yenilik yapılmıştır. Bu yeniliklerin yanı sıra kültürel
anlamda da bir dizi değişikliğe gidilmiştir.Dil, tarih,edebiyat, Halkevleri vb. alanlarda yapılan
yenilik hareketlerinde Batı medeniyetinden de belli ölçüde faydalanılmıştır. Atatürk’ün
Cumhurbaşkanı olduğu 1923-1938 dönemi yürütülen kültür politikalarında Türk Milliyetçiliği ön
plana çıkarılmıştır. Bu dönem, Dünyada da milliyetçiliğin oldukça yükseldiği, hatta İtalya ve
Almanya başta olmak üzere Faşizm boyutuna geldiği dönemdir. Dolayısla henüz çok genç olan
yeni Ulus devletin gerek yeni sisteminin yerleşmesi, gerekse de milliyetçiliğinin gelişmesi ço
önemsenmiş ve Tarih, dil, edebiyat gibi alanlarda yapılan çalışmalar bu doğrutuda
şekillendirilmeye çalışılmıştır.
İnönü dönemi (1938-1950)nde ise yine Dünyadaki gelişme, değişime bağlı bir politika
izlenmiştir. II. Dünya Savaşı ve sonuçları Kültür politikalarına da etki etmiştir. Bu dönemde
Faşizmin yıkılması, Batı’nın ve sisteminin yükselmesi, İnsan hakları, özgürlükler, vb alanlardaki
değişim İnönü dönemi kültür politikalarında, önceden beri devam eden Milliyetçilik vurgusunun
yanı sıra Batı ve Hümanizma vurgusu yapılarak Türk kimliği ile Batının bütünleştirlmesi çabası
etkili olmuştur.
Atatürk ve İnönü dönemlerinde uygulanan kültür politikalarında yöntemsel olarak önemli
farklılıklar görülür. Bu durumun nedeni hem değişen şartlar ile hem de dönem liderlerinin farklı
bakış açıları ile açıklanabilir.
Verbal Fluency: An Investigation of Time Variable among Elderly People
Authors: ÖZDEMİR Şevket , TUNÇER Aylin
Published: March 2021

Objective: Little is known about the impact of time on the verbal fluency performance among elderly population. The aims of this study were to (i) examine the verbal fluency (semantic and action fluency) performance across four quarters of 60 seconds and (ii) explore the relationship between demographic (education and age) and time variables on the performance of elderly individuals. Methods: A descriptive cross-sectional study of 58 elderly healthy subjects (>59 years) was carried out. Five semantic categories and action fluency were implemented. Participants were stratified into three education groups (Group 1, 2 and 3 including subjects with 5-8 years, 9-11 and more than 12 years of schooling) and each group involved 20, 21 and 17 participants respectively. Results: The findings revealed mean numbers of words among quarters decreased in a linear fashion. There was significant difference between the production in the first quarter and others. It was seen that age did not correlate with fluency performance across quarters. Significant production differences were found between education groups across all quarters. Conclusion: This study demonstrates the fluency scores of elderly healthy subjects with different levels of education along with production across four quarters. It is suggested that future studies include neuropathological conditions for the clinical utility of these measures.
The Bond Strength of Universal Adhesives with Different Acidities to Calcium Silicate-Based Materials
Authors: KALYONCUOĞLU Elif , KESKİN Cangül , ACAR Duygu , GONULOL Nihan
Published: March 2021

Objective: To compare the micro-shear bond strengths of 3 different universal adhesives to 2 different calcium silicate-based materials. Methods: A hole was prepared in the center of the top surfaces of 60 cylindrical acrylic blocks, and the blocks were randomly divided into 2 groups (n=30) according to biomaterial filling; NeoMTA Plus (Avalon Biomed Inc. Bradenton, FL, USA) and ProRoot MTA (Dentsply Tulsa, Tulsa, OK, USA). Biomaterials were prepared according to the manufacturers’ instructions. The sample surfaces were flattened after the initial setting, and the samples were incubated for 24h at 37°C. After placing the biomaterials in the prepared holes, the specimens were randomly divided into 3 subgroups (n=10) according to adhesive; G-Premio Bond (GC Corp., Tokyo, Japan), All-Bond Universal (Bisco, Inc., Schaumburg, IL, USA) and Single Bond Universal (3M ESPE, St Paul, MN, USA). Adhesives were applied to the specimens and polymerized. A micro-hybrid composite resin (Filtek Z250, 3M ESPE, MN, USA) was then placed on the specimen surfaces and polymerized. Micro-shear bond strengths were tested using a universal testing device (LRX, Lloyd Instruments, Farnham, UK). A Shapiro-Wilk test confirmed normal distribution, and 2-way ANOVA was used for statistical analysis. Result: No significant differences were found in the shear bond strengths of any of the tested adhesives to either of the calcium silicate-based materials (p>0.05). Conclusion: The results indicate that the acidity of a universal adhesive does not affect the bond strength of composite resin to calcium silicate-based materials.
The Changes in Balance During Pregnancy: A Prospective Longitudinal Study
Authors: SANCAR Şeyda , ATALAY GÜZEL Nevin , ÇOBANOĞLU Gamze , ÖZDEMİR Yaprak , BAYRAM Merih
Published: March 2021

