bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caenorhabditis elegans Lipin 1 moderates the lifespan‐shortening effects of dietary glucose by maintaining ω‐6 polyunsaturated fatty acids
Authors: Jung Yoonji , Kwon Sujeong , Ham Seokjin , Lee Dongyeop , Park Hae‐Eun H. , Yamaoka Yasuyo , Jeong Dae‐Eun , Artan Murat , Altintas Ozlem , Park Sangsoon , Hwang Wooseon , Lee Yujin , Son Heehwa G. , An Seon Woo A. , Kim Eun Ji E. , Seo Mihwa , Lee Seung‐Jae V. 
Published: May 2020

AbstractExcessive glucose causes various diseases and decreases lifespan by altering metabolic processes, but underlying mechanisms remain incompletely understood. Here, we show that Lipin 1/LPIN‐1, a phosphatidic acid phosphatase and a putative transcriptional coregulator, prevents life‐shortening effects of dietary glucose on Caenorhabditis elegans. We found that depletion of lpin‐1 decreased overall lipid levels, despite increasing the expression of genes that promote fat synthesis and desaturation, and downregulation of lipolysis. We then showed that knockdown of lpin‐1 altered the composition of various fatty acids in the opposite direction of dietary glucose. In particular, the levels of two ω‐6 polyunsaturated fatty acids (PUFAs), linoleic acid and arachidonic acid, were increased by knockdown of lpin‐1 but decreased by glucose feeding. Importantly, these ω‐6 PUFAs attenuated the short lifespan of glucose‐fed lpin‐1‐inhibited animals. Thus, the production of ω‐6 PUFAs is crucial for protecting animals from living very short under glucose‐rich conditions.
Poly (ADP‐ribose) polymerase 1 inhibition prevents neurodegeneration and promotes α‐synuclein degradation via transcription factor EB‐dependent autophagy in mutant α‐synucleinA53T model of Parkinson's disease
Authors: Mao Kanmin , Chen Jialong , Yu Honglin , Li Huihui , Ren Yixian , Wu Xian , Wen Yue , Zou Fei , Li Wenjun 
Published: May 2020

AbstractPoly (ADP‐ribose) polymerase 1 (PARP1) is a master regulator of diverse biological processes such as DNA repair, oxidative stress, and apoptosis. PARP1 can be activated by aggregated α‐synuclein, and this process in turn exacerbates toxicity of α‐synuclein. This circle is closely linked to the evolution of Parkinson's disease (PD) that characterized by progressive neurodegeneration and motor deficits. Here, we reported the PARP1, as a novel upstream molecular of transcription factor EB (TFEB), participates in regulation of autophagy in α‐synuclein aggregated cells and mice. PARP1 inhibition not only enhances the nuclear transcription of TFEB via SIRT1 mediated down‐regulation of mTOR signaling but also reduces nuclear export of TFEB by attenuating the TFEB‐CRM1 interaction. Our results revealed that PARP1 inhibition lessened the accumulation of α‐synuclein in PD models. Also, oral administration of PARP1 inhibitor Veliparib prevented neurodegeneration and improved motor ability in α‐synucleinA53T transgenic mice. These findings identify that PARP1 signaling pathway regulates TFEB‐mediated autophagy, pointing to potential therapeutic strategy of PD via enhancing protein degradation systems.
Melatonin In Acute Mania Investigation (MIAMI‐UK). A randomized controlled trial of add‐on melatonin in bipolar disorder
Authors: Quested Digby J. , Gibson Jessica C. , Sharpley Ann L. , Cordey Julia H. , Economou Alexis , De Crescenzo Franco , Voysey Merryn , Lawson Jennifer , Rendell Jennifer M. , Al‐Taiar Hasanen , Lennox Alison , Ahmad Farooq , Geddes John R. 
Published: May 2020

