bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells
Authors: Reinink Peter , Souter Michael N. T. , Cheng Tan‐Yun , van Gorkom Tamara , Lenz Stefanie , Kubler‐Kielb Joanna , Strle Klemen , Kremer Kristin , Thijsen Steven F.T. , Steere Allen C. , Godfrey Dale I. , Pellicci Daniel G. , Moody D. Branch , Van Rhijn Ildiko 
Published: March 2019

AbstractLyme disease is a common multisystem disease caused by infection with a tick‐transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL‐II) is a major target of antibodies in sera from infected individuals. Here, we show that CD1b presents BbGL‐II to human T cells and that the TCR mediates the recognition. However, we did not detect increased frequency of CD1b‐BbGL‐II binding T cells in the peripheral blood of Lyme disease patients compared to controls. Unexpectedly, mapping the T cell specificity for BbGL‐II‐like molecules using tetramers and activation assays revealed a concomitant response to CD1b‐expressing APCs in absence of BbGL‐II. Further, among all major classes of self‐lipid tested, BbGL‐II responsive TCRs show strong cross‐reactivity to diacylglycerol, a self‐lipid antigen with structural similarities to BbGL‐II. Extending prior work on MHC and CD1b, CD1c, and CD1d proteins, this study provides evidence for cross‐reactive CD1b‐restricted T cell responses to bacterial and self‐antigens, and identifies chemically defined targets for future discovery of self and foreign antigen cross‐reactive T cells.
Characterization of corn, cassava, and commercial flours: Use of amylase‐rich flours of germinated corn and sweet potato in the reduction of the consistency of the gruels made from these flours—Influence on the nutritional and energy value
Authors: Tambo Tene Stephano , Klang Julie Mathilde , Ndomou Houketchang Serge Cyrille , Teboukeu Boungo Gires , Womeni Hilaire Macaire 
Published: March 2019

AbstractMalnutrition appears in weaning age and is usually due to weaning food which is of low nutritional value. This problem led us to investigate the study of the physicochemical and functional properties of cassava flours and corn flours, and the fluidification of the gruels made from these flours by germinated yellow corn and sweet white potato flours. To do this, the approximate chemical composition, physical and functional properties, and ability of amylase‐rich flours to digest the starch in order to reduce consistency were evaluated. From these analyses, it emerges that the chemical composition, and physical and functional properties are influenced by the nature and the treatment undergone by the flours. It appears that the amylase‐rich flours that we used at a concentration of 1%–3% during the preparation of the gruels significantly reduced their consistencies. Given their strong liquefying power, this reduction was more marked with germinated corn flour where 1% permits to obtain desired consistency with 21.50 g of DM of bitter cassava flour, thereby multiplying the energy density and nutritional value of this flour by 5.18. It also appears that the action of flours rich in amylases was depending on the concentration, the nature of the flour, its composition, and the treatment undergone. In view of all these results, we can therefore consider the formulation of a weaning food with the consistency, and energy and nutritional value necessary for the proper growth of children.
Late Palaeozoic tectonic evolution of the southern North China Craton: Constraints from detrital zircon dating and Hf–O isotopic compositions of the Benxi Formation, Sanmenxia area, North China Craton
Authors: Wang An‐Qi , Yang De‐Bin , Yang Hao‐Tian , Mu Mao‐Song , Quan Yi‐Kang , Hao Le‐Ran , Xu Wen‐Liang 
Published: March 2019