Objective: The aim of this study was to examine the changes in static balance during the three trimesters of pregnancy.
Methods: Nineteen pregnant women who were in the first trimester of pregnancy were included in the study. The static balance assessment of the pregnant women was performed with Biodex-BioSwayTM Balance System. The balance was assessed with the Postural Stability Test, Limits of Stability Test (LOS) and Modified Clinical Test of Sensory Integration and Balance (mCTSIB). Measurements were repeated during the 1st trimester (10-12 weeks), the 2nd trimester (22-24 weeks) and the 3rd trimester (34th week) of the same pregnant women.
Results: There was no significant difference between trimesters in terms of the postural stability test (p>0.05). It was determined that there was a difference between the 3 trimesters in the LOS scores of the pregnant women (p<0.05). There was a significant increase in the LOS in the last trimester compared to the first trimester. According to the mCTSIB, there was only a difference between the three trimesters in the eyes closed firm surface parameter (p<0.05). Oscillations were higher in the third trimester than in the second trimester.
Conclusion: As a result of this study, which underlines the importance of evaluating static balance by follow-up of the same pregnant women during three trimesters, it is seen that there are changes in different parameters of balance. Considering the differences in the sub-parameters of balance in pregnant women; multi-directional evaluation involving different parameters may be beneficial when evaluating balances.
Substrate-Flexible Two-Stage Fed-Batch Cultivations for the Production of the PHA Copolymer P(HB-co-HHx) With Cupriavidus necator Re2058/pCB113
Authors: Santolin Lara , Waldburger Saskia , Neubauer Peter , Riedel Sebastian L.
Published: March 2021

Recent studies of the impact and dimension of plastic pollution have drawn the attention to finding more sustainable alternatives to fossil-based plastics. Microbially produced polyhydroxyalkanoates (PHAs) biopolymers are strong candidates to replace conventional plastic materials, due to their true biodegradability and versatile properties. However, widespread use of these polymers is still hindered by their high cost of production. In the present study, we target high yields of the PHA copolymer poly(hydroxybutyrate-co-hydroxyhexanoate) [P(HB-co-HHx)] using a substrate-flexible two-stage fed-batch approach for the cultivation of the recombinant Cupriavidus necator strain Re2058/pCB113. A more substrate-flexible process allows to cope with constant price fluctuations and discontinuous supply of feedstocks on the market. Utilizing fructose for biomass accumulation and rapeseed oil for polymer production resulted in a final biomass concentration of 124 g L–1 with a polymer content of 86 wt% holding 17 mol% of HHx. Productivities were further optimized by operating the biomass accumulation stage in a “drain and fill” modus where 10% of the culture broth was recycled for semi-continuous biomass accumulation, after transferring 90% to a second bioreactor for PHA production. This strategy succeeded in shortening process times rising productivity yields to ∼1.45 g L–1 h–1.
Chemotactic TEG3 Cells’ Guiding Platforms Based on PLA Fibers Functionalized With the SDF-1α/CXCL12 Chemokine for Neural Regeneration Therapy
Authors: Castaño Oscar , López-Mengual Ana , Reginensi Diego , Matamoros-Angles Andreu , Engel Elisabeth , del Rio José Antonio
Published: March 2021

(Following spinal cord injury, olfactory ensheathing cell (OEC) transplantation is a promising therapeutic approach in promoting functional improvement. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical concentration differences. Here we compare the attachment, morphology, and directionality of an OEC-derived cell line, TEG3 cells, seeded on functionalized nanoscale meshes of Poly(l/dl-lactic acid; PLA) nanofibers. The size of the nanofibers has a strong effect on TEG3 cell adhesion and migration, with the PLA nanofibers having a 950 nm diameter being the ones that show the best results. TEG3 cells are capable of adopting a bipolar morphology on 950 nm fiber surfaces, as well as a highly dynamic behavior in migratory terms. Finally, we observe that functionalized nanofibers, with a chemical concentration increment of SDF-1α/CXCL12, strongly enhance the migratory characteristics of TEG3 cells over inhibitory substrates.
Comparative Studies in the A30P and A53T α-Synuclein C. elegans Strains to Investigate the Molecular Origins of Parkinson's Disease
Authors: Perni Michele , van der Goot Annemieke , Limbocker Ryan , van Ham Tjakko J. , Aprile Francesco A. , Xu Catherine K. , Flagmeier Patrick , Thijssen Karen , Sormanni Pietro , Fusco Giuliana , Chen Serene W. , Challa Pavan K. , Kirkegaard Julius B. , Laine Romain F. , Ma Kai Yu , Müller Martin B. D. , Sinnige Tessa , Kumita Janet R. , Cohen Samuel I. A. , Seinstra Renée , Kaminski Schierle Gabriele S. , Kaminski Clemens F. , Barbut Denise , De Simone Alfonso , Knowles Tuomas P. J. , Zasloff Michael , Nollen Ellen A. A. , Vendruscolo Michele , Dobson Christopher M.
Published: March 2021

