bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ionospheric elves powered by corona discharges in overshooting thunderclouds
Authors: Liu Feifan , Neubert Torsten , Chanrion Olivier , ZHU Baoyou , Lu Gaopeng , Lyu Fanchao , koehn Christoph , Dimitriadou Krystallia , Lei Jiuhou , Østgaard Nikolai , Reglero Víctor 
Published: March 2022

Abstract
Elves are rapidly expanding rings of optical emissions in the lower ionosphere, excited by the transient electromagnetic pulses from lightning in the clouds below. Narrow bipolar events (NBEs) are signatures in radio signals from intra-cloud discharges. They are thought to be fast streamer breakdown that may trigger the onset of lightning and blue jets. Recent observations from space suggest they may carry sufficient current to excite elves. Here, we report the first simultaneous observation of NBEs and elves that confirm this hypothesis. Three negative NBEs produced in a tropical storm are observed from the ground by a radio wave receiver located in China and their optical signatures from space by the Atmosphere-Space Interactions Monitor (ASIM) on the International Space Station (ISS). The NBEs are associated with flashes of emissions in N22P at 337 nm, with faint or no activity in the dominant lightning leader line OI at 777.4 nm, confirming their streamer nature. The elves are seen as delayed emissions in the near-ultraviolet of the Lyman–Birge–Hopfield (LBH) band. Our analysis suggests that negative NBE discharges can generate weak, but observable elves when the associated impulse current is above ~ 140 kA. The appearance of elves would provide a new method to estimate the currents of corona discharges at cloud tops, crucial for the characterization of chemical perturbations to greenhouse gas agents at the tropical tropopause.
Opposing Actions of CRF-R1 and CB1 Receptor on Facial Stimulation-Induced MLI-PC Plasticity in Mouse Cerebellar Cortex
Authors: Li Guang-Gao , Wan Peng , Wu Wen-Yuan , Chu Chun-Ping , Qiu De-Lai , Piao Chun-Jian , Li Shu-Yu , Wei Yu-Xuan , Zhao Guo-Hun 
Published: March 2022

Abstract
Background
Corticotropin-releasing factor (CRF) is an important neuromodulator in cerebellar cortex, which plays critical roles in modulating synaptic transmission and plasticity via its receptors. Activation of cannabinoid receptor 1 (CB1) controls the sensory stimulation-induced interneuron–Purkinje cell long-term depression (MLI-PC LTD) in mouse cerebellar cortex. However, the cellular actions of CRF on MLI-PC LTD are poor understand. We here investigated the effect of CRF on the facial stimulation-evoked MLI-PC long-term depression (LTD) in urethane-anesthetized mice by cell-attached recording technique and pharmacological method.
Results
Facial stimulation at 1Hz induced a LTD of MLI-PC synaptic transmission under control conditions, but it was not induced in the presence of CRF (100 nM). The CRF-abolished MLI-PC LTD was restored by a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM), but it was not restored by a selective CRF-R2 antagonist, antisauvagine-30 (200 nM). Blocking cannabinoid type 1 (CB1) receptor, abolished the facial stimulation-induced MLI-PC LTD, and revealed a CRF-R1 receptor activation-dependent MLI-PC long-term potentiation (LTP). However, the CRF-R1 receptor activation-dependent MLI-PC LTP was abolished by inhibition of protein kinase C (PKC) with chelerythrine (5 µM) or depletion of intracellular Ca2+ with cyclopiazonic acid (100 µM).
Conclusions
The present results indicate that CRF opposes the CB1 receptor-dependent MLI-PC LTD produced by the facial stimulation train, which may be caused by triggering a MLI-PC LTP through CRF-R1/PKC and intracellular Ca2+ signaling pathway in mouse cerebellar cortex. Our results suggest that CRF-R1 and CB1 receptor play oppose actions on facial stimulation-induced cerebellar MLI-PC plasticity in vivo in mice.
Microbial induced corrosion in Zn-Ni-Cu and Zn-Ni-Cu-TiB2 coated mild steel
Authors: ALI sheikh Idrees , Ahmad sheikh Nazir 
Published: March 2022

