bluuebunny/crossref_metadata_2025 huggingface dataset:
Aleida Schot-prijs
Authors: Weststeijn Willem
Published: June 2021

‘Aleida G. Schot, vermaard om haar vertalingen uit de Russische literatuur, overleed in 1969. Gedreven als zij was door haar liefde en haar eerbied voor de kunst van het vertalen, liet zij een fonds na ter uitreiking van een vertaalprijs.’ Zo begint het ‘Ter inleiding’ in de brochure die werd uitgegeven naar aanleiding van de eerste uitreiking van de Aleida Schot-prijs in 1981. In de brochure wordt ook kort aangegeven waarom de naar haar genoemde prijs pas twaalf jaar na Aleida Schots overlijden voor het eerst werd toegekend. Bij haar beschikking had Aleida Schot drie personen aangewezen die ervoor zorg moesten dragen dat de prijs werd ingesteld, maar deze ‘waren er niet toe gekomen aan deze opdracht te voldoen’. De werkelijke reden dat er geen actie werd ondernomen, was dat er in het fonds te weinig middelen waren om, geregeld, een prijs uit te keren. Die middelen kwamen er wel nadat vrienden van Aleida Schot in 1979 een comité hadden samengesteld om haar laatste wens ten uitvoer te brengen. Stuwende kracht achter het comité was mr. H.C.S. Warendorf, bij wie Aleida Schot geregeld aan huis kwam en die ‘tante Leidje’ daardoor goed had gekend. Leden van het comité en vervolgens bestuursleden van de opgerichte Aleida Schot Stichting waren, behalve mr. Warendorf, prof.mr. A. Pitlo, mr. J. Oranje, mevr. M. van Doveren-Nopol en dr. H. Bonger. Het waren allen vrienden van Aleida Schot; geen van hen had iets te maken met de slavistiek. Tot op heden is mr. Warendorf de belangrijkste mecenas van de Stichting; zonder hem zou de Aleida Schot-prijs niet hebben bestaan. Het bestuur van de Stichting bepaalde dat de prijs (5000 gulden, later 2500 euro) eens in de twee jaar zou worden toegekend en beperkt zou blijven tot vertalingen van literatuur uit de Slavische talen.
Affekte in Bewegung
Authors: Weber Julia
Published: June 2021

This article examines the relationship between language, space, and movement in Ann Quin’s novel ‚Passages‘ (1969) from an affect-oriented theoretical perspective. After a brief overview of the relevant theoretical background, it analyses the literary techniques Quin uses to explore affective interrelations that defy common strategies of literary representation. By drawing attention to Quin’s engagement with the writings of Virginia Woolf, the article also reveals the underestimated importance of Woolf as a point of reference for understanding Quin’s experimental prose.
»Una ventata di pazzia«?
Authors: Schulz Karin
Published: June 2021

Luigi Pirandello’s novels are based on scenarios of extreme emotional movement. By focusing on the novel ‚Suo marito‘, the essay will question the textual presentation of extremes, in order to point out the structural patterns in Pirandello’s writing practice with regard to the issue of emotional self-discovery of the individual. How does the emotional dynamic emerge and develop in selected sequences of scenes? And which structural characteristics or aesthetic paradigms of the representation of emotional movement can be summarized? Pirandello shows a special conception of aesthetic functionality of emotions, which in its specific character of movement reflects individual self-experience. The special analytic focus lies on the protagonist Giustino Boggiolo, whose ambition to build on his wife’s literary success and to exploit it commercially puts him into an ecstatic rush, endangering not only his own existence and self-image, but also his family.
Opening (Policy): A new perspective on the global energy transition
Authors: Hepburn Cameron , Sha Fu , Snaith Henry , Grubb Michael , Khosla Radhika , Sharpe Simon
Published: June 2021

This session will communicate evidence on near-term mitigation opportunities for supporting CoP26 objectives, and invite policy response.
Macropolicy
Authors: Larkin Charlie , Shishlov Igor , Morris John , Hafner Sarah , Dikau Simon , Cojoianu Theodor
Published: June 2021

Climate policies have been advocated to foster investments in mitigation and adaptation. Most debated policies include fiscal measures (e.g. carbon tax and carbon pricing), but recently, green monetary policies (e.g. green asset purchases), green collaterals and macroprudential regulations (e.g. green supporting/brown penalizing factor) have gained policy attention. The conditions under which such policies can contribute to align the economy and finance to sustainability, while preventing unintended effects on financial instability and inequality, have still to be assessed and limitations of traditional macroeconomic and financial risk models to assess these impacts could lead to a false sense of control on risk. This session will bring together research that quantitatively assesses the direct and indirect impacts of green fiscal, monetary and macroprudential policies (or ensembles) on investors’ decisions and financial stability, considering the uncertainty and non-linearity of climate risks.
Green transportation
Authors: Giovannini Enrico , Anable Jillian , Rehmatulla Nishatabbas , Miller Robert , Campbell Siobhan
Published: June 2021