The aggregation of α-synuclein is a hallmark of Parkinson's disease (PD) and a variety of related neurological disorders. A number of mutations in this protein, including A30P and A53T, are associated with familial forms of the disease. Patients carrying the A30P mutation typically exhibit a similar age of onset and symptoms as sporadic PD, while those carrying the A53T mutation generally have an earlier age of onset and an accelerated progression. We report two C. elegans models of PD (PDA30P and PDA53T), which express these mutational variants in the muscle cells, and probed their behavior relative to animals expressing the wild-type protein (PDWT). PDA30P worms showed a reduced speed of movement and an increased paralysis rate, control worms, but no change in the frequency of body bends. By contrast, in PDA53T worms both speed and frequency of body bends were significantly decreased, and paralysis rate was increased. α-Synuclein was also observed to be less well localized into aggregates in PDA30P worms compared to PDA53T and PDWT worms, and amyloid-like features were evident later in the life of the animals, despite comparable levels of expression of α-synuclein. Furthermore, squalamine, a natural product currently in clinical trials for treating symptomatic aspects of PD, was found to reduce significantly the aggregation of α-synuclein and its associated toxicity in PDA53T and PDWT worms, but had less marked effects in PDA30P. In addition, using an antibody that targets the N-terminal region of α-synuclein, we observed a suppression of toxicity in PDA30P, PDA53T and PDWT worms. These results illustrate the use of these two C. elegans models in fundamental and applied PD research.
Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway
Authors: Wang Jin , Sun Xuefeng , Wang Xu , Cui Shaoyuan , Liu Ran , Liu Jiaona , Fu Bo , Gong Ming , Wang Conghui , Shi Yushen , Chen Qianqian , Cai Guangyan , Chen Xiangmei
Published: March 2021

Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3.
Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease
Authors: Lin Kai-Lieh , Chen Shang-Der , Lin Kai-Jung , Liou Chia-Wei , Chuang Yao-Chung , Wang Pei-Wen , Chuang Jiin-Haur , Lin Tsu-Kung
Published: March 2021

Cardiovascular diseases are one of the leading causes of death and global health problems worldwide. Multiple factors are known to affect the cardiovascular system from lifestyles, genes, underlying comorbidities, and age. Requiring high workload, metabolism of the heart is largely dependent on continuous power supply via mitochondria through effective oxidative respiration. Mitochondria not only serve as cellular power plants, but are also involved in many critical cellular processes, including the generation of intracellular reactive oxygen species (ROS) and regulating cellular survival. To cope with environmental stress, mitochondrial function has been suggested to be essential during bioenergetics adaptation resulting in cardiac pathological remodeling. Thus, mitochondrial dysfunction has been advocated in various aspects of cardiovascular pathology including the response to ischemia/reperfusion (I/R) injury, hypertension (HTN), and cardiovascular complications related to type 2 diabetes mellitus (DM). Therefore, mitochondrial homeostasis through mitochondrial dynamics and quality control is pivotal in the maintenance of cardiac health. Impairment of the segregation of damaged components and degradation of unhealthy mitochondria through autophagic mechanisms may play a crucial role in the pathogenesis of various cardiac disorders. This article provides in-depth understanding of the current literature regarding mitochondrial remodeling and dynamics in cardiovascular diseases.
AXL, an Important Host Factor for DENV and ZIKV Replication
Authors: Xie Shengda , Zhang Huiru , Liang Zhenjie , Yang Xingmiao , Cao Ruibing
Published: March 2021

Flaviviruses, as critically important pathogens, are still major public health problems all over the world. For instance, the evolution of ZIKV led to large-scale outbreaks in the Yap island in 2007. DENV was considered by the World Health Organization (WHO) as one of the 10 threats to global health in 2019. Enveloped viruses hijack a variety of host factors to complete its replication cycle. Phosphatidylserine (PS) receptor, AXL, is considered to be a candidate receptor for flavivirus invasion. In this review, we discuss the molecular structure of ZIKV and DENV, and how they interact with AXL to successfully invade host cells. A more comprehensive understanding of the molecular mechanisms of flavivirus-AXL interaction will provide crucial insights into the virus infection process and the development of anti-flavivirus therapeutics.
Influencing Factors, Energy Consumption, and Carbon Emission of Central Heating in China: A Supply Chain Perspective
Authors: Liu Guixian , Kong Zhaoyang , Dong Jiajia , Dong Xiucheng , Jiang Qingzhe , Wang Ke , Li Jiaman , Li Chade , Wan Xin
Published: March 2021

The rapid growth of energy demand in China’s central heating sector and the large differences in regions have posed challenges to its energy supply safety, which affected the progress of China’s energy transformation. From a supply chain perspective, this study uses the feasible generalized least squares method to conduct empirical research on the central heating data of 17 provinces in China from 2006 to 2017. The results shows that the main factors of central heating includes energy consumption structure, heat generation method, heat transport carrier, heating degree days and heating area; The main factor that increases the energy consumption of central heating in each province is the same, namely Heating area (HA). However, the main factors that reduce energy consumption in each province are different; using gas instead of coal for clean heating can reduce some greenhouse gas emissions while bringing huge gas supply pressure. According to the results, this study provides some policy suggestions.
Mouse Lemurs in an Assemblage of Cheirogaleid Primates in Menabe Central, Western Madagascar – Three Reasons to Coexist
Authors: Schäffler Livia , Kappeler Peter M. , Halley John M.
Published: March 2021

