bluuebunny/crossref_metadata_2025 huggingface dataset:
Le rapport centre-périphérie et les mobilités structurées : les jeunes Franco-Manitobains et Montréal
Authors: Breton-Carbonneau Gabrielle , Heller Monica
Published: November 2021

Cet article explore les relations ambivalentes de jeunes Franco-Manitobains pris entre deux pôles d’attraction, le domicile et le Montréal cosmopolite. Cette ambivalence émerge des tensions entre deux sources de légitimité francophone : Montréal en tant que métropole et capitale culturelle du Canada français, ainsi que ville internationale et cosmopolite attrayante, et le Manitoba en tant que lieu d’origine authentique et centre de la francophonie de l’Ouest, issu d’une histoire de colonialisme de peuplement. Déménager à Montréal met ces tensions au premier plan : on risque d’être perçu comme traître à la cause du développement de la communauté francophone minoritaire et du français au Manitoba, d’une part, et, d’autre part, on ignore si l’on sera accepté comme un francophone légitime par les Québécois francophones. Visibles dans la recherche d’amarrage chez les jeunes Franco-Manitobains, dans leurs allers-retours entre les deux pôles et leurs va-et-vient dans les réseaux sociaux et linguistiques, ces tensions rejoignent des tensions contemporaines plus larges entre le colonialisme de peuplement, l’ethnonationalisme minoritaire et le cosmopolitisme mondialisé.
Improving scheduling performance in congested networks
Authors: Husen Arif , Hasanain Chaudary Muhammad , Ahmad Farooq , Imtiaz Alam Muhammad , Sohail Abid , Asif Muhammad
Published: November 2021

With continuously rising trends in applications of information and communication technologies in diverse sectors of life, the networks are challenged to meet the stringent performance requirements. Increasing the bandwidth is one of the most common solutions to ensure that suitable resources are available to meet performance objectives such as sustained high data rates, minimal delays, and restricted delay variations. Guaranteed throughput, minimal latency, and the lowest probability of loss of the packets can ensure the quality of services over the networks. However, the traffic volumes that networks need to handle are not fixed and it changes with time, origin, and other factors. The traffic distributions generally follow some peak intervals and most of the time traffic remains on moderate levels. The network capacity determined by peak interval demands often requires higher capacities in comparison to the capacities required during the moderate intervals. Such an approach increases the cost of the network infrastructure and results in underutilized networks in moderate intervals. Suitable methods that can increase the network utilization in peak and moderate intervals can help the operators to contain the cost of network intrastate. This article proposes a novel technique to improve the network utilization and quality of services over networks by exploiting the packet scheduling-based erlang distribution of different serving areas. The experimental results show that significant improvement can be achieved in congested networks during the peak intervals with the proposed approach both in terms of utilization and quality of service in comparison to the traditional approaches of packet scheduling in the networks. Extensive experiments have been conducted to study the effects of the erlang-based packet scheduling in terms of packet-loss, end-to-end latency, delay variance and network utilization.
PLGA-PEG-PLGA hydrogel with NEP1-40 promotes the functional recovery of brachial plexus root avulsion in adult rats
Authors: Guo Wenlai , Pei Bingbing , Li Zehui , Ou Xiao Lan , Sun Tianwen , Zhu Zhe
Published: November 2021

Adult brachial plexus root avulsion can cause serious damage to nerve tissue and impair axonal regeneration, making the recovery of nerve function difficult. Nogo-A extracellular peptide residues 1-40 (NEP1-40) promote axonal regeneration by inhibiting the Nogo-66 receptor (NgR1), and poly (D, L-lactide-co-glycolide)-poly (ethylene glycol)-poly (D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel can be used to fill in tissue defects and concurrently function to sustain the release of NEP1-40. In this study, we established an adult rat model of brachial plexus nerve root avulsion injury and conducted nerve root replantation. PLGA-PEG-PLGA hydrogel combined with NEP1-40 was used to promote nerve regeneration and functional recovery in this rat model. Our results demonstrated that functional recovery was enhanced, and the survival rate of spinal anterior horn motoneurons was higher in rats that received a combination of PLGA-PEG-PLGA hydrogel and NEP1-40 than in those receiving other treatments. The combined therapy also significantly increased the number of fluorescent retrogradely labeled neurons, muscle fiber diameter, and motor endplate area of the biceps brachii. In conclusion, this study demonstrates that the effects of PLGA-PEG-PLGA hydrogel combined with NEP1-40 are superior to those of other therapies used to treat brachial plexus nerve root avulsion injury. Therefore, future studies should investigate the potential of PLGA-PEG-PLGA hydrogel as a primary treatment for brachial plexus root avulsion.
Degradation of lignocelluloses in straw using AC-1, a thermophilic composite microbial system
Authors: Liu Hongdou , Zhang Liqiang , Sun Yu , Xu Guangbo , Wang Weidong , Piao Renzhe , Cui Zongjun , Zhao Hongyan
Published: November 2021

In composting, the degradation of lignocellulose in straw is problematic due to its complex structures such as lignin. A common solution to this problem is the addition of exogenous inoculants. AC-1, a stable thermophilic microbial composite, was isolated from high temperature compost samples that can decompose lignocellulose at 50–70 °C. AC-1 had a best degradation efficiency of rice straw at 60 °C (78.92%), of hemicellulose, cellulose and lignin were 82.49%, 97.20% and 20.12%, respectively. It showed degrad-ability on both simple (filter paper, absorbent cotton) and complex (rice straw) cellulose materials. It produced acetic and formic acid during decomposition process and the pH had a trend of first downward then upward. High throughput sequencing revealed the main bacterial components of AC-1 were Tepidimicrobium, Haloplasma, norank-f-Limnochordaceae, Ruminiclostridium and Rhodothermus which provides major theoretical basis for further application of AC-1.
Trend Analysis of Temperature Data in Muğla
Authors: YILMAZ Ayça
Published: November 2021