Abstract
Zn-Ni-Cu and Zn-Ni-Cu-TiB 2 coatings were coated on a mild steel substrate utilizing a high-velocity oxy-fuel (HVOF) thermal spray process. A field emission scanning electron microscope (FESEM) was used to examine the microstructural characteristics of both coated and uncoated mild steel samples. Immersion tests following ASTM G-31, ASTM G1-03, standards were performed in Escherichia Coli (E-Coli) bacteria medium for 28 days (672 hrs), the weight loss of uncoated mild steel specimen was 982.5 mg, for Zn-Ni-Cu coated mild steel it was 116.5 mg, and for Zn-Ni-Cu-TiB 2 coated mild steel it was 115.1 mg. The uncoated mild steel specimen showed well-developed bacterial colonies on the surface and floating colonies of bacteria were observed in the medium solution. The coatings performed well and limited the growth of bacteria. Very few colonies of bacteria could be seen in both coated sample mediums. The presence of Zn and Cu prevented the bacterial attachment with coated surface and hence prevented the underlying substrate from being corroded substantially. Tafel polarization and electrochemical impedance spectroscopy (EIS) in Escherichia Coli (E-Coli) medium confirmed that coated samples were more corrosion resistant than uncoated mild steel specimens because the corrosion potential (Ecorr) values of both coated samples were higher than uncoated mild steel suggesting better anodic protection. The corrosion current density (Icorr) of both coated samples (Zn-Ni-Cu and Zn-Ni-Cu-TiB 2 ) were lower than uncoated mild steel specimens also inferring better performance of a coating in microbial induced corrosive environments.
Hydrogenotrophic bacteria of Arctic hydrothermal vent plumes belong to a novel cosmopolitan branch of aerobic deep-sea Sulfurimonas
Authors: Molari Massimiliano , Hassenrueck Christiane , Laso-Pérez Rafael , Wegener Gunter , Offre Pierre , Scilipoti Stefano , Boetius Antje 
Published: March 2022

Abstract
Members of the genus Sulfurimonas (phylum Campylobacterota) dominate microbial communities of benthic and pelagic redox clines, playing a key role in the biogeochemistry of these environments. Investigating neutrally buoyant hydrothermal plumes of the Central Arctic Ocean, we found a novel type of Sulfurimonas that inhabits hydrogen-rich and oxygen-saturated environments close to the freezing point. Using omics’ approaches, we compared the diversity and distribution of Sulfurimonas from Gakkel Ridge hydrothermal plumes with those from different Mid Ocean Ridges and other Sulfurimonas-hosting environments. A single and new Sulfurimonas species, USulfurimonas pluma, was found to be globally abundant and active in cold (<0-4 °C), oxygen-saturated hydrothermal plumes. US. pluma features substantial genome reduction and specific genomic traits (e.g., oxygen detoxification mechanisms, acquisition of A2-type oxidase, loss of nitrate and nitrite reductases) compared to other Sulfurimonas species. These traits are indicative for adaptation to an obligate aerobic chemolithotrophic life style in hydrogen-rich plumes, US. pluma dominates microbial communities of metal-rich neutrally-buoyant hydrothermal plumes, suggesting a so far neglected roles of Sulfurimonas in ocean biogeochemistry and food webs.
WILL (When to Induce Labour to Limit risk in pregnancy hypertension) – a multicentre randomised controlled trial - Adaptations to deliver a timing of birth trial during an international pandemic
Authors: Magee Laura A , Tohill Sue , Kirkham Katie Louise , Evans Ruth , Gkini Eleni , Moakes Catherine A , Stubbs Clive , Thornton Jim , von Dadelszen Peter 
Published: March 2022

Abstract
Background: As a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology. Methods: The trial (internal pilot) paused March 2020, re-opened July 2020, and is currently recruiting in 37 United Kingdom NHS consultant-led maternity units. We evaluated pandemic adaptations made to WILL processes, and surveyed sites for their views of these changes (20 sites, videoconference). Results: Despite 88% of sites favouring an electronic investigator site file (ISF), information technology requirements and clinical trial unit (CTU) operating procedures mandated ongoing use of paper ISFs; site start-up delays resulted from restricted access to the CTU. Site initiation visits (SIVs) were conducted remotely; 50% of sites preferred remote SIVs and 44% felt that it was trial-dependent, while few preferred SIVs in-person as standard procedure. The Central team felt remote SIVs provided scheduling and attendance flexibility (for sites and trial staff), the option of recording discussions for missing or future staff , improved efficiency by having multiple sites attend, and time and cost-savings; the negative impact on rapport-building and interaction was partially mitigated over time with more familiarity with technology and new ways-of-working. Two methods of remote consent were developed and used by 30/37 sites and for 54/156 recruits. Most (86%) sites using remote consenting felt it improved recruitment. For remote data monitoring (5 sites), advantages were primarily for the monitor (e.g., flexibility, no time constraints, reduced cost), and disadvantages primarily for the sites (e.g., document and access preparation, attendance at a follow-up meeting), but 81% of sites desired having the option of remote monitoring post-pandemic. Conclusions: COVID adaptations to WILL trial processes improved flexibility of trial delivery, for central and site staff, and participants. Flexibility to use these strategies should be retained post-pandemic.Trial registration: ISRCTN77258279
PTOV1 is a Prognostic Biomarker and Correlated with Poor Progression in Colorectal Cancer
Authors: Xie Si-An , Yang Yi , Bu Fan-Qin , Liu Si , Xu Jun-Xuan , Ning Ting-Ting , Zhang Nan , Wei Yan-Fei , Min Li , Chen Yi-Yang , Zhu Sheng-Tao , Zhang Shu-Tian 
Published: March 2022

