bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial oestrogen receptor α is dispensable for the development of oestrogen‐induced cervical neoplastic diseases
Authors: Son Jieun , Park Yuri , Chung Sang‐Hyuk 
Published: March 2018

AbstractHuman papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa) development. Oestradiol (E2) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin (K14) promoter. E2 mainly functions through oestrogen receptor α (ERα). However, the role of ERα in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERα‐coding gene) in the cervical stroma of K14E7 mice promotes regression of cervical intraepithelial neoplasia (CIN), the precursor lesion of CxCa. Here, we deleted Esr1 in the cervical epithelium but not in the stroma. We found that E2 induced cervical epithelial cell proliferation in epithelial ERα‐deficient mice. We also found that E2 promoted the development of CIN and CxCa in epithelial ERα‐deficient K14E7 mice and that all neoplastic epithelial cells were negative for ERα. In addition, proliferation indices were similar between ERα– and ERα+ CxCa. These results indicate that epithelial ERα is not necessary for E2‐induced CIN and CxCa. Taking these findings together, we conclude that stromal ERα rather than epithelial ERα mediates oncogenic E2 signalling in CxCa. Our results support stromal ERα signalling as a therapeutic target for the disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization
Authors: Gucciardo Erika , Loukovaara Sirpa , Korhonen Ani , Repo Pauliina , Martins Beatriz , Vihinen Helena , Jokitalo Eija , Lehti Kaisa 
Published: March 2018

AbstractProliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady‐state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions. We describe here a clinically relevant model, whereby the native multicellular PDR landscape and neo(fibro)vascular processes can be analysed ex vivo and related to clinical data. As characterized by three‐dimensional whole‐mount immunofluorescence and electron microscopy, heterogeneity in patient‐derived PDR neovascular tissues included discontinuous capillaries coupled with aberrantly differentiated, lymphatic‐like and tortuous endothelia. Spatially confined apoptosis and proliferation coexisted with inflammatory cell infiltration and unique vascular islet formation. Ex vivo‐cultured explants retained multicellularity, islet patterning and capillary or fibrotic outgrowth in response to vitreoretinal factors. Strikingly, PDR neovascular tissues, whose matched vitreous samples enhanced lymphatic endothelial cell sprouting, contained lymphatic‐like capillaries in vivo and developed Prox1+ capillaries and sprouts with lymphatic endothelial ultrastructures ex vivo. Among multiple vitreal components, vascular endothelial growth factor C was one factor found at lymphatic endothelium‐activating concentrations. These results indicate that the ischaemia‐induced and inflammation‐induced human PDR microenvironment supports pathological neolymphovascularization, providing a new concept regarding PDR mechanisms and targeting options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Need for tissue plasminogen activator for central venous catheter dysfunction is significantly associated with thrombosis in pediatric cancer patients
Authors: MacLean Jessica , MacDonald Tamara , Digout Carol , Smith Nadine , Rigby Krista , Kulkarni Ketan 
Published: March 2018

AbstractBackgroundCentral venous catheter (CVC) dysfunction is a common complication among pediatric cancer patients. Tissue plasminogen activator (tPA) is administered to resolve CVC dysfunction. The present study was designed to determine risk factors associated with requirement of tPA for CVC dysfunction and to assess the clinical impact of CVC dysfunction in terms of CVC loss and venous thrombotic events (VTE).ProcedureCase records of all pediatric patients with cancer from the Maritimes, Canada were reviewed following ethics approval. Data regarding demographics, clinical diagnosis, CVC dysfunction, characteristics of CVCs, and VTE were pooled from multiple data sources.ResultsSeven hundred and forty‐one patients required ≥1 CVC. 26.3% of patients required tPA for ≥1 episodes of CVC dysfunction. Requirement of one or more doses of tPA for episodes of CVC dysfunction increased the odds of VTE by two times (95% confidence interval, 1.1–3.6). Patients that required ≥1 doses of tPA required significantly more CVCs (2.05 ± 1.29 per individual patient, 55% of the patients needed >1 CVCs) as compared to the remainder (1.52 ± 0.95 per individual patient, 32% needed >1 CVCs) (P = 0.0001). Multivariate analysis revealed age > 10 years, diagnosis of sarcoma, and tunneled line were independently associated with tPA requirement.ConclusionWe determined independent risk factors associated with requirement of tPA for CVC dysfunction. Requirement of tPA for CVC dysfunction was associated with significantly increased risk of VTE and requirement of more CVCs. These observations can assist in identification of patients at increased risk of CVC dysfunction and inform approaches to reduce CVC loss and VTE.
Evaluation of the US Food and Drug Administration sentinel analysis tools in confirming previously observed drug‐outcome associations: The case of clindamycin and Clostridium difficile infection
Authors: Carnahan Ryan M. , Kuntz Jennifer L. , Wang Shirley V. , Fuller Candace , Gagne Joshua J. , Leonard Charles E. , Hennessy Sean , Meyer Tamra , Archdeacon Patrick , Chen Chih‐Ying , Panozzo Catherine A. , Toh Sengwee , Katcoff Hannah , Woodworth Tiffany , Iyer Aarthi , Axtman Sophia , Chrischilles Elizabeth A. 
Published: March 2018