AbstractObjectivesCurrent options for treating emergent episodes of hypomania and mania in bipolar disorder are limited. Our objective was to compare the effectiveness and safety of add‐on melatonin in hypomania or mania over 3 weeks as a well‐tolerated therapy.MethodsA randomized, double‐blind, parallel‐group, 3‐week comparison of modified release melatonin (n = 21) vs placebo (n = 20) in adult bipolar patients aged 18‐65 years. Permuted block randomization was used with participants and investigators masked to treatment allocation. Trial registration is ISRCTN28988273 and EUdraCT2008‐000281‐23. Approved by the South Central National Research Ethics Service (Oxford REC A) ref: 09/H0604/63.ResultsThe trial was negative as there was no significant difference between melatonin and placebo on the primary outcome—mean Young Mania Rating Scale (YMRS) score at Day 21: (mean difference [MD] −1.77 ([95% CI: −6.39 to 2.85]; P = .447). Significantly fewer patients on melatonin scored 10 or more on the Altman Self Rating Mania Scale: (odds ratio [OR] 0.164 [95% CI: 0.0260‐1.0002]; P = .05). Quick Inventory of Depression Symptomatology Clinician Version‐16 (QIDS‐C16) scores were not significantly different. (OR 1.77 [95% CI: 0.43‐7.29]; P = .430). The proportion of patients scoring less than or equal to 5 on the self‐report QIDS‐SR16 at end‐point was greater for the melatonin group (OR 8.35 [95% CI: 1.04‐67.23]; P = .046).ConclusionsIn this small trial, melatonin did not effectively treat emerging hypomania or mania as there was no significant difference on the primary outcome. The sample size limitation and secondary outcomes suggest further investigation of melatonin treatment in mood episodes is indicated.
Multimodal Learning Analytics research with young children: A systematic review
Authors: Crescenzi‐Lanna Lucrezia 
Published: May 2020

AbstractLearning Analytics and Multimodal Learning Analytics are changing the way of analysing the learning process while students interact with an educational content. This paper presents a systematic literature review aimed at describing practices in recent Multimodal Learning Analytics and Learning Analytics research literature in order to identify tools and strategies useful for the assessment of the progress and behaviour of children under 6 years old in respect of their learning. The purpose is to provide guidance for Multimodal Learning Analytics research with children under 6 years old to assess their engagement in a task, their emotions, attention, understanding and achievement of a goal. The current state of knowledge on Multimodal Learning Analytics research suggests how performance analytics, face and speech recognition systems, eye tracking, Kinect analytics and wristbands could be used with children. The results show the complexity of collecting data using non‐invasive methodologies with children under 6 years old. Ethical implications related to multimodal data from audio, visual, biometric and quantitative measures of child behaviour are discussed.
Analysis of students’ ideas and conceptual artifacts in knowledge‐building discourse
Authors: Oshima Jun , Oshima Ritsuko , Saruwatari Shunsuke 
Published: May 2020

AbstractThis study proposes a new methodological approach to evaluate students’ knowledge‐building discourse. First, we discuss the knowledge–creation metaphor of learning. In the metaphor, theories mention that learners should consider their collective knowledge objects or artifacts that materialize as a result of their collaborative discourse. Second, we argue the necessity of developing new analytics to evaluate student learning. We describe how students’ ideas and their conceptual artifacts can be examined in discourse analysis. Third, we demonstrate the application of our analytics to real discourse data. We conducted a new type of social network analysis of discourse to examine how students continuously improve their ideas. Further, we conducted another network analysis of discourse, called the Epistemic Network Analysis, by coding students’ epistemic actions as conceptual artifacts to create and examine their ideas.
cIMPACT‐NOW update 7: advancing the molecular classification of ependymal tumors
Authors: Ellison David W. , Aldape Kenneth D. , Capper David , Fouladi Maryam , Gilbert Mark R. , Gilbertson Richard J. , Hawkins Cynthia , Merchant Thomas E. , Pajtler Kristian , Venneti Sriram , Louis David N. 
Published: June 2020