Abstract
Background: The function of prostate tumor overexpressed 1 (PTOV1) as an oncogene has been reported in a growing number of publications. However, its role in colorectal cancer (CRC) is remain unclear.Methods: We using the online databases TIMER, SangerBox, TCGA, GEO, The Expression Atlas database, cBioPortal and GEPIA II to identified the relationship between PTOV1 and CRC tumorigenesis, progression, immunity, and prognosis. Western blot and qRT-PCR were used to detect PTOV1 expression in CRC cell lines. Immunohistochemistry was used to detect PTOV1 expression in CRC tissues. By using real-time tracking assay, EDU staining, colony formation, wound healing and transwell assay to evaluated CRC cell line proliferation, migration and invasion functions. KEGG and GO analysis to get the significant differences pathways in enrichment of PTOV1 expression.Results: PTOV1 mRNA expression was significantly higher in most human cancers including CRC. A significant correlation was observed between PTOV1 expression and the poor prognosis of CRC patients. Moreover, PTOV1 mRNA expression indicated a positive correlation with tumor-infiltrating B cells and CD8+ T cells. And also, PTOV1 coordinated the expression of immune checkpoint (ICP) genes that was associated with immune cell infiltration and potentially represented a promising immunotherapy target. In addition, the expression of PTOV1 was much higher in CRC cells lines compared with human colon normal epithelial cells line. Functional experiments showed that PTOV1 remarkably increased the proliferation, migration and invasion abilities of CRC cells. Conclusion: PTOV1 is differentially expressed in patients with CRC and affects the prognosis of patients. Besides, that implied that PTOV1 could be a potential prognostic biomarker for CRC progression.
Predicting conversion to Alzheimer’s Disease in individuals with Mild Cognitive Impairment using clinically transferable features
Authors: Rye Ingrid , Vik Alexandra , Kocinski Marek , Lundervold Alexander S. , Lundervold Astri J. 
Published: March 2022

Abstract
Patients with Mild Cognitive Impairment (MCI) have an increased risk of Alzheimer’s disease (AD). Early identification of underlying neurodegenerative processes is essential to provide treatment before the disease is well established in the brain. Here we used longitudinal data from the ADNI database to investigate prediction of a trajectory towards AD in a group of patients defined as MCI at a baseline examination. One group remained stable over time (sMCI, n = 357) and one converted to AD (cAD, n = 321). By running two independent classification methods within a machine learning framework, with cognitive function, hippocampal volume and genetic APOE status as features, we obtained a cross-validation classification accuracy of about 70%. This level of accuracy was confirmed across different classification methods and validation procedures. Moreover, the sets of misclassified subjects had a large overlap between the two models. Impaired memory function was found to be a core symptom in MCI patients on a trajectory towards AD. The prediction above chance level shown in the present study should inspire further work to develop tools that can aid clinicians in making prognostic decisions.
Biosynthesis of Valerenic acid by Engineered Saccharomyces cerevisiae
Authors: Zhao Mengya , Zhang Chuanbo , Wang Haibin , He Shifan , Lu Wenyu 
Published: March 2022

Abstract
Objective To produce valerenic acid (VA) in Saccharomyces cerevisiae by engineering a heterologous synthetic pathway.Result Valerena-4,7(11)-diene synthase (VDS) derived from Valeriana officinalis was expressed in S. cerevisiae to generate valerena-4,7(11)-diene as the precursor of VA. By overexpressing the key genes of mevalonate (MVA) pathway ERG8, ERG12 and ERG19 and integrating 4 copies of MBP (maltose binding protein)-VDS-ERG20 gene expression caskets into genome, the production of valerena-4,7(11)-diene was improved to 75 mg/L. On this basis, VA synthases from Lactuca sativa was expressed to produce VA and the most effective VA production strain was used for fermentation, and the yield of VA reached mg/L in the flask and 6.8 mg/L in a 5-L bioreactor fed glucose and ethanol. Conclusions The heterologous synthesis of VA in S. cerevisiae increases the production of VA and provides a reference method for the biosynthesis of other sesquiterpenes.
Long-term prognosis and clinical course after choking-induced cardiac arrest: A population- based community study from the Shizuoka Kokuho Database
Authors: Miyoshi Takahiro , Endo Hideki , Yamamoto Hiroyuki , Shimada Koki , Kumamaru Hiraku , Ichihara Nao , Miyachi Yoshiki , Miyata Hiroaki 
Published: March 2022