Ecological communities are structured by interactions between coexisting species that mutually influence their distribution and abundance. Ecologically similar species are expected to exclude one another from suitable habitat, so the coexistence of two mouse lemur species in an assemblage of several closely related cheirogaleid primates in the central Menabe region of Madagascar requires explanation. We assessed the occurrence of Madame Berthe’s mouse lemurs (Microcebus berthae) and Gray mouse lemurs (Microcebus murinus), and of two larger cheirogaleids, Coquerel’s giant mouse lemur (Mirza coquereli) and the western fat-tailed dwarf lemur (Cheirogaleus medius), by nocturnal line transect walks between 2003 and 2007. We explored interspecific interactions for four different scenarios with varying resource availability (degraded and non-degraded habitat in the wet and dry season), both on the regional spatial scale and on a finer local (transect) scale. We tested whether the interspecific distribution of mouse lemur individuals indicates interspecific competition and whether their regional coexistence might be stabilized by interactions withM. coquereliorC. medius. We developed the “Inter-Species Index of Attraction” (ISIA) to quantify the observed interspecific interactions within transects and determined if these were significantly different from a null model generated by a combination of randomization and bootstrapping to control for intraspecific aggregation. For the two mouse lemurs, interspecific spatial exclusion was most pronounced during the resource-poor dry season, consistent with the hypothesis of feeding competition. Seasonally varying distribution patterns indicated resource tracking in a spatio-temporally heterogeneous environment. The interspecific distribution of individuals suggested that the larger cheirogaleids benefitM. berthaeat the expense of the more abundantM. murinus: spatial associations of both,M. coquereliandC. medius, withM. murinuswere negative in most scenarios and across spatial scales, but neutral or even positive withM. berthae. Thus, our study revealed that coexistence among ecologically similar heterospecifics can rely on complex density-mediated interspecific processes varying with habitat quality and season. With regard to the stability of animal assemblages, this insight has major implications for biodiversity conservation.
Low Fe Availability for Photosynthesis of Sea-Ice Algae: Ex situ Incubation of the Ice Diatom Fragilariopsis cylindrus in Low-Fe Sea Ice Using an Ice Tank
Authors: Yoshida Kazuhiro , Seger Andreas , Corkill Matthew , Heil Petra , Karsh Kristen , McMinn Andrew , Suzuki Koji
Published: March 2021

Sea-ice algae play a crucial role in the ecology and biogeochemistry of sea-ice zones. They not only comprise the base of sea-ice ecosystems, but also seed populations of extensive ice-edge blooms during ice melt. Ice algae must rapidly acclimate to dynamic light environments, from the low light under sea ice to high light within open waters. Recently, iron (Fe) deficiency has been reported for diatoms in eastern Antarctic pack ice. Low Fe availability reduces photosynthetic plasticity, leading to reduced ice-algal primary production. We developed a low-Fe ice tank to manipulate Fe availability in sea ice. Over 20 days in the ice tank, the Antarctic ice diatomFragilariopsis cylindruswas incubated in artificial low-Fe sea ice ([total Fe] = 20 nM) in high light (HL) and low light (LL) conditions. Melted ice was also exposed to intense light to simulate light conditions typical for melting icein situ. When diatoms were frozen in, the maximum photochemical quantum efficiency of photosystem II (PSII),Fv/Fm, was suppressed by freezing stress. However, the diatoms maintained photosynthetic capability throughout the ice periods with a stableFv/Fmvalue and increased photoprotection through non-photochemical quenching (NPQ) via photoprotective xanthophyll cycling (XC) and increased photoprotective carotenoid levels compared to pre-freeze-up. Photoprotection was more pronounced in the HL treatment due to greater light stress. However, the functional absorption cross section of PSII, σPSII, inF. cylindrusconsistently increased after freezing, especially in the LL treatment (σPSII> 10 nm2PSII–1). Our study is the first to report such a large σPSIIin ice diatoms at low Fe conditions. When the melted sea ice was exposed to high light,Fv/Fmwas suppressed. NPQ and XC were slightly upregulated, but not to values normally observed when Fe is not limiting, which indicates reduced photosynthetic flexibility to adapt to environmental changes during ice melt under low Fe conditions. Although ice algae can optimize their photosynthesis to sea-ice environments, chronic Fe starvation led to less flexibility of photoacclimation, particularly in low light conditions. This may have detrimental consequences for ice algal production and trophic interactions in sea-ice ecosystems if the recent reduction in sea-ice extent continues.
3D Classification of Cold-Water Coral Reefs: A Comparison of Classification Techniques for 3D Reconstructions of Cold-Water Coral Reefs and Seabed
Authors: de Oliveira Larissa Macedo Cruz , Lim Aaron , Conti Luis A. , Wheeler Andrew J.
Published: March 2021