This session will discuss the trends, challenges and opportunities for decarbonising transport including electrification of freight (shipping and air).
Climate Finance and Offsetting: investments in NbS and new financial mechanisms
Authors: Girardin Cécile , Goldberg Jonathan , Prouchet Léna , Mitchell-Larson Eli , Chomba Susan
Published: June 2021

We urgently need to increase the flow of investment to high quality Nature-based Solutions (NbS) that are people led and support biodiversity. NbS has a significant contribution to make to mitigating and adapting to climate change, yet remains dramatically under-invested. Carbon markets such as cap-and-trade, involving carbon offsets, are increasingly considered as mechanisms for financing NbS. However, offsets present a number of problems if poorly implemented. In this session, we will briefly explore the debates around carbon offsets and NbS, and discuss options for a range of finance options that reward high quality Nature-based Solutions, including public financing, the carbon offset market, risk management and blended finances to jumpstart the NbS market.
The Climate Adaptation Challenge: How can government, academia and wider society work together to support the UK’s domestic adaptation objectives?
Authors: Crossfield Amanda , Gamper Catherine , Jones Keith , Dessai Suraje , Handysides Tom , Henderson Gideon
Published: June 2021

Defra is one of the key UK government departments in terms of climate policy, being responsible for domestic adaptation activities mandated by the Climate Change Act. The Capabilities in Academic Policy Engagement (CAPE) project is working to strengthen and expand engagement between universities and public policy. This session will explore some of the key needs of climate teams within Defra and how the evidence community can respond to support post-COP needs.
Conditions Mimicking the Cancer Microenvironment Modulate the Functional Outcome of Human Chorionic Villus Mesenchymal Stem/Stromal Cells in vitro
Authors: Basmaeil Yasser , Al Subayyil Abdullah , Abumaree Mohammad , Khatlani Tanvir
Published: June 2021

Mesenchymal stem/stromal cells isolated from chorionic villi of human term placentae (CV-MSCs) possess unique biological characters. They exhibit self-renewal, directional migration, differentiation, and immunomodulatory effects on other cell lineages, by virtue of which they can be utilized as therapeutic carriers, for drug targeting, and therapy. Tumors display characteristic features of a damaged tissue microenvironment, which is saturated with conditions such as hypoxia, sustained inflammation, and increased oxidative stress. CV-MSCs function normally in a high oxidative stress environment induced by hydrogen peroxide (H2O2) and glucose and also protect endothelial cells from their damaging effects. For their therapeutic applications in a disease like cancer, it is necessary to ascertain the effects of tumor microenvironment on their functional outcome. In this study, we investigated the functional activities, of CV-MSCs in response to conditioned media (CM) obtained from the culture of breast cancer cell line MDA-231 (CM-MDA231). CV-MSCs were exposed to CM-MDA231 for different spatio-temporal conditions, and their biological functions as well as modulation in gene expression were evaluated. Effect of CM-MDA231 on factors responsible for changes in functional outcome were also investigated at the protein levels. CV-MSCs exhibited significant reduction in proliferation but increased adhesion and migration after CM-MDA231 treatment. Interestingly, there was no change in their invasion potential. CM-MDA231 treatment modulated expression of various genes involved in important cellular events including, integration, survival, message delivery and favorable outcome after transplantation. Analysis of pathways related to cell cycle regulation revealed significant changes in the expression of p53, and increased phosphorylation of Retinoblastoma (Rb) and Checkpoint Kinase 2 in CV-MSCs treated with CM-MDA231. To summarize, these data reveal that CV-MSCs retain the ability to survive, adhere, and migrate after sustained treatment with CM-MDA231, a medium that mimics the cancer microenvironment. These properties of CV-MSCs to withstand the inflammatory tumor like microenvironment prove that they may make useful candidate in a stem cell based therapy against cancer. However, further pre-clinical studies are needed to validate their therapeutic usage.
Plasma Lipidomics Profiling Reveals Biomarkers for Papillary Thyroid Cancer Diagnosis
Authors: Jiang Nan , Zhang Zhenya , Chen Xianyang , Zhang Guofen , Wang Ying , Pan Lijie , Yan Chengping , Yang Guoshan , Zhao Li , Han Jiarui , Xue Teng
Published: June 2021

The objective of this study was to identify potential biomarkers and possible metabolic pathways of malignant and benign thyroid nodules through lipidomics study. A total of 47 papillary thyroid carcinomas (PTC) and 33 control check (CK) were enrolled. Plasma samples were collected for UPLC-Q-TOF MS system detection, and then OPLS-DA model was used to identify differential metabolites. Based on classical statistical methods and machine learning, potential biomarkers were characterized and related metabolic pathways were identified. According to the metabolic spectrum, 13 metabolites were identified between PTC group and CK group, and a total of five metabolites were obtained after further screening. Its metabolic pathways were involved in glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, glycosylphosphatidylinositol (GPI)—anchor biosynthesis, Phosphatidylinositol signaling system and the metabolism of arachidonic acid metabolism. The metabolomics method based on PROTON nuclear magnetic resonance (NMR) had great potential for distinguishing normal subjects from PTC. GlcCer(d14:1/24:1), PE-NME (18:1/18:1), SM(d16:1/24:1), SM(d18:1/15:0), and SM(d18:1/16:1) can be used as potential serum markers for the diagnosis of PTC.
Binding Features and Functions of ATG3
Authors: Fang Dongmei , Xie Huazhong , Hu Tao , Shan Hao , Li Min
Published: June 2021

Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular, tissue, and organismal homeostasis. Autophagy-related (ATG) genes are indispensable for autophagosome formation. ATG3 is one of the key genes involved in autophagy, and its homologs are common in eukaryotes. During autophagy, ATG3 acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 conjugation system, contributing to phagophore elongation. ATG3 has also been found to participate in many physiological and pathological processes in an autophagy-dependent manner, such as tumor occurrence and progression, ischemia–reperfusion injury, clearance of pathogens, and maintenance of organelle homeostasis. Intriguingly, a few studies have recently discovered the autophagy-independent functions of ATG3, including cell differentiation and mitosis. Here, we summarize the current knowledge of ATG3 in autophagosome formation, highlight its binding partners and binding sites, review its autophagy-dependent functions, and provide a brief introduction into its autophagy-independent functions.
Human Amniotic Fluid Stem Cell-Derived Exosomes as a Novel Cell-Free Therapy for Cutaneous Regeneration
Authors: Zhang Yan , Yan Jiaqing , Liu Yanhong , Chen Zhenyu , Li Xiheng , Tang Liang , Li Jiang , Duan Mengna , Zhang Guokun
Published: June 2021

Adult wound healing often results in fibrotic scarring that is caused by myofibroblast aggregation. Human amniotic fluid stem cells (hAFSCs) exhibit significantly anti-fibrotic scarring properties during wound healing. However, it is little known whether hAFSCs directly or indirectly (paracrine) contribute to this process. Using the full-thickness skin-wounded rats, we investigated the therapeutic potential of hAFSC-derived exosomes (hAFSC-exo). Our results showed that hAFSC-exo accelerated the wound healing rate and improved the regeneration of hair follicles, nerves, and vessels, as well as increased proliferation of cutaneous cells and the natural distribution of collagen during wound healing. Additionally, hAFSC-exo suppressed the excessive aggregation of myofibroblasts and the extracellular matrix. We identified several miRNAs, including let-7-5p, miR-22-3p, miR-27a-3p, miR-21-5p, and miR-23a-3p, that were presented in hAFSC-exo. The functional analysis demonstrated that these hAFSC-exo-miRNAs contribute to the inhibition of the transforming growth factor-β (TGF-β) signaling pathway by targeting the TGF-β receptor type I (TGF-βR1) and TGF-β receptor type II (TGF-βR2). The reduction of TGF-βR1 and TGF-βR2 expression induced by hAFSC-exo was also confirmed in the healing tissue. Finally, using mimics of miRNAs, we found that hAFSC-exo-miRNAs were essential for myofibroblast suppression during the TGF-β1-induced human dermal fibroblast-to-myofibroblast transition in vitro. In summary, this study is the first to show that exosomal miRNAs used in hAFSC-based therapy inhibit myofibroblast differentiation. Our study suggests that hAFSC-exo may represent a strategic tool for suppressing fibrotic scarring during wound healing.
Additive Antiproliferative and Antiangiogenic Effects of Metformin and Pemetrexed in a Non-Small-Cell Lung Cancer Xenograft Model
Authors: Wang Jiun-Long , Lan Ying-Wei , Tsai Yi-Ting , Chen Ying-Cheng , Staniczek Theresa , Tsou Yung-An , Yen Chih-Ching , Chen Chuan-Mu
Published: June 2021

Lung cancer is heterogeneous and challenging to cope with once it has progressed. Chemotherapy is the first step once no active driver mutation has been discovered. Non-antitumor drugs have been found to be beneficial when used as adjuvants to chemotherapy. In this study, the additive effect and mechanism of metformin combined with pemetrexed in non-small-cell lung cancer (NSCLC) cells were elucidated. Three NSCLC cell lines, A549, H1975, and HCC827, were used to analyze tumor cell proliferation, colony formation and the cell cycle in vitro when exposed to metformin alone, pemetrexed alone or their combination. We found that combination treatment in three cell lines exerted antiproliferative effects through cell cycle arrest in the S phase. An ex vivo chicken chorioallantoic membrane (CAM) assay was used to examine the antiangiogenic effect of metformin combined with pemetrexed on vascular structure formation. We further created an A549 orthotopic xenograft model with an in vivo imaging system (IVIS) and explored the associated indicators involved in the tumorigenic process. The in vitro results showed that the combination of metformin and pemetrexed exhibited an antiproliferative effect in reducing cell viability and colony formation, the downregulation of cyclin D1 and A2 and the upregulation of CDKN1B, which are involved in the G1/S phase. For antiangiogenic effects, the combination therapy inhibited the vascular structure, as proven by the CAM assay. We elucidated that combination therapy could target VEGFA and Endoglin by RT-qPCR, ELISA and histopathological findings in an A549 orthotopic NSCLC xenograft model. Our research demonstrated the additive antiproliferative and antiangiogenic effects of the combination of metformin with pemetrexed in NSCLC and could be applied to clinical lung cancer therapy.
KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway
Authors: Che Di , Wang Mingshuo , Sun Juan , Li Bo , Xu Tao , Lu Yuxiong , Pan Haiyan , Lu Zhaoliang , Gu Xiaoqiong
Published: June 2021