AbstractAdvances in our understanding of the biological basis and molecular characteristics of ependymal tumors since the latest iteration of the World Health Organization (WHO) classification of CNS tumors (2016) have prompted the cIMPACT‐NOW group to recommend a new classification. Separation of ependymal tumors by anatomic site is an important principle of the new classification and was prompted by methylome profiling data to indicate that molecular groups of ependymal tumors in the posterior fossa and supratentorial and spinal compartments are distinct. Common recurrent genetic or epigenetic alterations found in tumors belonging to the main molecular groups have been used to define tumor types at intracranial sites; C11orf95 and YAP1 fusion genes for supratentorial tumors and two types of posterior fossa ependymoma defined by methylation group, PFA and PFB. A recently described type of aggressive spinal ependymoma with MYCN amplification has also been included. Myxopapillary ependymoma and subependymoma have been retained as histopathologically defined tumor types, but the classification has dropped the distinction between classic and anaplastic ependymoma. While the cIMPACT‐NOW group considered that data to inform assignment of grade to molecularly defined ependymomas are insufficiently mature, it recommends assigning WHO grade 2 to myxopapillary ependymoma and allows grade 2 or grade 3 to be assigned to ependymomas not defined by molecular status.
Protective role of Galectin‐7 for skin barrier impairment in atopic dermatitis
Authors: Umayahara Takatsune , Shimauchi Takatoshi , Iwasaki Manami , Sakabe Jun‐ichi , Aoshima Masahiro , Nakazawa Shinsuke , Yatagai Tsuyoshi , Yamaguchi Hayato , Phadungsaksawasdi Pawit , Kurihara Kazuo , Tokura Yoshiki 
Published: May 2020

AbstractBackgroundAtopic dermatitis (AD) patients have a barrier disorder in association with Th2 dominant skin inflammation. Galectin‐7 (Gal‐7), a soluble unglycosylated lectin, is highly expressed in the stratum corneum of AD patients. However, the biological significance of increased Gal‐7 expression in AD skin lesions remains unclear.ObjectiveWe aimed to investigate the production mechanism and functional role of Gal‐7 in AD patients and IL‐4/IL‐13–stimulated epidermal keratinocytes.MethodsWe assessed the Gal‐7 expression levels in skin lesions and sera from AD patients. Gal‐7 levels were also measured in monolayered normal human epidermal keratinocytes (NHEKs) and 3‐dimensional (3D)–reconstructed epidermis in the presence or absence of IL‐4/IL‐13 with or without Stat3, Stat6 or Gal‐7 gene silencing.ResultsGal‐7 was highly expressed in the stratum corneum or intercellular space of AD lesional epidermis as assessed by the stratum corneum proteome analysis and immunohistochemistry. A positive correlation was noted between serum Gal‐7 level and transepidermal water loss in patients with AD. These clinical findings were corroborated by our in vitro data, which showed that IL‐4/IL‐13 facilitated the extracellular release of endogenous Gal‐7 in both monolayered NHEKs and 3D‐reconstructed epidermis. This machinery was caused by IL‐4/IL‐13–induced cell damage and inhibited by knockdown of Stat6 but not Stat3 in NHEKs. Moreover, we performed Gal‐7 knockdown experiment on 3D‐reconstructed epidermis and the result suggested that endogenous Gal‐7 serves as a protector from IL‐4/IL‐13–induced disruption of cell‐to‐cell adhesion and/or cell‐to‐extracellular matrix adhesion.Conclusion and Clinical RelevanceOur study unveils the characteristic of Gal‐7 and its possible role as an alarmin that reflects the IL‐4/IL‐13–induced skin barrier impairment in AD.
Long‐term prognosis of adolescent and middle‐aged Chinese patients with low‐medium risk community‐acquired pneumonia: A cohort study
Authors: Yin Hongjun , Wang Shengfeng , Qu Jiuxin , Zhou Fei , Wang Chen , Cao Bin ,   CAP‐China
Published: May 2020

