bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDGFRα monoclonal antibody: Assessment of embryo‐fetal toxicity and time‐dependent placental transfer of a murine surrogate antibody of olaratumab in mice
Authors: Luffer‐Atlas Debra , Reddy Vijayapal R. , Hilbish Kim G. , Grace Curtis E. , Breslin William J 
Published: October 2018

BackgroundOlaratumab (Lartruvo™) is a recombinant human IgG1 monoclonal antibody that specifically binds PDGFRα. The maternal and in utero embryo‐fetal toxicity and toxicokinetics of a human anti‐mouse PDGFRα antibody (LSN3338786) were investigated in pregnant mice.MethodsA pilot study was used to set doses for the definitive study. In the definitive study, mice were administered vehicle, 5, 50, or 150 mg/kg LSN3338786 by intravenous injection on gestation days (GD) 6, 9, 12, and 15. Fetal tissues and/or serum samples were collected on GD 10, 12, 15, and 18 to evaluate exposure of antibody.ResultsThere were no adverse maternal effects at 50 and 150 mg/kg although maternal deaths and adverse clinical signs were observed at 5 mg/kg. LSN3338786 crossed the placenta as early as GD 10 during organogenesis. Elimination half‐life of LSN3338786 in dams decreased between GD 6 and 15. On GD 18, fetal serum concentrations of antibody were substantially higher than maternal serum concentrations at all doses. Increased incidences of malformations consisting of open and partially open eye and increased incidences of skeletal variation frontal/parietal additional ossification site occurred in fetuses from mid‐ and high‐dose groups.ConclusionsThe majority of transplacental migration of antibody occurred in concert with rapid maternal serum clearance before parturition. The no‐observed effect level for teratogenicity of 5 mg/kg was associated with GD 15 maternal serum concentrations 3–11 times lower than clinical exposure of olaratumab, suggesting that olaratumab may cause fetal harm when administered to pregnant women.
Pharmacokinetics and bioavailability of gelsenicine in mice by UPLC–MS/MS
Authors: Li Jianbo , Jin Yue , Fu Huiyan , Huang Yihui , Wang Xianqin , Zhou Yunfang 
Published: October 2018

AbstractGelsenicine is an indole alkaloid isolated from Gelsemium elegans Benth. In recent years, the role of G. elegans Benth preparations in anti‐tumor, analgesic, dilatation and dermatological treatment has attracted attention, and it has been applied clinically, but it is easy to cause poisoning with its use. An UPLC–MS/MS method was established to determine the gelsenicine in mouse blood, and the pharmacokinetics of gelsenicine after intravenous (0.1 mg/kg) and intragastric (0.5 and 1 mg/kg) administration was studied. Deltalin was used as internal standard; a UPLC BEH C18 column was used for chromatographic separation. The mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) with a gradient elution flow rate of 0.4 mL/min. Multiple reaction monitoring mode was used for quantitative analysis of gelsenicine in electrospray ionization positive interface. Proteins from mouse blood were removed by acetonitrile precipitation. A validation of this method was performed in accordance with the US Food and Drug Administration guidelines. In the concentration range of 0.05–100 ng/mL, the gelsenicine in the mouse blood was linear (r > 0.995), and the lower limit of quantification was 0.05 ng/mL. In the mouse blood, the intra‐day precision RSD was <12%, the inter‐day precision RSD was <15%, the accuracy ranged from 89.8 to 112.3%, the average recovery was >76.8%, and the matrix effect was between 103.7 and 108.4%, which meet the pharmacokinetic research requirements of gelsenicine. The UPLC–MS/MS method is sensitive, rapid and selective, and has been successfully applied to the pharmacokinetic study of gelsenicine in mice. The absolute bioavailability of gelsenicine is 1.13%.
Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63
Authors: Tanaka Nobuyuki , Katayama Shintaro , Reddy Aparna , Nishimura Kaneyasu , Niwa Naoya , Hongo Hiroshi , Ogihara Koichiro , Kosaka Takeo , Mizuno Ryuichi , Kikuchi Eiji , Mikami Shuji , Miyakawa Ayako , Arenas Ernest , Kere Juha , Oya Mototsugu , Uhlén Per 
Published: October 2018

