bluuebunny/crossref_metadata_2025 huggingface dataset:
Winter crop choice and body condition loss change the eco-efficiency of sheep flocks
Authors: Taylor Anna , Stevens David , McCoard Sue
Published: February 2022

Lamb survival (ewe reproductive performance) and lamb growth are key levers to changing eco-efficiency, particularly in hill country systems. New research has highlighted reproduction losses when feeding some winter crop options such as fodder beet. Current research findings are used to understand the impact of changes in reproductive performance of sheep flocks caused by body condition change and winter forage crop choices on whole farm eco-efficiency. Eight farms were anonymously selected from an existing database, four with ‘low rainfall’ and four with ‘high rainfall’, averaging 590 and 1090 mm/annum respectively to represent the cool temperate climates of southern New Zealand.  Ewe and lamb survival, and lamb liveweight gain to weaning were altered to reflect the impacts of either losing or retaining body condition in late gestation, either on a fodder beet or brassica diet in mid-late gestation.  Ewes retaining body condition with fodder beet scenarios were fed a supplement added to ensure adequate protein nutrition using a combination of Lucerne hay, soy meal, and urea. General adjustments made to maintain pasture use similar to the original farms included adjusting lamb sales date, supplement making, stocking rate and autumn nitrogen use. Eco-efficiency was reduced using fodder beet as a winter forage as greenhouse gas emissions were increased per unit of product. The loss of condition score during mid to late pregnancy also led to a reduction in eco-efficiency, though this was more severe when feeding fodder beet. The impacts of fodder beet were mitigated if the diet was balanced for protein. Nitrogen and phosphorus loss from soil was low, and reduced under fodder beet feeding conditions, due to the smaller area of cropping than traditional brassicas.
Sheep dung disappearance from grazed hill country landscapes
Authors: Vibart Ronaldo Eduardo , Mackay Alec , Devantier Brian , Noakes Emma , Maclean Paul
Published: February 2022

Two experiments were conducted to examine the effects of biological (composition and site history) and topographic (slope and aspect) factors affecting sheep dung disappearance rates in hill country pastures. We used three of the farmlets that have been receiving 0 (NF), 125 (LF) or 375 (HF) kg of single superphosphate (SSP)/ha since 1980) from the long-term phosphorus fertiliser trial at Ballantrae. Experiment one examined the effect of farmlet, slope (low and medium slope class), and aspect (E, SW, NW), whereas Experiment two examined the effect of farmlet, both as a source of dung (from LF or HF farmlets) and as a site in the landscape (on LF or HF farmlets). In both experiments, disappearance of dung followed a quadratic curve, and no improvements were made using higher-order polynomials. Despite a lower fibre concentration, dung from sheep grazing the HF farmlet did not disappear at a faster rate than dung from the other farmlets, but soil activity in situ (placement) was pivotal to the rate of dung disappearance. A faster rate of dung disappearance on the HF farmlet is consistent with a greater capacity for turnover of plant biomass and animal excreta in this high fertility environment. These experiments contribute to our understanding of the influence of biological and topographic drivers of dung disappearance rates, and enable further advances to be made in the modelling of nutrients in these topographically complex agroecosystems.
Forecasting the genetic and economic impacts of genomic selection in perennial ryegrass
Authors: Barrett Brent , Jahufer Zulfi , Arojju Sai , Sise Jude , Faville Marty
Published: February 2022

Simulation offers a way to explore questions about implementation, value and impacts of various breeding methodologies for pasture species in New Zealand (NZ).  We present genetic modelling and farm system-based economic simulations demonstrating the potential of genomic selection (GS) and high-throughput phenotyping (HTP) to improve breeding outcomes in perennial ryegrass, and assess the potential value for farmers.  Predicted genetic gain (∆G) from half-sibling family selection without GS ranged up to 4.9% per cycle, depending on selection pressure. Including GS for within-family selection, ∆G ranged up to 7.6% per cycle. Across 12 scenarios tested for a single cycle, increasing ∆G per cycle doubled cost-efficiency per unit gain, even though cost per cycle increased.  Simulation of 10 cycles of selection within a population with and without GS showed higher levels of ∆G were maintained over multiple cycles for GS.  Farm system-based economic analysis, focused on agronomic traits, indicated full commercialisation of GS and HTP technology harnessing increased ∆G in 2026 creates new value rising by 2040 to a range of $74M - $221M per annum for NZ red meat farmers, and $399M to $1,260M per annum for dairy farmers in NZ and Australia.  This study indicated incorporating GS in pasture plant breeding can increase the rate and cost-efficiency of genetic improvement, with pasture performance and sector economic benefits realised through the value chain.
AgYields - a national database for collation of past, present and future pasture and crop yield data
Authors: Moot Derrick , Griffiths Wendy , Chapman David , Dodd Mike , Teixeira Carmen
Published: February 2022

