bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR mutations in early‐stage and advanced‐stage lung adenocarcinoma: Analysis based on large‐scale data from China
Authors: Pi Can , Xu Chong‐Rui , Zhang Ming‐feng , Peng Xiao‐xiao , Wei Xue‐wu , Gao Xing , Yan Hong‐Hong , Zhou Qing 
Published: May 2018

BackgroundEGFR‐tyrosine kinase inhibitors play an important role in the treatment of advanced non‐small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early‐stage lung adenocarcinoma remain unclear.MethodsWe retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA–IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition.ResultsA total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early‐stage and 949 to the advanced‐stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced‐stage group (P < 0.001). The total EGFR mutation rate in the early‐stage group was similar to that in the advanced‐stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early‐stage and advanced‐stage groups.ConclusionEarly‐stage and advanced‐stage groups exhibited the same EGFR mutation frequencies and types.
Parabens generate reactive oxygen species in human spermatozoa
Authors: Samarasinghe S. V. A. C. , Krishnan K. , Naidu R. , Megharaj M. , Miller K. , Fraser B. , Aitken R. J. 
Published: May 2018

SummaryParabens are used as antimicrobial preservative agent in many commercial products including cosmetics and pharmaceuticals. Weak oestrogenic and antiandrogenic activities have been attributed to parabens in in vitro and in vivo studies. In this study, human spermatozoa were exposed to different concentrations of an equimolar paraben mixture containing methyl, ethyl, propyl and butylparaben as well as to methylparaben alone at a concentration that is typical of commercially available vaginal lubricants. The induction of oxidative stress and DNA damage was then assessed at different time points. Our results demonstrate that the paraben mixture was capable of stimulating the generation of mitochondrial and cytosolic reactive oxygen species (ROS), inhibiting sperm motility and viability in a dose‐dependent manner. The ability of individual parabens to activate ROS generation and induce oxidative DNA damage was related to alkyl chain length. At the concentration used clinically, methylparaben inhibited sperm motility after both 2 and 5 h exposure (p < 0.05) and affected cell viability (p < 0.01) while augmenting ROS production and oxidative DNA damage. However, DNA fragmentation was not evident following methylparaben exposure. Based on these results, we conclude that, at the concentrations used in commercially available formulations, parabens may impair sperm motility, enhance the generation of mitochondrial ROS and stimulate the formation of oxidative DNA adducts. Taken together, these data underline the potential cytotoxic and genotoxic impact of such compounds in a clinical setting.
Neonatologists can impede or support parents’ participation in decision‐making during medical rounds in neonatal intensive care units
Authors: Axelin Anna , Outinen Jyri , Lainema Kirsi , Lehtonen Liisa , Franck Linda S. 
Published: May 2018

AbstractAimWe explored the dynamics of neonatologist–parent communication and decision‐making during medical rounds in a level three neonatal intensive care unit.MethodsThis was a qualitative study, with an ethnographic approach, that was conducted at Turku University Hospital, Finland, from 2013 to 2014. We recruited eight mothers and seven couples, their 11 singletons and four sets of twins and two neonatologists and observed and video recorded 15 medical rounds. The infants were born at 23 + 5 to 40 + 1 weeks, and the parents were aged 24–47. The neonatologists and parents were interviewed separately after the rounds.ResultsFour patterns of interaction emerged. The collaborative pattern was most consistent, with the ideal of shared decision‐making, as the parents’ preferences were genuinely and visibly integrated into the treatment decisions. In the neonatologist‐led interactional pattern, the decision‐making process was only somewhat inclusive of the parents’ observations and preferences. The remaining two patterns, emergency and disconnected, were characterised by a paternalistic decision‐making model where the parents’ observations and preferences had minimal to no influence on the communication or decision‐making.ConclusionThe neonatologists played a central role in facilitating parental participation and their interaction during medical rounds were characterised by the level of parent participation in decision‐making.
Placentophagy among women planning community births in the United States: Frequency, rationale, and associated neonatal outcomes
Authors: Benyshek Daniel C. , Cheyney Melissa , Brown Jennifer , Bovbjerg Marit L. 
Published: May 2018

