bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postpartum psychoactive substance abuse after severe maternal morbidity
Authors: Pereira Cynara M. , Pacagnella Rodolfo C. , Parpinelli Mary A. , Andreucci Carla B. , Zanardi Dulce M. , Souza Renato T. , Angelini Carina R. , Silveira Carla , Cecatti José G. 
Published: September 2019

AbstractObjectiveTo evaluate drug use among mothers during the postpartum period after a severe pregnancy‐related complication.MethodsA retrospective cohort study of maternal morbidity including maternal near‐miss and control groups conducted in a tertiary hospital in Campinas, Brazil, between July 2008 and June 2012. The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was used to assess drug use during lifetime, pregnancy, and in the previous 3 months.ResultsOf 638 women evaluated, drug use was reported by 165 (25.8%). Alcohol was the most common substance used (n=133, 20.6%), followed by tobacco (n=85, 13.2%), and cocaine (n=15, 2.3%). The highest risk for postpartum drug use was among those using drugs during pregnancy. There were no differences between the morbidity and control groups, but there was a significant difference in the need for intervention to reduce alcohol consumption in the severe maternal morbidity group. Risk for substance abuse intervention increased three‐fold in women with PTSD criteria, and all aspects of quality of life were worse among drug users.ConclusionDrug use during pregnancy and maternal complications are linked to postpartum drug abuse. These women should be managed during pregnancy; postpartum follow‐up requires updated guidance and must go beyond family planning.
Screening of significant biomarkers related with prognosis of liver cancer by lncRNA‐associated ceRNAs analysis
Authors: He Jiefeng , Zhao Haichao , Deng Dongfeng , Wang Yadong , Zhang Xiao , Zhao Haoliang , Xu Zongquan 
Published: September 2019

AbstractThis study aimed to identify significant biomarkers related to the prognosis of liver cancer using long noncoding RNA (lncRNA)‐associated competing endogenous RNAs (ceRNAs) analysis. Differentially expressed mRNA and lncRNAs between liver cancer and paracancerous tissues were screened, and the functions of these mRNAs were predicted by gene ontology and pathway enrichment analyses. A ceRNA network consisting of differentially expressed mRNAs and lncRNAs was constructed. LncRNAFENDRRand lncRNAHAND2‐AS1were hub nodes in the ceRNA network. A risk score assessment model consisting of eight genes (PDE2A, ESR1, FBLN5, ALDH8A1, AKR1D1, EHHADH, ADRA1A, andGNE) associated with prognosis were developed. Multivariate Cox regression suggested that both pathologic_T and risk group could be regarded as independent prognostic factors. Furthermore, a nomogram model consisting of pathologic_T and risk group showed a good prediction ability for predicting the survival rate of liver cancer patients. The nomogram model consisting of pathologic_T and a risk score assessment model could be regarded as an independent factor for predicting prognosis of liver cancer.
Microvesicles promote megakaryopoiesis by regulating DNA methyltransferase and methylation of Notch1 promoter
Authors: Chattapadhyaya Saran , Haldar Srijan , Banerjee Subrata 
Published: September 2019

AbstractMegakaryopoiesis is the process of formation of mature megakaryocytes that takes place in the bone marrow niche resulting in the release of platelets into the peripheral blood. It has been suggested that cell to cell communication in this dense bone marrow niche may influence the fate of the cells. Numerous studies point to the role of exosomes and microvesicles not only as a messenger of the cellular crosstalk but also in growth and developmental process of various cell types. In the current study, we explored the effects of megakaryocyte‐derived microvesicles in hematopoietic cell lines in the context of differentiation. Our study demonstrated that microvesicles isolated from the induced megakaryocytic cell lines have the ability to stimulate noninduced cells specifically into that particular lineage. We showed that this lineage commencement comes from the change in the methylation status of Notch1 promoter, which is regulated by DNA methyltransferases.
Ontogeny of Phase I Metabolism of Drugs
Authors: Allegaert Karel , van den Anker John 
Published: September 2019