This study presents new detrital zircon laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) U–Pb ages and in situ Hf–O isotopic data in order to constrain the depositional age and provenance of the Benxi Formation in the Sanmenxia area of the southern North China Craton (NCC). Detrital zircons in quartz sandstone drillcore from the Benxi Formation are euhedral–subhedral, oscillatory zoned, and have high Th/U ratios (0.03–1.60, generally greater than 0.3) that are indicative of a magmatic origin. Detrital zircons from samples 13H16A and 13H16B yield seven (2544, 1788, 1123, 955, 737, 441, and 344 Ma) and six main age populations (2440, 1583, 951, 759, 434, and 348 Ma), respectively. The εHf(t) values of the Neoarchean–Paleoproterozoic zircons range from −11.3 to +13.9, and these zircons have δ18O values that range from 5.68‰ to 8.83‰. The Neoproterozoic zircons have variable εHf(t) (−9.2 to +12.5) and δ18O (5.58‰ to 9.85‰) values, whereas the Palaeozoic zircons have εHf(t) values between −19.9 and +13.4 and δ18O values of 5.23‰–9.43‰. The Benxi Formation was deposited during the late Carboniferous and contains sediments derived from igneous rocks of the North Qinling Orogen combined with a small amount of material derived from Precambrian basement of the NCC. The northward subduction of the South Qinling Orogen caused the uplift and erosion of the North Qinling Orogen during the late Carboniferous.
Mineral phase equilibria and zircon geochronology constrain multiple metamorphic events of high‐pressure pelitic granulites in south‐easternTibetan Plateau
Authors: Ji Lei , Liu Fulai , Wang Fang , Santosh M. , Tian Zhonghua , Sun Zaibo 
Published: March 2019

The Ailao Shan (ALS) metamorphic belt separates the Indochina Block to the west from the South China Block and is an important region for understanding the history of evolution of the Palaeo‐Tethys in relation to the collision of the Indian and Eurasian plates and the formation of the Tibetan Plateau. The multiple metamorphic events andP–T–tpaths of the ALS belt remain debated. Here, we present the results of an integrated study of the petrography, mineral chemistry, phase equilibria modelling, and zircon U–Pb geochronology of high‐grade metasedimentary rocks from this belt. Abundant metamorphic zircon grains with mineral inclusions of Sil/Ky + Bt + Pl + Qz ± Mnz record two metamorphic events, the first one during the Triassic (227–220 Ma), although intense shearing overlapped during the Cenozoic and mineral assemblages of this thermal event were not preserved. The second metamorphic event occurred during the Palaeogene (49 –23 Ma) and involved three stages: (a) a peak high‐pressure (HP) granulite‐facies metamorphism (M1) with a mineral assemblage of Ky + Grt1 + Bt1 + Pl + Qz ± Kfs; (b) a postpeak near‐isothermal decompression (M2) characterized by Sil1–2 + Grt2 + Bt1 + Pl + Qz + Kfs + Ilm and the decompression reactions of Grt + Ky + Qz = 3An and Ky = Sil; and (c) a late decompressional cooling (M3) with a mineral assemblage of Sil3 + Grt3 + Bt2 + Pl + Qz + Mnz ± Kfs, followed by a series of hydration reactions. The metamorphic evolution occurred along a clockwiseP–T–tpath with peakP–Tconditions of 13.5–14.0 kbar and 810–820°C. Our new data, combined with those from previous studies, reveal that the Diancang Shan–Ailao Shan Complex Belt is not a single suture that represents the closure of the Palaeo‐Tethyan Ocean during the Triassic, but that it also represents a typical continent–continent collisional orogenic belt that formed during the Eocene–Oligocene prior to the strong left‐lateral, ductile deformation along the Ailao Shan–Red River shear zone.
Machine learning approaches to studying the role of cognitive reserve in conversion from mild cognitive impairment to dementia
Authors: Facal David , Valladares‐Rodriguez Sonia , Lojo‐Seoane Cristina , Pereiro Arturo X. , Anido‐Rifon Luis , Juncos‐Rabadán Onésimo 
Published: March 2019