Cold-water coral (CWC) reefs are complex structural habitats that are considered biodiversity “hotspots” in deep-sea environments and are subject to several climate and anthropogenic threats. As three-dimensional structural habitats, there is a need for robust and accessible technologies to enable more accurate reef assessments. Photogrammetry derived from remotely operated vehicle video data is an effective and non-destructive method that creates high-resolution reconstructions of CWC habitats. Here, three classification workflows [Multiscale Geometrical Classification (MGC), Colour and Geometrical Classification (CGC) and Object-Based Image Classification(OBIA)] are presented and applied to photogrammetric reconstructions of CWC habitats in the Porcupine Bank Canyon, NE Atlantic. In total, six point clouds, orthomosaics, and digital elevation models, generated from structure-from-motion photogrammetry, are used to evaluate each classification workflow. Our results show that 3D Multiscale Geometrical Classification outperforms the Colour and Geometrical Classification method. However, each method has advantages for specific applications pertinent to the wider marine scientific community. Results suggest that advancing from commonly employed 2D image analysis techniques to 3D photogrammetric classification methods is advantageous and provides a more realistic representation of CWC habitat composition.
Neutrophil Extracellular Traps in the Autoimmunity Context
Authors: Bruschi Maurizio , Moroni Gabriella , Sinico Renato Alberto , Franceschini Franco , Fredi Micaela , Vaglio Augusto , Cavagna Lorenzo , Petretto Andrea , Pratesi Federico , Migliorini Paola , Manfredi Angelo , Ramirez Giuseppe A. , Esposito Pasquale , Negrini Simone , Trezzi Barbara , Emmi Giacomo , Santoro Domenico , Scolari Francesco , Volpi Stefano , Mosca Marta , Tincani Angela , Candiano Giovanni , Prunotto Marco , Verrina Enrico , Angeletti Andrea , Ravelli Angelo , Ghiggeri Gian Marco
Published: March 2021

The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to achieving NET formation: signaling from infectious triggers comes first, followed by decondensation of chromatin and extrusion of the nucleosome components (DNA, histones) from the nucleus and, after cell membrane breakdown, outside the cell. NETs are composed of either DNA or nucleosome proteins and hundreds of cytoplasm proteins, a part of which undergo post-translational modification during the steps leading to NETs. There is a thin balance between the production and the removal of circulating NETs from blood where digestion of DNA by circulating DNases 1 and IL3 has a critical role. A delay in NET removal may have consequences for autoimmunity. Recent studies have shown that circulating NET levels are increased in systemic lupus erythematosus (SLE) for a functional block of NET removal mediated by anti-DNase antibodies or, in rare cases, by DNase IL3 mutations. In SLE, the persistence in circulation of NETs signifies elevated concentrations of either free DNA/nucleosome components and oxidized proteins that, in some cases, are recognized as non-self and presented to B-cells by Toll-like receptor 9 (TLR9). In this way, it is activated as an immunologic response, leading to the formation of IgG2 auto-antibody. Monitoring serum NET levels represents a potential new way to herald the development of renal lesions and has clinical implications. Modulating the balance between NET formation and removal is one of the objectives of basic research that are aimed to design new drugs for SLE.

Clinical Trial Registration Number: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).
Generation of Bacterial Diversity by Segregation of DNA Strands
Authors: Norris Vic , Ripoll Camille
Published: March 2021

The generation in a bacterial population of a diversity that is coherent with present and future environments is a fundamental problem. Here, we use modeling to investigate growth rate diversity. We show that the combination of (1) association of extended assemblies of macromolecules with the DNA strands and (2) the segregation of DNA strands during cell division allows cells to generate different patterns of growth rate diversity with little effect on the overall growth rate of the population and thereby constitutes an example of “order for free” on which evolution can act.
Coupling Hierarchical Ultrathin Co Nanosheets With N-Doped Carbon Plate as High-Efficiency Oxygen Evolution Electrocatalysts
Authors: Wang Yue , Li Meng , Zhou Qixing , Wang Qin , Zhang Xingyuan , Sun Dongmei , Tang Yawen
Published: March 2021

The rational design of cost-effective and highly efficient catalysts for the oxygen evolution reaction (OER) is vastly desirable for advanced renewable energy conversion and storage systems. Tailoring the composition and architecture of electrocatalysts is a reliable approach for improving their catalytic performance. Herein, we developed hierarchical ultra-thin Co nanosheets coupled with N-doped carbon plate (Co-NS@NCP) as an efficient OER catalyst through a feasible and easily scalable NaCl template method. The rapid dissolution-recrystallization-carbonization synthesis process allows Co nanosheets to self-assemble into plenty of secondary building units and to distribute uniformly on N-doped carbon plate. Benefitting from the vertically aligned Co nanosheet arrays and hierarchical architecture, the obtained Co-NS@NCP possess an extremely high specific surface area up to 446.49 m2 g−1, which provides sufficient exposed active sites, excellent structure stability, and multidimensional mass transfer channels. Thus, the Co-NS@NCP affords remarkable electrocatalytic performance for OER in an alkaline medium with a low overpotential of only 278 mV at 10 mA cm−2, a small Tafel slope, as well as robust electrocatalytic stability for long-term electrolysis operation. The present findings here emphasize a rational and promising perspective for designing high-efficiency non-precious electrocatalysts for the OER process and sustainable energy storage and conversion system.
Prediction of Freezing of Gait in Parkinson’s Disease Using a Random Forest Model Based on an Orthogonal Experimental Design: A Pilot Study
Authors: Chen Zhonelue , Li Gen , Gao Chao , Tan Yuyan , Liu Jun , Zhao Jin , Ling Yun , Yu Xiaoliu , Ren Kang , Chen Shengdi
Published: March 2021

Purpose

The purpose of this study was to introduce an orthogonal experimental design (OED) to improve the efficiency of building and optimizing models for freezing of gait (FOG) prediction.

Methods

A random forest (RF) model was developed to predict FOG by using acceleration signals and angular velocity signals to recognize possible precursor signs of FOG (preFOG). An OED was introduced to optimize the feature extraction parameters.

Results

The main effects and interaction among the feature extraction hyperparameters were analyzed. The false-positive rate, hit rate, and mean prediction time (MPT) were 27%, 68%, and 2.99 s, respectively.