AbstractCapturing ontogeny of enzymes involved in phase I metabolism is crucial to improve prediction of dose‐concentration and concentration‐effect relationships throughout infancy and childhood. Once captured, these patterns can be integrated in semiphysiologically or physiology‐based pharmacokinetic models to support predictions in specific pediatric settings or to support pediatric drug development. Although these translational efforts are crucial, isoenzyme‐specific ontogeny‐based models should also incorporate data on variability of maturational and nonmaturational covariates (eg, disease, treatment modalities, pharmacogenetics). Therefore, this review provides a summary of the ontogeny of phase I drug‐metabolizing enzymes, indicating current knowledge gaps and recent progresses. Furthermore, we tried to illustrate that straightforward translation of isoenzyme‐specific ontogeny to predictions does not allow full exploration of scenarios of potential variability related to maturational (non–age‐related variability, other isoenzymes or transporters) or nonmaturational (disease, pharmacogenetics) covariates, and necessitates integration in a “systems” concept.
Pediatric Renal Ontogeny and Applications in Drug Development
Authors: Zhang Yifei , Mehta Neha , Muhari‐Stark Edit , Burckart Gilbert J. , van den Anker John , Wang Jian 
Published: September 2019

AbstractThe clinical applications of renal ontogeny mainly include renal function evaluation and optimal dosing of renally eliminated drugs in pediatric patients, which rely on pharmacometric models and/or bedside estimated glomerular filtration rate equations. However, these applications in drug development are based on an understanding of renal function development, especially when considering premature infants, and the renal biomarkers that can be used for renal function assessment. This review provides a general overview on (1) renal function development, (2) the biomarkers that are used to assess renal function, and (3) the practical application of this knowledge to drug dosing for renally eliminated drugs during pediatric development. While pharmacometric approaches for estimating renal function during development have improved considerably, the number of drug development programs that have studied premature infants is small and suggests that caution should be taken in estimating doses for renally eliminated drugs during periods of rapid change in renal function.
Characterization of the Ontogeny of Hepatic UDP‐Glucuronosyltransferase Enzymes Based on Glucuronidation Activity Measured in Human Liver Microsomes
Authors: Badée Justine , Qiu Nahong , Collier Abby C. , Takahashi Ryan H. , Forrest William F. , Parrott Neil , Schmidt Stephan , Fowler Stephen 
Published: September 2019

AbstractAn understanding of the postnatal development of hepatic UDP‐glucuronosyltransferase (UGT) enzymes is required for accurate prediction of the age‐dependent changes in pharmacokinetics of many drugs used in children. However, the maturation rate of hepatic UGT isoforms remains a major knowledge gap. This study aimed to establish the age‐associated changes in glucuronidation activity of 10 major hepatic UGT isoforms in humans, namely, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17. Human liver microsomes from pediatric and adult donors were incubated under optimized incubation conditions to assess the activity rates of hepatic UGT isoforms using a panel of 19 in vitro UGT probe substrates and clinically used drugs. Statistically strong correlations of glucuronidation activities allowed the ontogeny of UGT1A1, UGT1A4, UGT2B7, UGT2B10, and UGT2B15 to be established using multiple selective UGT substrates and matched human liver microsome samples. The postnatal development of hepatic UGTs is isoform‐dependent using either individual or cross‐correlated selective isoform substrates. Maximal adult activity was reached at different times ranging from within a month (UGT1A1, UGT2B4, UGT2B7, UGT2B10, and UGT2B15), during infancy (UGT1A3, UGT1A4, and UGT1A9), to adolescence (UGT1A6 and UGT2B17). This study provides an extensive characterization of the postnatal ontogeny profiles of hepatic UGT enzymes that are instrumental for predicting drug disposition via in vitro–in vivo extrapolation algorithms and verifying pharmacokinetic predictions against in vivo observations via pediatric physiologically based pharmacokinetic modeling in pediatric patients.
Predictive Pediatric Modeling and Simulation Using Ontogeny Information
Authors: Ince Ibrahim , Solodenko Juri , Frechen Sebastian , Dallmann André , Niederalt Christoph , Schlender Jan , Burghaus Rolf , Lippert Jörg , Willmann Stefan 
Published: September 2019

