bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1
Authors: Planche Vincent , Koubiyr Ismail , Romero José E. , Manjon José V. , Coupé Pierrick , Deloire Mathilde , Dousset Vincent , Brochet Bruno , Ruet Aurélie , Tourdias Thomas 
Published: January 2018

AbstractBackgroundWhether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate.MethodWe prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1‐year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques.ResultsAt baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (−6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum‐pyramidale and the stratum radiatum‐lacunosum‐moleculare, −5.6%, p < .001 and −6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R2 = 0.44 to 0.47, p < .001, with age, T2 lesion‐load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow‐up, independently of T2‐lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05).ConclusionThe hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal‐dependent memory performance.
Controlling the Temporal Structure of Brain Oscillations by Focused Attention Meditation
Authors: Irrmischer Mona , Houtman Simon J. , Mansvelder Huibert D. , Tremmel Michael , Ott Ulrich , Linkenkaer‐Hansen Klaus 
Published: January 2018

AbstractOur focus of attention naturally fluctuates between different sources of information even when we desire to focus on a single object. Focused attention (FA) meditation is associated with greater control over this process, yet the neuronal mechanisms underlying this ability are not entirely understood. Here, we hypothesize that the capacity of attention to transiently focus and swiftly change relates to the critical dynamics emerging when neuronal systems balance at a point of instability between order and disorder. In FA meditation, however, the ability to stay focused is trained, which may be associated with a more homogeneous brain state. To test this hypothesis, we applied analytical tools from criticality theory to EEG in meditation practitioners and meditation‐naïve participants from two independent labs. We show that in practitioners—but not in controls—FA meditation strongly suppressed long‐range temporal correlations (LRTC) of neuronal oscillations relative to eyes‐closed rest with remarkable consistency across frequency bands and scalp locations. The ability to reduce LRTC during meditation increased after one year of additional training and was associated with the subjective experience of fully engaging one's attentional resources, also known as absorption. Sustained practice also affected normal waking brain dynamics as reflected in increased LRTC during an eyes‐closed rest state, indicating that brain dynamics are altered beyond the meditative state. Taken together, our findings suggest that the framework of critical brain dynamics is promising for understanding neuronal mechanisms of meditative states and, specifically, we have identified a clear electrophysiological correlate of the FA meditation state.
Submental artery island flap with simultaneous level I neck dissection
Authors: Eskander Antoine , Strigenz Daniel , Seim Nolan , Ozer Enver 
Published: January 2018

AbstractBackgroundThe purpose of this study was to illustrate the submental island flap elevation technique with simultaneous level I neck dissection followed by the inset and reconstruction of an oropharyngeal defect.MethodsA 63‐year‐old patient with a T2N1M0 human papillomavirus‐positive squamous cell carcinoma of the tonsil was treated with concurrent chemoradiotherapy (cisplatin + 66 Gy). A local recurrence 2.5 years after treatment was treated surgically and reconstructed with a submental island flap.ResultsThere were no complications and oral diet was initiated at 2 weeks and the gastrostomy tube was removed 1 month postoperatively. A video demonstration of the submental island flap elevation is included with a focus on how levels 1A and 1B can be dissected safely and this can be viewed online on Head & Neck's home page at http://onlinelibrary.wiley.com/.ConclusionThe submental island flap can be performed safely with a level I neck dissection for head and neck reconstruction.
Self‐perceived long‐term transfer of learning after postpartum hemorrhage simulation training
Authors: de Melo Brena Carvalho Pinto , Rodrigues Falbo Ana , Sorensen Jette Led , van Merriënboer Jeroen J.G. , van der Vleuten Cees 
Published: January 2018