Keratin 6A (KRT6A) belongs to the keratin protein family which is a critical component of cytoskeleton in mammalian cells. Although KRT6A upregulation in non-small cell lung cancer (NSCLC) has been reported, the regulatory mechanism and functional role of KRT6A in NSCLC development have been less well investigated. In this study, KRT6A was confirmed to be highly expressed in NSCLC tissue samples, and its high expression correlated with poor patient prognosis. Furthermore, overexpression of KRT6A promotes NSCLC cell proliferation and invasion. Mechanistically, KRT6A overexpression is sufficient to upregulate glucose-6-phosphate dehydrogenase (G6PD) levels and increase the pentose phosphate pathway flux, an essential metabolic pathway to support cancer cell growth and invasion. In addition, we discovered that lysine-specific demethylase 1A (LSD1) functions upstream to promote KRT6A gene expression. We also found that the MYC family members c-MYC/MYCN are involved in KRT6A-induced G6PD upregulation. Therefore, this study reveals an underappreciated mechanism that KRT6A acts downstream of LSD1 and functions as a pivotal driver for NSCLC progression by upregulating G6PD through the MYC signaling pathway. Together, KRT6A and LSD1 may serve as potential prognostic indictors and therapeutic targets for NSCLC.
Neutronic Design for Heat Pipe Reactor With Annular and Accident Tolerant Fuels
Authors: Cai Boshuai , Chen Shengli , Wu Tianfan , Wang Yujing , Zhang Zhaozhan , Yuan Cenxi , Zhang Chunyu , Ge Yulin
Published: June 2021

Several core designs of heat pipe reactors with megawatt power were proposed for extreme environments, such as the deep space, the deep sea, and the earthquake locations. However, the existing designs have either the difficulty of manufacture or potential issues of transport. In the present work, a heat pipe design is proposed with an annular fuel element to replace the cylindrical and hexagon fuel elements. In addition, candidate accident tolerant fuels, such as the UN and U3Si2 fuels, are implemented. The neutronic properties of the new reactor design are systematically investigated by the OpenMC Monte Carlo code simulations. It is found that BeO presents a better effect of reducing the axial power deviation than Al2O3. The criticality of the proposed design is verified by two configurations of control drums. The depletion calculations show that each design can operate for decades of years.
Case Report: Talaromyces marneffei Infection in a Chinese Child With a Complex Heterozygous CARD9 Mutation
Authors: Ba Hongjun , Peng Huimin , Cheng Liangping , Lin Yuese , Li Xuandi , He Xiufang , Li Shujuan , Wang Huishen , Qin Youzhen
Published: June 2021

Talaromyces marneffei (TM) infection is rarely seen in clinical practice, and its pathogenesis may be related to deficiency in antifungal immune function. Human caspase recruitment domain-containing protein 9 (CARD9) is a key molecule in fungal immune surveillance. There have been no previous case reports of TM infection in individuals with CARD9 gene mutations. Herein, we report the case of a 7-month-old Chinese boy who was admitted to our hospital with recurring cough and fever with a papular rash. A blood culture produced TM growth, which was confirmed by metagenomic next-generation sequencing. One of the patient’s sisters had died of TM septicaemia at 9 months of age. Whole exome sequencing revealed that the patient had a complex heterozygous CARD9 gene mutation with a c.1118G>C p.R373P variation in exon 8 and a c.610C>T p.R204C variation in exon 4. Based on the culture results, voriconazole antifungal therapy was administered. On the third day of antifungal administration, his temperature dropped to within normal range, the rash gradually subsided, and the enlargement of his lymph nodes, liver, and spleen improved. Two months after discharge, he returned to the hospital for a follow-up examination. His general condition was good, and no specific abnormalities were detected. Oral voriconazole treatment was continued. Unexplained TM infection in HIV-negative individuals warrants investigation for immune deficiencies.
Heavy Metal Adsorption and Release on Polystyrene Particles at Various Salinities
Authors: Barus Beta Susanto , Chen Kai , Cai Minggang , Li Rongmao , Chen Huorong , Li Cong , Wang Jun , Cheng Sha-Yen
Published: June 2021