İklimde meydana gelen kısa veya uzun süreli değişiklikler çeşitli yönlerden ciddi sorunlara yol açmaktadır. Bu sebeple iklimsel eğilimleri/değişimleri belirlemeye yönelik analizlerin gerçekleştirilmesi büyük önem taşımaktadır. İklimdeki
değişim ise en iyi sıcaklık ve yağış parametreleriyle gösterilebilmektedir. Bu hususa dayanarak araştırma ile Muğla ilinde bulunan meteoroloji istasyonlarının 1966-2020 yılları arasında sıcaklık verilerinde göstermiş olduğu yıllık
ve mevsimlik trendleri ortaya koymak ve alan yazına katkı sağlamak amaçlanmıştır. Araştırma kapsamında Bodrum, Dalaman, Datça, Fethiye, Köyceğiz, Marmaris, Milas, Muğla ve Yatağan istasyonlarının Meteoroloji İşleri Genel Müdürlüğü’nden
temin edilen ortalama sıcaklık, ortalama maksimum sıcaklık ve ortalama minimum sıcaklık verilerinden yararlanılmıştır. Sıcaklık verilerinin öncelikli olarak dağılımı (Kolmogorov-Smirnov) ve homojenliği (Kruskal-Wallis) test edilmiştir.
Testlerden elde edilen sonuçlar verilerin büyük ölçüde homojen yapıda olmadığını ortaya koymuştur. Trend analizleri için parametrik olmayan yöntemlerden Mann-Kendall, Spearman’s Rho ve Mann-Kendall Mertebe Korelasyon testlerinin
sonuçlarından yararlanılmıştır. Analizler neticesinde istasyonlara ait sıcaklıklarda büyük ölçüde artış eğilimi olduğu tespit edilmiştir ve bu eğilimler istatistiki olarak anlamlılık göstermektedir. En kuvvetli artış eğilimi, yıllık
ortalama sıcaklıklarda Milas, ortalama maksimum sıcaklıklarda Bodrum (Mann-Kendall) ve Yatağan (Spearman’s Rho), minimum sıcaklıklarda ise Fethiye istasyonuna aittir. Mevsimsel açıdan yaz ve sonbahar mevsimlerinde artış eğilimi
en belirginken; kış mevsimi artış eğiliminin en zayıf olduğu dönemi temsil etmektedir. İklim değişiminin meydana getirdiği sorunların çözümüne dair oluşturulacak planlamalara yol göstermesi bakımından yapılan çalışmanın sahaya
katkı sağlayacağı düşünülmektedir.
Examination of Tourism Destinations in Turkey on the Basis of the Number and Types of Tourism Transport Authorization Documents
Authors: ALPASLANOĞLU Alpaslan
Published: November 2021

Turizm sektörü hem küresel ekonomi hem de ülkeler ekonomisi içerisinde önemli döviz girdisi ve istihdam sağlayan iş dallarının başlıcası olmakla beraber hizmetler sektörü içerisinde de en önemli iş alanlarından birisi konumundadır.
Buna rağmen turizm, asla sadece iktisadi bir iş alanı değildir. Türkiye sahip olduğu çok sayıda ve çok çeşitli turizm potansiyeli ile global ölçekte önemli turizm merkezlerinden birisi durumundadır. Ülke dışı turist sayısı ve toplam
turizm getirileri itibari ile dikkate alınmış olan Türkiye’nin sahip olduğu destinasyonlara gelen turistlerin ulaşım türlerine göre incelendiği bu çalışmada; turist akışına göre turizm taşıma Yetki Belgelerinin dağılımı da araştırılmıştır.
Ayrıca turizm taşımasında kullanılan turizm taşıma araçları ile Yetki Belgelerinin mahiyet ve sayıları ve turizm bölgelerine göre dağılımları içerik analizleri ile incelenmiştir. Araştırma için kullanılan veriler resmi, kamuya
açık nitelikte olup; Dünya Ticaret Örgütü, Birleşmiş Milletler Dünya Turizm Örgütü (UNWTO), Dünya Ticaret Örgütü (WTO), UNECE, T.C. Kültür ve Turizm Bakanlığı, T.C. Ulaştırma ve Altyapı Bakanlığı, E-Devlet Kapısı, TÜİK, gibi kurum
ve kuruluşlar ile ilgili sektör dernek ve birliklerinden elde edilmiştir. Bu nedenle etik açıdan üst düzey standartları karşılamaktadır ve etik kurul kararı gerektirmemektedir. Araştırma, literatürde benzeri bir çalışmanın yapılmamış
olması, turizm taşıma Yetki Belgeleri ile turizme ilişkin bazı oransal hesaplamaları ortaya koyması, Türkiye turizm destinasyonlarının taşıma altyapısı verimliliklerini artırmak için bulgular sunması nedenleri dolayısıyla önemli
görülmektedir. Araştırma bulgularına göre; turizm akışı ve yoğunluğu ile turizm taşımacılığı Yetki Belgeleri ve turizm taşıma araçlarının homojen bir dağılım göstermediği, dağılımlarda dikkate değer bölgesel farklılıklar olduğu,
turizm destinasyonlarına göre fazla kapasiteye sahip olan turizm taşımacılığının mevcut olduğu gözlemlenmiştir. Öte yandan turizm taşımacılığı Yetki Belgeleri ve turizm taşıma araçları sayılarının, planlama ve tasarımdan ziyade
kısa dönem piyasa koşulları ile geçici arz-talep dengesi çerçevesinde oluştuğu gözlemlenmiştir.
An Analysis on the Interactions, Transformations and Differentiations of the Thought Worlds of Cemil Meriç and Ümit Meriç
Authors: ÇAV Erkan
Published: November 2021