AbstractBackgroundLimited systematic research on maternal placentophagy is available to maternity care providers whose clients/patients may be considering this increasingly popular practice. Our purpose was to characterize the practice of placentophagy and its attendant neonatal outcomes among a large sample of women in the United States.MethodsWe used a medical records–based data set (n = 23 242) containing pregnancy, birth, and postpartum information for women who planned community births. We used logistic regression to determine demographic and clinical predictors of placentophagy. Finally, we compared neonatal outcomes (hospitalization, neonatal intensive unit admission, or neonatal death in the first 6 weeks) between placenta consumers and nonconsumers, and participants who consumed placenta raw vs cooked.ResultsNearly one‐third (30.8%) of women consumed their placenta. Consumers were more likely to have reported pregravid anxiety or depression compared with nonconsumers. Most (85.3%) placentophagic mothers consumed their placentas in encapsulated form, and nearly half (48.4%) consumed capsules containing dehydrated, uncooked placenta. Placentophagy was not associated with any adverse neonatal outcomes. Women with home births were more likely to engage in placentophagy than women with birth center births. The most common reason given (73.1%) for engaging in placentophagy was to prevent postpartum depression. [Corrections added on 16 May 2018, after first online publication: The percentage values in the Results sections were updated.]ConclusionsThe majority of women consumed their placentas in uncooked/encapsulated form and hoping to avoid postpartum depression, although no evidence currently exists to support this strategy. Preparation technique (cooked vs uncooked) did not influence adverse neonatal outcomes. Maternity care providers should discuss the range of options available to prevent/treat postpartum depression, in addition to current evidence with respect to the safety of placentophagy.
A 1286‐year hydro‐climate reconstruction for the Balkan Peninsula
Authors: Klippel Lara , Krusic Paul J. , Brandes Robert , Hartl Claudia , Belmecheri Soumaya , Dienst Manuel , Esper Jan 
Published: May 2018

We present a June–July drought reconstruction based on the standardized precipitation index (SPI) for the Balkan Peninsula over the period 730–2015 CE. The reconstruction is developed using a composite Pinus heldreichii tree‐ring width chronology, from a high‐elevation network of eight sites in the Pindus Mountains in northwest Greece, composed of living trees and relict wood. The dataset includes the ring width series of Europe's currently oldest known living tree, dendrochronologically dated to be more than 1075 years old. The spatial coverage of the reconstruction is improved by using an averaged gridded SPI data target derived from a response field that is located north of the study region. Justification for this approach includes the remoteness of instrumental data, the spatial variability of precipitation and synoptic scale circulation patterns. Over the past 1286 years, there have been 51 dry and 43 pluvial events. The driest year during the 1286‐year‐long period was 1660 and the wettest year was 1482. Comparison with shorter reconstructions and documentary evidence validates the new reconstruction, and provides additional insight into socioeconomic impacts and spatial patterns of extreme events. Fifty‐nine of 72 previously undescribed extremes occurred prior to the 17th century. The new reconstruction reveals long‐term changes in the number of extremes, including substantially fewer drought and pluvial events in the 20th century. Additional tests on the long‐term effects of age structure, replication and covariance changes support the heteroscedastic nature of the reconstructed hydro‐climatic extremes.
Pathogenic variants in theABCC6gene are associated with an increased risk for ischemic stroke
Authors: De Vilder Eva Y.G. , Cardoen Stefanie , Hosen Mohammad J. , Le Saux Olivier , De Zaeytijd Julie , Leroy Bart P. , De Reuck Jacques , Coucke Paul J. , De Paepe Anne , Hemelsoet Dimitri , Vanakker Olivier M. 
Published: May 2018