AbstractObjectiveTo explore long‐term transfer (application of acquired knowledge and skills on the job) after postpartum hemorrhage simulation training based on either instructional design (ID) principles or conventional best practice.MethodsIn this qualitative study, semi‐structured interviews with obstetrics and gynecology healthcare practitioners were conducted between August 7 and September 26, 2015, in Recife, Brazil. The participants were randomly selected from each of two postpartum hemorrhage simulations attended 2 years earlier (one ID and one conventional best practice). Thematic analysis was used to explore (1) residents' perceptions of long‐term transfer of learning, (2) ID elements influencing the perceived long‐term transfer, and (3) differences in the participants' perceptions according to the type of simulation attended.ResultsThere were 12 interview participants. After either simulation format, residents perceived long‐term transfer effects. Training design factors influencing transfer were, in their opinion, related to trainees' characteristics, simulation design, and workplace environment. Trainees who participated in the ID‐based simulation perceived better communication skills and better overall situational awareness: “I didn't do that before.”ConclusionAll residents perceived long‐term transfer after simulation training for postpartum hemorrhage. Those who attended the ID format additionally perceived improvements in communication skills and situational awareness, which are fundamental factors in the management of postpartum hemorrhage.
Genetic and Molecular Insights Into Genotype-Phenotype Relationships in Osteopathia Striata With Cranial Sclerosis (OSCS) Through the Analysis of Novel Mouse Wtx Mutant Alleles
Authors: Comai Glenda , Boutet Agnès , Tanneberger Kristina , Massa Filippo , Rocha Ana-Sofia , Charlet Aurelie , Panzolini Clara , Jian Motamedi Fariba , Brommage Robert , Hans Wolfgang , Funck-Brentano Thomas , Hrabe de Angelis Martin , Hartmann Christine , Cohen-Solal Martine , Behrens Jürgen , Schedl Andreas 
Published: January 2018

ABSTRACT The X-linked WTX/AMER1 protein constitutes an important component of the β-catenin destruction complex that can both enhance and suppress canonical β-catenin signaling. Somatic mutations in WTX/AMER1 have been found in a proportion of the pediatric kidney cancer Wilms’ tumor. By contrast, germline mutations cause the severe sclerosing bone dysplasia osteopathia striata congenita with cranial sclerosis (OSCS), a condition usually associated with fetal or perinatal lethality in male patients. Here we address the developmental and molecular function of WTX by generating two novel mouse alleles. We show that in addition to the previously reported skeletal abnormalities, loss of Wtx causes severe midline fusion defects including cleft palate and ectopic synostosis at the base of the skull. By contrast, deletion of the C-terminal part of the protein results in only mild developmental abnormalities permitting survival beyond birth. Adult analysis, however, revealed skeletal defects including changed skull morphology and an increased whole-body bone density, resembling a subgroup of male patients carrying a milder, survivable phenotype. Molecular analysis in vitro showed that while β-catenin fails to co-immunoprecipitate with the truncated protein, partial recruitment appears to be achieved in an indirect manner using AXIN/AXIN2 as a molecular bridge. Taken together our analysis provides a novel model for WTX-caused bone diseases and explains on the molecular level how truncation mutations in this gene may retain some of WTX-protein functions. © 2018 American Society for Bone and Mineral Research.
Prognostic significance of miR‐21 and PDCD4 in patients with stage II esophageal carcinoma after surgical resection
Authors: Zhang Jiandong , Ma Lei , Shi Daimeng , Zhang Zhen , Yao Chuanshan , Zhao Xulin , Xu Quanxiao , Wen Penghao , He Limin 
Published: January 2018

AbstractMany studies have shown that randomized clinical trial with long‐term follow‐up found no improvement in stage II esophageal carcinoma (EC) patients receiving preoperative neoadjuvant chemoradiotherapy or chemotherapy treatment, this limitation underscored the urgent need for novel and reliable biomarkers for prognosis and prediction in stage II EC. miR‐21 is frequently over‐expressed while programmed cell death 4 (PDCD4) is often down‐regulated in solid tumors. This study aimed to investigate the clinicopathological and prognostic significance of miR‐21 and PDCD4 expression and to elucidate any correlation between miR‐21 and PDCD4 expression in stage II EC patients. The expression level of miR‐21 was up‐regulated while the PDCD4 protein was down‐regulated in stage II EC tissues compared with the adjacent non‐cancerous tissues. Analyses of the clinicopathological parameters indicated that miR‐21 expression was associated with differentiation grade, T stage, and N stage. PDCD4 protein expression was associated with T stage, N stage, and tumor size. The univariate linear regression analysis suggested a significant negative correlation between miR‐21 and PDCD4 expression. The Kaplan‐Meier curve showed that high miR‐21 expression or low PDCD4 expression predicted poor progression‐free survival (PFS) and overall survival (OS) of patients with stag II EC. In conclusion, both up‐regulated miR‐21 and down‐regulated PDCD4 expression were associated with the aggressive progression and poor prognosis of stage II EC. miR‐21 and PDCD4 might be potential biomarkers of tumor progression and indicators of prognosis of stag II EC.
Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells
Authors: Yang Zhikuan , Wei Danping , Liu Feifei , Liu Jing , Wu Xiaoming , Stevens Malcolm F. G. , Bradshaw Tracey D. , Luo Ying , Zhang Jihong 
Published: January 2018