ObjectivesThe overall aim of the present study was to explore the role of cognitive reserve (CR) in the conversion from mild cognitive impairment (MCI) to dementia. We used traditional and machine learning (ML) techniques to compare converter and nonconverter participants. We also discuss the predictive value of CR proxies in relation to the ML model performance.MethodsIn total, 169 participants completed the longitudinal study. Participants were divided into a control group and three MCI subgroups, according to the Petersen criteria for diagnosis. Information about the participants was compared using nine ML classification techniques. Seven relevant performance metrics were computed in order to evaluate the accuracy of prediction regarding converter and nonconverter participants.ResultsML algorithms applied to socio‐demographic, basic health, and CR proxy data enabled prediction of conversion to dementia. The best performing models were the gradient boosting classifier (accuracy (ACC) = 0.93; F1 = 0.86, and Cohen κ = 0.82) and random forest classifier (ACC = 0.92; F1 = 0.79, and Cohen κ = 0.71). Use of ML techniques corroborated the protective role of CR as a mediator of conversion to dementia, whereby participants with more years of education and higher vocabulary scores survived longer without developing dementia.ConclusionsWe used ML approaches to explore the role of CR in conversion from MCI to dementia. The findings indicate the potential value of ML algorithms for detecting risk of conversion to dementia in cognitive aging and CR studies. Further research is required to develop an ML‐based procedure that can be used to make robust predictions.
Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment‐resistant late‐life depression
Authors: Trevizol Alisson Paulino , Goldberger Kyle W. , Mulsant Benoit H. , Rajji Tarek K. , Downar Jonathan , Daskalakis Zafiris J. , Blumberger Daniel M. 
Published: March 2019

BackgroundThe management of late‐life depression is challenged by high rates of treatment‐resistance and adverse effects, along with medical comorbidities and polypharmacy. Together with the limited data on managing treatment‐resistant depression in older adults, there is a need for investigating the efficacy of nonpharmacological treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is one modality that may better serve this patient population.MethodsThe present study examines data from two previous clinical trials (NCT00305045 and NCT01515215) to explore the efficacy of bilateral and unilateral high‐frequency left‐sided (HFL) rTMS in older adults suffering from treatment‐resistant depression. A total of 43 adults aged 60 or older with a current major depressive episode were randomized to bilateral sequential, unilateral HFL, or sham. Bilateral sequential stimulation involved low‐frequency (1 Hz) right dorsolateral prefrontal cortex (DLPFC) stimulation followed immediately by high‐frequency (10 Hz) left DLPFC. The unilateral condition was HFL stimulation alone, and the placebo condition was either HFL or sequential bilateral form of sham. The primary outcome was remission of depression.ResultsParticipants receiving bilateral rTMS experienced greater remission rates (40%) compared with unilateral (0%) or sham (0%) groups. Response to rTMS in the Hamilton Depression Rating Scale scores similarly favored the efficacy of bilateral rTMS.ConclusionThis study suggests that sequential bilateral treatment may be an optimal form of rTMS when used for treatment‐resistant depression in older adults. Further large‐scale comparative effectiveness trials of bilateral rTMS in this population are warranted.
Awareness and its relationships with neuropsychiatric symptoms in people with Korsakoff syndrome or other alcohol‐related cognitive disorders living in specialized nursing homes
Authors: Gerridzen Ineke J. , Joling Karlijn J. , Depla Marja F. , Veenhuizen Ruth B. , Verschuur Els M.L. , Twisk Jos W.R. , Hertogh Cees M.P.M. 
Published: March 2019