The New Zealand agricultural sector has a rich heritage of measuring yield and growth rates for pastures and crops. Historically these datasets were collected by Government departments, Crown research institutes, Universities and more latterly seed companies and private research providers as well as on-farm. These data are expensive to collect, spatially and temporally patchy, and stored in a range of electronic and physical platforms. Meanwhile the potential value of such data is increasing with the ability to create meta-analyses and simulation modelling to create resilience in crop and pasture systems to meet the needs of the changing regulatory and climate environment. A challenge of data collection is the different priorities and skill sets of those undertaking the task. Thus, there is a need to provide guidelines for the collection, collation and publication of such data to standardize best practice and maximize the value gained from increasingly scarce resources available for pasture and crop research to support the primary industries.  In addition, declining funding for field research, means there is an urgent need to draw together existing and future data into a publicly accessible industry good resource. This paper outlines the development of the AgYields web-based repository for pasture and crop growth rate and yield data. It describes the rationale for the database and the need for standardization of data collection to maximize the value of stored data in common formats. The intent is to provide a resource to enhance livestock and crop production systems throughout New Zealand and provide guidelines for future data collection.
Writing the Life of Natalie Clifford Barney's Salon: ‘le cercle d'enchantement et d'inspiration’
Authors: Eells Emily
Published: February 2022

This paper focuses on the expatriate American poet Natalie Clifford Barney and her life as salon hostess in Paris which spanned the sixty-year period from 1908 to 1968. It explores how Barney embodied transnationalism, adopting the French language in her writing and creating an international friendship circle around herself. That transnationalism granted her both sexual freedom as a promiscuous lesbian and freedom of speech as an active feminist. Her unconventional salon not only openly supported homosexuality but also served as a forum fostering exchange between prominent politicians, writers, musicians and artists from all over the world. Her life as a salon hostess became the object of two innovative forms of life writing, both dating from the late 1920s: André Rouveyre's sketch map of the guest list of the international figureheads of modernism who frequented Barney's salon, and Djuna Barnes's satirical portrait of the salon written and illustrated under the title The Ladies Almanack. The study of these two little-known pieces as original forms of life writing highlights Barney's pivotal role at the centre of a forward-looking cosmopolitan artistic circle.
Cross-Border Narratives and Life Writing: Émile Verhaeren by Stefan Zweig and its English Translation in Wartime
Authors: Dessy Clément
Published: February 2022

In 1910, the young Austrian writer Stefan Zweig dedicated a biographical study to the internationally acclaimed Belgian poet Émile Verhaeren. As part of Zweig's international publishing strategy, the study was translated into French and published in Paris a few months before it came out in its original language, German. An English translation was intended for publication at the same time, but was delayed until November 1914, when the First World War was to separate Verhaeren and Zweig forever. Zweig's biography permitted him to define his own European and cosmopolitan ideals through Verhaeren's life narrative. This article shows that one and the same text of life writing can be appropriated through national(ist) and cosmopolitan lenses within the context of ideological and political agendas. Zweig's biography presents Verhaeren as a ‘New European’, but at the same time as ‘part and parcel of German culture’. The publication of the English translation by Jethro Bithell in 1914 provoked criticism in the British press that was directed against Zweig's nationally biased perception and his alleged closeness to the Belgian poet. The example illustrates how claims of cosmopolitan openness are not always incompatible with a national or patriotic agenda. It also qualifies Zweig's reputation as the epitome of Europeanism and pacifism by providing new insight into his ideas before 1914.
Effect of Cognitive Therapy and Family Psychoeducation in Stroke Clients with Depression and Disability
Authors: Ramadia Arya Ramadia , Keliat Budi Anna Keliat , Wardani Ice Yulia Wardani
Published: February 2022

Stroke patients who were take care in the hospital 30-40% in depression condition. This research aim was to determine the effect of cognitive therapy and psycho Education for depression, helplessness, and ability to change negative thoughts for stroke patients. This research design was quasi experimental pre and post test  with control group with a total of sample 87 person with 29 persons  are given cognitive therapy and family psychoeducation therapy, 29 persons are given only cognitive therapy and 29 persons are not given therapy. Analysis by anova test and Pair t-test. The result of research show a decrease in  depression and helplessness condition and increase the ability to change negative thoughts of stroke clients whom received cognitive therapy and family psychoeducation group larger than whom just only receive cognitive therapy and the group without therapy (p value <0,05). There was factor that contribute depression condition of stroke client is age.  Cognitive therapy and Family Psychoeducation are recommended for stroke klien who got depression and helpless to increases the ability to change negative thinking.
Immune Characteristics of LYN in Tumor Microenvironment of Gliomas
Authors: Jiang Chonghua , Zhang Hao , Wu Wantao , Wang Zeyu , Dai Ziyu , Zhang Liyang , Liu Zhixiong , Cheng Quan
Published: February 2022

