bluuebunny/crossref_metadata_2025 huggingface dataset:
Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice
Authors: Bisht Kanchan , Okojie Kenneth A. , Sharma Kaushik , Lentferink Dennis H. , Sun Yu-Yo , Chen Hong-Ru , Uweru Joseph O. , Amancherla Saipranusha , Calcuttawala Zainab , Campos-Salazar Antony Brayan , Corliss Bruce , Jabbour Lara , Benderoth Jordan , Friestad Bria , Mills William A. , Isakson Brant E. , Tremblay Marie-Ève , Kuan Chia-Yi , Eyo Ukpong B.
Published: September 2021

Microglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 + myeloid cell somata and brain capillaries. We confirm that these cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then, we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing them with parenchymal microglia (PCMs) in their morphological activities including during microglial depletion and repopulation. Molecularly, we identify P2RY12 receptors as a regulator of CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, microglial elimination triggered capillary dilation, blood flow increase, and impaired vasodilation that were recapitulated in P2RY12−/− and PANX1−/− mice suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function.
Structural proof of a [C–F–C]+ fluoronium cation
Authors: Hoffmann Kurt F. , Wiesner Anja , Müller Carsten , Steinhauer Simon , Beckers Helmut , Kazim Muhammad , Pitts Cody Ross , Lectka Thomas , Riedel Sebastian
Published: September 2021

Organic fluoronium ions can be described as positively charged molecules in which the most electronegative and least polarizable element fluorine engages in two partially covalent bonding interactions to two carbon centers. While recent solvolysis experiments and NMR spectroscopic studies on a metastable [C–F–C]+fluoronium ion strongly support the divalent fluoronium structure over the alternative rapidly equilibrating classical carbocation, the model system has, to date, eluded crystallographic analysis to confirm this phenomenon in the solid state. Herein, we report the single crystal structure of a symmetrical [C–F–C]+fluoronium cation. Besides its synthesis and crystallographic characterization as the [Sb2F11]−salt, vibrational spectra are discussed and a detailed analysis concerning the nature of the bonding situation in this fluoronium ion and its heavier halonium homologues is performed, which provides detailed insights on this molecular structure.
Regulation of functional groups on graphene quantum dots directs selective CO2 to CH4 conversion
Authors: Zhang Tianyu , Li Weitao , Huang Kai , Guo Huazhang , Li Zhengyuan , Fang Yanbo , Yadav Ram Manohar , Shanov Vesselin , Ajayan Pulickel M. , Wang Liang , Lian Cheng , Wu Jingjie
Published: September 2021

A catalyst system with dedicated selectivity toward a single hydrocarbon or oxygenate product is essential to enable the industrial application of electrochemical conversion of CO2 to high-value chemicals. Cu is the only known metal catalyst that can convert CO2 to high-order hydrocarbons and oxygenates. However, the Cu-based catalysts suffer from diverse selectivity. Here, we report that the functionalized graphene quantum dots can direct CO2 to CH4 conversion with simultaneous high selectivity and production rate. The electron-donating groups facilitate the yield of CH4 from CO2 electro-reduction while electron-withdrawing groups suppress CO2 electro-reduction. The yield of CH4 on electron-donating group functionalized graphene quantum dots is positively correlated to the electron-donating ability and content of electron-donating group. The graphene quantum dots functionalized by either –OH or –NH2 functional group could achieve Faradaic efficiency of 70.0% for CH4 at −200 mA cm−2 partial current density of CH4. The superior yield of CH4 on electron-donating group- over the electron-withdrawing group-functionalized graphene quantum dots possibly originates from the maintenance of higher charge density of potential active sites (neighboring C or N) and the interaction between the electron-donating group and key intermediates. This work provides insight into the design of active carbon catalysts at the molecular scale for the CO2 electro-reduction.
Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance
Authors: Cui Miao , Atmanli Ayhan , Morales Maria Gabriela , Tan Wei , Chen Kenian , Xiao Xue , Xu Lin , Liu Ning , Bassel-Duby Rhonda , Olson Eric N.
Published: September 2021

Following injury, cells in regenerative tissues have the ability to regrow. The mechanisms whereby regenerating cells adapt to injury-induced stress conditions and activate the regenerative program remain to be defined. Here, using the mammalian neonatal heart regeneration model, we show that Nrf1, a stress-responsive transcription factor encoded by the Nuclear Factor Erythroid 2 Like 1 (Nfe2l1) gene, is activated in regenerating cardiomyocytes. Genetic deletion of Nrf1 prevented regenerating cardiomyocytes from activating a transcriptional program required for heart regeneration. Conversely, Nrf1 overexpression protected the adult mouse heart from ischemia/reperfusion (I/R) injury. Nrf1 also protected human induced pluripotent stem cell-derived cardiomyocytes from doxorubicin-induced cardiotoxicity and other cardiotoxins. The protective function of Nrf1 is mediated by a dual stress response mechanism involving activation of the proteasome and redox balance. Our findings reveal that the adaptive stress response mechanism mediated by Nrf1 is required for neonatal heart regeneration and confers cardioprotection in the adult heart.
Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin
Authors: Mao Hua , Li Luge , Fan Qiying , Angelini Aude , Saha Pradip K. , Coarfa Cristian , Rajapakshe Kimal , Perera Dimuthu , Cheng Jizhong , Wu Huaizhu , Ballantyne Christie M. , Sun Zheng , Xie Liang , Pi Xinchun
Published: September 2021