ObjectivesImpaired awareness of functional deficits is often observed in people with Korsakoff syndrome (KS) and may result in refusal of care, although this area has been understudied. This study aimed to investigate levels of impaired awareness and their relationships with neuropsychiatric symptoms (NPS) in people with KS residing in specialized nursing homes.MethodsA cross‐sectional, observational study was conducted among 215 residents with KS or other alcohol‐related cognitive disorders. Awareness was measured with the Patient Competency Rating Scale (PCRS). NPS and subsyndromes were measured with the Neuropsychiatric Inventory–Questionnaire (NPI‐Q). Adjusted multilevel regression analyses were performed to examine the relationships between the level of awareness and NPS.ResultsThe mean level of impaired awareness was 39.3 (SD = 19.9) indicating moderate impairment. Twenty‐nine percent of the residents had no or mildly impaired awareness; 37% were moderately impaired, and 34% were severely impaired. Residents with moderately impaired awareness showed more severe apathy than residents with no or mildly impaired awareness (difference 1.23; 95% CI 1.02‐1.48; p = 0.03). No associations were found between the level of awareness and other NPI outcomes. Cognitive functioning seems to have the strongest impact on the association between level of awareness and NPS in KS residents.ConclusionsImpaired awareness of functional deficits is highly common in KS residents; however, apart from apathy, is not significantly related with NPS. Additional research should further examine, which interventions are effective in dealing with impaired awareness in these people, particularly when apathy is present.
Genome‐wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis
Authors: Wang Chan , Zheng Xiaodong , Jiang Peng , Tang Ruqi , Gong Yuhua , Dai Yaping , Wang Lan , Xu Ping , Sun Wenjuan , Wang Lu , Han Chongxu , Jiang Yuzhang , Wei Yiran , Zhang Kui , Wu Jian , Shao Youlin , Gao Yueqiu , Yu Jianjiang , Hu Zhigang , Zang Zhidong , Zhao Yi , Wu Xudong , Dai Na , Liu Lei , Nie Jinshan , Jiang Bo , Lin Maosong , Li Li , Li You , Chen Sufang , Shu Lixin , Qiu Fang , Wu Qiuyuan , Zhang Mingming , Chen Ru , Jawed Rohil , Zhang Yu , Shi Xingjuan , Zhu Zhen , Pei Hao , Huang Lihua , Zhao Weifeng , Tian Ye , Zhu Xiang , Qiu Hong , Gershwin M. Eric , Chen Weichang , Seldin Michael F. , Liu Xiangdong , Sun Liangdan , Ma Xiong 
Published: March 2019

Anti‐nuclear antibodies to speckled 100 kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome‐wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single‐nucleotide polymorphisms rs492899 (P = 3.27 × 10−22; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34‐3.66) and rs1794280 (P = 5.78 × 10−28; OR, 3.89; 95% CI, 3.05‐4.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti‐sp100‐positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA‐DRβ1‐Asn77/Arg74, DRβ1‐Ser37, and DPβ1‐Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with DRB1*03:01 (P = 1.51 × 10−9; OR, 2.97; 95% CI, 2.06‐4.29). Regression analysis with classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 alleles can explain most of the HLA association with sp100 autoantibody. Conclusion: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and/or therapeutics.
“It Broadens Our Horizon”: English Learners Learn Through Global Literature and Cultural Discussion
Authors: Wang Yang 
Published: March 2019

AbstractIn this qualitative case study, the author explored how reading global literature books and interacting with U.S. literacy teachers influenced Chinese college students’ intercultural understandings and English‐language learning. Students read the selected picture books, discussed in small groups, conducted freewritings, made video clips, and created e‐books and PowerPoint presentations. The author found that students learned about different cultures, developed global awareness, and showed their respect and empathy for cultural differences. Reading global picture books and engaging in cultural discussion about the books helped students reflect on their own culture, think critically, and advocate for others. Students became interested in global literature books and developed English‐language skills by interacting with literature and U.S. teachers. Educational implications for English‐language and literacy teachers are provided.
Total flavonoids, extracted from Polygonum knotweed L, exert beneficial hepatoprotection against liver injury
Authors: Xu Lingyuan , Huang Guikun , Guo Xiaobao , Zhou Qiji , He Silu 
Published: March 2019

AbstractHepatic function is of great concern in metabolic and immunological homeostasis. Traditionally, medical management to liver damage may benefit from phytomedicine, such as Chinese herbs. In southern China, Polygonum perfoliatum L can contribute to alleviating pathological symptoms of liver disease, such as hepatitis. However, bioactive compounds of hepatoprotection in this herb are still less to be investigated. In this study, clinical data of patients with drug‐induced liver injury were collected on the basis of serological analyses. In addition, we extracted and identified total flavonoids from Polygonum perfoliatum L (TFPPL) before implementing biochemical experiments in vivo. In human data, the blood contents of liver function enzymes were visibly elevated, and the percentage of immune cells were abnormally changed. The data from the animal study showed that TFPPL‐treated carbon tetrachloride‐exposed mice resulted in reduced absolute liver mass and lowered blood levels of liver functional enzymes (alanine transaminase and aspartate transaminase). In enzyme‐linked immunosorbent assay, the comparable data indicated that serological tumor necrosis factor α (TNF‐α), interleukin 6, and heat shock protein 90 (Hsp90) contents were reduced in TFPPL‐treated mice. In histopathological observations, TFPPL‐treated mice exhibited reduced hepatocellular Hsp90, TNF‐α, nuclear factor κ‐light‐chain‐enhancer of activated B cells‐p65 positive cells, and lowered Bax and caspase‐3‐labeled cells in the livers. Further, intrasplenic integrin β1, 5′‐nucleotidase, and antigen KI‐67 positive cells were increased after TFPPL treatments. Taken together, our present findings demonstrate that herb‐extracted TFPPL exert potential hepatoprotective activities against chemical‐induced liver damage in mice, possibly through the pharmacological mechanisms of inhibiting inflammatory stress and apoptosis, inactivating Hsp90 bioactivity in the liver, and improving splenic immunocompetence.
miR‐193b‐5p regulates chondrocytes metabolism by directly targeting histone deacetylase 7 in interleukin‐1β‐induced osteoarthritis
Authors: Zhang Chengyun , Zhang Zhiqi , Chang Zongkun , Mao Guping , Hu Shu , Zeng Anyu , Fu Ming 
Published: March 2019