The prognosis of gliomas is poor and there are limited therapeutic approaches. Immunotherapy has become a promising treatment for gliomas. Here, we explored the expression pattern of Lck/yes-related protein tyrosine kinase (LYN) in gliomas and assessed its value as an immunotherapy biomarker. Transcriptional data was mined from two publicly available datasets, TCGA and CGGA, and used to investigate the correlation between LYN and clinical characteristics including patient prognosis, somatic mutation, and immune infiltrating features in gliomas. Besides, the correlation between LYN and classical immune checkpoint molecules was explored. Glioma samples obtained from the Xiangya Hospital cohort were used for immunohistochemistry staining. High expression level of LYN was observed in advanced gliomas and other cancer types, which predicted a worse prognosis. LYN stratified patients’ survival in the Xiangya cohort and was also significantly associated with infiltrating immune cell types and inflammatory activities in the tumor microenvironment. LYN was involved in tumor mutation, correlated with the regulation of oncogenic genes, and also showed a significant positive correlation with PD-L1. LYN can be a potential diagnostic marker and immunotherapy marker in gliomas.
The Histone H3K27me3 Demethylases KDM6A/B Resist Anoikis and Transcriptionally Regulate Stemness-Related Genes
Authors: Shait Mohammed Mohammed Razeeth , Zamzami Mazin , Choudhry Hani , Ahmed Firoz , Ateeq Bushra , Khan Mohammad Imran
Published: February 2022

Epithelial cancer cells that lose attachment from the extracellular matrix (ECM) to seed in a distant organ often undergo anoikis’s specialized form of apoptosis. Recently, KDM3A (H3K9 demethylase) has been identified as a critical effector of anoikis in cancer cells. However, whether other histone demethylases are involved in promoting or resisting anoikis remains elusive. We screened the major histone demethylases and found that both H3K27 histone demethylases, namely, KDM6A/B were highly expressed during ECM detachment. Inhibition of the KDM6A/B activity by using a specific inhibitor results in reduced sphere formation capacity and increased apoptosis. Knockout of KDM6B leads to the loss of stem cell properties in solitary cells. Furthermore, we found that KDM6B maintains stemness by transcriptionally regulating the expression of stemness genes SOX2, SOX9, and CD44 in detached cells. KDM6B occupies the promoter region of both SOX2 and CD44 to regulate their expression epigenetically. We also noticed an increased occupancy of the HIF1α promoter by KDM6B, suggesting its regulatory role in maintaining hypoxia in detached cancer cells. This observation was further strengthened as we found a significant positive association in the expression of both KDM6B and HIF1α in various cancer types. Overall, our results reveal a novel transcriptional program that regulates resistance against anoikis and maintains stemness-like properties.
The LncRNA DUXAP10 Could Function as a Promising Oncogene in Human Cancer
Authors: Zhao Junjie , Xu Lixia , Dong Zihui , Zhang Yize , Cao Junhua , Yao Jie , Xing Jiyuan
Published: February 2022

Cancer is one of the most prevalent and deadliest diseases globally, with an increasing morbidity of approximately 14 million new cancer cases per year. Identifying novel diagnostic and prognostic biomarkers for cancers is important for developing cancer therapeutic strategies and lowering mortality rates. Long noncoding RNAs (lncRNAs) represent a group of noncoding RNAs of more than 200 nucleotides that have been shown to participate in the development of human cancers. The novel lncRNA DUXAP10 was newly reported to be abnormally overexpressed in several cancers and positively correlated with poor clinical characteristics of cancer patients. Multiple studies have found that DUXAP10 widely regulates vital biological functions related to the development and progression of cancers, including cell proliferation, apoptosis, invasion, migration, and stemness, through different molecular mechanisms. The aim of this review was to recapitulate current findings regarding the roles of DUXAP10 in cancers and evaluate the potential of DUXAP10 as a novel biomarker for cancer diagnosis, treatment, and prognostic assessment.
Solid Electrolyte Interphase Growth in Lithium Metal Cells With Normal Electrolyte Flow
Authors: Parekh Mihir N. , Rahn Christopher D.
Published: February 2022

In high energy density lithium metal batteries (LMBs), dendrite and solid electrolyte interphase (SEI) growth reduce safety and longevity, respectively. A stable SEI layer enables high efficiency cycling but continued SEI growth can lead to reduced capacity and coulombic efficiency. In this paper, we develop a steady-state model that predicts the effect of small advective electrolyte flow towards the lithium metal electrode on SEI growth during charging. For a fixed current density, increasing the electrolyte flow rate improves the coulombic efficiency and decreases SEI layer growth rate. Decreasing the charging current density at a constant flow rate also decreases the SEI layer growth rate. Low flow rates (μm/s) can increase coulombic efficiency by up to 6%. The sensitivity of the coulombic efficiency to plating and SEI layer reaction rates is also explored.
Genome Sequences of Two Strains of Prototheca wickerhamii Provide Insight Into the Protothecosis Evolution
Authors: Guo Jian , Jian Jianbo , Wang Lili , Xiong Lijuan , Lin Huiping , Zhou Ziyi , Sonnenschein Eva C. , Wu Wenjuan
Published: February 2022