Microplastics (MPs) and heavy metals are two major types of pollutants that interact with each other, but they are poorly understood. Polystyrene (PS) is one type of MPs that is often detected in aquatic environments. In this study, we examined the adsorption capacity and release rate of heavy metals with respect to different particle sizes of PS, heavy metals, initial heavy metal concentrations, and salinities. Virgin (new) PS with diameters of 20, 50, 130, and 250 μm was used in this study, and four heavy metals (lead, cadmium, copper, and zinc) were used. The results showed that larger PS particle sizes adsorbed more heavy metals even though it took longer to achieve equilibrium adsorption. An increase in heavy metal concentration caused the adsorption capacity (μg g–1) of PS particles to also increase, but the adsorption rate (%) decreased. Increased salinity of the heavy metal solution resulted in a slower adsorption time and a lower adsorption capacity and release rate from the surface of PS particles. Different heavy metals also had different adsorption capacities. Pb was consistently more highly adsorbed by MPs, followed by Cu, Zn, and Cd. Larger PS sizes released heavy metals faster than smaller PS sizes, and the amounts of heavy metals released were higher. The heavy metal with the highest release rate was Cd, followed by Pb, Cu, and Zn. Finally, our findings highlight the interactions between PS and heavy metals and strongly support that PS particles can act as vectors for heavy metals in aquatic systems.
Characterization of Individual Projections Reveal That Neuromasts of the Zebrafish Lateral Line are Innervated by Multiple Inhibitory Efferent Cells
Authors: Manuel Remy , Iglesias Gonzalez Ana Belen , Habicher Judith , Koning Harmen Kornelis , Boije Henrik
Published: June 2021

The zebrafish lateral line is a sensory system used to detect changes in water flow. It is comprized of clusters of superficial hair cells called neuromasts. Modulation occurs via excitatory and inhibitory efferent neurons located in the brain. Using mosaic transgenic labeling we provide an anatomical overview of the lateral line projections made by individual inhibitory efferent neurons in 5-day old zebrafish larvae. For each hemisphere we estimate there to be six inhibitory efferent neurons located in two different nuclei. Three distinct cell types were classified based on their projections; to the anterior lateral line around the head, to the posterior lateral line along the body, or to both. Our analyses corroborate previous studies employing back-fills, but our transgenic labeling allowed a more thorough characterization of their morphology. We found that individual inhibitory efferent cells connect to multiple neuromasts and that a single neuromast is connected by multiple inhibitory efferent cells. The efferent axons project to the sensory ganglia and follow the sensory axon tract along the lateral line. Time-lapse imaging revealed that inhibitory efferent axons do not migrate with the primordium as the primary sensory afferent does, but follow with an 8–14 h lag. These data bring new insights into the formation of a sensory circuit and support the hypothesis that different classes of inhibitory efferent cells have different functions. Our findings provide a foundation for future studies focussed toward unraveling how and when sensory perception is modulated by different efferent cells.
Neural Correlates of Attentional Modulation of Prepulse Inhibition
Authors: Lei Ming , Ding Yu , Meng Qingxin
Published: June 2021

Prepulse inhibition (PPI) refers to the suppression of the startle reflex when the intense startling stimulus is shortly (20–500 ms) preceded by a weak non-startling stimulus (prepulse). Although the main neural correlates of PPI lie in the brainstem, previous research has revealed that PPI can be top-down modulated by attention. However, in the previous attend-to-prepulse PPI paradigm, only continuous prepulse but not discrete prepulse (20 ms) could elicit attentional modulation of PPI. Also, the relationship between the attentional enhancement of PPI and the changes in early cortical representations of prepulse signals is unclear. This study develops a novel attend-to-prepulse PPI task, when the discrete prepulse is set at 150 ms at a lead interval of 270 ms, and reveals that the PPI with attended prepulse is larger than the PPI with ignored prepulse. In addition, the early cortical representations (N1/P2 complex) of the prepulse show dissociation between the attended and ignored prepulse. N1 component is enhanced by directed attention, and the attentional increase of the N1 component is positively correlated with the attentional enhancement of PPI, whereas the P2 component is not affected by attentional modulation. Thus, directed attention to the prepulse can enhance both PPI and the early cortical representation of the prepulse signal (N1).
Long Non-coding RNA LINC01119 Promotes Neuropathic Pain by Stabilizing BDNF Transcript
Authors: Zhang Le , Feng Hao , Jin Yanwu , Zhan Yufeng , Han Qi , Zhao Xin , Li Peilong
Published: June 2021

Neuropathic pain (NP) is caused by primary injury or dysfunction of the peripheral and the central nervous system. Long non-coding RNAs were critical regulators involved in nervous system diseases, however, the precise regulatory mechanism remains unclear. This study aims to uncover the essential role of LINC01119 in NP progression and further clarify the underlying regulatory mechanism at post-transcriptional level. LINC01119 was significantly upregulated in rats of spare nerve injury (SNI) group compared to sham group. Functionally, silencing of LINC01119 significantly alleviated the neuropathic pain-induced hypersensitivity and reduced the increase in IL−6, IL−1β, and TNF−α caused by SNI. Mechanistically, Brain-derived neurotrophic factor (BDNF) was identified as the functional target of LINC01119. Besides, an RNA binding protein, ELAVL1 could directly interact with LINC01119, and this formed LINC01119- ELAVL1 complex binds to BDNF mRNA, strengthening its RNA stability and increasing the expression level of BDNF at both transcript and protein levels. Clinically, serum LINC01119 was verified as a promising diagnostic biomarker for NP patients. LINC01119 induces NP progression via binding with ELAVL1 and increasing BDNF mRNA stability and expression level. Therefore, LINC01119 may serve as a promising diagnostic marker and therapeutic target for NP treatment.
Targeting the Gut Microbiota to Improve Dietary Protein Efficacy to Mitigate Sarcopenia
Authors: de Marco Castro Elena , Murphy Caoileann H. , Roche Helen M.
Published: June 2021

Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins.
Outcomes and Complications of Aggressive Resection Strategy for Pituitary Adenomas in Knosp Grade 4 With Transsphenoidal Endoscopy
Authors: Ouyang Taohui , Zhang Na , Xie Shenhao , Tang Bin , Li Junjun , Xiao Limin , Zhang Fabao , Wu Bowen , Zhou Dongwei , Li Meihua , Hong Tao
Published: June 2021

Surgery for pituitary adenomas (PAs) with cavernous sinus (CS) invasion in Knosp grade 4 is a great challenge and whether to adopt a conservative or aggressive surgical strategy is controversial. The aim of this study is to provide the outcomes and complications of an aggressive resection strategy for Knosp grade 4 PAs with transsphenoidal endoscopic surgery. Outcomes and complications were retrospectively analyzed in 102 patients with Knosp grade 4 PAs. Among them, primary PAs were seen in 60 patients and recurrent PAs were seen in 42 cases. Gross total resection (GTR) of the entire tumor was achieved in 72 cases (70.6%), subtotal tumor resection (STR) in 18 cases (17.6%), and partial tumor resection (PTR) in 12 cases (11.8%). Additionally, GTR of the tumor within the CS was achieved in 82 patients (80.4%), STR in 17 patients (16.7%), and PTR in 3 patients (2.9%). Statistical analyses showed that both recurrent tumors and firm consistency tumors were adverse factors for complete resection (P<0.05). Patients with GTR of the entire tumor were more likely to have favorable endocrine and visual outcomes than those with incomplete resection (P<0.05). Overall, the most common surgical complication was new cranial nerve palsy (n=7, 6.8%). The incidence of internal carotid artery (ICA) injury and postoperative cerebrospinal fluid (CSF) leakage was 2.0% (n=2) and 5.9% (n=6), respectively. Six patients (5.9%) experienced tumor recurrence postoperatively. For experienced neuroendoscopists, an aggressive tumor resection strategy via transsphenoidal endoscopic surgery may be an effective and safe option for Knosp grade 4 PAs.
Remodeling the Epigenetic Landscape of Cancer—Application Potential of Flavonoids in the Prevention and Treatment of Cancer
Authors: Jiang Weiyi , Xia Tingting , Liu Cun , Li Jie , Zhang Wenfeng , Sun Changgang
Published: June 2021

Epigenetics, including DNA methylation, histone modification, and noncoding RNA regulation, are physiological regulatory changes that affect gene expression without modifying the DNA sequence. Although epigenetic disorders are considered a sign of cell carcinogenesis and malignant events that affect tumor progression and drug resistance, in view of the reversible nature of epigenetic modifications, clinicians believe that associated mechanisms can be a key target for cancer prevention and treatment. In contrast, epidemiological and preclinical studies indicated that the epigenome is constantly reprogrammed by intake of natural organic compounds and the environment, suggesting the possibility of utilizing natural compounds to influence epigenetics in cancer therapy. Flavonoids, although not synthesized in the human body, can be consumed daily and are common in medicinal plants, vegetables, fruits, and tea. Recently, numerous reports provided evidence for the regulation of cancer epigenetics by flavonoids. Considering their origin in natural and food sources, few side effects, and remarkable biological activity, the epigenetic antitumor effects of flavonoids warrant further investigation. In this article, we summarized and analyzed the multi-dimensional epigenetic effects of all 6 subtypes of flavonoids (including flavonols, flavones, isoflavones, flavanones, flavanols, and anthocyanidin) in different cancer types. Additionally, our report also provides new insights and a promising direction for future research and development of flavonoids in tumor prevention and treatmentviaepigenetic modification, in order to realize their potential as cancer therapeutic agents.
Pharmacogenomics of NSAID-Induced Upper Gastrointestinal Toxicity
Authors: McEvoy L. , Carr D. F. , Pirmohamed M.
Published: June 2021

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.
Rufinamide-Loaded Chitosan Nanoparticles in Xyloglucan-Based Thermoresponsive In Situ Gel for Direct Nose to Brain Delivery
Authors: Dalvi Avantika , Ravi Punna Rao , Uppuluri Chandra Teja
Published: June 2021