AbstractFood and Drug Administration submissions of physiologically based pharmacokinetic (PBPK) modeling and simulation of small‐molecule drugs document the relevance of pediatric drug development and, in particular, information on dosing strategies in children. The most relevant prerequisite for reliable PBPK‐based translation of adult pharmacokinetics of a small molecule to children is knowledge of the drug‐specific absorption, distribution, metabolism, and elimination (ADME) processes in adults together with existing information about ontogeny of ADME processes relevant for the drug. All mechanisms driving a drug's clearance are of specific importance. For other drug modalities, our knowledge of ADME processes and ontogeny is still limited. More research is required, for example, to understand why some therapeutic proteins show complex differences in pharmacokinetics between adults and children, whereas other proteins seem to follow simple allometric scaling rules. Ontogeny information originates from various sources, such as (semi)quantitative mRNA expression, in vitro activity data, and deconvolution of in vivo pharmacokinetic data. The workflow for pediatric predictions is well described in several articles documenting successful translation from adults to children. The technical hurdles for PBPK modeling are low. State‐of‐the‐art PBPK modeling software tools provide integrated pediatric translation workflows. For example, PK‐Sim and MoBi are freely available as fully transparent open‐source software via Open Systems Pharmacology (OSP). With the latest 2019 software release, version 8.0, OSP even provides a fully integrated technical framework for the qualification (and requalification) of any specific intended PBPK use in line with Food and Drug Administration and European Medicines Agency PBPK guidance. Qualification packages for pediatric translation are available on the OSP platform.
Severe fever with thrombocytopenia syndrome complicated with subdural hematoma: A rare case and literature review
Authors: Endo Takeshi , Yamamoto Norio , Inoue Shinichiro , Yoshikane Tsutomu , Fujisawa Naoki , Imada Toshihiro , Hattori Shuzo 
Published: September 2019

AbstractA 79‐year‐old woman presented with fever and general malaise. Examination revealed hepatic injury, thrombocytopenia, skin lesions, and regional lymphadenopathy; severe fever with thrombocytopenia syndrome (SFTS) was diagnosed using polymerase chain reaction. The patient developed impaired consciousness that worsened after 4 days. Magnetic resonance imaging of the head revealed a subdural hematoma in the occipital region with an uncertain onset time. As SFTS rarely causes intracranial hemorrhage, the associated risk factors are unknown. Clinicians may overlook potential intracranial hemorrhage in stuporous SFTS patients.
Enteric tube placement in patients with esophageal varices: Risks and predictors of postinsertion gastrointestinal bleeding
Authors: Al‐Obaid Lolwa N , Bazarbashi Ahmad Najdat , Cohen Margot E. , Kim Judith , Lei Yuxiu , Axelrad Jordan E. , Fox Alyson , Chandra Subani , Gordon Fredric D. 
Published: September 2019

Background and AimEnteric tube (ET) placement is approached with caution in patients with esophageal varices (EV) due to concern of causing variceal bleeding. Data are limited on rates and predictors of gastrointestinal bleeding (GIB) in these patients. This study aims to assess the rate and predictors of bleeding from EV after ET placement.MethodsWe performed a retrospective chart review on patients requiring ET access with known EV. Inclusion criteria were age >18 with endoscopically proven EV who required ET placement. Patients who were admitted with, or developed a GIB prior to placement of ET were excluded, as were patients admitted for liver transplantation. Primary outcome was incidence of GIB within 48 h of tube placement. Secondary outcome was a >2 g/dL drop in hemoglobin within 48 h of placement without evidence of bleed. Statistical analysis was performed using Fischer's exact test, Mann–Whitney U test, and univariate logistic regression model.ResultsA total of 75 patients were included in the analysis. The most common etiology of cirrhosis was alcohol (44%). The most common location of EV was in the lower third of the esophagus (61%). The primary outcome was observed in 11 (14.6%) patients. The secondary outcome was found in eight (10.6%) patients. On univariate analysis, GIB was associated with higher MELD‐Na (P = 0.026) and EV located in the lower third of the esophagus (P = 0.048).ConclusionET placement in patients with EV is associated with low risk of bleeding. Elevated MELD‐Na and lower EV location conferred a higher risk of bleeding after ET placement.
Exclusive enteral nutrition: An optimal care pathway for use in adult patients with active Crohn's disease
Authors: Day Alice , Wood Jessica , Melton Sarah , Bryant Robert V 
Published: September 2019