Abstract
Background : Choking is increasing with aging, and cases of choking-induced cardiac arrest are increasing. However, few studies have examined the prognosis of choking-induced cardiac arrest. The aim of this study was to reveal the long-term prognosis of choking-induced cardiac arrest after resuscitation.Methods : W We used the Shizuoka Kokuho Database. This database consists of claim data of approximately 2.2 million people during April 2012 to September 2018. From the database, we selected patients with choking-induced cardiac arrest who received cardiopulmonary resuscitation in the hospital.. Patients were excluded if they were under 20 years old, had an upper airway tumor, were on ventilator control, were fed enteral nutrition in the month prior to cardiac arrest. The primary outcome was death, and secondary outcomes were the 3-month survival rate, independence on devices. Descriptive statistics are presented and compared across age groups (20-64 years, 65-74 years, 75-84 years, 85 years and older), and survival time analysis (Kaplan-Meier method) was performed.Results : A total of 268 patients were analyzed: 26 patients in the 20-64 age group, 33 patients in the 65-74 age group, 70 patients in the 75-84 age group, and 139 patients in the ≥85 age group. The 3-month survival rate was 5.6% (15/268). For each group, it was 3.8% (1/26) in the 20-64 age group; 15.2% (5/33) in the 65-74 age group; 8.6% (6/70) in the 75-84 age group; and 2.2% (3/139) in the ≥85 age group. The 12-month survival rate was 2.6% (7/268). Of the 7 patients who survived 12 months, 3 were on ventilator management and 5 were on tube and intravenous feedings at 3 months. These survivors were still on ventilators and tube feedings in the hospital and had not been discharged at 12 months.Conclusions : The prognosis of choking-induced cardiac arrest was extremely poor when patients were not resuscitated before arrival at the hospital. Even if they survived, they were mostly dependent on assistive devices. In addition, none of the survivors dependent on assistive devices had discontinued the use of the devices even at long-term follow-up.
Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping
Authors: Lee Hee Seung , Han Dai Hoon , Cho Kyungjoo , Park Soo Been , Kim Chanyang , Leem Galam , Jung Dawoon E. , Kwon Soon Sung , Kim Chul Hoon , Jo Jung Hyun , Lee Hye Won , Song Si Young , Park Jun Yong 
Published: March 2022

Abstract
As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. However, there are no truly representative models of ICC subtypes for use in studying developmental differences, carcinogenesis, and personalized drug response. Here, we sought to develop ICC organoid models that reflect the phenotypic, molecular and genetic properties of the parent tumor, and performed integrative clustering of multiple genomic data—with subtype analysis—using these models. ICC organoids from 17 patients pathologically diagnosed with cholangiocarcinoma were prepared according to a previously established organoid culture protocol. ICC patients were subclassified into small-duct (SD) type and large-duct (LD) type according to histological characteristics and S100P, N-cadherin, and CD56 expression. ICC organoids were successfully established within one month and exhibited a morphology similar to that of their matching primary cancer. LD- and SD-type organoids exhibited histologic phenotypes and staining patterns characteristic of the corresponding ICC subtypes. ICC organoids showed high concordance of somatic mutations with primary tumors. Unsupervised principal component analysis clustering effectively separated each type of ICC. Differential gene expression revealed significant enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type ICC (P < 0.05). Gene set enrichment analysis further demonstrated that the cholangiocarcinoma class 2 signature, defined by Andersen et al., was significantly enriched in the LD-type (enrichment score = 2.19, P < 0.001). A protein-protein interaction network analysis identified ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We successfully performed prospective modeling of histological subtype specification using patient-derived ICC organoids. Moreover, gene expression profiling of ICC organoids enabled identification of type-specific targetable pathways.
LMNA R527C mutation causes an inflammation driven progeria via triggering DNA-sensing pathways
Authors: Zhao Yingchi , Shu Wei , Liu Xiaoyu , Jiao Xuyao , Li Jianshuang , Liu Tao , Kuang Ming , Li Ridong , Du Hongqiang , Zhang Zeming , Zhou Zhe , Guo Xuefei , Wei Xuemei , Wang Dandan , Liu Tongtong , Li Yunfei , Liu Shengde , Chen Jingxuan , Luo Yujie , Xia Huawei , Cao Lili , Tian Wenmin , Sun Xue , Dong Wei , Zhou Guangqian , Gao Xiang , Zhou Qinghua , You Fuping 
Published: March 2022