Conclusion

The OED was an effective method for analyzing the main effects and interactions among the feature extraction parameters. It was also beneficial for optimizing the feature extraction parameters of the FOG prediction model.
A Systematic Review on the Effect of Transcranial Direct Current and Magnetic Stimulation on Fear Memory and Extinction
Authors: Marković Vuk , Vicario Carmelo M. , Yavari Fatemeh , Salehinejad Mohammad A. , Nitsche Michael A.
Published: March 2021

Anxiety disorders are among the most prevalent mental disorders. Present treatments such as cognitive behavior therapy and pharmacological treatments show only moderate success, which emphasizes the importance for the development of new treatment protocols. Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been probed as therapeutic option for anxiety disorders in recent years. Mechanistic information about their mode of action, and most efficient protocols is however limited. Here the fear extinction model can serve as a model of exposure therapies for studying therapeutic mechanisms, and development of appropriate intervention protocols. We systematically reviewed 30 research articles that investigated the impact of rTMS and tDCS on fear memory and extinction in animal models and humans, in clinical and healthy populations. The results of these studies suggest that tDCS and rTMS can be efficient methods to modulate fear memory and extinction. Furthermore, excitability-enhancing stimulation applied over the vmPFC showed the strongest potential to enhance fear extinction. We further discuss factors that determine the efficacy of rTMS and tDCS in the context of the fear extinction model and provide future directions to optimize parameters and protocols of stimulation for research and treatment.
Decreasing the Surgical Errors by Neurostimulation of Primary Motor Cortex and the Associated Brain Activation via Neuroimaging
Authors: Gao Yuanyuan , Cavuoto Lora , Dutta Anirban , Kruger Uwe , Yan Pingkun , Nemani Arun , Norfleet Jack E. , Makled Basiel A. , Silvestri Jessica , Schwaitzberg Steven , Intes Xavier , De Suvranu
Published: March 2021

Acquisition of fine motor skills is a time-consuming process as it is based on learning via frequent repetitions. Transcranial electrical stimulation (tES) is a promising means of enhancing simple motor skill development via neuromodulatory mechanisms. Here, we report that non-invasive neurostimulation facilitates the learning of complex fine bimanual motor skills associated with a surgical task. During the training of 12 medical students on the Fundamentals of Laparoscopic Surgery (FLS) pattern cutting task over a period of 12 days, we observed that transcranial direct current stimulation (tDCS) decreased error level and the variability in performance, compared to the Sham group. Furthermore, by concurrently monitoring the cortical activations of the subjects via functional near-infrared spectroscopy (fNIRS), our study showed that the cortical activation patterns were significantly different between the tDCS and Sham group, with the activation of primary motor cortex (M1) and prefrontal cortex (PFC) contralateral to the anodal electrode significantly decreased while supplemental motor area (SMA) increased by tDCS. The lowered performance errors were retained after 1-month post-training. This work supports the use of tDCS to enhance performance accuracy in fine bimanual motor tasks.
Identification of IFN-Induced Transmembrane Protein 1 With Prognostic Value in Pancreatic Cancer Using Network Module-Based Analysis
Authors: Wu Lingyun , Zhu Xinli , Yan Danfang , Tang Mengmeng , Ma Chiyuan , Yan Senxiang
Published: March 2021

Despite improvements reported in diagnosis and treatments in recent decades, pancreatic cancer is still characterized by poor prognosis and low survival rate among solid tumors. Intensive interests have grown in exploring novel predictive biomarkers, aiming to enhance the efficiency in early detection and treatment prognosis. In this study, we identified the differentially expressed genes (DEGs) in pancreatic cancer by analyzing five gene expression profiles and established the functional modules according to the functional interaction (FI) network between the DEGs. A significant upregulation of the selected DEG, interferon (IFN)-induced transmembrane protein 1 (IFITM1), was evaluated in several bioinformatics online tools and verified with immunohistochemistry staining from samples of 90 patients with pancreatic cancer. Prognostic data showed that high expression of IFITM1 associated with poor survival, and multivariate Cox regression analysis showed IFITM1 was one of the independent prognostic factors for overall survival. Meanwhile, significant correlations of the expression of IFITM1 and the infiltration of immune cells were found by TIMER. Furthermore, a higher level of IFITM1 was assessed in pancreatic cancer cell lines compared to normal human pancreatic duct epithelial cells, and silencing IFITM1 in tumor cells remarkedly inhibited cancer tumorigenicity. Collectively, our findings suggested that IFITM1 might have promising utility for pancreatic cancer.
Challenging Giant Insular Gliomas With Brain Mapping: Evaluation of Neurosurgical, Neurological, Neuropsychological, and Quality of Life Results in a Large Mono-Institutional Series
Authors: Rossi Marco , Gay Lorenzo , Conti Nibali Marco , Sciortino Tommaso , Ambrogi Federico , Leonetti Antonella , Puglisi Guglielmo , Howells Henrietta , Zito Paola , Villa Federico , Ciroi Gjulio , Riva Marco , Bello Lorenzo
Published: March 2021

Objective

Giant insular tumors are commonly not amenable to complete resection and are associated with a high postoperative morbidity rate. Transcortical approach and brain mapping techniques allow to identify peri-insular functional networks and, with neurophysiological monitoring, to reduce vascular-associated insults. Cognitive functions to be mapped are still under debate, and the analysis of the functional risk of surgery is currently limited to neurological examination. This work aimed to investigate the neurosurgical outcome (extent of resection, EOR) and functional impact of giant insular gliomas resection, focusing on neuropsychological and Quality of Life (QoL) outcomes.