The Prototheca alga is the only chlorophyte known to be involved in a series of clinically relevant opportunistic infections in humans and animals, namely, protothecosis. Most pathogenic cases in humans are caused by Prototheca wickerhamii. In order to investigate the evolution of Prototheca and the genetic basis for its pathogenicity, the genomes of two P. wickerhamii strains S1 and S931 were sequenced using Nanopore long-read and Illumina short-read technologies. The mitochondrial, plastid, and nuclear genomes were assembled and annotated including a transcriptomic data set. The assembled nuclear genome size was 17.57 Mb with 19 contigs and 17.45 Mb with 26 contigs for strains S1 and S931, respectively. The number of predicted protein-coding genes was approximately 5,700, and more than 96% of the genes could be annotated with a gene function. A total of 2,798 gene families were shared between the five currently available Prototheca genomes. According to the phylogenetic analysis, the genus of Prototheca was classified in the same clade with A. protothecoides and diverged from Chlorella ~500 million years ago (Mya). A total of 134 expanded genes were enriched in several pathways, mostly in metabolic pathways, followed by biosynthesis of secondary metabolites and RNA transport. Comparative analysis demonstrated more than 96% consistency between the two herein sequenced strains. At present, due to the lack of sufficient understanding of the Prototheca biology and pathogenicity, the diagnosis rate of protothecosis is much lower than the actual infection rate. This study provides an in-depth insight into the genome sequences of two strains of P. wickerhamii isolated from the clinic to contribute to the basic understanding of this alga and explore future prevention and treatment strategies.
Computational Measures of Deceptive Language: Prospects and Issues
Authors: Tomas Frédéric , Dodier Olivier , Demarchi Samuel
Published: February 2022

In this article, we wish to foster a dialogue between theory-based and classification-oriented stylometric approaches regarding deception detection. To do so, we review how cue-based and model-based stylometric systems are used to detect deceit. Baseline methods, common cues, recent methods, and field studies are presented. After reviewing how computational stylometric tools have been used for deception detection purposes, we show that the he stylometric methods and tools cannot be applied to deception detection problems on the field in their current state. We then identify important advantages and issues of stylometric tools. Advantages encompass quickness of extraction and robustness, allowing for best interviewing practices. Issues are discussed in terms of oral data transcription issues and automation bias emergence. We finally establish future research proposals: We emphasize the importance of baseline assessment and the need for transcription methods, and the concern of ethical standards regarding the applicability of stylometry for deception detection purposes in practical settings, while encouraging the cooperation between linguists, psychologists, engineers, and practitioners requiring deception detection methods.
Augmenting Human Appearance Through Technological Design Layers
Authors: Genç Çağlar , Raudanjoki Özge , Colley Ashley , Häkkilä Jonna
Published: February 2022

Augmenting human appearance with the means of technology can focus on different layers attached to or around the body. In this article, we present a categorization of human appearance and expression, with augmenting skin and its appendages, clothing and textile, accessories, body parts, and digital aura around the body. We report a non-systematic review of related works in each category and discuss their means in expressing functional, hedonic, and social aspects. In conclusion, our study contributes design perspectives on augmenting human appearances, as well as reveals challenges and opportunities.
The Humpty Dumpty Effect on Planet Earth
Authors: Berger Joel , Lambert Joanna E.
Published: February 2022

Humans have treated the earth harshly. Degradation of extant ecosystems leaves little chance that they might function as they have in the past. Putting back the pieces and restoring what once existed is no longer possible even with re-wildling—an effect analogous to the Humpty Dumpty parable. However, we do have conservation successes after concerted efforts related to habitat protection, species and ecosystem restoration, and planning. While the changes to Earth's biosphere are grave, necessitating immediate and exhaustive action, our Humpty Dumpty world reassembles with progressive conservation victories at all regional scales from local to global which should lead to a modicum of optimism rather than despair. We suggest that to be truly effective our work as academic scientists must be more than publishing in scholarly journals. At the least, this should include changes in how success is measured in science and how university tenure is awarded.
p53 SUMOylation Mediates AOPP-Induced Endothelial Senescence and Apoptosis Evasion
Authors: Chen Yanjia , Liu Zhuanhua , Chen Hongyu , Huang Xingfu , Huang Xiaoxia , Lei Yang , Liang Qing , Wei Jiayi , Zhang Qin , Guo Xiaohua , Huang Qiaobing
Published: February 2022

The aging of endothelial cells plays a critical role in the development of age-related vascular disease. We established a model of endothelial premature senescence by application of Advanced oxidation protein products (AOPPs) modified bovine serum albumin (AOPP-BSA) in human umbilical vein endothelial cells (HUVECs). This cellular senescence was accompanied with endothelial barrier dysfunction and angiogenesis impairment. It was further revealed that these senescent HUVECs underwent apoptosis evasion and the receptor for advanced glycation endproducts (RAGE) played a role in these processes. The AOPP-induced senescence was regulated by the state of autophagy in HUVECs. We further proved that AOPP-BSA attenuated the autophagy of HUVECs, led to p53 SUMOylation at K386, resulting in endothelial senescence. We also established the animal model of vascular senescence by using ApoE−/− mice fed with high-fat diet plus daily injection of AOPP-BSA to verify the role of p53 SUMOylation in vascular senescence. Combined with intraperitoneal injection of rapamycin, the effect of autophagy on AOPP-induced p53 SUMOylation was also confirmed in vivo. Our data indicates that p53 SUMOylation at K386 plays an important role in AOPP-induced endothelial senescence and apoptosis evasion, suggesting that p53 K386 SUMOylation may serve as a potential therapeutic target in protecting against vascular senescence.
High-Fiber Diet or Combined With Acarbose Alleviates Heterogeneous Phenotypes of Polycystic Ovary Syndrome by Regulating Gut Microbiota
Authors: Wang Xuejiao , Xu Ting , Liu Rui , Wu Guojun , Gu Liping , Zhang Yahui , Zhang Feng , Fu Huaqing , Ling Yunxia , Wei Xiaohui , Luo Yunchen , Shen Jian , Zhao Liping , Peng Yongde , Zhang Chenhong , Ding Xiaoying
Published: February 2022

Objective

Gut microbial dysbiosis is associated with high heterogeneity of polycystic ovary syndrome (PCOS); however, studies about gut microbiota targeted clinical intervention in PCOS are limited. Our study aimed to evaluate the effects of high-fiber diet or combined with acarbose on the clinical phenotypes of PCOS, focusing on the possible influence of gut microbiota in this process.