Abstract
Homozygous mutations in Ig-like domain of LMNA cause severe progeria. Unlike typical HGPS mediated by progerin due to LMNAWT/G608G mutation, it remains elusive how these homozygous mutations cause progeria. We here found that patients with LMNAR527C/R527C mutation developed an atypical progeria with autoimmune symptoms. Compare to LMNAWT/G608G mutation, this mutation led to more severe inflammation in patients. MSCs from LMNAR527C/R527C patients exhibited overt inflammation and cellular senescence. Mechanistically, LMNAR527C/R527C mutation attenuated its binding to DNA binding protein BAF, which led to aberrant aggregation of Lamin A and activation of DNA sensing pathways. Inhibition of DNA sensors, cGAS or AIM2, can suppress inflammation and rescue the senescence of patient-derived MSCs. LmnaR527C/R527C mice showed enhanced inflammation, and developed accelerated aging and dead at an early age after high-fat diet (HFD) feeding, which could be rescued by deficiency of AIM2 or treatment by a small molecule inhibitor of cGAS-STING. Therefore, we demonstrated that LMNAR527C/R527C mutation damped its interaction with DNA-binding proteins and exposed damaged DNA to the cytosolic DNA sensors, which triggered aberrant inflammatory responses and promoted the onset of accelerated aging. The present study uncovered that an inflammation driven progeria was caused by LMNA mutation and DNA sensing pathways could be potential therapeutic targets for progeria syndromes caused by homozygous mutations in Ig-like domain of LMNA.
CD3+CD4-CD8- Double-Negative Lymphocytes Are Increased In The Aqueous Humour Of Patients Affected By Retinitis Pigmentosa: Their Possible Role In Mediating Inflammation
Authors: Bacherini Daniela , Maggi Laura , Sodi Andrea , Vannozzi Lorenzo , Mazzoni Alessio , Capone Manuela , Virgili Gianni , Falsini Benedetto , Cosmi Lorenzo , Rizzo Stanislao , Annunziato Francesco , Giansanti Fabrizio , Liotta Francesco 
Published: March 2022

Abstract
Background: Recently, evidence has arisen supporting a significant role for immune and oxidative mediated damage underlying the pathogenesis of different types of retinal diseases, including retinitis pigmentosa (RP). Our study aims to evaluate the possible presence of immune cells and mediators in patients affected by RP using flow cytometric analysis of the aqueous humour (AH).Methods: We recruited 12 patients affected by RP and 9 controls undergoing cataract surgery. All patients underwent a complete ophthalmological examination, fundus color photography, optical coherence tomography (OCT), Goldmann kinetic perimetry, electroretinographic and genetic tests. Flow cytometric analysis of of peripheral blood (PB) and AH samples provided a membrane staining which targeted surface molecules (CD14, CD16, CD19, CD3 and CD4, CD8, CD161) identifying monocytes, natural killer (NK), B, T cells, and T subpopulations respectively. Moreover, lymphocytes were polyclonally stimulated to evaluate cytokine (CK) production at single cell level.Results: The circulating immune-cell distribution was comparable between RP patients and controls. Conversely, in the AH of controls we could detect no cells, while in the RP AH samples we found infiltrating leucocytes, consisting of T (CD3+), B (CD19+), NK (CD16+CD3-) cells and monocytes (CD14+). In the RP patients the frequency of most infiltrating cell populations was substantially comparable between the AH and PB, while among T subpopulations, the frequency of CD3+CD4+ T cells was significantly reduced in the RP AH compared to PB, and CD3+CD4-CD8- double-negative (DN) T cells resulted markedly and significantly increased in the RP AH. The analysis of the cytokine production showed a trend towards an increased frequency of CD3+CD8-CD161+IFNgamma-producing cells and a decrease of CD3+CD8+IL-4-producing cells in the RP AH.Conclusions: The detection of immune cells in the AH of patients with RP is consistent with the hypothesis of an immune-mediated pathogenesis of the disease. The presence of CD3+CD4-CD8- DN T cells and of a Th1-skewed phenotype in the AH could be related to a potential involvement of immune-mediated and inflammatory mechanisms in the disease. A better understanding of the fundamental features of inflammation pathways will provide significant insights in the pathogenesis of RP, and a possible avenue toward new therapeutic approaches.