AbstractIntroductionThe long‐term mortality rate in adolescent and middle‐aged patients with low‐medium risk community‐acquired pneumonia (CAP) remains unelucidated.ObjectiveUnderstanding the long‐term mortality rate in adolescent and middle‐aged patients with low‐medium risk CAP in Beijing, China, to provide a basis for the long‐term management of CAP patient.MethodsA follow‐up survey was conducted telephonically from December 2017 to January 2018 to assess the survival status among 808 patients from a CAP‐China cohort enrolled from 10 general hospitals in Beijing between November 2010 and April 2012. The all‐cause mortality rate was determined and Cox’s proportional hazard model was performed to identify potential factors predicting mortality.ResultsAmong the 808 patients, the mean age (SD) was 45.4 (19.6) year‐old and the median (IQR) pneumonia severity index (PSI) score was 42.0 (35.8). Survival status for a total of 426 (52.7%) were determined during the follow‐up and the non‐follow‐up patients were with slightly larger PSI score. The mean age (SD) for the follow‐up patients were 44.6 (18.7) year‐old and the median (IQR) PSI score was 42.0 (33.3). Over a median of 7 years, 32 participants died and the cumulative 1‐, 3‐, 5‐ and 7‐year all‐cause mortality rates were 1.6%, 4.2%, 5.9% and 7.5%, respectively. The average annual standardized mortality rate among the study participants was 9.79‰, which was significantly higher than the mortality rate of 5.20‰ among Beijing residents in 2016. Multivariable Cox proportional hazards analyses revealed that age, comorbidity and PSI were independent prognostic factors associated with long‐term mortality, with hazard ratios of 4.953 (95% confidence interval [CI]3.270‐7.502), 2.393 (95% CI 1.148‐4.985) and 3.553 (95% CI 2.607‐4.843), respectively. [Correction added on 20 August 2020, after first online publication: “9.79%” has been corrected to “9.79‰”.]ConclusionThe long‐term mortality rate is higher among patients with CAP compared with the age‐adjusted general population in the same city. Age, comorbidity and initial PSI class are independently prognostic factors for the long‐term mortality rate.
Dose‐Dependent Acute Effects of Everolimus Administration on Immunological, Neuroendocrine and Psychological Parameters in Healthy Men
Authors: Hörbelt Tina , Kahl Anna Lena , Kolbe Frederike , Hetze Susann , Wilde Benjamin , Witzke Oliver , Schedlowski Manfred 
Published: May 2020

The rapamycin analogue everolimus (EVR) is a potent inhibitor of the mammalian target of rapamycin (mTOR) and clinically used to prevent allograft rejections as well as tumor growth. The pharmacokinetic and immunosuppressive efficacy of EVR have been extensively reported in patient populations and in vitro studies. However, dose‐dependent ex vivo effects upon acute EVR administration in healthy volunteers are rare. Moreover, immunosuppressive drugs are associated with neuroendocrine changes and psychological disturbances. It is largely unknown so far whether and to what extend EVR affects neuroendocrine functions, mood, and anxiety in healthy individuals. Thus, in the present study, we analyzed the effects of three different clinically applied EVR doses (1.5, 2.25, and 3 mg) orally administered 4 times in a 12‐hour cycle to healthy male volunteers on immunological, neuroendocrine, and psychological parameters. We observed that oral intake of medium (2.25 mg) and high doses (3 mg) of EVR efficiently suppressed T cell proliferation as well as IL‐10 cytokine production in ex vivo mitogen‐stimulated peripheral blood mononuclear cell. Further, acute low (1.5 mg) and medium (2.25 mg) EVR administration increased state anxiety levels accompanied by significantly elevated noradrenaline (NA) concentrations. In contrast, high‐dose EVR significantly reduced plasma and saliva cortisol as well as NA levels and perceived state anxiety. Hence, these data confirm the acute immunosuppressive effects of the mTOR inhibitor EVR and provide evidence for EVR‐induced alterations in neuroendocrine parameters and behavior under physiological conditions in healthy volunteers.
Pharmacokinetics of Favipiravir in Critically Ill Patients With COVID‐19
Authors: Irie Kei , Nakagawa Atsushi , Fujita Hirotoshi , Tamura Ryo , Eto Masaaki , Ikesue Hiroaki , Muroi Nobuyuki , Tomii Keisuke , Hashida Tohru 
Published: May 2020