AbstractThere is increasing evidence regarding the pivotal roles of microRNAs (miRNAs) and histone deacetylases (HDACs) in the development of osteoarthritis (OA). This study aimed to determine whether miR‐193b‐5p regulates HDAC7 expression directly to affect cartilage degeneration. Expression levels of miR‐193b‐5p, HDAC7, matrix metalloproteinase 3 (MMP3), and MMP13 were determined in normal and OA cartilage and primary human chondrocytes (PHCs) stimulated with interleukin‐1β (IL‐1β). PHCs were transfected with a miR‐193b‐5p mimic or inhibitor to verify whether miR‐193b‐5p influences the expression of HDAC7 and MMPs. A luciferase reporter assay was performed to demonstrate the binding between miR‐193b‐5p and the 3′‐untranslated region (UTR) of HDAC7. Expression of miR‐193b‐5p was reduced in IL‐1β‐stimulated PHCs and in OA cartilage compared to that in normal cartilage. Luciferase reporter assay exhibited the repressed activity of the reporter construct containing the 3′UTR of HDAC7. Both miR‐193b‐5p overexpression and HDAC7 inhibition decreased the expression of MMP3 and MMP13, whereas the inhibition of miR‐193b‐5p enhanced HDAC7, MMP3, and MMP13 expression. miR‐193b‐5p downregulates HDAC7 directly and, as a result, inhibits MMP3 and MMP13 expression, which suggests that miR‐193b‐5p has a protective role in OA.
Distinguishing the optimal binding mechanism of an E3 ubiquitin ligase: Covalent versus noncovalent inhibition
Authors: Bjij Imane , Khan Shama , Ramharak Pritika , Cherqaoui Driss , Soliman Mahmoud E. S. 
Published: March 2019

AbstractThe development of covalent drugs, specifically in cancer therapeutics, has recently sparked interest among the pharmaceutical research community. While representing a significant fraction of the drugs in the market, very few have been deliberately designed to interact covalently with their biological target. One of the enzymes that have been both covalently and noncovalently targeted is the Neural Precursor Cell Expressed Developmentally Downregulated gene 4‐1 (Nedd4‐1). This enzyme has been found to have multiple physiological implications, including its involvement in cancer invasion. A critical gap still remains in the molecular understanding of the structural mechanism upon the covalent and noncovalent binding to Nedd4‐1. In this study, we explore the most optimal binding mechanism in the inhibition of the catalytic site of the Nedd4‐1. Our results exhibited a greater stability in the covalent complex compared with the noncovalent complex. This was supported by the secondary structure elements that were more dominant in the covalently inhibited complex. This complex disclosed an optimal free binding energy landscape, induced by the catalytic site energy contributions that showed to be more favorable. The insights demonstrating the above binding mechanism of Nedd4‐1 establishes covalent inhibition as the preferred method of inhibition of the enzyme. This investigation aids in the understanding of the structural mechanism of Nedd4‐1 inhibition and would assist in the design of more potent covalent inhibitors at the catalytic site of Nedd4‐1.