In 2004, the US FDA approved Rufinamide, an anti-epileptic drug under the brand name Banzel®. In 2015, Banzel® received approval for its use in pediatric patients (ages 1–4 years). Rufinamide shows low oral bioavailability due to a low dissolution rate resulting in less of the drug reaching the brain. This has led to the high dose and dosing frequency of Rufinamide. In this work, using the principle of design of experiments (DoE), we have formulated Rufinamide-loaded chitosan nanoparticles and suspended them in a solution of a thermoresponsive polymer–tamarind seed xyloglucan to form a nasal in situ gel for direct nose to brain delivery of Rufinamide. The nanoparticles were characterized for particle size, entrapment efficiency, zeta potential, and physical stability. The in situ gel formulations were characterized for rheological properties, stability, and in vivo plasma and brain pharmacokinetics. Pharmacokinetic parameters were computed for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles and compared with the pharmacokinetic parameters of an aqueous suspension of plain Rufinamide. The percentage of direct transport efficiency (% DTE) and direct transport percentage (%DTP) values were calculated for all the formulations. The optimized nanoparticle formulation showed a size of 180 ± 1.5 nm, a zeta potential of 38.3 ± 1.5 mV, entrapment efficiency of 75 ± 2.0%, and drug loading of 11 ± 0.3%. The in situ gelling formulation of nanoparticles showed a solution to the gel transition temperature of 32°C. The %DTE values for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles were 988.5 and 1177.3 and the %DTP values were 86.06 and 91.5 respectively.
Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy
Authors: Adornetto Annagrazia , Gesualdo Carlo , Laganà Maria Luisa , Trotta Maria Consiglia , Rossi Settimio , Russo Rossella
Published: June 2021

Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches.
Physiological and Biochemical Traits of Two Major Arabidopsis Accessions, Col-0 and Ws, Under Salinity
Authors: Leschevin Maïté , Ismael Marwa , Quero Anthony , San Clemente Hélène , Roulard Romain , Bassard Solène , Marcelo Paulo , Pageau Karine , Jamet Elisabeth , Rayon Catherine
Published: June 2021

Salinity affects plant growth and development as shown with the glycophyte model plant, Arabidopsis thaliana (Arabidopsis). Two Arabidopsis accessions, Wassilewskija (Ws) and Columbia (Col-0), are widely used to generate mutants available from various Arabidopsis seed resources. However, these two ecotypes are known to be salt-sensitive with different degrees of tolerance. In our study, 3-week-old Col-0 and Ws plants were treated with and without 150 mM NaCl for 48, 72, or 96 h, and several physiological and biochemical traits were characterized on shoots to identify any specific traits in their tolerance to salinity. Before salt treatment was carried out, a different phenotype was observed between Col-0 and Ws, whose main inflorescence stem became elongated in contrast to Col-0, which only displayed rosette leaves. Our results showed that Col-0 and Ws were both affected by salt stress with limited growth associated with a reduction in nutrient uptake, a degradation of photosynthetic pigments, an increase in protein degradation, as well as showing changes in carbohydrate metabolism and cell wall composition. These traits were often more pronounced in Col-0 and occurred usually earlier than in Ws. Tandem Mass Tags quantitative proteomics data correlated well with the physiological and biochemical results. The Col-0 response to salt stress was specifically characterized by a greater accumulation of osmoprotectants such as anthocyanin, galactinol, and raffinose; a lower reactive oxygen detoxification capacity; and a transient reduction in galacturonic acid content. Pectin degradation was associated with an overaccumulation of the wall-associated kinase 1, WAK1, which plays a role in cell wall integrity (CWI) upon salt stress exposure. Under control conditions, Ws produced more antioxidant enzymes than Col-0. Fewer specific changes occurred in Ws in response to salt stress apart from a higher number of different fascilin-like arabinogalactan proteins and a greater abundance of expansin-like proteins, which could participate in CWI. Altogether, these data indicate that Col-0 and Ws trigger similar mechanisms to cope with salt stress, and specific changes are more likely related to the developmental stage than to their respective genetic background.
Participation of Multifunctional RNA in Replication, Recombination and Regulation of Endogenous Plant Pararetroviruses (EPRVs)
Authors: Richert-Pöggeler Katja R. , Vijverberg Kitty , Alisawi Osamah , Chofong Gilbert N. , Heslop-Harrison J. S. (Pat) , Schwarzacher Trude
Published: June 2021