AbstractCancers acquire resistance to systemic treatment with platinum‐based chemotherapy (eg, cisplatin [CDDP]) as a result of a dynamic intratumoral heterogeneity (ITH) and clonal repopulation. However, little is known about the influence of chemotherapy on ITH at the single‐cell level. Here, mapping the transcriptome of cancers treated with CDDP by scRNA‐seq, we uncovered a novel gene, COX7B, associated with platinum‐resistance, and surrogate marker, CD63. Knockdown of COX7B in cancer cells decreased the sensitivity of CDDP whereas overexpression recovered the sensitivity of CDDP. Low COX7B levels correlated with higher mortality rates in patients with various types of cancer and were significantly associated with poor response to chemotherapy in urinary bladder cancer. Tumor samples from patients, who underwent CDDP therapy, showed decreased COX7B protein levels after the treatment. Analyzing scRNA‐seq data from platinum‐naïve cancer cells demonstrated a low‐COX7B subclone that could be sorted out from bulk cancer cells by assaying CD63. This low‐COX7B subclone behaved as cells with acquired platinum‐resistance when challenged to CDDP. Our results offer a new transcriptome landscape of platinum‐resistance that provides valuable insights into chemosensitivity and drug resistance in cancers, and we identify a novel platinum resistance gene, COX7B, and a surrogate marker, CD63.
Patent foramen ovale in an elderly male with multiple embolic infarcts
Authors: Aarli Sander Johan , Kråkenes Jostein , Omdal Tom Roar , Waje‐Andreassen Ulrike 
Published: October 2018

Key Clinical MessagePatent foramen ovale (PFO) is associated with embolic stroke, particularly in younger patients. In older patients, atrial fibrillation is a more common cause of embolic stroke. A PFO may be considered culpable at higher age when other potential embolic sources are absent or after recurrent stroke despite prophylactic treatment.
Rare NF1 microdeletion syndrome in an Omani patient
Authors: Al‐Araimi Musallam , Hamza Nishath , Al Yahmadi Ali , Al Mazrooey Hiba , Elsheikh Afaf , Al Amri Amira , Al Harrasi Salma , Hausdorf Lena , Mula‐Abed Waad‐Allah 
Published: October 2018

Key Clinical MessageNeurofibromatosis‐1 phenotype combined with webbed neck and short stature in a young Omani patient was revealed to be due to a de novo germ‐line heterozygous 1.7 Mb microdeletion at 17q11.2. This lead to the diagnosis of NF1 microdeletion syndrome.
Relationship of left ventricular thrombus formation and adverse outcomes in acute anterior myocardial infarction in patients treated with primary percutaneous coronary intervention
Authors: Zhang Qian , Wang Chun‐Mei , Shi Shu‐Tian , Chen Hong , Zhou Yu‐Jie 
Published: October 2018

BackgroundThe incidence of left ventricular thrombus (LVT) is 4% to 15% in patients with anterior acute ST‐segment elevation myocardial infarction (ant‐AMI) in the era of primary percutaneous coronary intervention (PPCI). And patients with LVT have higher in‐hospital mortality.HypothesisThere is a relationship between LVT formation and 1‐year major adverse cardio‐cerebrovascular events (MACCE) in patients with ant‐AMI treated by PPCI.MethodsOur study population included 1488 consecutive patients with ant‐AMI. The primary endpoint was the incidence of MACCE within 1 year after AMI. The secondary endpoint was the thrombosis disappearance.ResultsA total of 106 (7.1%) patients were diagnosed with LVT and 1382 (92.9%) patients without LVT. Patients with LVT had a higher incidence of MACCE than in patients without LVT (21.7%vs10.3%; P < 0.001). Univariate analysis showed LVT was associated with an increase in MACCE risk (odds ratio [OR] = 2.40; 95% confidence interval [CI] [1.37‐4.21]; P < 0.001). When examining MACCE components individually, LVT was only associated with the incidence of congestive heart failure (OR = 2.41; 95% CI [1.29‐4.58]; P = 0.001). After adjustment for principal confounders, LVT remained an independent risk factor for MACCE (HR = 2.28; 95% CI [1.12‐6.38]; P = 0.020). Other independent predictors include 24‐hour LVEF, creatine kinase peak value, and age. Further analysis found patients with LVT in international normalized ratio (INR) ≥ 2 group had lower MACCE risk and higher thrombus disappearance than in INR < 2 group (13.5%vs29.6%; P = 0.044; 90.4%vs74.1%; P = 0.029).ConclusionFor patients with ant‐AMI treated by PPCI, LVT is an independent predictor of 1‐year MACCE events. Treatment with vitamin K antagonist in the therapeutic range (INR ≥ 2) has the potential to reduce MACCE risk and promote disappearance of thrombus.
Development and validation of the Maxillary Canine Aesthetic Index
Authors: Grisar Koenraad , Claeys Gilles , Raes Margot , Albdour Emad Ali , Willems Guy , Politis Constantinus , Jacobs Reinhilde 
Published: October 2018