Methods

Twenty-five patients with PCOS were recruited and randomly divided into two groups, W group (n = 14) received the WTP diet (a high-fiber diet composed of whole grains, traditional Chinese medicinal foods, and prebiotics), and A group (n = 11) received the WTP diet combined with acarbose. The follow-up time was 12 weeks. The sex hormonal and glycolipid metabolic parameters, inflammatory factors, brain–gut peptides, and alteration of gut microbiota were evaluated.

Results

The PCOS clinical phenotypes, inflammatory state, and brain–gut peptides secretion were all alleviated in both groups, while the hyperandrogenism, insulin resistance, and brain–gut peptides secretion were better improved in the A group. Alpha and beta diversities were altered more significantly in the A group. Amplicon sequence variants (ASVs) were clustered into 14 co-abundant groups (CAGs) as potential functional groups that may respond to the intervention. The CAGs predominantly comprised of Bifidobacterium and Lactobacillus were more enriched, while the CAGs predominantly comprised of Bacteroides vulgatus, Alistipes, Blautia, Lachnospira, and Roseburia were more inhibited in the A group than in W group. Moreover, the CAGs enriched in the A group had a stronger negative correlation with the luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, testosterone, homeostasis model assessment-insulin resistance (HOMA-IR), α-1-acid glycoprotein (α-AGP), and leptin, and positive correlation with adiponectin and spexin, while the CAGs inhibited showed an opposite trend.

Conclusions

High-fiber diet could alleviate the chronic metabolic inflammation, reproductive function, and brain–gut peptides secretion of patients with PCOS, and high-fiber diet combined with acarbose could better improve the PCOS clinical phenotypes. The remodeling of gut microbiota by our intervention may play an important role in these improvements.

Clinical Trial Registration

http://www.chictr.org.cn/showproj.aspx?proj=4500, ChiCTR-TRC-14005075
Domestic Migration and the Risk of Households Being Defrauded in Urban China
Authors: Ye Mengqian , Lian Nan , Lai Jennifer
Published: February 2022

This paper investigates whether domestic migration of households in urban China has any impact on their risks of being defrauded. By utilizing the China Household Finance Survey (CHFS) in 2015, we find that domestic migration is significantly positively related to households’ risk of being defrauded. After controlling the corresponding individual and household characteristics, the result indicates that the probability of being defrauded with any losses and the amount of money being defrauded of migrant households in urban areas increased significantly by 0.98 and 7.43% compared to local urban households, respectively. This positive relationship between the risk of being defrauded and migration status of households is mainly concentrated in eastern China and highly educated households. Besides, the baseline results remain robust when we perform robustness checks, including the IV estimation which tackles the potential endogeneity of the migration status of the household head. Furthermore, we find that migrant households with fewer local social networks or less satisfaction of the current level of social security tend to be defrauded more intensively. The findings call for reflections on policies of domestic migration and urbanization and their unintentional consequences of social integration and security.
RSV Infection in Neonatal Mice Induces Pulmonary Eosinophilia Responsible for Asthmatic Reaction
Authors: Zhang Dan , Yang Jie , Zhao Yuanhui , Shan Jinjun , Wang Lingling , Yang Guang , He Susu , Li Erguang
Published: February 2022

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and young children. Severe respiratory viral infection in early life is intimately associated with childhood recurrent wheezing and is a risk factor for asthma later in life. Although eosinophilic airway inflammation is an important trait in asthma of children, the roles of pulmonary eosinophils in the disease have been inadequately understood. Here, we show that RSV infection in neonatal mice causes eosinophilia after allergen stimulation. We showed that RSV infection in neonatal mice exacerbated allergic asthma to allergen stimulation that was accompanied with increased detection of eosinophils in the lungs. In addition, we also detected accumulation of ILC2, CD4+T cells, and macrophages. Importantly, adoptive transfer of eosinophils from asthmatic mice with early-life RSV infection exacerbated pulmonary pathologies associated with allergic respiratory inflammation in naive mice in response to foreign antigen. The induction of asthmatic symptoms including AHR, tracheal wall thickening, and mucus production became more severe after further stimulation in those mice. The expression of antigen presentation-related molecules like CD80, CD86, and especially MHC II was markedly induced in eosinophils from OVA-stimulated asthmatic mice. The accumulation of CD4+T cells in the lungs was also significantly increased as a result of adoptive transfer of eosinophils. Importantly, the deterioration of lung pathology caused by adoptive transfer could be effectively attenuated by treatment with indomethacin, a nonsteroidal anti-inflammatory drug. Our findings highlight the significance of eosinophil-mediated proinflammatory response in allergic disease associated with early-life infection of the respiratory tract.
Small Differences in Diet Facilitate the Coexistence of Three Forage Fish Species in an Inshore Northern Patagonian Habitat
Authors: Wiesebron Lauren E. , Castro Leonardo R. , Soto Samuel , Castillo Jorge
Published: February 2022