AbstractIschemic stroke causes a high mortality and morbidity worldwide. It results from a complex interplay of incompletely known environmental and genetic risk factors. We investigated theABCC6gene as a candidate risk factor for ischemic stroke because of the increased ischemic stroke incidence in the autosomal recessive disorder pseudoxanthoma elasticum, caused by biallelic pathogenicABCC6variants, the higher cardiovascular risk in heterozygous carriers and the established role ofABCC6dysfunction in myocardial ischemia. We established segregation of a known pathogenicABCC6variant (p.[Arg1314Gln]) in 11/19 family members of an ischemic stroke patient in a large multigenerational family suffering from ischemic stroke and/or cardiovascular disease at a relatively young age. In an independent case‐control study in 424 ischemic stroke patients and 250 healthy controls, pathogenicABCC6variants were 4.9 times more frequent (P= 0.036; 95% CI 1.11–21.33) in the ischemic stroke patient cohort. To study cellular consequences ofABCC6deficiency in the brain, immunostaining of brain sections inAbcc6‐deficient mice and wild‐type controls were performed. An upregulation of Bmp4 and Eng and a downregulation of Alk2 was identified inAbcc6−/− mice, suggesting an increase in apoptosis and angiogenesis. As both of these processes are induced in ischemia, we propose that a pro‐ischemic state may explain the higher risk to suffer from ischemic stroke in patients carrying a pathogenicABCC6variant, as this may lower the threshold to develop acute ischemic events in these patients. In conclusion, this study identified heterozygousABCC6variants as a risk factor for ischemic stroke. Further, dysregulation of Bmp (Bmp4, Alk2) and Tgfβ (Eng) signaling in the brain ofAbcc6−/− mice could lead to a pro‐ischemic state, lowering the threshold to develop acute ischemic events. These data demonstrate the importance of a molecular analysis of theABCC6gene in patients diagnosed with cryptogenic ischemic stroke.
Cigarette smoke up‐regulates PDE3 and PDE4 to decrease cAMP in airway cells
Authors: Zuo Haoxiao , Han Bing , Poppinga Wilfred J , Ringnalda Lennard , Kistemaker Loes E M , Halayko Andrew J , Gosens Reinoud , Nikolaev Viacheslav O , Schmidt Martina 
Published: May 2018

Background and PurposecAMP is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease, a lung disease primarily provoked by cigarette smoke (CS), the activation of cAMP‐dependent pathways, via inhibition of hydrolyzing PDEs, is a major therapeutic strategy. Mechanisms that disrupt cAMP signalling in airway cells, in particular regulation of endogenous PDEs, are poorly understood.Experimental ApproachWe used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mice in vivo, ex vivo precision cut lung slices (PCLS) and in human cell models, in vitro, to track the effects of CS exposure.Key ResultsUnder fenoterol stimulation, FRET responses to cilostamide were significantly increased in in vivo, ex vivo PCLS exposed to CS and in human airway smooth muscle cells exposed to CS extract. FRET signals to rolipram were only increased in the in vivo CS model. Under basal conditions, FRET responses to cilostamide and rolipram were significantly increased in in vivo, ex vivo PCLS exposed to CS. Elevated FRET signals to rolipram correlated with a protein up‐regulation of PDE4 subtypes. In ex vivo PCLS exposed to CS extract, rolipram reversed down‐regulation of ciliary beating frequency, whereas only cilostamide significantly increased airway relaxation of methacholine pre‐contracted airways.Conclusion and ImplicationsExposure to CS, in vitro or in vivo, up‐regulated expression and activity of both PDE3 and PDE4, which affected real‐time cAMP dynamics. These mechanisms determine the availability of cAMP and can contribute to CS‐induced pulmonary pathophysiology.
Tolerance to high‐internalizing δ opioid receptor agonist is critically mediated by arrestin 2
Authors: Vicente‐Sanchez Ana , Dripps Isaac J , Tipton Alycia F , Akbari Heba , Akbari Areeb , Jutkiewicz Emily M , Pradhan Amynah A 
Published: May 2018