AbstractAesthetic appraisal is rarely included in the objective assessment of outcome studies of impacted maxillary canines treatment. The present study aimed to validate a new index for assessing the aesthetic appearance of maxillary canines and adjacent soft tissues. The Department of Oral and Maxillofacial Surgery at University Hospitals Leuven. Four oral‐maxillofacial surgeons, two orthodontists, two prosthodontists, and two lay persons rated 11 maxillary canines and adjacent soft tissues according to the new index. Each of the examiners repeated the examination three times with a 2‐week interval. Twelve relevant aesthetic variables were selected on the basis of the anatomic form, color, and surface characteristics of the canine crown and on the basis of the anatomic form, color, and surface characteristics of the adjacent soft tissues. Intraclass correlation (ICC) coefficient and Fleiss' kappa statistics were performed to analyze the intrarater and interrater agreement. The index proofed to be a reliable assessment tool. Considering the cumulative assessment of the Maxillary Canine Aesthetic Index (MCAI), the mean ICC value for the interrater agreement of the 10 examiners was 0.71, representing a good agreement. Intrarater agreement ranged from 0.10 to 0.91. Interrater agreement (Fleiss' kappa statistics) calculated for each variable ranged from 0.08 to 0.98. The MCAI is a tool in rating aesthetic outcome of impacted canine treatment and adjacent soft tissues. The MCAI can be used to evaluate the aesthetic outcome after surgical exposure or transalveolar transplantation of maxillary canines.
Bush encroachment dynamics and rangeland management implications in southern Ethiopia
Authors: Liao Chuan , Clark Patrick E. , DeGloria Stephen D. 
Published: October 2018

AbstractRangelands in southern Ethiopia have been undergoing a rapid regime shift from herbaceous to woody plant dominance in the past decades, reducing indigenous plant biodiversity, altering ecosystem function, and threatening subsistence pastoralism. Despite significant rangeland management implications, quantification of spatial encroachment extent and transitional pathways that result in encroachment remain largely under‐explored. This paper develops a phenology‐based approach to map rangeland vegetation states in southern Ethiopia, and examines transition pathways among states using the state‐and‐transition model. The results indicate that nearly 80% of landscape was dominated by woody plants in 2013. While stable encroached states have been established in both high and low lands through different transition pathways between 2003 and 2013, we identified spatial locations where bush encroachment occurred rapidly. The multiplicity in the transition pathways indicates opportunities for positive transformation in the entire rangeland system in southern Ethiopia and other semi‐arid regions of Africa.
Cardiac expression of neutrophil gelatinase‐associated lipocalin in a model of cancer cachexia‐induced cardiomyopathy
Authors: Musolino Vincenzo , Palus Sandra , Latouche Celine , Gliozzi Micaela , Bosco Francesca , Scarano Federica , Nucera Saverio , Carresi Cristina , Scicchitano Miriam , von Haehling Stephan , Jaisser Frederic , Hasenfuss Gerd , Anker Stefan D. , Mollace Vincenzo , Springer Jochen 
Published: October 2018