Since December 2019, a novel coronavirus (severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2)) infection has been rapidly spreading worldwide and causing the respiratory illness, coronavirus disease 2019 (COVID‐19). The antiretroviral drug favipiravir (FPV) has been experimentally used for COVID‐19 treatment since March 2020 in Japan. However, the pharmacokinetics of FPV in critically ill patients is unknown. We measured the serum concentration of FPV using high‐performance liquid chromatography in patients with severe COVID‐19 who were admitted to the intensive care unit and placed on mechanical ventilation. The patients were administered 1,600 mg of FPV twice daily on day 1, followed by 600 mg twice daily from day 2 to day 5 (or more if needed). Suspensions of FPV tablets were administered through a nasogastric tube. Seven patients were enrolled in this study. Forty‐nine blood samples were obtained from the eligible patients to evaluate FPV concentration. The FPV trough (after 8–12 hours) concentrations of most samples were lower than the lower limit of quantification (1 µg/mL) and half‐maximal effective concentration (9.7 µg/mL) against SARS‐CoV‐2 previously tested in vitro. FPV trough concentration in critically ill patients was much lower than that of healthy subjects in a previous clinical trial, which is a cause for great concern. Further study is required to determine the optimal strategy for treatment of patients with severe COVID‐19.
Immune thrombocytopenia in adults: A single‐centre review of demographics, clinical features and treatment outcomes
Authors: Woolley Philippa , Newton Rosalind , Mc Guckin Siobhan , Thomas Mari , Westwood John‐Paul , Scully Marie A. 
Published: May 2020

AbstractObjectivesPrimary immune thrombocytopenia (ITP) is a bleeding disorder characterised by an isolated thrombocytopenia in the absence of an alternative diagnosis. The condition is highly heterogeneous with some patients requiring multiple of therapy before achieving response. In this study, we collected data on a large cohort of primary ITP patients with the objective of identifying variables which may predict treatment requirements.MethodsWe collected data on 379 patients, 275 with a confirmed diagnosis of primary ITP included demographics, baseline laboratory results and treatments. These were compared against treatment responses and lines of therapy.ResultsPatients who presented with a platelet count of <30 × 109/L or bleeding symptoms were observed to require more subsequent lines of therapy (P‐value <0.001). 32% of patients (n = 87) received no treatment, and these patients had a significantly higher median count compared to those with required >2 lines of therapy (P‐value <0.001). Superior response rates were demonstrated with thrombopoietin receptor agonists when compared with other agents irrespective of baseline characteristics.ConclusionsPlatelet counts at diagnosis are a potentially strong predictive indicator of subsequent lines of therapy. Patients with bleeding symptoms at diagnosis were more likely to have lower median platelets counts.
Insights into conjugative transfer of antibiotic resistance genes affected by soil minerals
Authors: Wu Shan , Wu Yichao , Huang Qiaoyun , Cai Peng 
Published: May 2020