Ömrünü düşünceye adayan her insan, dünyanın düşünce birikimini zenginleştirir. Entelektüelin ürettiği duygu ve düşünceler, onunla doğrudan iletişim ve ilişkide olan çevresindeki insanlardan başlar, yazılarını ve eserlerini okuyan,
konuşmalarını dinleyen, fikirlerini inceleyen herkese ulaşır. 38 yaşında âmâ olan Cemil Meriç’in (1916-1987), kitapları okuyabilmek için yardımcıya ihtiyaç duyduğu ömrünün kalan döneminde, bu hizmeti en fazla yürüten isim kuşkusuz
kızı Ümit Meriç’tir (d.1946). Entelektüel Cemil Meriç’in 71 yıllık ömründe, kızı, öğrencisi, asistanı, fikirdaşı ve yoldaşı olan, bu görevini özellikle babası âmâ olduktan sonra 33 yıl kesintisiz olarak yıllarını adayan bir sorumluluk
ve ciddiyet ile gerçekleştiren kızı Ümit Meriç’in babasından aldığı entelektüel miras nedir? Ümit Meriç ile Cemil Meriç’in düşünce dünyalarının etkileşimleri, dönüşümleri ve farklılaşmaları nelerdir, nasıl tanımlanabilir, bu düşünsel
ilişki hangi yönelimleri göstermiştir? Cemil Meriç’in 71 yıllık, Ümit Meriç’in bugün 75 yılı bulan verimli ömürlerinin entelektüel boyutlarını belli başlı bazı izlekler üzerinden tanımlamak, tasniflemek, ilişkilendirmek ve açıklamak
mümkündür. Bunlar, entelektüel hayatlarının filizlendiği ortamlar, bulundukları düşünce dünyaları ve ilerleyişleri, Doğu ve Batı düşüncesine yaklaşımları, milliyetçilik ve din karşısındaki tavırları olmak üzere dört boyutta değerlendirilebilir.
33 yıl, neredeyse kesintisiz bir entelektüel yolculuk içinde olan baba-kız etkileşimleri ile düşünsel olgunluk örneği verirler. Hayatları boyunca öğrenmeyi ve öğretmeyi kendilerine ilke edinmiş Cemil Meriç ile Ümit Meriç’in düşünce
dünyalarının karşılaştırmalı incelemesi, Türkiye’nin XX. yüzyılına ait düşünce tarihinin ana izleklerini ortaya koyar. Bu karşılaştırma, aynı zamanda birlikte okuyan, düşünen ve yazan iki insanın entelektüel bağını fikirler ekseninde
anlamlandırır ve nihayetinde babadan kızına aktarılan entelektüel mirasın çok yönlü bir haritasını verir.
The Construction of Chinese Indonesians in Ngenest Film
Authors: Christian Yoel
Published: October 2021

The thesis focuses on how Chinese Indonesians are constructed in Ngenest and why they are constructed that way. Chinese Indonesians become a scapegoat and considered bad ethnic group since they are the minority. By using the Ethnic Construction and Stereotype theory it helps me to reveal the constructions of Chinese Indonesians in Ngenest, and also why they are constructed that way. I would analyze the Chinese Indonesian major and minor characters in Ngenest. This can be revealed from the way they interact with the society in Ngenest. In conclusion, Chinese Indonesians are not accepted as one’s own in their land because of their construction as perpetual foreigners, being loyal to Chinese traditions which makes them different from the rest of the Indonesian society, and being rich by exploiting non-Chinese Indonesians. Since the Chinese Indonesians are the minority, they become a scapegoat and target of non-Chinese Indonesians in the society. Keywords: racism, ethnic construction, stereotyping, representation, Chinese Indonesians
Managing Jasapindah.id Instagram Account Effectively to Increase Its Brand Awareness
Authors: Laiman Sylvia Pratiwi
Published: October 2021

Jasapindah.id is a relocation service under PT 3 Permata Logistics management. They provide relocation, packing, and warehouse services. However, the main problem that Jasapindah.id faced was the ineffective use of the social media of Instagram. The current Instagram contents were not good because the information needed was not complete, the quality of the picture was low, and the content was not updated regularly. Hence, the solution was managing its Instagram account by giving comprehensive information, improving the quality of the pictures, and making the content schedules. I improved the Instagram contents and pictures based on the theories from Walter and Gioglio (2014) and Simone (2013). After I managed the account, the brand awareness has increased, as proved by the increasing number of followers and accounts who contacted Jasapindah.id through direct messages and comments. Hopefully, the revised Instagram contents can increase the brand awareness of Jasapindah.id and led to better sales. Keyword: brand awareness, social media, Instagram
Recent Advances in Antibacterial Superhydrophobic Coatings
Authors: Zhan Yanlong , Yu Sirong , Amirfazli Alidad , Rahim Siddiqui Abdul , Li Wen
Published: October 2021