AbstractAimsCachexia is a severe consequence of cancer. Although cancer‐induced heart atrophy leads to cardiac dysfunction and heart failure (HF), biomarkers for their diagnosis have not been identified. Neutrophil gelatinase‐associated lipocalin (NGAL) is an aldosterone‐responsive gene increased in HF. We studied NGAL and its association with aldosterone levels in a model of cancer cachexia‐induced cardiomyopathy.Methods and resultsRats were injected with Yoshida 108 AH‐130 hepatoma cells to induce tumour. Cachectic rats were treated daily, for 16 days, with placebo or with 5 or 50 mg/kg/day of spironolactone. Cardiac function was analysed by echocardiography at baseline and at Day 11. Weight loss and atrophy of lean body and fat mass of cachectic rats were significantly attenuated by spironolactone. Cardiac dysfunction of tumour‐bearing rats was improved by spironolactone. Plasma aldosterone was up‐regulated from 337 ± 7 pg/mL in sham animals to 591 ± 31 pg/mL in the cachectic rats (P < 0.001 vs. sham). Treatment with 50 or 5 mg/kg/day of spironolactone reduced plasma aldosterone to 396 ± 22 and 391 ± 25 pg/mL (P < 0.01 vs. placebo). Plasma levels of NGAL were also increased in cachectic rats (1.462 ± 0.3603 μg/mL) than in controls (0.0936 ± 6 μg/mL, P < 0.001). Spironolactone treatment (50 mg/kg/day) significantly reduced cardiac mRNA and protein NGAL levels (P < 0.05 and P < 0.001 vs. placebo, respectively). NGAL mRNA and protein levels were overexpressed in cachectic animal hearts treated with placebo, compared with control (P < 0.05 and P < 0.01 vs. sham). Spironolactone treatment at 50 mg/kg/day reduced significantly cardiac NGAL (P < 0.05 and P < 0.001 vs. placebo).ConclusionsCancer cachexia induced increased levels of aldosterone and NGAL, contributing to worsening cardiac damage in cancer cachexia‐induced cardiomyopathy. Spironolactone treatment may greatly attenuate cardiac dysfunction and lean mass atrophy associated with cancer cachexia.
Antecedents and consequences of autonomy‐ and dependency‐oriented help toward refugees
Authors: Becker Julia C. , Ksenofontov Inna , Siem Birte , Love Angelika 
Published: October 2018

AbstractWe tested antecedents (paternalistic beliefs; Study 1) and consequences (social change potential; Study 2) of autonomy‐ and dependency‐oriented help and developed scales assessing paternalistic beliefs and both forms of help. In Study 1 (N = 143 Germans), we focused on paternalistic beliefs as an antagonist to social change and a key distinguishing variable between engagement in both forms of help. As expected, paternalistic beliefs were positively related to dependency‐oriented help, mediated by concern for a positive national moral image, but negatively related to autonomy‐oriented help, mediated by perceived competence of refugees. In Study 2, both refugees (N = 80) and Germans (N = 94) perceived autonomy‐oriented help to have more potential for social change than dependency‐oriented help.
Directed functional connections underlying spontaneous brain activity
Authors: Coito Ana , Michel Christoph M. , Vulliemoz Serge , Plomp Gijs 
Published: October 2018

AbstractNeuroimaging studies have shown that spontaneous brain activity is characterized as changing networks of coherent activity across multiple brain areas. However, the directionality of functional interactions between the most active regions in our brain at rest remains poorly understood. Here, we examined, at the whole‐brain scale, the main drivers and directionality of interactions that underlie spontaneous human brain activity by applying directed functional connectivity analysis to electroencephalography (EEG) source signals. We found that the main drivers of electrophysiological activity were the posterior cingulate cortex (PCC), the medial temporal lobes (MTL), and the anterior cingulate cortex (ACC). Among those regions, the PCC was the strongest driver and had both the highest integration and segregation importance, followed by the MTL regions. The driving role of the PCC and MTL resulted in an effective directed interaction directed from posterior toward anterior brain regions. Our results strongly suggest that the PCC and MTL structures are the main drivers of electrophysiological spontaneous activity throughout the brain and suggest that EEG‐based directed functional connectivity analysis is a promising tool to better understand the dynamics of spontaneous brain activity in healthy subjects and in various brain disorders.
Comparison of EEG microstates with resting state fMRI and FDG‐PET measures in the default mode network via simultaneously recorded trimodal (PET/MR/EEG) data
Authors: Rajkumar Ravichandran , Farrher Ezequiel , Mauler Jörg , Sripad Praveen , Régio Brambilla Cláudia , Rota Kops Elena , Scheins Jürgen , Dammers Jürgen , Lerche Christoph , Langen Karl‐Josef , Herzog Hans , Biswal Bharat , Shah N. Jon , Neuner Irene 
Published: October 2018