AbstractThe efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6‐methylguanine‐DNA methyltransferase (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8‐methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT‐overexpressing and mismatch repair (MMR)‐deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels. We found that PMX 465 could reduce MGMT expression by increasing the binding of wild‐type p53 to the MGMT promoter and reducing the binding of Sp1 to the MGMT promoter.
Pharmacokinetic Interactions Between Elbasvir/Grazoprevir and Immunosuppressant Drugs in Healthy Volunteers
Authors: Feng Hwa‐Ping , Caro Luzelena , Fandozzi Christine M. , Guo Zifang , Talaty Jennifer , Wolford Dennis , Panebianco Deborah , Iwamoto Marian , Butterton Joan R. , Yeh Wendy W. 
Published: January 2018

AbstractElbasvir (EBR)/grazoprevir (GZR) may be coadministered with immunosuppressant drugs in posttransplant people who are infected with hepatitis C virus. The aim of the present study was to assess the safety and pharmacokinetic interactions between EBR and GZR and single doses of cyclosporine, tacrolimus, mycophenolate mofetil (MMF), and prednisone. This was a 4‐part, open‐label study in 58 healthy volunteers. Participants received single doses of cyclosporine 400 mg, tacrolimus 2 mg, MMF 1 g, or prednisone 40 mg alone or in the presence of once‐daily EBR 50 mg/GZR 200 mg. Multiple oral doses of EBR + GZR had no significant effect on cyclosporine. However, in the presence of cyclosporine, the 24‐hour area under the concentration‐time curve of GZR was increased by approximately 15‐fold (geometric mean ratio [90%CI] 15.21 [12.83; 18.04]); the concentration of EBR was increased approximately 2‐fold in the presence of cyclosporine. Coadministration of EBR/GZR and tacrolimus did not affect the pharmacokinetics of EBR or GZR, but resulted in an increase in tacrolimus AUC (geometric mean ratio [90%CI] 1.43 [1.24; 1.64]). There were no clinically relevant interactions between EBR/GZR and either MMF or prednisone. Data from the present study indicate that EBR/GZR may be coadministered in people receiving tacrolimus, MMF, and prednisolone. EBR/GZR is contraindicated in people receiving cyclosporine because the significantly higher concentrations of GZR may increase the risk of transaminase elevations.
Mycophenolic Acid and Its Metabolites in Kidney Transplant Recipients: A Semimechanistic Enterohepatic Circulation Model to Improve Estimating Exposure
Authors: Okour Malek , Jacobson Pamala A. , Ahmed Mariam A. , Israni Ajay K. , Brundage Richard C. 
Published: January 2018