The vascular endothelium is present within metabolic organs and actively regulates energy metabolism. Here we show osteocalcin, recognized as a bone-secreted metabolic hormone, is expressed in mouse primary endothelial cells isolated from heart, lung and liver. In human osteocalcin promoter-driven green fluorescent protein transgenic mice, green fluorescent protein signals are enriched in endothelial cells lining aorta, small vessels and capillaries and abundant in aorta, skeletal muscle and eye of adult mice. The depletion of lipoprotein receptor-related protein 1 induces osteocalcin through a Forkhead box O -dependent pathway in endothelial cells. Whereas depletion of osteocalcin abolishes the glucose-lowering effect of low-density lipoprotein receptor-related protein 1 depletion, osteocalcin treatment normalizes hyperglycemia in multiple mouse models. Mechanistically, osteocalcin receptor-G protein-coupled receptor family C group 6 member A and insulin-like-growth-factor-1 receptor are in the same complex with osteocalcin and required for osteocalcin-promoted insulin signaling pathway. Therefore, our results reveal an endocrine/paracrine role of endothelial cells in regulating insulin sensitivity, which may have therapeutic implications in treating diabetes and insulin resistance through manipulating vascular endothelium.
Structural basis of RNA processing by human mitochondrial RNase P
Authors: Bhatta Arjun , Dienemann Christian , Cramer Patrick , Hillen Hauke S.
Published: September 2021

Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In contrast to nuclear or bacterial RNase P, mtRNase P is not a ribozyme but comprises three protein subunits that carry out RNA cleavage and methylation by unknown mechanisms. Here, we present the cryo-EM structure of human mtRNase P bound to precursor tRNA, which reveals a unique mechanism of substrate recognition and processing. Subunits TRMT10C and SDR5C1 form a subcomplex that binds conserved mitochondrial tRNA elements, including the anticodon loop, and positions the tRNA for methylation. The endonuclease PRORP is recruited and activated through interactions with its PPR and nuclease domains to ensure precise pre-tRNA cleavage. The structure provides the molecular basis for the first step of RNA processing in human mitochondria.
Intra-group decision-making in agent-based models
Authors: Beal Cohen Allegra A. , Muneepeerakul Rachata , Kiker Gregory
Published: September 2021

Many agent-based models (ABMs) try to explain large-scale phenomena by reducing them to behaviors at lower scales. At these scales in social systems are functional groups such as households, religious congregations, coops and local governments. The intra-group dynamics of functional groups often generate inefficient or unexpected behavior that cannot be predicted by modeling groups as basic units. We introduce a framework for modeling intra-group decision-making and its interaction with social norms, using the household as our focus. We select phenomena related to women’s empowerment in agriculture as examples influenced by both intra-household dynamics and gender norms. Our framework proves more capable of replicating these phenomena than two common types of ABMs. We conclude that it is not enough to build multi-scale models; explaining social behaviors entails modeling intra-scale dynamics.
Dectin-2 mediates phagocytosis of Lactobacillus paracasei KW3110 and IL-10 production by macrophages
Authors: Yoshikawa Mia , Yamada Sayuri , Sugamata Miho , Kanauchi Osamu , Morita Yuji
Published: September 2021

Lactic acid bacteria (LAB) are most generally used as probiotics and some strains of LAB are known to have anti-inflammatory effects. A specific strain of lactic acid bacteria, Lactobacillus paracasei KW3110 (KW3110), activates macrophages to produce interleukin-10 (IL-10), an anti-inflammatory cytokine; however, the biological mechanism remains unclear. In this study, we showed that the amount of incorporated KW3110 into a macrophage cell line, RAW 264.7, was higher than other genetically related strains using fluorescence microscopy. RNA-seq analysis indicated that treatment of macrophages with KW3110 induced Dectin-2 gene expression, which is a pattern recognition receptor, recognizing α-mannose. In addition, antibody treatment and knock down of Dectin-2, or factors downstream in the signaling pathway, decreased the amount of incorporated KW3110 and IL-10 production. Substantial lectin array analysis also revealed that KW3110 had higher binding affinities to lectins, which recognize the carbohydrate chains comprised of α-mannose, than two other LAB. In conclusion, KW3110 is readily incorporated into macrophages, leading to IL-10 production. Dectin-2 mediated the phagocytosis of KW3110 into macrophages and this may be involved with the characteristic carbohydrate chains of KW3110.
Soret vector for description of multicomponent mixtures
Authors: Mialdun Aliaksandr , Bou-Ali Mounir , Shevtsova Valentina
Published: September 2021

The Soret effect describes the transport of constituent species in multicomponent mixtures that occurs due to a temperature gradient. This cross-coupling effect of heat and mass transfer has been successfully examined in binary liquid mixtures, while experiments with ternary mixtures are rare as they impose significant difficulties. We introduce a new and innovative concept, the Soret vector, for the characterization of Soret driven separation in ternary mixtures. The presentation of the component separation in the vector form offers several advantages: (i) to predict the Soret sign of a ternary mixture from knowledge of the Soret coefficients in binary subsystems; (ii) to control consistency of measured coefficients, this is especially important when results are obtained using different instruments and methods; (iii) to determine in which regions and which components cause the greatest separation; (iv) to identify the regions where the Soret separation is inaccessible for optical techniques or gravitationally unstable. We demonstrate these features by exploring ternary mixtures of different origins: (a) nearly ideal mixture composed by THN–IBB–nC12 when Soret coefficients in binary subsystems ($$S_{T}^{bin}$$

S

T

bin

) are positive, (b) non-ideal mixture containing water and ethanol TEG–Wat–EtOH when $$S_{T}^{bin}$$