Background and AimExclusive enteral nutrition (EEN) is progressively being used as a therapeutic option for adults with Crohn's Disease (CD); however, there is no standardized approach to delivering this therapy. The aim of this study is to develop an optimal care pathway for using EEN in adults with CD. This will create a standard of care that can be used as a benchmark practice and will provide direction for future research.MethodsA working group of 12 multidisciplinary inflammatory bowel disease specialists across Australia and New Zealand was convened to develop a practical, clinically focused care pathway for using EEN in adults with active CD. Six key areas were identified as part of the care pathway: clinical indications, nutrition assessment, EEN protocol, monitoring, accessing formula, and food reintroduction. Current literature was identified via systematic review, and quality of evidence was graded. Consensus expert opinion was used where literature gaps were identified.ResultsAn optimal care pathway for using EEN in adults with CD was developed with six key consensus statements on how to use EEN in adults with active CD. These key statements identify clinical indications for use, nutrition assessment, enteral prescription and duration of therapy, monitoring criteria, food reintroduction, and the role of partial EEN. An accompanying patient resource was also developed.ConclusionEEN is recommended as a treatment option to induce remission in adults with active CD. The consensus statements developed are practical and are based on best available evidence and expert opinion to assist in developing a standardized approach to delivering EEN therapy.
Early neurodevelopmental characterization in children with cobalamin C/defect
Authors: Ricci Daniela , Martinelli Diego , Ferrantini Gloria , Lucibello Simona , Gambardella MLuigia , Olivieri Giorgia , Chieffo Daniela , Battaglia Domenica , Diodato Daria , Iarossi Giancarlo , Donati Alice M. , Dionisi‐Vici Carlo , Battini Roberta , Mercuri Eugenio M. 
Published: September 2019

AbstractCobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism. Developmental delay, behavioral problems, and maculopathy are common, but they have not been systematically investigated. The aim of this study was to define early neurodevelopment in cblC patients and the possible contribution of different factors, such as mode of diagnosis, age at diagnosis, presence of brain lesions and epilepsy. Children up to the age of 4 years with a visual acuity ≥1/10 were evaluated using the Griffiths' Mental Development Scales. Eighteen children were enrolled (age range 12‐48 months). Four were diagnosed by newborn screening (NBS); in the others mean age at diagnosis was 3.5 months (range 0.3‐18 months). Eight had seizures: three in the first year, and five after the second year of life. Fourteen had brain lesions on magnetic resonance imaging (MRI). Neurovisual assessment evidenced low visual acuity (<3/10) in 4/18. NBS diagnosed patients had higher general and subquotients neurodevelopmental scores, normal brain MRI, and no epilepsy. The others showed a progressive reduction of the developmental quotient with age and language impairment, which was evident after 24 months of age. Our findings showed a progressive neurodevelopmental deterioration and a specific fall in language development after 24 months in cblC defect. The presence of brain lesions and epilepsy was associated with a worst neurodevelopmental outcome. NBS, avoiding major disease‐related events and allowing an earlier treatment initiation, appeared to have a protective effect on the development of brain lesions and to promote a more favorable neurodevelopment.
Cofilin, an intracellular marker for HIV‐associated CD4 T‐cell motility dysregulation, shed light on the mechanisms of incomplete immune reconstitution in the patients with HIV
Authors: Syed Fahim , Yu Qigui 
Published: September 2019

Highlights

People living with HIV do not achieve an optional immune reconstitution despite the sustained virologic suppression.
Circulating CD4 T cells fail to replenish their lymphoid tissue counterparts in people living with HIV.
Irrespective of ART, coffin hyperactivation and impaired T cell mobility persist in people living with HIV.
Cofilin may represent a novel therapeutic target to restore T cell mobility in people living with HIV.
Why are vaccines against many human viral diseases still unavailable; an historic perspective?
Authors: Tannock Gregory A. , Kim Hyunsuh , Xue Lumin 
Published: September 2019

AbstractThe number of new and improved human viral vaccines licensed in recent years contrasts sharply with what could be termed the golden era (1955‐1990) when vaccines against polio‐, measles, mumps, rubella, and hepatitis B viruses first became available. Here, we attempt to explain why vaccines, mainly against viruses other than human immunodeficiency virus and hepatitis C virus, are still unavailable. They include human herpesviruses other than varicella‐zoster virus, respiratory syncytial and most other respiratory, enteric and arthropod‐borne viruses. Improved oral poliovirus vaccines are also urgently required. Their unavailability is attributable to regulatory/economic factors and the properties of individual viruses, but also to an absence of relevant animal models and ethical problems for the conduct of clinical of trials in pediatric and other critical populations. All are portents of likely difficulties for the licensing of effective vaccines against emerging pathogens, such as avian influenza, Ebola, and Zika viruses.
Using periodontal staging and grading system as a prognostic factor for future tooth loss: A long‐term retrospective study
Authors: Ravidà Andrea , Qazi Musa , Troiano Giuseppe , Saleh Muhammad H. A. , Greenwell Henry , Kornman Kenneth , Wang Hom‐Lay 
Published: September 2019