AbstractSimultaneous trimodal positron emission tomography/magnetic resonance imaging/electroencephalography (PET/MRI/EEG) resting state (rs) brain data were acquired from 10 healthy male volunteers. The rs‐functional MRI (fMRI) metrics, such as regional homogeneity (ReHo), degree centrality (DC) and fractional amplitude of low‐frequency fluctuations (fALFFs), as well as 2‐[18F]fluoro‐2‐desoxy‐d‐glucose (FDG)‐PET standardised uptake value (SUV), were calculated and the measures were extracted from the default mode network (DMN) regions of the brain. Similarly, four microstates for each subject, showing the diverse functional states of the whole brain via topographical variations due to global field power (GFP), were estimated from artefact‐corrected EEG signals. In this exploratory analysis, the GFP of microstates was nonparametrically compared to rs‐fMRI metrics and FDG‐PET SUV measured in the DMN of the brain. The rs‐fMRI metrics (ReHO, fALFF) and FDG‐PET SUV did not show any significant correlations with any of the microstates. The DC metric showed a significant positive correlation with microstate C (rs = 0.73, p = .01). FDG‐PET SUVs indicate a trend for a negative correlation with microstates A, B and C. The positive correlation of microstate C with DC metrics suggests a functional relationship between cortical hubs in the frontal and occipital lobes. The results of this study suggest further exploration of this method in a larger sample and in patients with neuropsychiatric disorders. The aim of this exploratory pilot study is to lay the foundation for the development of such multimodal measures to be applied as biomarkers for diagnosis, disease staging, treatment response and monitoring of neuropsychiatric disorders.
Reduced cortical thickness in Heschl's gyrus as an in vivo marker for human primary auditory cortex
Authors: Zoellner Simeon , Benner Jan , Zeidler Bettina , Seither‐Preisler Annemarie , Christiner Markus , Seitz Angelika , Goebel Rainer , Heinecke Armin , Wengenroth Martina , Blatow Maria , Schneider Peter 
Published: October 2018

AbstractThe primary auditory cortex (PAC) is located in the region of Heschl's gyrus (HG), as confirmed by histological, cytoarchitectonical, and neurofunctional studies. Applying cortical thickness (CTH) analysis based on high‐resolution magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 60 primary school children and 60 adults, we investigated the CTH distribution of left and right auditory cortex (AC) and primary auditory source activity at the group and individual level. Both groups showed contoured regions of reduced auditory cortex (redAC) along the mediolateral extension of HG, illustrating large inter‐individual variability with respect to shape, localization, and lateralization. In the right hemisphere, redAC localized more within the medial portion of HG, extending typically across HG duplications. In the left hemisphere, redAC was distributed significantly more laterally, reaching toward the anterolateral portion of HG. In both hemispheres, redAC was found to be significantly thinner (mean CTH of 2.34 mm) as compared to surrounding areas (2.99 mm). This effect was more dominant in the right hemisphere rather than in the left one. Moreover, localization of the primary component of auditory evoked activity (P1), as measured by MEG in response to complex harmonic sounds, strictly co‐localized with redAC. This structure–function link was found consistently at the group and individual level, suggesting PAC to be represented by areas of reduced cortex in HG. Thus, we propose reduced CTH as an in vivo marker for identifying shape and localization of PAC in the individual brain.
Hippocampal subfields alterations in adolescents with post‐traumatic stress disorder
Authors: Postel Charlotte , Viard Armelle , André Claire , Guénolé Fabian , de Flores Robin , Baleyte Jean‐Marc , Gerardin Priscille , Eustache Francis , Dayan Jacques , Guillery‐Girard Bérengère 
Published: October 2018

AbstractReexperiencing symptoms in adolescent Post‐Traumatic Stress Disorder (PTSD) are characterized by the apparition of vivid intrusive images of the traumatic event. The emergence of these intrusions is thought to be related to a deficiency in context processing and could then be related to hippocampal alterations. The hippocampus is a complex structure which can be divided into several subfields, namely, the Cornu Ammonis (CA1, CA2, and CA3), the subiculum, and the dentate gyrus (DG). As each subfield presents different histological characteristics and functions, it appears more relevant to consider hippocampal subfields, instead of only assessing the whole hippocampus, to understand the neurobiology of PTSD. Hence, this study presents the first investigation of structural alterations within hippocampal subfields and their links to reexperiencing symptoms in adolescent PTSD. Hippocampal subfields were manually delineated on high‐resolution MRI images in 15 adolescents (13–18 years old) with PTSD and 24 age‐matched healthy controls. The volume of the region CA2‐3/DG region was significantly smaller in the PTSD group compared to controls in both hemispheres. No other significant difference was found for other subfields. Moreover, the volume of the left CA2‐3/DG was negatively correlated with the intrusion score (as measured by the Impact of Events Scale‐Revised) in the PTSD group. To conclude, an alteration in the hippocampal subregion CA2‐3/DG, known to resolve interferences between new and similar stored memories, could participate in the apparition of intrusive trauma memories in adolescents with PTSD.