AbstractMycophenolic acid (MPA) is an approved immunosuppressive agent widely prescribed to prevent rejection after kidney transplantation. Wide between‐subject variability (BSV) in MPA exposure exists which in part may be due to variability in enterohepatic recirculation (EHC). Several modeling strategies were developed to evaluate EHC as part of MPA pharmacokinetics, however mechanistic representation of EHC is limited. These models have not provided a satisfactory representation of the physiology of EHC in their modeling assumptions. The aim of this study was i) to develop an integrated model of MPA (total and unbound) and its metabolites (MPAG and acyl‐MPAG) in kidney recipients, where this model provides a more physiological representation of EHC process, and ii) to evaluate the effect of donor and recipient clinical covariates and genotypes on MPA disposition. A five‐compartment model with first‐order input into an unbound MPA compartment connected to the MPAG, acyl‐MPAG, and gallbladder compartment best fit the data. To represent the EHC process, the model was built based on the physiological concepts related to the hepatobiliary system and the gallbladder filling and emptying processes. The effect of cyclosporine versus tacrolimus on clearance of unbound MPA was included in the base model. Covariate analysis showed creatinine clearance to be significant on oral clearance of unbound MPA. The hepatic nuclear factor 1 alpha (HNF1A) genetic single nucleotide polymorphism (SNP) (rs2393791) in the recipient significantly affected the fraction of enterohepatically‐circulated drug. Oral clearance of MPAG was affected by recipient IMPDH1 SNP (rs2288553), diabetes at the time of transplant, and donor sex.
Eliminating hepatitis C virus as a public health threat among HIV‐positive men who have sex with men: a multi‐modelling approach to understand differences in sexual risk behaviour
Authors: Scott Nick , Stoové Mark , Wilson David P , Keiser Olivia , El‐Hayek Carol , Doyle Joseph , Hellard Margaret 
Published: January 2018

AbstractIntroductionOutbreaks of hepatitis C virus (HCV) infections among HIV‐positive men who have sex with men (MSM) have been observed globally. Using a multi‐modelling approach we estimate the time and number of direct‐acting antiviral treatment courses required to achieve an 80% reduction in HCV prevalence among HIV‐positive MSM in the state of Victoria, Australia.MethodsThree models of HCV transmission, testing and treatment among MSM were compared: a dynamic compartmental model; an agent‐based model (ABM) parametrized to local surveillance and behavioural data (“ABM1”); and an ABM with a more heterogeneous population (“ABM2”) to determine the influence of extreme variations in sexual risk behaviour.ResultsAmong approximately 5000 diagnosed HIV‐positive MSM in Victoria, 10% are co‐infected with HCV. ABM1 estimated that an 80% reduction in HCV prevalence could be achieved in 122 (inter‐quartile range (IQR) 112 to 133) weeks with 523 (IQR 479 to 553) treatments if the average time from HCV diagnosis to treatment was six months. This was reduced to 77 (IQR 69 to 81) weeks if the average time between HCV diagnosis and treatment commencement was decreased to 16 weeks. Estimates were consistent across modelling approaches; however ABM2 produced fewer incident HCV cases, suggesting that treatment‐as‐prevention may be more effective in behaviourally heterogeneous populations.ConclusionsMajor reductions in HCV prevalence can be achieved among HIV‐positive MSM within two years through routine HCV monitoring and prompt treatment as a part of HIV care. Compartmental models constructed with limited behavioural data are likely to produce conservative estimates compared to models of the same setting with more complex parametrizations.
The lesion characteristics assessed by LGE‐MRI after the cryoballoon ablation and conventional radiofrequency ablation
Authors: Kurose Jun , Kiuchi Kunihiko , Fukuzawa Koji , Mori Shumpei , Ichibori Hirotoshi , Konishi Hiroki , Taniguchi Yayoi , Hyogo Kiyohiro , Imada Hiroshi , Suehiro Hideya , Nagamatsu Yu‐ichi , Akita Tomomi , Takemoto Makoto , Hirata Ken‐ichi , Shimoyama Shinsuke , Watanabe Yoshiaki , Nishii Tatsuya , Negi Noriyuki , Kyotani Katsusuke 
Published: January 2018