New strategies to overcome the defects of conventional antibacterial ways are imminently required due to the rapid growth of bacterial resistance by the overuse and misuse of antibiotics. The bioinspired superhydrophobic coatings as innovative scheme to prevent bacterial adhesion and infections have attracted increasing attention. The purpose of this review is to present recent advances and challenges related to the antibacterial superhydrophobic coatings. First, the formation of bacterial film and the hazard of bacterial infections are introduced. Subsequently, the concept and mechanism of antibacterial superhydrophobic coatings are explained. Moreover, the research progress of antibacterial superhydrophobic coatings based on metals and metallic oxides, quaternary ammonium compounds (QACs), andN‐halamines are reviewed and summarized with a cutting‐edge perspective. Finally, the challenges and future research directions of the antibacterial superhydrophobic coatings are prospected with the expectation of providing guidance for the coming researches and applications.
Emission‐Tunable Room‐Temperature Phosphorescent Polymers Based on Dynamic Reversible Supramolecule‐Mediated Photocrosslinking
Authors: Lin Xiaohan , Xu Qingyang , Ma Xiang
Published: October 2021

Pure organic room‐temperature phosphorescence (RTP) materials can be used in optoelectronics, biochemical equipment, sensors and biological imaging. In the past few years, dynamic covalent chemistry has attracted significant attention because it provides a new way to produce intelligent optical materials with feedback functions. Two polymers are synthesized through supramolecular‐mediated [4+4] photocyclodimerization of anthracene, which can be reversibly transformed by photoreversible dynamic covalent bonds. The polymers show decent phosphorescence emission with different colors at room temperature, achieving the conversion between blue phosphorescence and cyan phosphorescence. This study provides a novel method for designing and synthesizing pure organic RTP materials with tunable emissions through dynamic covalent bonds.
Cascade Reaction of o‐Haloaryl Ynone and 2‐Hydroxy‐2‐Methylchromene: Synthesis of Chromone Derivative Enabled by Oxygen‐Migration
Authors: Shen Jie , Xiao Yao , Zhao Peichao , Li Dong , Jia Xueshun , Peng Xin , Li Jian
Published: October 2021

We developed a cascade reaction of o‐haloaryl ynone and 2‐hydroxy‐2‐methylchromene under transition metal‐free conditions. This strategy proceeds through double Michael addition and oxygen‐migration, thus providing a straight way for the synthesis of chromone derivatives.

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Inhibition of the PLK1‐Coupled Cell Cycle Machinery Overcomes Resistance to Oxaliplatin in Colorectal Cancer
Authors: Yu Zhaoliang , Deng Peng , Chen Yufeng , Liu Shini , Chen Jinghong , Yang Zihuan , Chen Jianfeng , Fan Xinjuan , Wang Peili , Cai Zerong , Wang Yali , Hu Peishan , Lin Dezheng , Xiao Rong , Zou Yifeng , Huang Yan , Yu Qiang , Lan Ping , Tan Jing , Wu Xiaojian
Published: October 2021

Dysregulation of the cell cycle machinery leads to genomic instability and is a hallmark of cancer associated with chemoresistance and poor prognosis in colorectal cancer (CRC). Identifying and targeting aberrant cell cycle machinery is expected to improve current therapies for CRC patients. Here,upregulated polo‐like kinase 1 (PLK1) signaling, accompanied by deregulation of cell cycle‐related pathways in CRC is identified. It is shown that aberrant PLK1 signaling correlates with recurrence and poor prognosis in CRC patients. Genetic and pharmacological blockade of PLK1 significantly increases the sensitivity to oxaliplatin in vitro and in vivo. Mechanistically, transcriptomic profiling analysis reveals that cell cycle‐related pathways are activated by oxaliplatin treatment but suppressed by a PLK1 inhibitor. Cell division cycle 7 (CDC7) is further identified as a critical downstream effector of PLK1 signaling, which is transactivated via the PLK1‐MYC axis. Increased CDC7 expression is also found to be positively correlated with aberrant PLK1 signaling in CRC and is associated with poor prognosis. Moreover, a CDC7 inhibitor synergistically enhances the anti‐tumor effect of oxaliplatin in CRC models, demonstrating the potential utility of targeting the PLK1‐MYC‐CDC7 axis in the treatment of oxaliplatin‐based chemotherapy.
Effects of Docetaxel Injection and Docetaxel Micelles on the Intestinal Barrier and Intestinal Microbiota
Authors: Liu Qingya , Lu Yi , Xiao Yao , Yuan Liping , Hu Danrong , Hao Ying , Han Ruxia , Peng Jinrong , Qian Zhiyong
Published: October 2021

Increasing evidence has suggested that chemotherapeutics affect the integrity of the intestinal barrier and alter the intestinal microbiota, thus limiting the therapeutic outcomes of cancer chemotherapy. Docetaxel (DTX) is used for breast cancer treatment and has gastrointestinal side effects, but the influence of DTX formulations on the intestinal barrier and intestinal microbiota remains unknown. Therefore, in this work, the influence of DTX injection (free DTX, commercial formulation) and DTX/methoxy poly(ethylene glycol)‐block‐poly(D,L‐lactide) (mPEG‐PDLLA) (DTX micelles, nanoformulation) on the integrity of the intestinal barrier and the intestinal microbiota is investigated. It is found that the free DTX causes significantly greater intestinal barrier damage than the DTX micelles. The diversity of the intestinal microbiota, and the relative abundance of Akkermansia muciniphila and Ruminococcus gnavus in the DTX micelle‐treated group is significantly higher than that in the free DTX‐treated group. Moreover, the tumor growth rate is elevated in antibiotic mixture‐pretreated mice, demonstrating that the diversity and composition of the intestinal microbiota may be associated with tumor progression. This work demonstrates that different formulations of chemotherapeutics have different effects on the integrity of the intestinal barrier and the intestinal microbiota.
Chemiluminescence: From mechanism to applications in biological imaging and therapy
Authors: Wang Zhijia , Huang Jiaguo , Huang Jingsheng , Yu Bingran , Pu Kanyi , Xu Fu‐Jian
Published: October 2021