S

T

bin

are positive and negative and (c) Tol–MeOH–Ch mixture containing demixing zone with positive and negative $$S_{T}^{bin}$$

S

T

bin

. Our approach provides a promising systematic framework for the future research of an important and challenging problem of thermodiffusion in multicomponent liquids.
Validation of inner ear MRI in patients with Ménière’s disease by comparing endolymphatic hydrops from histopathologic specimens
Authors: Cho Young Sang , Kim Jong Sei , Kim Min Bum , Koh Sung Min , Lee Chang Hee , Kim Yi-Kyung , Kim Hyung-Jin , Chung Won-Ho
Published: September 2021

Intravenous gadolinium-enhanced inner-ear magnetic resonance imaging (IV-Gd inner-ear MRI) has been used to visualize endolymphatic hydrops (EH) in clinical diagnosis of Ménière’s disease (MD). However, lack of histological validation has led to several concerns regarding how best to interpret the resulting images. Here, we compared hydropic changes in temporal bone specimens with the results of IV-Gd inner-ear MRI in patients with MD. Histopathologic images of temporal bones from 37 patients with MD and 10 healthy controls were collected from the National Temporal Bone Bank of the Massachusetts Eye and Ear Infirmary in the United States. The EH ratios in the vestibule and cochlea were calculated from temporal bones using the methods used for IV-Gd inner-ear MRI, and the degree to which the saccular and utricular hydrops contributed to vestibular hydrops was measured. The presence of hydropic change in each semicircular canal was assessed using temporal bone images and compared with IV-Gd inner-ear MRI scans of 74 patients with MD. Based on human temporal bone imagery, the EH ratios in the cochlea and the vestibule on the affected side were 0.314 and 0.757, respectively. In the healthy control group, the ratio was 0.064 for the cochlea and 0.289 for the vestibule; these values were significantly different from those for the affected side of MD patients. The values for the affected ear were similar to the ratios from the IV-Gd inner-ear MRI scans in MD patients. In the vestibule, saccular hydrops were more common than utricular hydrops. The average EH ratios in the saccule and utricle were 0.513 and 0.242, respectively. No significant hydropic change from each of three semicircular canals was evident in temporal bone histopathology. However, herniation of otolithic organs (saccule or utricle) into the lateral semicircular canal was found in 44.4% of the patients, with saccular herniation (24.8%) more common than utricular herniation (16.7%). Although IV-Gd inner-ear MRI might not reflect fully the results of actual histopathology due to the limited resolution of MRI and image-processing techniques, the measured EH ratios from temporal bone specimens and IV-Gd inner-ear MRI scans were similar. Hydropic change in the three semicircular canals was not significant at either the ampullated or nonampullated end. Canal invasion of vestibular hydrops seen on MRI also appeared in temporal bone histopathology, and saccular invasion was dominant.
Secondhand smoke increases the risk of developing kidney stone disease
Authors: Chen Chien-Heng , Lee Jia-In , Jhan Jhen-Hao , Lee Yung-Chin , Geng Jiun-Hung , Chen Szu-Chia , Hung Chih-Hsing , Kuo Chao-Hung
Published: September 2021

Research indicates smoking increases the risk of various kidney diseases, although the risk of developing kidney stone disease in non-smokers exposed to secondhand smoke is unknown. This study analyzed a total of 19,430 never-smokers with no history of kidney stone disease who participated in the Taiwan Biobank from 2008 to 2019. They were divided into two groups by secondhand smoke exposure; no exposure and exposure groups; the mean age of participants was 51 years, and 81% were women. Incident kidney stone development was observed in 352 (2.0%) and 50 (3.3%) participants in the no exposure and exposure groups during a mean follow-up of 47 months. The odds ratio (OR) of incident kidney stone was significantly higher in the exposure group than the no exposure group [OR, 1.64; 95% confidence interval (95% CI) 1.21 to 2.23]. Participants with > 1.2 h per week exposure were associated with almost twofold risk of developing kidney stones compared with no exposure (OR, 1.92; 95% CI 1.29 to 2.86). Our study suggests that secondhand smoke is a risk factor for development of kidney stones and supports the need for a prospective evaluation of this finding.
In situ gelling and dissolvable hydrogels for use as on-demand wound dressings for burns
Authors: Cook Katherine A. , Naguib Nada , Kirsch Jack , Hohl Katherine , Colby Aaron H. , Sheridan Robert , Rodriguez Edward K. , Nazarian Ara , Grinstaff Mark W.
Published: September 2021

Currently, no dressings utilized in burn clinics provide adhesion, hydration or mechanical strength on the same order as human skin as well as the ability to be atraumatically removed.
Solvent-free benzylic oxidation of aromatics over Cu(ii)-containing propylsalicylaldimine anchored on the surface of mesoporous silica catalysts
Authors: Selvaraj Manickam , Assiri Mohammed A. , Rokhum Samuel Lalthazuala , Manjunatha C. , Appaturi Jimmy Nelson , Murugesan Sepperumal , Bhaumik Asim , Subrahmanyam Ch.
Published: September 2021

A highly active mesoporous catalyst W-CPSA-SBA-15(0.2) shows unprecedented catalytic activity for the selective synthesis of aromatic ketones with 99–100% selectivity, among other CPSA functionalized mesoporous catalysts.
Chlorogenic acid inhibits trimethylamine-N-oxide formation and remodels intestinal microbiota to alleviate liver dysfunction in high l-carnitine feeding mice
Authors: Zhang Xiangnan , Shi Lin , Chen Rui , Zhao Yan , Ren Daoyuan , Yang Xingbin
Published: September 2021