AbstractPurposeThe Food and Drug Administration's Sentinel System developed parameterized, reusable analytic programs for evaluation of medical product safety. Research on outpatient antibiotic exposures, and Clostridium difficile infection (CDI) with non‐user reference groups led us to expect a higher rate of CDI among outpatient clindamycin users vs penicillin users. We evaluated the ability of the Cohort Identification and Descriptive Analysis and Propensity Score Matching tools to identify a higher rate of CDI among clindamycin users.MethodsWe matched new users of outpatient dispensings of oral clindamycin or penicillin from 13 Data Partners 1:1 on propensity score and followed them for up to 60 days for development of CDI. We used Cox proportional hazards regression stratified by Data Partner and matched pair to compare CDI incidence.ResultsPropensity score models at 3 Data Partners had convergence warnings and a limited range of predicted values. We excluded these Data Partners despite adequate covariate balance after matching. From the 10 Data Partners where these models converged without warnings, we identified 807 919 new clindamycin users and 8 815 441 new penicillin users eligible for the analysis. The stratified analysis of 807 769 matched pairs included 840 events among clindamycin users and 290 among penicillin users (hazard ratio 2.90, 95% confidence interval 2.53, 3.31).ConclusionsThis evaluation produced an expected result and identified several potential enhancements to the Propensity Score Matching tool. This study has important limitations. CDI risk may have been related to factors other than the inherent properties of the drugs, such as duration of use or subsequent exposures.
Development of algorithms for identifying fatal cardiovascular disease in Medicare claims
Authors: Xie Fenglong , Colantonio Lisandro D. , Curtis Jeffrey R. , Kilgore Meredith L. , Levitan Emily B. , Monda Keri L. , Safford Monika M. , Taylor Ben , Woodward Mark , Muntner Paul 
Published: March 2018

AbstractBackgroundCause of death is often not available in administrative claims data.ObjectiveTo develop claims‐based algorithms to identify deaths due to fatal cardiovascular disease (CVD; ie, fatal coronary heart disease [CHD] or stroke), CHD, and stroke.MethodsReasons for Geographic and Racial Differences in Stroke (REGARDS) study data were linked with Medicare claims to develop the algorithms. Events adjudicated by REGARDS study investigators were used as the gold standard. Stepwise selection was used to choose predictors from Medicare data for inclusion in the algorithms. C‐index, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to assess algorithm performance. Net reclassification index (NRI) was used to compare the algorithms with an approach of classifying all deaths within 28 days following hospitalization for myocardial infarction and stroke to be fatal CVD.ResultsData from 2,685 REGARDS participants with linkage to Medicare, who died between 2003 and 2013, were analyzed. The C‐index for discriminating fatal CVD from other causes of death was 0.87. Using a cut‐point that provided the closest observed‐to‐predicted number of fatal CVD events, the sensitivity was 0.64, specificity 0.90, PPV 0.65, and NPV 0.90. The algorithms resulted in positive NRIs compared with using deaths within 28 days following hospitalization for myocardial infarction and stroke. Claims‐based algorithms for discriminating fatal CHD and fatal stroke performed similarly to fatal CVD.ConclusionThe claims‐based algorithms developed to discriminate fatal CVD events from other causes of death performed better than the method of using hospital discharge diagnosis codes.
Folding of granulin domains
Authors: Dastpeyman Mohadeseh , Smout Michael J. , Wilson David , Loukas Alex , Daly Norelle L. 
Published: March 2018