Chemiluminescence (CL) is an emission phenomenon induced by chemical reaction. Different from the photoluminescence, CL is free from external excitation source, which is expected to show great advantages such as higher signal‐to‐background ratio (SBR) in bioimaging, and deeper tissue penetration in photodynamic therapy (PDT). This review introduces the theoretical aspects of CL mechanism, such as classification, energy consideration and chemiexcited/photoexcited states. Application of CL in bioimaging is highlighted. In particular, the approaches to modulate the brightness and the wavelength of CL are summarized, which are two fundamental parameters in bioimaging. Finally, the application of CL in PDT is introduced. The potential challenges and perspectives of CL in bioimaging and therapy are also discussed.
Framework Nucleic Acids in Nuclear Medicine Imaging: Shedding Light on Nano–Bio Interactions
Authors: Wang Hao , Liu Qingyao , Lan Xiaoli , Jiang Dawei
Published: October 2021

Framework nucleic acids (FNAs) represent nanoscale oligonucleotide assemblies with unique physical, chemical, and biological properties that are different from their building blocks. Following simple Watson–Crick base‐pairing rules, arbitrary DNA frameworks with diverse shapes, sizes, and dimensions can be prepared with high reproducibility and stability. The programmable assembly of nucleic acids into FNAs presents a highly controllable model for studies on nano–bio interactions and allows scrutiny of “nanostructure‐activity relationships.” Herein, we present an overview of recent progress with FNAs in the hope of deepening our understanding of nano–bio interfacing. We summarize the biological profiles and immune responses of various FNAs as functions of their shape, sizes, and surface charges. We then highlight recent efforts to apply FNAs for biomedical applications and discuss the challenges of FNAs for potential clinical translation. We believe that this Minireview can bring up‐to‐date information on FNAs and shed light on how their design may be harnessed for selective biomedical applications.
Case Study of N‐iPr versus N‐Mes Substituted NHC Ligands in Nickel Chemistry: The Coordination and Cyclotrimerization of Alkynes at [Ni(NHC)2]
Authors: Tendera Lukas , Helm Moritz , Krahfuss Mirjam J. , Kuntze‐Fechner Maximilian W. , Radius Udo
Published: October 2021

A case study on the effect of the employment of two different NHC ligands in complexes [Ni(NHC)2] (NHC=iPr2ImMe 1Me, Mes2Im 2) and their behavior towards alkynes is reported. The reaction of a mixture of [Ni2(iPr2ImMe)4(μ‐(η2 : η2)‐COD)] B/ [Ni(iPr2ImMe)2(η4‐COD)] B’ or [Ni(Mes2Im)2] 2, respectively, with alkynes afforded complexes [Ni(NHC)2(η2‐alkyne)] (NHC=iPr2ImMe: alkyne=MeC≡CMe 3, H7C3C≡CC3H7 4, PhC≡CPh 5, MeOOCC≡CCOOMe 6, Me3SiC≡CSiMe3 7, PhC≡CMe 8, HC≡CC3H7 9, HC≡CPh 10, HC≡C(p‐Tol) 11, HC≡C(4‐tBu‐C6H4) 12, HC≡CCOOMe 13; NHC=Mes2Im: alkyne=MeC≡CMe 14, MeOOCC≡CCOOMe 15, PhC≡CMe 16, HC≡C(4‐tBu‐C6H4) 17, HC≡CCOOMe 18). Unusual rearrangement products 11 a and 12 a were identified for the complexes of the terminal alkynes HC≡C(p‐Tol) and HC≡C(4‐tBu‐C6H4), 11 and 12, which were formed by addition of a C−H bond of one of the NHC N‐iPr methyl groups to the C≡C triple bond of the coordinated alkyne. Complex 2 catalyzes the cyclotrimerization of 2‐butyne, 4‐octyne, diphenylacetylene, dimethyl acetylendicarboxylate, 1‐pentyne, phenylacetylene and methyl propiolate at ambient conditions, whereas 1Me is not a good catalyst. The reaction of 2 with 2‐butyne was monitored in some detail, which led to a mechanistic proposal for the cyclotrimerization at [Ni(NHC)2]. DFT calculations reveal that the differences between 1Me and 2 for alkyne cyclotrimerization lie in the energy profile of the initiation steps, which is very shallow for 2, and each step is associated with only a moderate energy change. The higher stability of 3 compared to 14 is attributed to a better electron transfer from the NHC to the metal to the alkyne ligand for the N‐alkyl substituted NHC, to enhanced Ni‐alkyne backbonding due to a smaller CNHC−Ni−CNHC bite angle, and to less steric repulsion of the smaller NHC iPr2ImMe.
Base‐Mediated Radical Borylation of Alkyl Sulfones
Authors: Huang Mingming , Hu Jiefeng , Krummenacher Ivo , Friedrich Alexandra , Braunschweig Holger , Westcott Stephen A. , Radius Udo , Marder Todd B.
Published: October 2021

A practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal‐free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2neop2), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late‐stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates.
A case of splenic artery aneurysm and rupture in a patient on a vascular endothelial growth factor inhibitor for renal cell carcinoma
Authors: Tesolin Daniel , Alaref Amer , Ibrahim Mohammed F. K.
Published: October 2021

Background

Pazopanib is a vascular endothelial growth factor inhibitor that is used in the treatment of metastatic renal cell carcinoma. Post market reports demonstrate an increasing awareness of the association of arterial aneurysms and dissections with vascular endothelial growth factor inhibitor use, although, few reports exist for pazopanib.