Chlorogenic acid alleviates liver dysfunction in l-carnitine feeding mice via inhibiting trimethylamine-N-oxide (TMAO) formation and reconstructing the intestinal microbiota.
Robust three-dimensional nanotube-in-micropillar array electrodes to facilitate size independent electroporation in blood cell therapy
Authors: Liu Xuan , Chang An-Yi , Ma Yifan , Hua Liping , Yang Zhaogang , Wang Shengnian
Published: September 2021

Plasmid transfection in individual blood cell type (e.g., K562), blood samples and their mixture.
Rational design of near-infrared fluorophores with a phenolic D–A type structure and construction of a fluorescent probe for cysteine imaging
Authors: Chen Dugang , Nie Gang , Dang Yecheng , Liang Wenjie , Li Wanqing , Zhong Cheng
Published: September 2021

The structural modulation of phenolic D–A type fluorophores and a NIR fluorescent probe for cysteine imaging in vitro and in vivo.
Ultra-homogeneous NIR-II fluorescent self-assembled nanoprobe with AIE properties for photothermal therapy of prostate cancer
Authors: Cui Shengsheng , Fan Shanshan , Tan Haisong , Lu Yi , Zha Yiqian , Xu Bin , Liu Yanlei , Cui Daxiang
Published: September 2021

Illustration of the procedure for preparation of an NIR-II nanoprobe and its application in photothermal treatment under the guidance of two-zone fluorescence imaging.
Lithographic in-mold patterning for CsPbBr3 nanocrystals distributed Bragg reflector single-mode laser
Authors: Ahmad Kamal Ahmad Syazwan , Lin Cheng-Chieh , Xing Di , Lee Yang-Chun , Wang Zhiyu , Chen Mu-Hsin , Ho Ya-Lun , Chen Chun-Wei , Delaunay Jean-Jacques
Published: September 2021

A newly developed lithographic in-mold patterning process is proposed to fabricate on-chip single-mode distributed-Bragg-reflector waveguide small lasers that utilized CsPbBr3 perovskite nanocrystals as the gain material.
Eco-friendly functional two-component flame-retardant waterborne polyurethane coatings: a review
Authors: Yin Xuan , Pang Haosheng , Luo Yunjun , Zhang Bing
Published: September 2021

Green functional two-component flame-retardant waterborne polyurethane (2K-FWPU) coatings possess outstanding green traits, such as providing eco-friendly protection, having low toxicity, and generating no pollution.
The wavelength-regulated stereodivergent synthesis of (Z)- and (E)-1,4-enediones from phosphonium ylides
Authors: Wang Mei , He Yong-Qin , Zhu Yao , Song Zhi-Bin , Wang Xiao-Yu , Huang Hai-Yang , Cao Ban-Peng , Tian Wan-Fa , Xiao Qiang
Published: September 2021

The wavelength-regulated, photoredox-catalyzed stereodivergent synthesis of (Z)- and (E)-1,4-enediones from phosphonium ylides is reported.
Synthesis, characterization, and evaluation of selective molecularly imprinted polymers for the fast determination of synthetic cathinones
Authors: Chen Hong , Wu Fangsheng , Xu Yibing , Liu Yuan , Song Lun , Chen Xiujuan , He Qun , Liu Wei , Han Qiaoying , Zhang Zihua , Zou Yun , Liu Wenbin
Published: September 2021

Molecularly imprinted polymers, as an adsorbent for extraction and selective recognition of 4-methyldimethcathinone, were firstly synthesized through coprecipitation polymerization.
Highly selective enrichment of Au using enaminone covalent organic polymers (COP)
Authors: Li An , Zheng Naixia , Yang Tao , Xie Jun , Li LiJun , Tang KeWen , Zhou CongShan
Published: September 2021

The second recovery of gold has fundamental environmental and economic significance.
ZnCl2-promoted domino reaction of 2-hydroxybenzonitriles with ketones for synthesis of 1,3-benzoxazin-4-ones
Authors: Su Ziqi , Chai Hongxin , Xu Juan , Li Jiarong
Published: September 2021

A method for the synthesis of 1,3-benzoxazine-4-ketone was developed using 2-hydroxybenzonitriles and ketones as raw materials with the promotion of ZnCl2.
Recent progress in cadmium fluorescent and colorimetric probes
Authors: Shi Chun-tian , Huang Zhi-yu , Wu Ai-bin , Hu Yan-xiong , Wang Ning-chen , Zhang Ying , Shu Wen-ming , Yu Wei-chu
Published: September 2021

Cadmium is a heavy metal which exists widely in industrial and agricultural production and can induce a variety of diseases in organisms.
Discovery of SARS-CoV-2 Mpro peptide inhibitors from modelling substrate and ligand binding
Authors: Chan H. T. Henry , Moesser Marc A. , Walters Rebecca K. , Malla Tika R. , Twidale Rebecca M. , John Tobias , Deeks Helen M. , Johnston-Wood Tristan , Mikhailov Victor , Sessions Richard B. , Dawson William , Salah Eidarus , Lukacik Petra , Strain-Damerell Claire , Owen C. David , Nakajima Takahito , Świderek Katarzyna , Lodola Alessio , Moliner Vicent , Glowacki David R. , Spencer James , Walsh Martin A. , Schofield Christopher J. , Genovese Luigi , Shoemark Deborah K. , Mulholland Adrian J. , Duarte Fernanda , Morris Garrett M.
Published: September 2021