Background and PurposeOpioid δ receptor agonists are potent antihyperalgesics in chronic pain models, but tolerance develops after prolonged use. Previous evidence indicates that distinct forms of tolerance occur depending on the internalization properties of δ receptor agonists. As arrestins are important in receptor internalization, we investigated the role of arrestin 2 (β‐arrestin 1) in mediating the development of tolerance induced by high‐ and low‐internalizing δ receptor agonists.Experimental ApproachWe evaluated the effect of two δ receptor agonists with similar analgesic potencies, but either high‐(SNC80) or low‐(ARM390) internalization properties in wild‐type (WT) and arrestin 2 knockout (KO) mice. We compared tolerance to the antihyperalgesic effects of these compounds in a model of inflammatory pain. We also examined tolerance to the convulsant effect of SNC80. Furthermore, effect of chronic treatment with SNC80 on δ agonist‐stimulated [35S]‐GTPγS binding was determined in WT and KO mice.Key ResultsArrestin 2 KO resulted in increased drug potency, duration of action and decreased acute tolerance to the antihyperalgesic effects of SNC80. In contrast, ARM390 produced similar effects in both WT and KO animals. Following chronic treatment, we found a marked decrease in the extent of tolerance to SNC80‐induced antihyperalgesia and convulsions in arrestin 2 KO mice. Accordingly, δ receptors remained functionally coupled to G proteins in arrestin 2 KO mice chronically treated with SNC80.Conclusions and ImplicationsOverall, these results suggest that δ receptor agonists interact with arrestins in a ligand‐specific manner, and tolerance to high‐ but not low‐internalizing agonists are preferentially regulated by arrestin 2.
Administration of Cripto in GRP78 overexpressed human MSCs enhances stem cell viability and angiogenesis during human MSC transplantation therapy
Authors: Kim S. , Yoon Y.M. , Han Y.‐S. , Lee J. H. , Hur J. , Lee S. H. 
Published: May 2018

AbstractObjectivesThe purpose of this study was to explore the effectiveness of concurrent GRP78 overexpression combined with Cripto on hMSC proliferation and migration both in vitro and in vivo. Specifically, we explored whether the treatment enhances effectiveness of hMSC transplantation in ischaemic tissue.Materials and methodsHuman MSCs obtained from human adipose tissue were cultured in α‐minimum essential medium (Hyclone, Logan, UT, USA) supplemented with 10% (v/v) foetal bovine serum (Hyclone), 100 U mL−1 penicillin and 100 μg mL−1 streptomycin. Murine hindlimb ischaemic model was generated with 8‐week‐old male nude BALB/c mice (Biogenomics, Seoul, Korea) maintained under a 12‐h light/dark cycle following the established protocol with minor modification. Cellular injection was performed no later than 3 hour after surgery. Lipofectamine transfection, single‐cell cultivation assay, transwell assay, scratch wound‐healing migration assay, immunohistochemistry and western blotting assays were performed.ResultsOverexpression of GRP78 along with Cripto enhanced hMSC proliferation, migration and invasion. It increased interaction of surface GRP78 receptor with Cripto via JAK2/STAT3 pathway. We confirmed our proposed mechanism by showing that treatment with GRP78 antibody blocks the enhancement in vitro. In vivo, we observed that Cripto induced by the hypoxic environment in hindlimb ischaemic model interacts with the overexpressed GRP78 and increases hMSC proliferation, migration and invasion potentials as well as angiogenesis around transplanted ischaemic site via cytokine secretions.ConclusionsThese results demonstrate supporting evidences that GRP78‐Cripto combination technique offers novel strategy to enhance MSC proliferation, migration and invasion potentials as well as angiogenesis around ischaemic site, ultimately facilitating MSC‐based transplantation therapy in ischaemic conditions.
SurePath® LBC improves the diagnostic accuracy of intrahepatic and hilar cholangiocarcinoma
Authors: Naito Y. , Kawahara A. , Okabe Y. , Ishida Y. , Sadashima E. , Murata K. , Takase Y. , Abe H. , Yamaguchi T. , Tanigawa M. , Mihara Y. , Kondo R. , Kusano H. , Nakayama M. , Shimamatsu K. , Yano H. , Akiba J. 
Published: May 2018