Case

Here we report a 69‐year‐old patient with minimal cardiovascular risk factors who developed a rupture of a splenic arterial aneurysm after more than 5 years of effective treatment with pazopanib for metastatic renal cell carcinoma.

Conclusion

This case report outlines the necessity to monitor patients while on pazopanib, even when there are minimal risk factors and long periods of tolerance.
Pharmacokinetics and Safety of Letermovir and Midazolam Coadministration in Healthy Subjects
Authors: Kropeit Dirk , McCormick David , Erb‐Zohar Katharina , Stobernack Hans‐Peter , Zimmermann Holger , Rübsamen‐Schaeff Helga
Published: October 2021

Letermovir is a human cytomegalovirus (CMV) terminase inhibitor for the prophylaxis of CMV infection and disease in allogeneic hematopoietic stem‐cell transplant recipients. In vitro studies have identified letermovir as a potential cytochrome P450 (CYP) 3A inhibitor. Thus, the effect of letermovir on the CYP3A isoenzyme‐specific probe drug midazolam was investigated in a phase 1 trial. Healthy female subjects received single‐dose intravenous (IV; 1 mg) and oral (2 mg) midazolam on days –4 and –2, respectively. Letermovir 240 mg once daily was administered on days 1 to 6, and further single doses of midazolam 1 mg IV and oral midazolam 2 mg were administered on days 4 and 6, respectively. Pharmacokinetics, tolerability, and safety were monitored throughout the trial. Following coadministration with letermovir, the least square means ratio for maximum plasma concentration and area under the plasma concentration–time curve from time 0 to the last measurable concentration was 172.4% and 225.3%, respectively, for oral midazolam, and 105.2% and 146.6%, respectively, for midazolam IV. The area under the plasma concentration–time curve from time 0 to the last measurable concentration ratio of midazolam to 1‐hydroxymidazolam increased slightly in the presence of letermovir following IV (8.8‐13.1; 49% increase) and oral (3.3‐5.3; 59% increase) midazolam. Letermovir reached steady state, on average, by days 5 to 6. All treatments were generally well tolerated. Letermovir demonstrated moderate CYP3A inhibition.
Clinical Pharmacokinetics of Daprodustat: Results of an Absorption, Distribution, and Excretion Study With Intravenous Microtracer and Concomitant Oral Doses for Bioavailability Determination
Authors: Mahar Kelly M. , Caltabiano Stephen , Andrews Susan , Ramanjineyulu Bandi , Chen Liangfu , Young Graeme , Pereira Adrian , Lindsay Alistair C. , van den Berg Frans , Cobitz Alexander R.
Published: October 2021

Daprodustat, an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease. This phase 1, nonrandomized, 2‐period, crossover study in 6 healthy men characterized the absorption, distribution, and excretion of daprodustat when administered as oral and intravenous (IV) doses of unlabeled and radiolabeled daprodustat ([14C]‐GSK1278863). Tolerability and pharmacokinetic properties of daprodustat, and its 6 metabolites in the systemic circulation, were also evaluated. The mean recovery of radiolabeled daprodustat was ≈95% by day 5, with the majority in feces and minor renal elimination, indicating that daprodustat and metabolites are primarily eliminated via hepatobiliary and fecal routes. Approximately 40% of total circulating radioactivity in plasma following both IV and oral administration was daprodustat; thus, 60% was attributed to metabolites. It was estimated that ≈80% of daprodustat was absorbed across the gastrointestinal tract, and ≈18% cleared by hepatic extraction. Pharmacokinetics were essentially dose proportional, with moderate (≈66%) oral tablet bioavailability. Following IV administration, daprodustat plasma clearance (19.3 L/h) and volume of distribution (14.6 L) were low, suggesting low tissue distribution outside systemic circulation with likely low penetration into tissues. Daprodustat was generally well tolerated, with no deaths or serious or significant adverse events reported.
Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials
Authors: Leong Ruby , Liu Qi , Li Lingjue , Liu Jiang , Ren Yunzhao R. , Lee Peter , Chuk Meredith , Reaman Gregory , Wang Yaning
Published: October 2021

Our research supported the dose selection recommendations for adolescents in the US Food and Drug Administration (FDA) Guidance on Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. The FDA Guidance states that for drugs administered as a flat dose in adults and data showing no clinically meaningful effect of body size on drug exposure and toxicity in adults, a minimum body weight threshold may need to be defined to prevent adolescents who have a lower body weight from exceeding adult exposures. Our review of adult population pharmacokinetic analyses of new molecular entities approved for oncology between January 2015 and March 2021 suggested that 40 kg (the approximate median body weight of a 12‐year‐old) is generally the lower end of the body weight range that has no clinically relevant effect on drug pharmacokinetics or safety. The minimum body weight threshold and selection of an appropriate dose for adolescents in relevant adult oncology clinical trials should ultimately be determined based on available data on pharmacokinetics or pharmacodynamics of the investigational drug with consideration of body size effect on drug exposure, toxicity, and efficacy data (if available), the therapeutic index of the drug, and dose‐ and exposure‐response relationships in adults.
Peri‐implant marginal bone loss and systemic statin use: A retrospective cohort pilot study
Authors: Bahrami‐Hessari Behzad , Jansson Leif
Published: October 2021

Objectives

The aim was to analyze clinical parameters of peri‐implantitis in human subjects exposed and non‐exposed to use of systemic statins.