The main protease (Mpro) of SARS-CoV-2 is central to viral maturation and is a promising drug target. In silico methods reveal structural aspects of how it binds to its 11 natural cleavage sites, the design of novel peptide inhibitors, and insights into drug design.
Enhanced polysulfide regulation via honeycomb-like carbon with catalytic MoC for lithium–sulfur batteries
Authors: Deng Wenjing , Xu Zhixiao , Deng Zhiping , Wang Xiaolei
Published: September 2021

A honeycomb-structured, nitrogen-doped interconnected carbon framework H-MoC-NC with catalytic MoC nanoparticles as a sulfur host is designed to improve polysulfide regulation and cycling performance in lithium-sulfur batteries.
Enhanced photon harvesting by embedding cost-effective polystyrene microspheres as light scatterers in the perovskite photodetector
Authors: Fu Xinran , Wang Qiying , Wang Jingtao , Huang Zhijian , Li Xueqian , Wen Da , Fang Junyu , Li Bobo , Zhou Shuang , Zhang Haixi
Published: September 2021

Solution processed perovskite photodetectors have attracted extensive interest in recent years.
A zero-thermal-quenching perovskite-like phosphor with an ultra-narrow-band blue-emission for wide color gamut backlight display applications
Authors: Leng Zhihua , Zhang Dan , Bai Hao , He Hongbo , Qing Qing , Zhao Jin , Tang Zuobin
Published: September 2021

A novel perovskite-like K2BaPO4F:Eu2+phosphor exhibits an unprecedented ultra-narrow-band (FWHM = 25 nm) blue-emission (λem= 439 nm) and a zero-thermal-quenching property up to a temperature of 125 °C.
Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats
Authors: Neckář Jan , Alánová Petra , Olejníčková Veronika , Papoušek František , Hejnová Lucie , Šilhavý Jan , Behuliak Michal , Bencze Michal , Hrdlička Jaroslav , Vecka Marek , Jarkovská Dagmar , Švíglerová Jitka , Mistrová Eliška , Štengl Milan , Novotný Jiří , Ošťádal Bohuslav , Pravenec Michal , Kolář František
Published: September 2021

Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.
KMT-2021-BLG-0322: Severe degeneracy between triple-lens and higher-order binary-lens interpretations
Authors: Han Cheongho , Gould Andrew , Hirao Yuki , Lee Chung-Uk , Albrow Michael D. , Chung Sun-Ju , Hwang Kyu-Ha , Jung Youn Kil , Kim Doeon , Mao Shude , Ryu Yoon-Hyun , Shin In-Gu , Shvartzvald Yossi , Yee Jennifer C. , Zang Weicheng , Cha Sang-Mok , Kim Dong-Jin , Kim Hyoun-Woo , Kim Seung-Lee , Lee Dong-Joo , Lee Yongseok , Park Byeong-Gon , Pogge Richard W. , Abe Fumio , Barry Richard , Bennett David P. , Bhattacharya Aparna , Bond Ian , Donachie Martin , Fujii Hirosane , Fukui Akihiko , Itow Yoshitaka , Kirikawa Rintaro , Kondo Iona , Koshimoto Naoki , Alex Li Man Cheung , Matsubara Yutaka , Muraki Yasushi , Miyazaki Shota , Ranc Clément , Rattenbury Nicholas J. , Satoh Yuki , Shoji Hikaru , Sumi Takahiro , Suzuki Daisuke , Tanaka Yuzuru , Tristram Paul J. , Yamawaki Tsubasa , Yonehara Atsunori
Published: September 2021

Aims. We investigate the microlensing event KMT-2021-BLG-0322, for which the light curve exhibits three distinctive sets of caustic-crossing features. It is found that the overall features of the light curve are approximately described by a binary-lens (2L1S) model, but the model leaves substantial residuals. We test various interpretations with the aim of explaining the residuals.

Methods. We find that the residuals can be explained either by considering a nonrectilinear lens-source motion caused by the microlens-parallax and lens-orbital effects or by adding a low-mass companion to the binary lens (3L1S model). The degeneracy between the higher-order 2L1S model and the 3L1S model is very severe, making it difficult to single out a correct solution based on the photometric data. This degeneracy was known before for two previous events (MACHO-97-BLG-41 and OGLE-2013-BLG-0723), which led to the false detections of planets in binary systems, and thus the identification of the degeneracy for KMT-2021-BLG-0322 illustrates that the degeneracy can be not only common but also very severe, emphasizing the need to check both interpretations of deviations from 2L1S models.

Results. From the Bayesian analysis conducted with the measured lensing observables of the event timescale, angular Einstein radius, and microlens parallax, it was estimated that the binary lens components have masses (M1,M2) = (0.62−0.26+0.25 M⊙, 0.07−0.03+0.03 M⊙), for both 2L1S and 3L1S solutions, and the mass of the tertiary lens component according to the 3L1S solution is M3 = 6.40−2.78+2.64 MJ.
In Kontakt mit sich selbst
Authors: Spies Stefan
Published: September 2021

Unser heutiges Leben ist frei und vielfältig, aber auch schnell, oftmals hektisch und mit Stress verbunden. Wir sind verführt viele Dinge gleichzeitig tun zu wollen. Oft denken wir an den nächsten und übernächsten Schritt, als uns einfach unserer aktuellen Tätigkeit hinzugeben. Möglicherweise kennen Sie dies von sich, sicher aber von einigen Patienten/innen oder Ihren Mitarbeiter/innen, die gestresst sind. Hier kann ein Achtsamkeitstraining sehr hilfreich sein.
Mild COVID-19 and Impaired Blood Cell–Endothelial Crosstalk: Considering Long-Term Use of Antithrombotics?
Authors: Melkumyants Arthur , Buryachkovskaya Ludmila , Lomakin Nikita , Antonova Olga , Serebruany Victor
Published: September 2021

Background Current coronavirus disease 2019 (COVID-19) pandemic reveals thrombotic, vascular, and endothelial dysfunctions at peak disease. However, the duration, degree of damage, and appropriate long-term use of antithrombotic strategies are unclear. Most COVID data are yielded from random clinical observations or autopsy of postmortem samples, while precise blood cellular data in survivors are insufficient.