IntroductionThe current study aimed to compare cytology using SurePath® (SP)‐LBC and biliary tissue histology (BTH) for the diagnosis of biliary disease.MethodsBetween January 2014 and December 2016, 57 patients underwent endoscopic retrograde cholangiopancreatography for the diagnosis of biliary disease. Biliary cytological samples were processed using SP‐LBC and subsequently BTH was performed. A final diagnosis was confirmed by surgery (23 malignant cases) and clinical follow‐up (34 benign and malignant cases): 18 extrahepatic cholangiocarcinoma; 17 intrahepatic/hilar cholangiocarcinoma (intra/H‐CC); eight other malignant disease; and 14 benign biliary disease. The diagnoses made using SP‐LBC and BTH were classified into four categories: (1) benign; (2) indeterminate; (3) suspicious for malignancy/malignant; and (4) inadequate. In addition, diagnostic accuracy was compared between SP‐LBC and BTH.ResultsAlthough 23% (13/57) of BTH samples were classified as inadequate, all SP‐LBC cases were classified as adequate. Among 43 malignant cases, 11 normal, four indeterminate and 28 suspicious for malignancy/malignant were found using SP‐LBC (26%, 9% and 65%, respectively), in contrast to 10 inadequate, nine normal, 10 indeterminate and 14 suspicious for malignancy/malignant observed using BTH (23%, 21%, 23%, and 33%, respectively). The identification of malignant cells was strikingly different between SP‐LBC and BTH. Furthermore, limited to intra/H‐CC, accuracy was significantly higher using SP‐LBC than using BTH (P < .001).ConclusionsSP‐LBC of the biliary tract is a useful and reliable method for diagnosing biliary malignant disease and has an advantage over BTH for detecting malignant cells and accurately diagnosing intra/H‐CC.
Complications related to chronic supratherapeutic use of codeine containing compound analgesics in a cohort of patients presenting for codeine withdrawal
Authors: Cock Victoria , Edmonds Carolyn , Cock Charles 
Published: May 2018

AbstractIntroduction and AimsThis study aimed to compare complications arising due to the supratherapeutic use of paracetamol/codeine or ibuprofen/codeine containing compound analgesics in primary codeine‐dependent patients presenting to a drug and alcohol withdrawal service. Data was compared to determine if there was any difference in the number of complications observed between the two groups.Design and MethodsA retrospective case review of patients presenting for primary codeine dependence from 2009 to 2014. Sixty patients (42F, 36 ± 10 years) using ibuprofen/codeine and 46 (26F, 39 ± 10 years) using paracetamol/codeine containing compound analgesics were compared. A P value of <0.05 was considered significant.ResultsPatients consumed similar daily doses of codeine (699 ± 45 vs. 636 ± 50 mg) with those consuming ibuprofen/codeine containing compound analgesics ingesting twice as many tablets daily (median 60 vs. 30 tablets; P < 0.0001). Complications related to supratherapeutic use of codeine containing compound analgesics occurred more commonly in patients taking ibuprofen/codeine (52/60; 87%) versus paracetamol/codeine compound analgesics (30/46; 65%) (P < 0.01). Patients taking ibuprofen/codeine containing compound analgesics were more likely to have gastrointestinal bleeding (P < 0.05), anaemia (P < 0.0001) and renal tubular acidosis (P < 0.05). There were two deaths in the group abusing ibuprofen/codeine compound analgesics.Discussion and ConclusionsIn patients with primary codeine dependence, there were more complications related to the supratherapeutic use of ibuprofen/codeine versus paracetamol/codeine containing compound analgesics. The patients in both groups ingested similar total daily codeine amounts. Increased daily tablet intake in the ibuprofen/codeine group could possibly have been linked to lower codeine content per tablet.
Measures of Father Engagement for Nonresident Fathers
Authors: Dyer W. Justin , Kauffman Rebecca , Fagan Jay , Pearson Jessica , Cabrera Natasha 
Published: May 2018

ObjectiveTo develop reliable and valid measures of nonresident father engagement.BackgroundAlthough engagement measures exist for resident fathers, they have not been validated for nonresident fathers. Without valid and reliable measures, research on and programs for these fathers are limited in their ability to capture this salient dimension of fathering.MethodFrom a focus group of 71 nonresident biological fathers, father–child engagement scales were created. Separate scales were created for fathers of children aged 0 to 1 years, 1 to 5 years, 6 to 11 years, and 12 to 18 years. Scales were administered to 542 nonresident (primarily low income) fathers to test reliability and convergent and predictive validity.ResultsAnalyses identified a “caregiving play” domain of engagement across all age groups. For fathers of children 0 to 1 years, a “cognitive stimulation” domain emerged. For all age groups, a “support” domain emerged. All measures had acceptable reliability and (except in 1 instance) were related to at least 1 validity construct. Measures were nonequivalent across groups except for support in 2 groups.ConclusionMeasures of nonresident father engagement had good reliability and validity. Further, with a minimal number of items, the scales are relatively easy and cost‐effective to administer.ImplicationsWith reliable and valid measures of engagement, those researching or intervening with nonresident fathers can more accurately capture this highly relevant construct.