Material and methods

This retrospective cohort pilot study compared patient records of 60 exposed individuals to 196 non‐exposed individuals as of 2011 throughout 2017. Source of records were specialist and general dentistry clinics in Public Dental Service, Stockholm County, Sweden. Extent/severity of peri‐implantitis and peri‐implant bone loss were registered as well as intake of systemic statins. Background variables considered were bleeding on probing, bone‐loss, age, gender, earlier periodontitis, prosthetic quality, and smoking. Stepwise linear and logistic regression analysis at the individual level was adopted in order to study the influence of statin use on the severity of peri‐implantitis and the incidence of peri‐implant bone loss. Results were considered statistically significant at p < 0.05.

Results

Peri‐implant bone loss was significantly correlated to use of statin after compensation for age and sex.

Conclusions

The results render an actual effect of statins on peri‐implant bone loss plausible. Further research is warranted.
Palladium Nanoparticles Hardwired in Carbon Nanoreactors Enable Continually Increasing Electrocatalytic Activity During the Hydrogen Evolution Reaction
Authors: Aygün Mehtap , Guillen‐Soler Melanie , Vila‐Fungueiriño Jose M. , Kurtoglu Abdullah , Chamberlain Thomas W. , Khlobystov Andrei N. , del Carmen Gimenez‐Lopez Maria
Published: October 2021

Invited for this month's cover is the group of Maria Gimenez‐Lopez at the University of Santiago de Compostela. The image shows the self‐improving electrochemical activity of palladium nanoparticles hardwired into a graphitic step‐edge for hydrogen production. The Full Paper itself is available at 10.1002/cssc.202101236.
Spatial distribution patterns and predictors of fish beta‐diversity in a large dam‐free tributary from a Neotropical floodplain
Authors: Frota Augusto , Ganassin Maria J. M. , Pacifico Ricardo , Gomes Luiz C. , da Graça Weferson J.
Published: October 2021

Understanding how and why fish species composition varies between locations through beta‐diversity has received increased interest recently. The physical structure, extension and environmental characteristics along the river basins influence the dispersal of organisms, which ultimately affects metacommunity dynamics and biodiversity patterns. Here, we aimed to identify major breaks delimiting fish assemblages in a large dam‐free river basin on its main channel, which is almost pristine in hidrology, and to evaluate the influence of geo‐climatic variables in the observed beta‐diversity patterns. We used the statistical techniques Species Composition Interpolation (SCI) and Generalized Dissimilarity Modeling (GDM) to analyse beta‐diversity patterns based on georeferenced fish records from the Ivaí River basin. Ichthyofauna units were delimited, estimating the association between geo‐climatic predictors and beta‐diversity. We identified three major breaks delimiting fish assemblages in the Ivaí River basin (i.e. the upper, middle and lower sections). The fish communities were very distinct at the upper and lower sections, while the middle section was recovered as less differentiated. Turnover was the main component contributing to total beta‐diversity, and dissimilarity in fish species composition was moderately associated with geo‐climatic variables. Fish communities from the Ivaí River basin must be associated with niche‐based processes, and we hypothesize that dispersal processes can be equally significant at the basin scale. The investigations may produce insights on strategies for conservation and restoration of degraded rivers, contributing to the long‐term maintenance of fish communities and to the delimitation of new strategic areas for the effective conservation of freshwater biodiversity.
Steric Properties of N‐Heterocyclic Carbenes affect the Performance of Electronic Probes
Authors: Barnett Christopher , Cole Marcus L. , Harper Jason B.
Published: October 2021

Electronic probes of ligands, particularly carbenes, are widely used in assessing electronic properties; the results inform the selection of a ligand for a given application. As such, it is important to ensure the data obtained is reliable and unaffected by other factors, such as the steric bulk of the ligand. The effects of such steric factors on two commonly used electronic probes (based on palladium and selenium) are investigated here, with the selenium adduct found to be particularly sensitive. It is hoped that this serves as a cautionary tale to always critically evaluate what a probe is measuring.
Structure‐Proving Syntheses of the Polyenoyltetramic Acids Pyranonigrin J and I
Authors: Drescher Christian , Brückner Reinhard
Published: October 2021

The polyenoyltetramic acids pyranonigrin J (3) and pyranonigrin I (4) had been isolated from Aspergillus niger. Their origins from and roles in biosynthesis as well as the S‐configurations of their stereocenter had been deduced from expression experiments with modifications of the corresponding gene cluster. We corroborated this stereochemical assignment after executing the first total syntheses of both compounds because they had essentially the same specific rotations as their natural counterparts. Our syntheses used the β‐ketothioester 18 as a conjunctive reagent. It was combined with the l‐serine derivatives (S)‐19 or (S)‐21 (“Western building blocks”), respectively, through aminolyses. Stille couplings with the stannane 13 (“Eastern building block”) followed. The resulting β‐ketoamides (S)‐11 and (S)‐12 underwent desilylative Lacey‐Dieckmann cyclizations when exposed to 8 equiv. of Bu4NF. They rendered the polyenoyltetramic acids (S)‐26 [acidolysis: → (S)‐3] and (S)‐4, respectively.
Identification of biomarkers related to glycolysis with weighted gene co‐expression network analysis in oral squamous cell carcinoma
Authors: Zhou Xiongming , Xue Danfeng , Qiu Jiaxuan
Published: October 2021

Background

Oral squamous cell carcinoma (OSCC) is the most common tumor in the oral cavity and maxillofacial region. Increasing evidence suggests that aerobic glycolysis plays an important role in the occurrence, development, and prognosis of OSCC. Therefore, the identification of biomarkers related to glycolysis in OSCC represents considerable potential for improving its treatment.