Methods We analyzed erythrocytes, circulating endothelial cells, and echinocytes by electron microscopy and flow cytometry in patients with confirmed COVID-19 (n = 31) and matched healthy controls (n = 32) on admission and at hospital discharge.

Results All patients experienced mild disease, none required pulmonary support, and all survived. Admission number of circulating endothelial cells was significantly (40–100 times) higher in COVID-19 patients. Cells were massively damaged by multiple fenestrae in membranes with diameter comparable to the size of supercapsid in SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. COVID-19 also provoked formation of stacked aggregated erythrocytes capable of clogging microvascular bed and of diminishing oxygen supply. In some patients, such abnormalities persisted at hospital discharge revealing remaining intracellular penetration of SARS-CoV-2 where it may be replicated and returned to circulation.

Conclusion These observational and descriptive data suggest that persistent viral cell injury may cause blood vessel damage; their increased permeability resulted in tissue edema, inflammation, platelet activation, and augmented thrombosis. There is a residual blood cell damage following the acute phase in some COVID-19 survivors. Controlled outcome-driven trials are urgently needed for exploring optimal use of long-term antithrombotics and vascular protection strategies even after mild COVID-19.
Maxacalcitol Pharmacokinetic–Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis
Authors: Fukazawa-Shinotsuka Mizuki , Saito Tomohisa , Abe Masaichi , Iida Satofumi , Wang I-Ting , Terao Kimio , Chen Hsi-Hsien , Liu Ming-Che
Published: September 2021

Background Maxacalcitol was approved in Taiwan in 2018 as the first active vitamin D3 injection for secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis. However, no data from any clinical study with maxacalcitol in Taiwanese patients is available.

Objectives This analysis aimed to evaluate the profiles of parathyroid hormone (PTH) and calcium (Ca) concentrations in Taiwanese SHPT patients on hemodialysis and maxacalcitol.

Methods We developed population pharmacokinetic (PK) and pharmacodynamic (PD) models using a modeling and simulation approach. The data for these analyses were obtained from two studies: a clinical pharmacology study in Japanese patients and an ethnic comparison study in healthy Japanese and -Taiwanese volunteers. We then conducted a simulation study with a PK-PD model comprising the PK and PD models developed here.

Results Serum maxacalcitol concentration profile was modeled using a two-compartment model that took into consideration the distribution of concentrations below the lower limit of quantification. An ethnic difference in clearance was included in the PK model as a covariate. A PD model that used a PTH/Ca feedback loop best described the observed data. There were no significant differences in Ca or PTH concentrations between Taiwanese and Japanese based on the simulation results from our PK-PD model, even though maxacalcitol exposure was approximately 40% higher in Taiwanese than in Japanese.

Conclusions On the basis of these population PK and PD analyses and the clinical study conducted in Japan, there is no clinically relevant difference between Taiwanese and Japanese in terms of serum Ca or PTH levels.
Ramucirumab in Indian Patients with Advanced Gastric Cancer—Does Borderline Performance Status and Heavy Burden of Disease in Real World Practice Impact Clinical Benefit?
Authors: Ramaswamy Anant , Bajaj Kripa , Talwar Vineet , Prabhash Kumar , Batra Ullas , Dhabhar Boman , Sharma Mansi , Ghadyalpatil Nikhil , CT Satish , Goyal Gautam , Muzamil Javvid , Bhatt Amit , Jain Parveen , Ranade Anantbhushan , Kamath Mangesh , Gawande Jayant Pundlik , Thippeswamy Ravi , Mirani Jimmy , Reddy Neelesh , Ganguly Sandip , Mishra Sourav Kumar , Madabhavi Irappa , HP Shashidhara , Panda Soumya Surath , Patil Shekar , Bhargava Prabhat , Ostwal Vikas
Published: September 2021

Background Ramucirumab is considered a standard of care as second-line therapy (CT2) in advanced gastric cancers (AGCs). The aim of this study was to assess practice patterns and outcomes with ramucirumab among Indian patients with AGCs.

Materials and Methods A computerized clinical data entry form was formulated by the coordinating center's (Tata Memorial Hospital) medical oncologists and disseminated through personal contacts at academic conferences as well as via email for anonymized patient data entry. The data was analyzed for clinical characteristics, response rates, and survival outcomes.

Results A total of 26 physicians contributed data, resulting in 55 patients receiving ramucirumab and being available for analysis. Median age was 53 years (range: 26–78), 69.1% of patients had greater than two sites of disease, and baseline Eastern Cooperative Oncology Group's performance score (ECOG PS) ≥ 2 was seen in 61.8% of patients. Ramucirumab was used as monotherapy in 10.9% of patients, while the remaining 89.1% received ramucirumab combined with chemotherapy. Median event-free survival (EFS) and median overall survival (OS) with ramucirumab were3.53 months (95% CI: 2.5–4.57) and 5.7 months (95% CI: 2.39–9.0), respectively. Common class specific grade adverse events seen with ramucirumab included gastrointestinal (GI) hemorrhage (9.1% - all grades) and uncontrolled hypertension (Grade 3/4 - 3.6%).