Methods

In our retrospective analysis, we included all patients admitted in a five-year period with a radiological diagnosis of giant insular glioma. A transcortical approach was adopted in all cases. Resections were pursued up to functional boundaries defined intraoperatively by brain mapping techniques. We examined clinical, radiological, and intra-operative factors possibly affecting EOR and postoperative neurological, neuropsychological, and Quality of Life (QoL) outcomes.

Results

We finally enrolled 95 patients in the analysis. Mean EOR was 92.3%. A Gross Total Resection (GTR) was obtained in 70 cases (73.7%). Five patients reported permanent morbidity (aphasia in 3, 3.2%, and superior quadrantanopia in 2, 2.1%). Suboptimal EOR associated with poor seizures control postoperatively. Extensive intraoperative mapping (inclusive of cognitive, visual, and haptic functions) decreased long-term neurological, neuropsychological, and QoL morbidity and increased EOR. Tumor infiltration of deep perforators (vessels arising either medial to lenticulostriate arteries through the anterior perforated substance or from the anterior choroidal artery) associated with a higher chance of postoperative ischemia in consonant areas, with the persistence of new-onset motor deficits 1-month post-op, and with minor EOR. Ischemic insults in eloquent sites represented the leading factor for long-term neurological and neuropsychological morbidity.

Conclusion

In giant insular gliomas, the use of a transcortical approach with extensive brain mapping under awake anesthesia ensures broad insular exposure and extension of the surgical resection preserving patients’ functional integrity. The relation between tumor mass and deep perforators predicts perioperative ischemic insults, the most relevant risk factor for long-term and permanent postoperative morbidity.
From Good to Bad: The Opposing Effects of PTHrP on Tumor Growth, Dormancy, and Metastasis Throughout Cancer Progression
Authors: Edwards Courtney M. , Johnson Rachelle W.
Published: March 2021

Parathyroid hormone related protein (PTHrP) is a multifaceted protein with several biologically active domains that regulate its many roles in normal physiology and human disease. PTHrP causes humoral hypercalcemia of malignancy (HHM) through its endocrine actions and tumor-induced bone destruction through its paracrine actions. PTHrP has more recently been investigated as a regulator of tumor dormancy owing to its roles in regulating tumor cell proliferation, apoptosis, and survival through autocrine/paracrine and intracrine signaling. Tumor expression of PTHrP in late stages of cancer progression has been shown to promote distant metastasis formation, especially in bone by promoting tumor-induced osteolysis and exit from dormancy. In contrast, PTHrP may protect against further tumor progression and improve patient survival in early disease stages. This review highlights current knowledge from preclinical and clinical studies examining the role of PTHrP in promoting tumor progression as well as skeletal and soft tissue metastasis, especially with regards to the protein as a regulator of tumor dormancy. The discussion will also provide perspectives on PTHrP as a prognostic factor and therapeutic target to inhibit tumor progression, prevent tumor recurrence, and improve patient survival.
P14/ARF-Positive Malignant Pleural Mesothelioma: A Phenotype With Distinct Immune Microenvironment
Authors: Pezzuto Federica , Lunardi Francesca , Vedovelli Luca , Fortarezza Francesco , Urso Loredana , Grosso Federica , Ceresoli Giovanni Luca , Kern Izidor , Vlacic Gregor , Faccioli Eleonora , Schiavon Marco , Gregori Dario , Rea Federico , Pasello Giulia , Calabrese Fiorella
Published: March 2021

Introduction

The CDKN2A gene plays a central role in the pathogenesis of malignant pleural mesothelioma (MPM). The gene encodes for two tumor suppressor proteins, p16/INK4A and p14/ARF, frequently lost in MPM tumors. The exact role of p14/ARF in MPM and overall its correlation with the immune microenvironment is unknown. We aimed to determine whether there is a relationship between p14/ARF expression, tumor morphological features, and the inflammatory tumor microenvironment.

Methods

Diagnostic biopsies from 76 chemo-naive MPMs were evaluated. Pathological assessments of histotype, necrosis, inflammation, grading, and mitosis were performed. We evaluated p14/ARF, PD-L1 (tumor proportion score, TPS), and Ki-67 (percentage) by immunohistochemistry. Inflammatory cell components (CD3+, CD4+, CD8+ T lymphocytes; CD20+ B-lymphocytes; CD68+ and CD163+ macrophages) were quantified as percentages of positive cells, distinguishing between intratumoral and peritumoral areas. The expression of p14/ARF was associated with several clinical and pathological characteristics. A random forest-based machine-learning algorithm (Boruta) was implemented to identify which variables were associated with p14/ARF expression.

Results

p14/ARF was evaluated in 68 patients who had a sufficient number of tumor cells. Strong positivity was detected in 14 patients (21%) (11 epithelioid and 3 biphasic MPMs). At univariate analysis, p14/ARF-positive epithelioid mesotheliomas showed higher nuclear grade (G3) (p = 0.023) and higher PD-L1 expression (≥50%) (p = 0.042). The percentages of CD4 and CD163 in peritumoral areas were respectively higher and lower in p14/ARF positive tumors but did not reach statistical significance with our sample size (both p = 0.066). The Boruta algorithm confirmed the predictive value of PD-L1 percentage for p14/ARF expression in all histotypes.