Forage fish play the crucial role of transferring energy from lower to upper trophic levels. These small pelagic fish feed on plankton and can compete with each other for food, leading to potentially complex interactions. Three forage fish species (Sprattus fuegensis, Strangomera bentincki, and Engraulis ringens) are commonly found in the inshore waters of Northern Chilean Patagonia, a region with large spatial variability in oceanographic conditions and in the zooplankton community. To better understand what factors may explain coexistence among these three forage fish species, we examined differences in resource availability (zooplankton community and abundances) in three locations (Chiloé, Cordillera, and Aysén regions) within Northern Patagonia. We compared the diet of the three fish species using both stable isotope and stomach content analyses, and we measured their gill rakers. S. fuegensis, the only species found in all three regions, had flexible diets which lent it greater success than the other two species at foraging in waters with fewer prey. We found little diet differentiation among the three species in the copepod-rich Cordillera region, but the diverging diets of S. bentincki and S. fuegensis in the copepod-poor Chiloé region suggest that diet partitioning in areas with fewer resources is due to competition. The small differences in diet facilitates coexistence among the three species, which may help explain the lack of correlation between the three species’ population abundances in the Cordillera region over the past 6 years. Finally, our results show that the high degree of oceanographic heterogeneity in Northern Patagonia may encourage species separation based on their specific environmental requirements.
Implications of Using Host Response-Based Molecular Diagnostics on the Management of Bacterial and Viral Infections: A Review
Authors: Atallah Johnny , Mansour Michael K.
Published: February 2022

Host-based diagnostics are a rapidly evolving field that may serve as an alternative to traditional pathogen-based diagnostics for infectious diseases. Understanding the exact mechanisms underlying a host-immune response and deriving specific host-response signatures, biomarkers and gene transcripts will potentially achieve improved diagnostics that will ultimately translate to better patient outcomes. Several studies have focused on novel techniques and assays focused on immunodiagnostics. In this review, we will highlight recent publications on the current use of host-based diagnostics alone or in combination with traditional microbiological assays and their potential future implications on the diagnosis and prognostic accuracy for the patient with infectious complications. Finally, we will address the cost-effectiveness implications from a healthcare and public health perspective.
Unraveling the Dichotomy of Enigmatic Serine Protease HtrA2
Authors: Chakraborty Ayon , Bose Roshnee , Bose Kakoli
Published: February 2022

Mitochondrial high-temperature requirement protease A2 (HtrA2) is an integral member of the HtrA family of serine proteases that are evolutionarily conserved from prokaryotes to humans. Involvement in manifold intricate cellular networks and diverse pathophysiological functions make HtrA2 the most enigmatic moonlighting protease amongst the human HtrAs. Despite perpetuating the oligomeric architecture and overall structural fold of its homologs that comprises serine protease and regulatory PDZ domains, subtle conformational alterations and dynamic enzymatic regulation through the distinct allosteric mode of action lead to its functional diversity. This mitochondrial protease upon maturation, exposes its one-of-a-kind N-terminal tetrapeptide (AVPS) motif that binds and subsequently cleaves Inhibitor of Apoptosis Proteins (IAPs) thus promoting cell death, and posing as an important molecule for therapeutic intervention. Interestingly, unlike its other human counterparts, HtrA2 has also been implicated in maintaining the mitochondrial integrity through a bi-functional chaperone-protease activity, the on-off switch of which is yet to be identified. Furthermore, its ability to activate a wide repertoire of substrates through both its N- and C-terminal regions presumably has calibrated its association with several cellular pathways and hence diseases including neurodegenerative disorders and cancer. Therefore, the exclusive structural attributes of HtrA2 that involve multimodal activation, intermolecular PDZ-protease crosstalk, and an allosterically-modulated trimeric active-site ensemble have enabled the protease to evolve across species and partake functions that are fine-tuned for maintaining cellular homeostasis and mitochondrial proteome quality control in humans. These unique features along with its multitasking potential make HtrA2 a promising therapeutic target both in cancer and neurodegeneration.
Elevated Glycated Hemoglobin Levels Are Associated With Poor Outcome in Acute Ischemic Stroke
Authors: Dong Nan , Shen Xiaozhu , Wu Xuan , Guo Xianghong , Fang Qi
Published: February 2022

Objective

Admission hyperglycemia is an established risk factor for functional outcome in patients with acute ischemic stroke. However, the association between glycated hemoglobin (HbA1c) and prognosis in patients with acute anterior circulation ischemic stroke (AACIS) remains controversial. This study aimed to explore whether elevated HbA1c levels are associated with functional outcome in AACIS patients.