Conclusions Ramucirumab appears to have similar efficacy in Indian AGC patients when compared with real-world data from other countries in terms of median EFS, but OS appears inferior due to more patients having borderline ECOG PS and high metastatic disease burden. GI hemorrhages appear more common than published data, although not unequivocally related to ramucirumab.
Estimating the Risk of Chemotherapy Toxicity in Indian Geriatric Patient Population and Utility of Chemotherapy Risk Assessment Scale for High Age Patients (CRASH) Score
Authors: Mittal Aditi , Rangaraju Ranga R. , Agarwal Amit , Chandragouda D. , Batra Sandeep , Qureshi Suhail
Published: September 2021

Background Aging is a heterogeneous process, and elderly population is diverse in health status and functional reserve. The present study was undertaken to predict severe chemotherapy toxicity using the Chemotherapy Risk Assessment Scale for High-Age Patients’ (CRASH) score.

Materials and Methods Elderly patients (age ≥65 years) with malignancy, who were planned to be treated with a new course of cytotoxic chemotherapy, were enrolled. The CRASH score was calculated, and patients were stratified into four categories, that is, low (0–3), intermediate (Int)-low (4–6), Int-high (7–9), and high (<9). Patients developing grade 3/4/5 nonhematologic (NH) or grade 4/5 hematologic (H) toxicity were taken as the development of severe toxicity.

Results Of 100 enrolled patients, 64 (64%) were able to complete their prescribed treatment. Forty-four percent of patients (44 patients) of our study cohort experienced grade-4 H or grade 3/4 NH toxicity. The highest score in each category (heme/nonheme/CRASH) predicts nearly 100% toxicity risk. At a critical value of CRASH ≥ 6.5, the sensitivity is calculated as 100%, while specificity is 89.09%. The accuracy of prediction is 93.88%. The median time taken to develop toxicity was 39.5 days.

Conclusion CRASH score utilizes clinical assessment and basic laboratory values. Yet, it accurately predicts severe chemotherapy toxicity above a critical value of 6.5. Based on the above study, the first 30 days are crucial as 45% of patients experienced toxicity in this time frame. With the help of these clinical predictive markers, the care of elderly will be optimized.
Evaluation of Burden and Anxiety in Caregivers of Patients with Pediatric Celiac Disease in the COVID-19 Pandemic
Authors: Bucak Ibrahim Hakan , Tumgor Gokhan , Almis Habip , Kose Sumeyye , Dogan Cagla Nur , Turgut Mehmet
Published: September 2021

Background Anxiety and caregiver burden increase among caregivers for individuals with chronic disease. The purpose of this study was to compare the anxiety levels and caregiver burden among caregivers for cases with pediatric celiac disease (CD) before and during the COVID-19 pandemic.

Materials The Zarit Burden Interview (ZBI) and the Beck Anxiety Inventory (BAI) were applied to 29 parents caring for pediatric CD patients in January 2020, when COVID-19 cases had not yet been seen in Turkey. The study was designed prospectively. The scales were also reapplied to the same study group online during the COVID-19 pandemic (May 2020). The results were then compared.

Results Parents caring for 29 cases of pediatric CD; 21 mothers (72.4%), six fathers (20.7%), and two aunts (6.9%) took part in the study. Mean ZBI scores before and during the COVID-19 pandemic were 27.51 ± 14.12 (8–73) and 38.68 ± 10.95 (21–57), respectively (p < 0.01). Mean BAI scores before and during the COVID-19 pandemic were 13.27 ± 7.65 (1–27) and 23.48 ± 12.40 (2–48), respectively (p < 0.01).

Conclusion Increased anxiety and caregiver burden among caregivers of pediatric CD cases during the COVID-19 pandemic were identified for the first time in the literature in this study.
Effects of photoperiod on thyroid gland development and function in growing chicks: a biochemical and morphometric study
Authors: Ozkanlar Seckin , Kara Hulya , Gür Cihan , Gedikli Semin , Kara Adem , Ozudogru Zekeriya , Ozdemir Dervis , Kurt Nezahat
Published: September 2021

Context Light treatment has a regulatory role in some growth-related functions, including thyroid development in chicks. Aims This study aimed to investigate the effects of different photoperiod treatments on thyroid organ weight and serum thyroid hormone concentrations of broilers by use of biochemical and histological methods. Methods After the hatching, 120 broiler chicks (Ross) were divided into two main groups according to sex. Both groups were then split into two sub-groups based on photoperiod treatment: 16 h (i.e. 16 h light:8 h dark) and 24 h (24 h light:0 h dark). Thyroid gland and blood samples of six animals from each group were obtained after slaughtering at 7-day intervals from Day 14 after hatching to Day 42. Serum concentrations of free triiodothyronine (FT3), free thyroxin (FT4) and thyroid-stimulating hormone (TSH) were determined by the chemiluminescence method for all groups. Thyroid weight, bodyweight and thyroid follicle diameter were also measured. Key results Thyroid weight:bodyweight ratio generally started to increase from Day 14 to Day 42, with no significant (P > 0.05) difference among the groups at the same age. For both male and female broiler chicks, morphometric measures increased as birds grew. Serum FT3 and TSH concentrations slightly decreased and serum FT4 concentrations increased in growing chicks of both sexes. Conclusions Extending the photoperiod from 16 to 24 h had no effects on thyroid gland development or functions in terms of both biochemical and morphometric parameters in broiler chicks. Implications Continuous light has minimal effects on thyroid functions of growing broiler chicks to Day 42.
Species replacement and transitional zones in natural grasslands with subtle environmental gradations
Authors: Vercelli Natalia , Entraigas Ilda
Published: September 2021