Pararetroviruses, taxon Caulimoviridae, are typical of retroelements with reverse transcriptase and share a common origin with retroviruses and LTR retrotransposons, presumably dating back 1.6 billion years and illustrating the transition from an RNA to a DNA world. After transcription of the viral genome in the host nucleus, viral DNA synthesis occurs in the cytoplasm on the generated terminally redundant RNA including inter- and intra-molecule recombination steps rather than relying on nuclear DNA replication. RNA recombination events between an ancestral genomic retroelement with exogenous RNA viruses were seminal in pararetrovirus evolution resulting in horizontal transmission and episomal replication. Instead of active integration, pararetroviruses use the host DNA repair machinery to prevail in genomes of angiosperms, gymnosperms and ferns. Pararetrovirus integration – leading to Endogenous ParaRetroViruses, EPRVs – by illegitimate recombination can happen if their sequences instead of homologous host genomic sequences on the sister chromatid (during mitosis) or homologous chromosome (during meiosis) are used as template. Multiple layers of RNA interference exist regulating episomal and chromosomal forms of the pararetrovirus. Pararetroviruses have evolved suppressors against this plant defense in the arms race during co-evolution which can result in deregulation of plant genes. Small RNAs serve as signaling molecules for Transcriptional and Post-Transcriptional Gene Silencing (TGS, PTGS) pathways. Different populations of small RNAs comprising 21–24 nt and 18–30 nt in length have been reported for Citrus, Fritillaria, Musa, Petunia, Solanum and Beta. Recombination and RNA interference are driving forces for evolution and regulation of EPRVs.
Biological and Psychosocial Factors, Risk Behaviors, and Perinatal Asphyxia in a University Hospital: Matched Case–Control Study, Cali, Colombia (2012–2014)
Authors: Torres-Muñoz Javier , Fonseca-Perez Javier Enrique , Laurent Katherine
Published: June 2021

Introduction: Perinatal asphyxia is one of the main causes of morbidity and mortality in newborns. It generates high costs, both social and economic, and presents modifiable risk factors.

Objective: To determine the biological and psychosocial factors and risk behaviors associated with the development of perinatal asphyxia (Sarnat II-III) in newborns from low socioeconomic status in a tier III university hospital in the city of Cali, Colombia.

Materials and Methods: With a case and control design, 216 patients were studied (54 cases/162 controls) (1 case/3 matched controls). The cases were defined as newborns with modified or severe perinatal asphyxia (Sarnat II-III) between 2012 and 2014, with gestational age ≥ 36 weeks, with neurological signs not attributable to other causes, multiorgan compromise, advanced reanimation, and presence of a sentinel event. For the analysis, conditional logistic regression models were developed to evaluate association (OR), considering that the cases and controls had been paired by the birth and gestational age variables.

Results: The final model showed that, from the group of biological variables, meconium amniotic fluid was identified as a risk factor (OR 15.28, 95%CI 2.78–83.94). Induction of labor lowered the risk of perinatal asphyxia by 97% (OR 0.03, 95%CI 0.01–0.21), and monitoring of fetal heart rate was associated with lower odds by 99% (OR 0.01, 95%CI 0.00–0.31) of developing perinatal asphyxia in the newborn. Regarding social variables, the lack of social support was identified as a risk factor for the development of perinatal asphyxia (OR 6.44, 95%CI 1.16–35.66); in contrast, secondary education lowered the odds of developing perinatal asphyxia by 85% when compared with pregnant women who only had primary school education (OR 0.15, 95%CI 0.03–0.77).

Conclusion: Assessment of biological and psychosocial factors and social support is important in pregnant women to determine the risk of developing perinatal asphyxia in a low-income population.
Clinical Significance of Peritoneal Fluid Examination for Free Cancer Cells in Patients Qualified for Surgery for Gastric Cancer
Authors: Cieśla Sławomir , Lisiecki Radosław , Ławnicka Agnieszka , Kudliński Bartosz , Ostrowska Paulina , Davì Alberto , Veroux Massimiliano , Murawa Dawid
Published: June 2021

Background: Peritoneal lavage cytology in patients with gastric cancer may correlate with an unfavorable prognosis. This study evaluated the presence of free cancer cells in the peritoneal lavage of a population of patients with gastric cancer and its correlation with the outcome of surgical treatment.

Methods: One hundred patients diagnosed with gastric or gastrointestinal junction adenocarcinoma underwent surgery. In all patients, a cytological and immunohistochemical analysis of peritoneal lavage was performed. Based on the presence of free cancer cells (fcc) at the cytological and immunohistochemical examination of peritoneal lavage, patients undergoing surgery for gastric cancer were divided into two groups: fcc (+) and fcc (–).

Results: A total of 100 patients, 37 women, and 63 men with a median age of 65 years were included in the study. In the entire study group, 16 (16%) patients were positive for the presence of free cancer cells (fcc +) at peritoneal lavage examination. However, in the group of patients who underwent gastrectomy, fcc (+) was found in 10 out of 77 (13%) patients. The presence of cancer cells in peritoneal lavage was a strong predictive factor in an unfavorable outcome after surgery, and 1-year and 2-year patient survival was 34 and 0% in fcc (+) patients and 79 and 59% in fcc (–), respectively. Moreover, the presence of free cancer cells was associated with a five-fold increased risk of death within 2 years after surgery. When analyzing the group of patients undergoing R0/R1 surgery, this difference was even more significant (p < 0.0001).

Conclusions: The presence of free cancer cells in peritoneal lavage may significantly affect the outcome of patients with gastric cancer. Radical surgery in patients with free cancer cells in the peritoneal lavage did not result in a survival advantage. Identification of free cancer cells could help for a better stratification of gastric cancer patients, identifying those patients who could better benefit from a radical surgical treatment, finally improving long-term survival.