Participants and Methods

We enrolled patients with AACIS hospitalized in the First Hospital Affiliated to Soochow University from March 2018 to January 2021. Patients were categorized into three groups based on baseline HbA1c: HbA1c ≤ 6.5%, 6.5% < HbA1c ≤ 8.0%, and HbA1c > 8.0%. Ninety-day modified Rankin Scale scores of 0–1 and 0–2 were defined as excellent and favorable functional outcome, respectively. Early neurological improvement was regarded as a reduction in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points compared with that on admission, or an NIHSS score of 0–1 at discharge. The association between HbA1c and clinical outcome in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Subgroup analyses by TOAST classification were also conducted.

Results

The study included 326 patients. The proportion with favorable outcome was significantly lower in the HbA1c > 8.0% group than the HbA1c ≤ 6.5% group (30.4 vs. 55.2%; p < 0.01). Binary logistic regression analysis demonstrated that increasing HbA1c levels (as a continuous variable) were associated with reduced functional independence (adjusted OR = 0.739; 95% CI: 0.605–0.904; p = 0.003). In subgroup analyses, higher HbA1c was also associated with favorable outcome in large-artery atherosclerosis (LAA)-type patients (adjusted OR = 0.776; 95% CI: 0.614–0.981; p = 0.034), but not in LAA group.

Conclusions

HbA1c level was an independent predictor of worse functional outcome in patients with AACIS, particularly in those with LAA. For patients with anterior circulation atherosclerosis, strict adherence to a target HbA1c < 6.5% may be required.
Physician-Confirmed and Administrative Definitions of Stroke in UK Biobank Reflect the Same Underlying Genetic Trait
Authors: Rannikmäe Kristiina , Rawlik Konrad , Ferguson Amy C. , Avramidis Nikos , Jiang Muchen , Pirastu Nicola , Shen Xia , Davidson Emma , Woodfield Rebecca , Malik Rainer , Dichgans Martin , Tenesa Albert , Sudlow Cathie
Published: February 2022

Background

Stroke in UK Biobank (UKB) is ascertained via linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation.

Methods

We compiled stroke-specific and broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants, we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci.

Results

The stroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg.81-1) and each other (rg.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using ≥1 UKB stroke definition.

Conclusions

Stroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date.
Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights
Authors: Abdalla Ali , Murali Chandraprabha , Amin Amr
Published: February 2022

Nature has a nearly infinite inventory of unexplored phytochemicals and biomolecules that have the potential to treat a variety of diseases. Safranal exhibits anti-cancer property and the present study explores its antiangiogenic property. Hepatocellular carcinoma (HCC) ranks as the sixth deadliest among all cancer types. Targeting the non-tumor vasculature supporting system is very promising as it has less plasticity, unlike malignant cells that are often associated with issues like drug resistance, poor prognosis, and relapse. In this study, we successfully inhibited the proliferation of primary human umbilical vein endothelial cells (HUVEC) with an IC50 of 300μM and blocked VEGF secretion in HepG2 cells. Furthermore, safranal inhibited VEGF-induced angiogenesis in vitro and ex vivo via scratch wound assay, tube formation assay, transmembrane assay, and aortic ring assay. In addition, safranal downregulated the in vitro expression of HIF-1α, VEGF, VEGFR2, p-AKT, p-ERK1/2, MMP9, p-FAK, and p-STAT3. The present study is the first to reveal the antiangiogenic potential of safranal and propose its possible underlying mechanism in HCC.
Adjuvant Chemotherapy Might Be Recommended to Patients With Positive Margin After Gastrectomy: A 20-Year Retrospective Analysis in a Single Center
Authors: Zhang Xiaojie , Zhao Lulu , Niu Penghui , Wang Tongbo , Wang Wanqing , Sun Chongyuan , Li Zefeng , Chen Yingtai , Zhao Dongbing
Published: February 2022

Background

Margin positivity after gastric cancer resection is associated with poorer outcomes. However, the prognostic factors and the choice of postoperative adjuvant treatment of patients with positive margin (PM) after gastrectomy are still being debated.

Methods

A single-center, retrospective analysis was conducted for patients with PM after gastrectomy from the China National Cancer Center Gastric Cancer Database (NCCGCDB) from 1998 to 2018. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS).

Results

A total of 449 patients were included in the study, including 192 (42.8%) in the proximal PM group (PPM), 205 (45.7%) in the distal PM group (DPM), and 52 (11.6%) in the bilateral PM group (BPM). The 3- and 5-year OS rates for the PM patients investigated were 47.5% and 39.3%, respectively, and the 3- and 5-year RFS rates were 60.0% and 53.6%, respectively. Multivariate Cox regression analysis proved total gastrectomy (hazard ratio (HR): 1.783, 95%CI: 1.133–2.805, p = 0.012), pT4 (HR: 5.264, 95%CI: 1.493–18.565, p = 0.01), pN2 (HR: 2.263, 95%CI: 1.164–4.397, p = 0.016), pN3 (HR: 2.327, 95%CI: 1.233–4.393, p = 0.009), and combined resection (HR: 1.952, 95%CI: 1.256–3.034, p = 0.003) to be independent risk factors of OS, and pT3 (HR: 9.257, 95%CI: 1.152–74.386, p = 0.036) and pT4 (HR: 11.361, 95%CI: 1.469–87.847, p = 0.020) to be independent risk factors for RFS. Adjuvant chemotherapy prolonged OS in the PPM group (p = 0.032) and prolonged RFS in the PPM group (p < 0.001) and the DPM group (p = 0.035) compared with surgery alone.