AbstractBackgroundA new classification of periodontal diseases aimed to identify periodontal disease based on a multidimensional staging and grading system has been recently proposed. However, up to date, its prognostic predictive capability has not been investigated. The aim of this study was to assess if parameters included in the new classification were predictive of tooth loss after a long‐term follow‐up (>10 years) in patients with periodontitis.MethodsPatients presented with periodontitis at the University of Michigan between January 1966 and January 2004 were screened and categorized according to the new classification of periodontitis. Number/Reasons of teeth loss in patients who underwent at least one session/year of maintenance during the entire follow‐up period were extracted and used to analyze the prognostic capabilities of variables (staging, grading, and Extent) included in the new classification.ResultsA total number of 292 patients with a mean follow‐up of 289.7 ± 79.6 months were included. 31 (10.6%) patients were classified as Stage 1, 85 (29.1%) as Stage 2, 146 (50%) as Stage 3, and 30 (10.3%) as Stage 4. For grading, 34 (11.7%) were classified as Grade A, 193 (66.1%) as Grade B, and 65 (22.2%) as Grade C. Results of multilevel Cox regression analyses revealed a statistically significant association between stage (HR:3.73 between Stage 4 and Stage 1) and grade (HR: 4.83 between Grade C and Grade A) at baseline and periodontal related tooth loss, whereas no differences were detected for the extent of periodontitis.ConclusionThis study provides the initial evidence regarding the predictive ability of the new classification of periodontitis. Patients in either Stage 4 or Grade C showed a significantly higher periodontal‐related tooth loss.
Helical Blood Flow in Hemodynamically Significant Carotid Stenosis
Authors: Kirsanov Roman Ivanovich , Kulikov Vladimir Pavlovich 
Published: September 2019

ObjectivesTo define helical blood flow (HBF) characteristics in hemodynamically significant atherosclerotic stenosis of the internal carotid artery (ICA) by means of duplex scanning.MethodsTwenty‐five hemodynamically significant (65.0% [range, 63.0%–69.0%]) carotid stenoses were examined in 23 patients. The severity of the stenosis was calculated by the European Carotid Surgery Trial grading method by transverse section scanning in the B‐mode. Rotational components were estimated in color flow mapping by transverse‐section scanning of a vessel at the most narrowed site, as well as in the prestenotic and poststenotic segments. A quantitative evaluation of HBF was performed on the basis of pulsed wave Doppler imaging of longitudinal and transverse sections of the arterial lumen.ResultsHelical blood flow was most often (68%) registered in the poststenotic segment of the ICA as a single vortex (52%) or double vortices (16%). At the most narrowed site, HBF was registered in 48% of the cases (44% single vortex and 4% double vortices), whereas in the prestenotic segment of the blood vessel, it was registered in only 16% of the cases (8% single vortex and 8% double vortices). The time‐averaged maximum blood flow velocities at the most narrowed site were 88.5 cm/s (25th–75th percentiles, 73.8‐127.8 cm/s) for the axial component and 33.1 cm/s (22.7–40.9 cm/s) for the rotational component. The calculated summary velocity of motion of the blood particles in helical paths was 92.2 cm/s (75.7–144.2 cm/s).ConclusionsIt has been shown that HBF can be registered by Doppler ultrasound in atherosclerotic stenosis, and its registration rate increases while passing through the narrowed segment of the ICA.
Parametric nonlinear resonant Robin problems
Authors: Papageorgiou Nikolaos S. , Rădulescu Vicenţiu D. , Repovš Dušan D. 
Published: September 2019

AbstractWe consider a nonlinear Robin problem driven by the p‐Laplacian. In the reaction we have the competing effects of two nonlinearities. One term is parametric, strictly ‐sublinear and the other one is ‐linear and resonant at any nonprincipal variational eigenvalue. Using variational tools from the critical theory (critical groups), we show that for all big values of the parameter λ the problem has at least five nontrivial smooth solutions.