Methods

In the present study, a single‐sample gene‐set enrichment analysis (ssGSEA) algorithm with weighted gene co‐expression network analysis (WGCNA) were used to quantify the degree of glycolysis and identify key modules with the greatest correlation with glycolysis.

Results

Glycolytic scores significantly correlated with prognosis. In the key module 5 HUB genes were finally selected, which displayed a robust predictive effect. The expressions of key genes were associated with glycolysis.

Conclusions

The research comprehensively analyzed the glycolysis of OSCC and identified several biomarkers related to glycolysis. These biomarkers may represent potential therapeutic targets for future OSCC therapy.
Large granular lymphocytosis: A novel association with immunotherapy
Authors: Nedumannil Rithin , Juneja Surender
Published: October 2021

Although reactive large granular lymphocytosis due to diverse etiologies is not an uncommon finding in clinical practice, isolated natural killer (NK)‐cell lymphocytosis is unusual and its association with immunotherapy has not been described thus far. We provide a brief analysis of a patient with this unique hematological corollary of immunotherapy being increasingly used in the setting of both solid organ and hematological malignancies, and highlight this as an additional differential to consider in the diagnosis of large granular lymphocytosis. Also explored is the importance of recognizing and monitoring the potential hematological manifestations of experimental immunotherapies, as well as the possible implicated mechanisms of action. It is hypothesized that quantification of large granular lymphocytosis may potentially be used as a surrogate marker of therapeutic efficacy in this setting.
An evaluation of Turkey's health tourism policies using a social network analysis approach
Authors: Uygun Meltem
Published: October 2021

Despite the health tourism sector's rapid growth in the past decade due to globalisation, there is little research analysing countries' health tourism policies. This study aimed to examine the relationships between stakeholders in the health tourism sector in Turkey in the context of Turkey's health tourism policies. This study connects theory and practice in multidisciplinary sectors, including health, tourism, and business, through an evaluation of major issues from a health management perspective. Social network analysis was used to assess the role of 107 stakeholders in Ankara and determine the extent of weak and strong ties among them. Issues confronting these stakeholders and the obstacles they faced in practice were also identified. The study found that, the relevant stakeholders faced comprehensive sectoral deficiencies and issues in building positive relationships. Governmental stakeholders as policymakers need to develop effective strategies to improve stakeholder collaboration and encourage greater inclusiveness through better‐targeted health tourism policies. The study contributes to social network theory, resource dependency theory, and stakeholder theory, and is, to our knowledge, the first study to use social network analysis to examine the role of stakeholders in the health tourism sector.
Vitamin D and Skeletal Muscle: Current Concepts From Preclinical Studies
Authors: Girgis Christian M. , Brennan‐Speranza Tara C.
Published: October 2021

Muscle weakness has been recognized as a hallmark feature of vitamin D deficiency for many years. Until recently, the direct biomolecular effects of vitamin D on skeletal muscle have been unclear. Although in the past, some reservations have been raised regarding the expression of the vitamin D receptor in muscle tissue, this special issue review article outlines the clear evidence from preclinical studies for not only the expression of the receptor in muscle but also the roles of vitamin D activity in muscle development, mass, and strength. Additionally, muscle may also serve as a dynamic storage site for vitamin D, and play a central role in the maintenance of circulating 25‐hydroxy vitamin D levels during periods of low sun exposure. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
The impact of Marfan syndrome on an Aboriginal Australian family: ‘I don’t like it as much as I don’t like cancer’
Authors: McInerney‐Leo Aideen M. , West Jennifer , Meiser Bettina , West Malcolm , Toombs Maree R. , Brown Matthew A. , Duncan Emma L.
Published: October 2021

Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder. Aortic dilatation/dissection and ectopia lentis are the most severe features, which affect physical functioning and psychological well‐being. In Aboriginal Australians, there is little psychosocial research on genetic conditions. This study explored the physical, psychological, and practical impacts of MFS on Aboriginal Australians. Eighteen (8 affected and 10 unaffected) members of a large Aboriginal Australian family with MFS participated in an ethically approved study. Semi‐structured qualitative interviews were conducted, transcribed verbatim, and analyzed thematically. All individuals reported challenges from MFS, negatively affecting day‐to‐day living. Severe vision impairment was perceived as the greatest challenge, contributing to feelings of stigma and exclusion. With aging, concerns shifted toward cardiac complications. The unpredictability of lens dislocation and aortic dissection was reported to be psychologically challenging. Participants described MFS‐related barriers to obtaining and retaining employment, especially following cardiac surgery; with consequential psychological and financial hardships. Participants articulated that their cultural drive to support the ill and respectfully mourn the deceased, regardless of distance, resulted in a significant financial burden. Additionally, when hospitalization and/or funerals occurred, financially solvent individuals were expected to share resources, without any expectation of repayment or reciprocity (i.e., ‘demand sharing’, common in Aboriginal Australian culture). This study documents the nature and pervasiveness of uncertainty for both affected and unaffected members of an MFS family. Many reported challenges are consistent with other MFS cohorts (including stigma, social exclusion, and unemployment). However, our findings suggest that cultural values may exacerbate the financial costs of MFS for Aboriginal Australians.