Conclusions

Advanced pathologic stage was associated with poor prognosis, and postoperative adjuvant chemotherapy might be recommended in PM patients after gastrectomy. Still, further prospective trials are warranted to verify and support our conclusions.
YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFβ1-SMAD2/3 Pathway
Authors: Zhao Teng , Wang Mingchao , Zhao Xin , Weng Shuang , Qian Kun , Shi Kejian , Gu Yanfei , Ying Wantao , Qian Xiaohong , Zhang Yi
Published: February 2022

Objective

YTH domain family 2 (YTHDF2) is an important N6-methyladenosine (m6A) reader, but its role in lung adenocarcinoma remains elusive. This study assessed its function in lung adenocarcinoma.

Methods

YTHDF2 expression in lung adenocarcinoma was explored using public databases, such as The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC). The effect of YTHDF2 on a lung adenocarcinoma cell line was explored by performing cytological and molecular experiments. Molecules downstream of YTHDF2 were identified using proteomics, and the related pathways were verified through cytological and molecular biology experiments.

Results

YTHDF2 expression was upregulated in lung adenocarcinoma, and patients with high YTHDF2 expression experienced prolonged overall survival. In two lung cancer cell lines, YTHDF2 knockdown inhibited proliferation but promoted migration, invasion, and the epithelial-mesenchymal transition. The proteomic analysis identified 142 molecules downstream of YTHDF2, and 11 were closely related to survival. Further experiments revealed that YTHDF2 inhibited expression of the family with sequence similarity 83D (FAM83D)-TGFβ1-SMAD2/3 pathway components. This study is the first to show that YTHDF2 regulated the downstream TGFβ1-SMAD2/3 pathway through FAM83D in lung adenocarcinoma.

Conclusion

YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFβ1-pSMAD2/3 pathway, which may play an important role in lung cancer metastasis.
Functional and Therapeutic Significance of Tumor-Associated Macrophages in Colorectal Cancer
Authors: Li Yitong , Chen Zhenmei , Han Jiahao , Ma Xiaochen , Zheng Xin , Chen Jinhong
Published: February 2022

The role of the tumor microenvironment (TME) in the progression of colorectal cancer (CRC) and its acquisition of resistance to treatment become the research hotspots. As an important component of TME, the tumor-associated macrophages (TAMs) regulate multiple critical oncogenic processes, namely, occurrence, proliferation, metastasis, and drug resistance in CRC. In this review, we have discussed the functional and therapeutic significance of TAMs in CRC. M1 macrophages act as the tumor suppressor while M2 macrophages promote CRC. The polarization of TAMs is mainly regulated by the pathways such as NFKB1 pathways, STAT3 pathways, WNT5A pathways, and PI3K pathways in CRC. Furthermore, the M2 polarization of TAMs is not only controllable but also reversible. Finally, we provide insights into the TAMs-targeted therapeutic strategies.
Multi-Center Analysis of Predictive Factors of Enteral Autonomy and Risk Factors of Complications of Pediatric Intestinal Failure in China
Authors: Jiang Weiwei , Chen Guanglin , Wang Ying , Zhong Wei , Zhou Chonggao , Zhang Jie , Lv Xiaofeng , Du Chunxia , Zhu Zhongxian , Geng Qiming , Tang Weibing
Published: February 2022

Objectives

The aim of this study was to identify predictors for enteral autonomy and intestinal failure (IF)-related complications and evaluate the outcomes of a multi-center pediatric cohort in China.

Methods

The medical records of pediatric patients with IF treated at four medical centers in China from January 1, 2012 to November 31, 2020 were retrospectively reviewed. Enteral autonomy was defined as sustained growth and cessation of parenteral nutrition for >90 days. Multivariate logistic regression analysis was used to identify factors predictive of enteral autonomy and the risk factors of complications, such as IF-associated liver disease (IFALD) and catheter-related bloodstream infection (CRBSI).

Results

The study cohort of 92 pediatric patients with IF included 71 (77%) who underwent surgery and 21 (23%) who received non-surgical treatment. Eventually, 63 (68.5%) patients achieved enteral autonomy by the end of the follow-up period. Multivariate logistic regression analysis indicated that longer duration of parenteral nutrition (PN), sepsis, and non-breastfeeding were risk factors for enteral autonomy. When considering the detailed intraoperative data, the presence of an ileocecal valve (ICV) and greater residual small bowel (RSB) length were reaffirmed as predictors of achieving enteral autonomy. Medium/long-chain (MCT/LCT) lipids or sepsis were identified as negative predictors for IFALD. Univariate analysis revealed that the use of MCT/LCT lipids was associated with a greater likelihood of CRBSI.

Conclusion

In this cohort, enteral autonomy was achieved at a percentage of 68.5%, and the risk factors for not achieving enteral autonomy were a longer duration of PN, sepsis, and non-breastfeeding. The presence of an ICV and a greater RSB length were important predictors of achieving enteral autonomy.