Heterogeneity creates borders, limits and contrasts between patches. In turn, this pattern generates new processes. Linked to heterogeneity, ecological systems have limits where layout is essential to understanding system organisation. This study analysed internal heterogeneity in natural grassland using: (1) estimation of species replacement in space, and (2) identification of transitional zones and definition of their ecological features in an extremely flat area of the Flooding Pampa, Argentina. Transition analysis was conducted at three sites; 77 plots in total. In each plot, all species, their cover percentage and the proportion of bare soil were recorded and soil samples (0–20 cm depth) measured for pH and electrical conductivity. With floristic data, we explored the relationship between pairwise similarities in community structure and pairwise differences in space, adjusting similarity as a linear or non-linear function of geographical distance. We then conducted a cluster analysis to identify transitional zones, which were associated with large vegetation units described for the Flooding Pampa. Floristic composition in transitional zones was analysed according to the proportions of species and combinations characteristic of the different plant communities. Finally, we synthetised topo-edaphic measured information with a Principal Component Analysis to analyse transitional zone environmental properties. Joining hierarchical classification methods and Indicator Species Analysis for single species and combinations, we highlighted internal heterogeneity, often not noticed in these environments. Rotational livestock grazing contribute to heterogeneity that is typical of these grasslands. Knowledge about transitional zones strongly supports the development of management strategies to prevent grassland degradation.
Quantifying sprint kayak training on a flowing river: Exploring the utility of novel power measures and its relationship to measures of relative boat speed
Authors: Hogan Cruz , Binnie Martyn J. , Doyle Matthew , Peeling Peter
Published: September 2021

Quantification of external training load for sprint kayak athletes can be challenging due to the influence of the water flow on boat velocity in a flowing river environment. Therefore, this study examined the utility of novel measures of power output (PO) and its relationship to measures of relative boat speed when training on a flowing river. Twelve (8 males, 4 female) well‐trained sprint kayak athletes completed 4 separate on‐water sessions comprising one time‐trial session (2 × 1000‐m maximal efforts) and three repeated sprint kayak training sessions (5 x split 1000‐m [2 × 500‐m up and down the river] submaximal efforts) in their individual (K1) kayak. For each session, a Kayak Power Meter recorded athletes’ PO, and a SpeedCoach device recorded relative land‐speed via a Global Positioning System (GPS) (S GPS), and relative water‐speed via an impeller mounted under the boat hull (S IMP). Non‐linear least squares regression were used to evaluate the curvilinear relationship between PO and speed (S GPS and S IMP) data. The exponents of velocity in the PO‐S IMP relationship (2.87 females, 2.94 males) were closer to theoretical values (3.00) and showed greater model accuracy (root mean squared error (RMSE) = 20–26 W) than the PO‐S GPS relationships (speed exponents = 1.58–2.02, RMSE = 31–40 W). Overall, PO measures could better account for the influence of water flow compared to traditional S GPS measures, and therefore, may be more suitable for quantifying athletes’ external load in their training environment.

Highlights

Since traditional S GPS and time‐to‐completion measures do not adjust for the water flow, these measures appear limited for prescribing and monitoring sprint kayak training within flowing river environments.

The prescription of paddling PO across a wide spectrum of relative PO values elicited similar internal and external athlete responses, regardless of the direction travelled on a flowing river (i.e. upstream or downstream).

The relationship between PO and S IMP during on‐water sprint kayaking appears similar to those observed in rowing, where every percent change in boat speed measured relative to water (S IMP) requires a 2.87 and 2.94‐fold percent change in paddling PO in female and male sprint kayak athletes, respectively.

Continued evaluation of the PO‐speed relationship for individual athletes may provide further insight into modelling performance and training targets for sprint kayak athletes.
Time-resolved optical emission spectroscopy in CO2 nanosecond pulsed discharges
Authors: Ceppelli M , Salden T P W , Martini L M , Dilecce G , Tosi P
Published: September 2021

Nanosecond repetitively pulsed discharges at atmospheric pressure have shown comparatively high performances for CO2 reduction to CO and O2. However, mechanisms of CO2 dissociation in these transient discharges are still a matter of discussion. In the present work, we have used time-resolved optical emission spectroscopy to investigate the CO2 discharge progression from the initial breakdown event to the final post-discharge. We discover a complex temporal structure of the spectrally resolved light, which gives some insights into the underlying electron and chemical kinetics. We could estimate the electron density using the Stark broadening of O and C lines and the electron temperature with C+ and C++ lines. By adding a small amount of nitrogen, we could also monitor the time evolution of the gas temperature using the second positive system bands of N2. We conclude that the discharge evolves from a breakdown to a spark phase, the latter being characterised by a peak electron density around 1018 cm−3 and a mean electron temperature around 2 eV. The spark phase offers beneficial conditions for vibrationally enhanced dissociation, which might explain the high CO2 conversion observed in these plasma discharges.
Erratum to “Designing thermal demultiplexer: Splitting phonons by negative mass and genetic algorithm optimization”
Authors: Tan Yu-Tao , Wang Lu-Qin , Wang Zi , Peng Jiebin , Ren Jie
Published: September 2021

Equations (8) and (9) in the original paper [Chin. Phys. B
30 036301 (2021)] are corrected.