AbstractGranulins are a family of protein growth factors that are involved in a range of biological functions, including wound repair, inflammation, and tumor growth. They are often expressed as part of large precursor proteins containing multiple granulin domains. Individual granulin domains are characterized by a conserved arrangement of 12 cysteine residues that form six disulfide bonds. Despite the conservation of the cysteine residues, there is significant sequence variation between granulins from different species. The initial structure determined for this family indicated the presence of a well‐defined structure with a laddered arrangement of the six disulfide bonds and a β‐hairpin stack. However, subsequent studies have shown the structure‐function relationships of granulins are quite complex. Recent studies have indicated some granulins might have potential as wound healing agents, and studies aimed at understanding the structure‐function relationships of this family are likely to enhance this potential in drug design. This review provides an overview of the structure‐based studies of granulins, including the folding of truncated peptides derived from granulins from different species.
Low‐cost bifunctional initiators for bidirectional living cationic polymerization of olefins. III. centrally functionalized polyisobutylenes
Authors: Nugay Turgut , Deodhar Tejal , Nugay Nihan , Kennedy Joseph Paul 
Published: March 2018

ABSTRACTAllyl‐telechelic polyisobutylene (A‐PIB‐A) produced by the bis‐benzocyclobutane dichloride (bBCB‐diCl) initiator contains the bis‐benzocyclobutane (bBCB) fragment at the center of the macromolecule (A‐PIB‐bBCB‐PIB‐A). Thermolysis of A‐PIB‐bBCB‐PIB‐A quantitatively converts the central bBCB fragment to a substituted conjugated tetraene (A‐PIB‐tetraene‐PIB‐A). The structure of A‐PIB‐tetraene‐PIB‐A was anticipated from small molecule models and identified/quantitated by 1H NMR spectroscopy. This is the first time a reactive functional group was introduced at the statistical center of a (telechelic) PIB. Subsequently, the A‐PIB‐tetraene‐PIB‐A was peroxidized to an epoxy derivative. Reaction of the A‐PIB‐tetraene‐PIB‐A with HSCH2CH2OH produced HOCH2‐telechelic PIB containing a central CH2OH function, and hydrosilation with HSi(Me2)‐O‐Si(Me2)H produced SiH‐telechelic PIB with a central SiH function. Reactions with maleic anhydride, tetracyanoethylene, butyl lithium, and potassium permanganate have also been examined. In sum, A‐PIB‐bBCB‐PIB‐A and A‐PIB‐tetraene‐PIB‐A are useful intermediates for the synthesis of novel PIB‐based materials for various end uses under investigation. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1140–1145
Study on the Curing System of Polytriazole Adhesive for Composite Solid Propellant
Authors: Liu Fang‐Bo , Zhang Xi‐Long , Jiang Wei‐Sheng , Yu Fang‐Yuan , Deng Jian‐Ru 
Published: March 2018

AbstractPolyether/polyester with terminal alkynyl groups, bis‐alkynyl chain extender (BEBA), tri‐alkynyl crosslinking agent (TMPTPE) and bis‐azide curing agent (BPDBA) were synthesized to prepare a series of polytriazole elastomers. The effects of factors including curing parameters (Rt), hard segment content (H%), and crosslinking agent content (C%) on the mechanical properties of cured films were investigated. And the crosslinking network of polytriazole elastomer was evaluated by swelling experiment. The compatibility and mechanical properties of polytriazole adhesive with plasticizer were also studied. The results showed that the tensile strength of the polytriazole adhesive and the elongation at break were changed from 0.71 MPa to 5.72 MPa, 300 % to 720 %, respectively. The polytriazole cross‐linked network structure was able to be well controlled by the loading of crosslinking agent. Moreover, the strong polar plasticizer was compatible with polytriazole adhesive and formed a high plasticizer elastomer.
Cervical flexor muscle training reduces pain, anxiety, and depression levels in patients with chronic neck pain by a clinically important amount: A prospective cohort study
Authors: Nazari Goris , Bobos Pavlos , Billis Evdokia , MacDermid Joy C. 
Published: March 2018