AbstractBackgroundRhythm outcomes after the pulmonary vein isolation (PVI) using the cryoballoon (CB) are reported to be excellent. However, the lesions after CB ablation have not been well discussed. We sought to characterize and compare the lesion formation after CB ablation with that after radiofrequency (RF) ablation.MethodsA total of 42 consecutive patients who underwent PVI were enrolled (29 in the CB group and 13 in the RF group). The PVI lesions were assessed by late gadolinium enhancement magnetic resonance imaging 1–3 months after the PVI. The region around the PVs was divided into eight segments: roof, anterior‐superior, anterior‐carina, anterior‐inferior, bottom, posterior‐inferior, posterior‐carina, and posterior‐superior segment. The lesion width and lesion gap in each segment were compared between the two groups. Lesion gaps were defined as no‐enhancement sites of >4 mm.ResultsAs compared to the RF group, the overall lesion width was significantly wider and lesion gaps significantly fewer at the anterior‐superior segment of the left PV (LAS) and anterior‐inferior segment of the right PV (RAI) in the CB group (lesion width: 8.2 ± 2.2 mm vs 5.6 ± 2.0 mm, P = .001; lesion gap at LAS: 7% vs 38%, P = .02; lesion gap at RAI: 7% vs 46%, P = .006).ConclusionsThe PVI lesions after CB ablation were characterized by extremely wider and more continuous lesions than those after RF ablation.
Characteristics and intestinal immunomodulating activities of water‐soluble pectic polysaccharides from Chenpi with different storage periods
Authors: Tian Changcheng , Xu Hui , Li Jing , Han Zhuo 
Published: January 2018

AbstractBACKGROUNDThe traditional view considers that Chenpi (dried citrus peel) stored over the long‐term has better health efficacies compared to fresh Chenpi, although the detailed mechanism responsible for this remains obscure.RESULTSThe three water‐soluble pectic polysaccharides (CPP1, CPP5 and CPP10) were obtained from 1‐, 5‐ and 10‐year Chenpi, respectively, and their physicochemical characteristics and intestinal immunomodulating activities were investigated and compared. The results obtained showed that CPP5 and CPP10 demonstrated a lower dynamic viscosity and degree of methylesterification, as well as a higher molecular heterogeneity, compared to CPP1. Monosaccharide composition analysis indicated that CPP1 was composed of arabinose, galacturonic acid and galactose, and a small amount of rhamnose; however, CPP5 and CPP10 consisted of arabinose, galacturonic acid, galactose, glucose and xylose, and a small amount of rhamnose. With the extension of storage period of Chenpi, the content of soluble conjugate phenolic acids increased in the pectic polysaccharide. Furthermore, it was confirmed that the pectic polysaccharides extracted from the 5‐year and 10‐year Chenpi could significantly enhance the proliferation of bone marrow cells via activating the Peyer's patch cells in vitro.CONCLUSIONThe present study demonstrates the differences in the pectic polysaccharides from Chenpi with different storage periods and also confirms that the pectic polysaccharides extracted from Chenpi stored over the long‐term had more significant intestinal activities compared to that obtained from the fresh Chenpi. This phenomenon might partly explain why the Chenpi stored over the long‐term has better healthcare effects. © 2018 Society of Chemical Industry
Determination of phthalate esters in soil using a quick, easy, cheap, effective, rugged, and safe method followed by GC–MS
Authors: Liu Qianjun , Chen Di , Wu Jiyuan , Yin Guangcai , Lin Qintie , Zhang Min , Hu Huawen 
Published: January 2018

AbstractA quick, easy, cheap, effective, rugged, and safe procedure was designed to extract pesticide residues from fruits and vegetables with a high percentage of water. It has not been used extensively for the extraction of phthalate esters from sediments, soils, and sludges. In this work, this procedure was combined with gas chromatography with mass spectrometry to determine 16 selected phthalate esters in soil. The extraction efficiency of the samples was improved by ultrasonic extraction and dissolution of the soil samples in ultra‐pure water, which promoted the dispersion of the samples. Furthermore, we have simplified the extraction step and reduced the risk of organic solvent contamination by minimizing the use of organic solvents. Different extraction solvents and clean‐up adsorbents were compared to optimize the procedure. Dichloromethane/n‐hexane (1:1, v/v) and n‐hexane/acetone (1:1, v/v) were selected as the extractants from the six extraction solvents tested. C18/primary secondary amine (1:1, m/m) was selected as the sorbent from the five clean‐up adsorbents tested. The recoveries from the spiked soils ranged from 70.00 to 117.90% with relative standard deviation values of 0.67–4.62%. The proposed approach was satisfactorily applied for the determination of phthalate esters in 12 contaminated soil samples.