Conclusions

p14/ARF-positive epithelioid mesotheliomas may mark a more aggressive pathological phenotype (higher nuclear grade and PD-L1 expression). Considering the results regarding the tumor immune microenvironment, p14/ARF-negative tumors seem to have an immune microenvironment less sensitive to immune checkpoint inhibitors, being associated with low PD-L1 and CD4 expression, and high CD163 percentage. The association between p14/ARF-positive MPMs and PD-L1 expression suggests a possible interaction of the two pathways. Confirmation of our preliminary results could be important for patient selection and recruitment in future clinical trials with anticancer immunotherapy.
Primary Mediastinal B-Cell Lymphoma: Novel Precision Therapies and Future Directions
Authors: Chen Huan , Pan Tao , He Yizi , Zeng Ruolan , Li Yajun , Yi Liming , Zang Hui , Chen Siwei , Duan Qintong , Xiao Ling , Zhou Hui
Published: March 2021

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinicopathologic disease from other types of diffuse large B-cell lymphoma (DLBCL) with unique prognostic features and limited availability of clinical data. The current standard treatment for newly diagnosed PMBCL has long been dependent on a dose-intensive, dose-adjusted multi-agent chemotherapy regimen of rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Recent randomized trials have provided evidence that R-CHOP followed by consolidation radiotherapy (RT) is a valuable alternative option to first-line treatment. For recurrent/refractory PMBCL (rrPMBCL), new drugs such as pembrolizumab and CAR-T cell therapy have proven to be effective in a few studies. Positron emission tomography-computed tomography (PET-CT) is the preferred imaging modality of choice for the initial phase of lymphoma treatment and to assess response to treatment. In the future, baseline quantitative PET-CT can be used to predict prognosis in PMBCL. This review focuses on the pathology of PMBCL, underlying molecular basis, treatment options, radiotherapy, targeted therapies, and the potential role of PET-CT to guide treatment choices in this disease.
Current Limitations of Intraoperative Ultrasound in Brain Tumor Surgery
Authors: Šteňo Andrej , Buvala Ján , Babková Veronika , Kiss Adrián , Toma David , Lysak Alexander
Published: March 2021

While benefits of intraoperative ultrasound (IOUS) have been frequently described, data on IOUS limitations are relatively sparse. Suboptimal ultrasound imaging of some pathologies, various types of ultrasound artifacts, challenging patient positioning during some IOUS-guided surgeries, and absence of an optimal IOUS probe depicting the entire sellar region during transsphenoidal pituitary surgery are some of the most important pitfalls. This review aims to summarize prominent limitations of current IOUS systems, and to present possibilities to reduce them by using ultrasound technology suitable for a specific procedure and by proper scanning techniques. In addition, future trends of IOUS imaging optimization are described in this article.
High Salinity Reduces Plant Growth and Photosynthetic Performance but Enhances Certain Nutritional Quality of C4 Halophyte Portulaca oleracea L. Grown Hydroponically Under LED Lighting
Authors: He Jie , You Xueli , Qin Lin
Published: March 2021

Portulaca oleracea L. (known as purslane) is one of the most nutritious leafy vegetables owing to its high content of antioxidants. In this study, all plants were grown indoors hydroponically with different NaCl salinities. Photosynthetic photo flux density (PPFD) at 200 μmol m−2 s−1 (12 h) was provided to all plants by LED with red:blue ratio of 2.2. Thirty days after transplanting, plants grown with100 mM NaCl had the highest productivity and the fastest leaf growth followed by those with 0, 200 and 300 mM NaCl. Grown with 300 mM NaCl, purslane had the lowest specific leaf area due to its highest leaf dry matter content and its lowest water content. All plants had similar values of leaf succulence except for those with 300 mM NaCl. Total chlorophyll and carotenoids contents were significantly higher in plants grown with 0 and 100 mM NaCl than with 200, and 300 mM NaCl. All plants had Fv/Fm ratios close to 0.8. However, electron transport rate and ΔF/Fm′ were significantly higher in plants grown with 0 and 100 mM NaCl than with 200 and 300 mM NaCl. CAM-induced purslane with 300 mM NaCl had higher non-photochemical quenching. Maximum net photosynthetic O2 evolution rate and Cyt b6f concentration were significantly lower with 300 mM NaCl compared to all other plants while all plants had similar PS II concentration. Proline concentration increased with increasing salinities. All plants had similar levels of total soluble sugars. Plants grown with 0 and 100 mM NaCl had significantly higher concentrations of NO3−, total reduced nitrogen, total leaf soluble protein, Rubisco protein, total ascorbic acid, and total phenolic compounds than with 200 and 300 mM NaCl. The highest concentrations of K, Ca, and Mg were found in purslane grown under 0 mM NaCl. Statistically, no significant differences in Fe concentrations were observed among all plants. However, salinity seems to increase Fe concentration. In conclusion, it is feasible to grow purslane under 100 mM NaCl as it is the most optimal condition to achieve higher productivity and better quality. However, the production of antioxidants may depend on not only salinity but also other growth conditions.