AbstractBackground and PurposeNeck pain is the fourth leading cause of disability in the United States and exerts an important socio‐economic burden around the world. The aims of this study were to determine the effectiveness of deep and superficial flexor muscle training in addition to home‐based exercises in reducing chronic neck pain and anxiety/depression levels.MethodsThis was a prospective cohort study. Patients between 18 and 65 years old with chronic neck pain were eligible to participate if they had disability levels at least 5 out of 50 on the Neck Disability Index. Patients were divided into three groups: Group A received deep neck flexor and home‐based exercises; Group B received superficial muscle and home‐based exercises; and Group C received home‐based exercises only. The Numeric Pain Rating Scale (NPRS), Neck Disability Index, and Hospital Anxiety and Depression Scale were administered at baseline and 7 weeks later.ResultsThe highest improvements in pain intensity levels were observed in Group A with 4.75 (1.74) NPRS points, and the lowest were in Group C with 1.00 (1.10). The highest reductions in anxiety and depression levels were noted in Group A (2.80) and Group B (1.65), respectively. The highest improvements in pain intensity levels were observed among Groups A versus C with 2.80 (0.52) NPRS. The highest reductions in anxiety and depression levels were noted among Groups A versus C with 1.75 (1.10) points and Groups B versus C with 1.60 (0.90) points, respectively.ConclusionsDeep and superficial flexor muscle training along with home‐based exercises is likely to reduce chronic neck pain and anxiety/depression levels by a clinically relevant amount. Future larger scaled randomized controlled trials are warranted to further support these findings.
MAGI2 is an independent predictor of biochemical recurrence in prostate cancer
Authors: David Stephanie N. , Arnold Egloff Shanna A. , Goyal Rajen , Clark Peter E. , Phillips Sharon , Gellert Lan L. , Hameed Omar , Giannico Giovanna A. 
Published: March 2018

BackgroundMembrane‐associated guanylate kinase, WW and PDZ domain‐containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer.MethodsTissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed. Immunohistochemistry with double staining for MAGI2 and p63 was performed and analyzed by image analysis as percent of analyzed area (%AREA). Multivariable logistic regression was used to correlate MAGI2 expression with clinical outcomes. Generalized Estimating Equations (GEE) with linear and logistic regression was used to correlate MAGI2 with intrapatient histology.ResultsMAGI2 %AREA was inversely associated with progression from HGPIN to adenocarcinoma of low to high Gleason score (OR, 0.980; slope, −0.02; P = 0.005) and HGPIN to cancer of any Gleason score (OR, 0.969; P = 0.007). After adjusting for grade, stage, and margin status, MAGI2 %AREA was a significant independent predictor of biochemical recurrence (BCR) (OR, 0.936; 95%CI, 0.880‐0.996; P = 0.037; bootstrap P = 0.017). The addition of MAGI2 %AREA to these standard clinical parameters improved accuracy of predicting BCR by 2.9% (91.0% vs 88.1%).ConclusionsThese results reveal that MAGI2 expression is reduced during prostate cancer progression and that retention of MAGI2 signal reduces odds of BCR. The study results further suggest a possible role of MAGI2 in prostate neoplasia. Decreased MAGI2 expression may help predict prostate cancer aggressiveness and provide new insight for treatment decisions and post‐operative surveillance intervals.
Repeat prostate biopsies prior to radical prostatectomy do not impact erectile function recovery and mid‐ to long‐term continence
Authors: Furrer Marc A. , Vilaseca Antoni , Corradi Renato B. , Boxler Silvan , Thalmann George N. , Nguyen Daniel P. 
Published: March 2018