AbstractWidespread antibiotic resistance genes (ARGs) have caused critical threats to public health on a global scale. Soil, composed mainly of minerals, acts as a source of resistance determinants, playing a considerable role in the development and dissemination of ARGs. The great abundance of ARGs in the soil environment raises concern about the effect of minerals on the spread of ARGs. Herein, the horizontal transfer of a model plasmid pMP2463 containing ARGs from Escherichia coli S17‐1 to Pseudomonas putida KT2440 was monitored following exposure to four common soil minerals, namely, kaolinite, montmorillonite, goethite and birnessite. Birnessite resulted in concentration‐dependent increases in conjugative transfer of plasmid pMP2463 by 1.3–4.3 fold, compared with that in the control group. However, no obvious laws were found in the change of conjugative transfer rate at different concentrations of kaolinite and montmorillonite. As for goethite, the conjugative transfer rate increased firstly and then decreased as the concentration increased. The possible mechanisms underlying birnessite‐induced conjugative transfer of plasmid were explored; birnessite is capable of initiating intracellular reactive oxygen species (ROS) formation, inducing the oxidative stress response. Additionally, birnessite notably facilitated the mRNA expression of the outer membrane protein genes, which contributed to cellular membrane pore formation and horizontal gene transfer, and altered the mRNA expression of conjugative‐related genes that are responsible for conjugative transfer of mobile genetic elements between bacteria. This study triggers questions regarding the potential role of soil minerals in the global dissemination of antimicrobial resistance and provides insights into the interactions between bacteria and minerals in the natural soil environment.Highlights
The effect of soil minerals on conjugative transfer of ARGs was explored.
Birnessite induced the concentration‐dependent increase of conjugative transfer.
Mechanisms underlying ROS formation, membrane permeability increase, gene expression alteration were revealed.
Our results provide evidence for the effect of birnessite on antibiotic resistance dissemination.
Subchondral focal osteopenia associated with proximal sesamoid bone fracture in Thoroughbred racehorses
Authors: Shaffer Sarah K. , To Celeste , Garcia Tanya C. , Fyhrie David P. , Uzal Francisco A. , Stover Susan M. 
Published: May 2020

AbstractBackgroundProximal sesamoid bone (PSB) fracture is the most common fatal injury in Thoroughbred (TB) racehorses in the United States. Epidemiological and pathological evidence indicates PSB fracture is likely the acute culmination of a chronic stress‐related process. However, the aetiopathogenesis of PSB fracture is poorly understood.ObjectiveTo characterise bone abnormalities that precede PSB fracture.Study designTwo retrospective case‐control groups of PSBs from TB racehorses with, and without, unilateral biaxial PSB fracture.MethodsProximal sesamoid bones were harvested post‐mortem from TB racehorses subjected to euthanasia for unilateral biaxial PSB fracture (cases) or causes unrelated to PSB fracture (controls) while racing or training. The fractured medial PSB (FX‐PSB) and contralateral intact medial PSB (CLI‐PSB) from racehorses that sustained PSB fracture, and an intact medial PSB (CTRL‐PSB) from racehorses that did not have a PSB fracture were collected as case and control specimens.Study 1distributions of morphological features were compared among case and control groups using visual examination, photographs, radiographs and histology of whole PSBs and serial sagittal sections (10 FX‐PSB, 10 CLI‐PSB and 10 CTRL‐PSB).Study 2local bone volume fraction and mineral densities were compared among case and control PSBs using microcomputed tomography (9 FX‐PSB, 9 CLI‐PSB and 9 CTRL‐PSB).ResultsA focal subchondral lesion characterised by colocalised focal discoloration, radiolucency, osteopenia, low tissue mineral density and a surrounding region of dense cancellous bone was identified in most case horses but not in controls. This subchondral lesion was found in a slightly abaxial mid‐body location and was bilaterally present in most case horses.Main limitationsThe post‐mortem samples may not represent the spectrum of abnormalities that occur throughout the development of the subchondral lesion. Lateral PSBs were not examined, so their contribution to biaxial PSB fracture pathogenesis is unknown.ConclusionAbaxial subchondral lesions are consistent with pre‐existing injury and likely associated with PSB fracture.