BackgroundA growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long‐term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy.MethodsFrom 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for >2 years follow‐up. One‐fourth of patients (275; 27%) had ≥2 biopsies before prostatectomy. Logistic regression models tested whether repeat biopsy before prostatectomy predicted continence or erectile function recovery.ResultsFor the overall cohort, continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, and 24 months, respectively. Repeat biopsy before prostatectomy was associated with lower continence rate at 3 months compared to single biopsy (P = 0.03); however, no significant differences were observed at 6, 12, or 24 months. In multivariable analyses adjusting for age, body mass index and diabetes/cardiovascular disease/smoking, the association between repeat biopsy and lower likelihood of continence at 3 months remained (odds ratio 0.67, 95% confidence interval 0.47‐0.97; P = 0.03). Overall erectile function recovery rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No difference in erectile function recovery rates was seen at any time point for single biopsy versus repeat biopsy. In multivariable analyses, repeat biopsy was not predictive of erectile function recovery at any time point.ConclusionsRepeat biopsy before radical prostatectomy impairs early continence after surgery. However, erectile function recovery and mid‐term to long‐term continence are not affected. These data support the current trend towards active surveillance and delayed local treatment in patients with low‐ to intermediate‐risk prostate cancer.
Temporal efficacy of neonicotinoid seed treatments against Frankliniella fusca on cotton
Authors: D'Ambrosio Damon A , Huseth Anders S , Kennedy George G 
Published: March 2018

AbstractBACKGROUNDReports of neonicotinoid seed treatment (NST) failure against Frankliniella fusca in the mid‐south and southeastern USA led to the discovery of widespread resistance in these insect populations. Previous studies of NSTs in other crops have shown the concentration of the insecticide to change over time, which could reduce its efficacy. To understand this temporal effect in cotton with F. fusca, our study examined how plant age alters the effects of NSTs (imidacloprid, imidacloprid + thiodicarb and thiamethoxam) by examining larval establishment at multiple seedling ages during the period of cotton seedling susceptibility to this insect. Additionally, we used F. fusca populations with differing neonicotinoid sensitivity levels to understand how resistance impacts this changing efficacy.RESULTSGreenhouse studies showed that larval numbers were significantly greater on older NST‐grown cotton seedlings. The population with elevated neonicotinoid resistance had a more rapid increase in larval number on thiamethoxam‐treated plants over time.CONCLUSIONNSTs reduce the number of F. fusca larvae on younger seedlings, but this effect declines as seedlings age. The duration of efficacy is shorter against neonicotinoid‐resistant populations. Neonicotinoid resistance in cotton‐infesting F. fusca populations may be accelerated by this time‐dependent decrease in efficacy, which likely encourages low‐dose exposure to these insecticides. © 2018 Society of Chemical Industry
Cascading effects of combining synthetic herbivore‐induced plant volatiles with companion plants to manipulate natural enemies in an agro‐ecosystem
Authors: Salamanca Jordano , Souza Brígida , Rodriguez‐Saona Cesar 
Published: March 2018

AbstractBACKGROUNDWhether tactics to manipulate natural enemies in agro‐ecosystems enhance their ecosystem function and services remains debatable. We conducted field experiments in 2015–2016 to test the hypothesis that attraction of natural enemies to herbivore‐induced plant volatiles (HIPVs), alone or in combination with companion plants, increases crop productivity. Our treatments consisted of bean plants alone or baited with methyl salicylate (MeSA; an HIPV), or combined with coriander (a companion plant), or with both MeSA and coriander. Numbers of arthropods were visually sampled in each treatment. Sentinel aphids were used to measure ecosystem function (i.e. predation). Plant damage and biomass, and the number and weight of pods and seeds, were measured as a proxy for ecosystem services.RESULTSMeSA and coriander, when alone or combined, increased the abundance of insect predators from six families, reduced herbivore (e.g. spider mite and thrips) populations, and increased aphid predation. MeSA and coriander also reduced damage by spider mites. MeSA with or without coriander did not, however, increase crop biomass or any yield parameters.CONCLUSIONSMeSA alone or combined with coriander attracted different predator communities, altered pest communities, and reduced damage; however, these results did not cascade down to improve crop productivity. © 2018 Society of Chemical Industry