bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Novel Membrane Proteins, TcpD and TcpE, Are Essential for Conjugative Transfer of pCW3 in Clostridium perfringens
Authors: Wisniewski Jessica A. , Teng Wee L. , Bannam Trudi L. , Rood Julian I. 
Published: December 2014

ABSTRACT

The anaerobic pathogen
Clostridium perfringens
encodes either toxin genes or antibiotic resistance determinants on a unique family of conjugative plasmids that have a novel conjugation region, the
tcp
locus. Studies of the paradigm conjugative plasmid from
C. perfringens
, the 47-kb tetracycline resistance plasmid pCW3, have identified several
tcp
-encoded proteins that are involved in conjugative transfer and form part of the transfer apparatus. In this study, the role of the conserved hypothetical proteins TcpD, TcpE, and TcpJ was examined. Mutation and complementation analyses showed that TcpD and TcpE were essential for the conjugative transfer of pCW3, whereas TcpJ was not required. To analyze the TcpD and TcpE proteins in
C. perfringens
, functional hemagglutinin (HA)-tagged derivatives were constructed. Western blots showed that TcpD and TcpE localized to the cell envelope fraction independently of the presence of other pCW3-encoded proteins. Finally, examination of the subcellular localization of TcpD and TcpE by immunofluorescence showed that these proteins were concentrated at both poles of
C. perfringens
donor cells, where they are postulated to form essential components of the multiprotein complex that comprises the transfer apparatus.
Developing An Acupuncture Protocol for Treating Phantom Limb Pain: A Delphi Consensus Study
Authors: Trevelyan Esmé G , Turner Warren A , Robinson Nicola 
Published: December 2014

Background Little is known about how a Traditional Chinese Medicine (TCM) approach could be used to treat phantom limb pain (PLP). There is currently no standard acupuncture protocol in the literature to treat this syndrome. Objectives To achieve consensus among a group of acupuncture practitioners on the pathology and recommended treatment of PLP and devise an acupuncture protocol for the treatment of this condition. Methods A classical Delphi approach was used using two parallel online Delphi studies. One study focused on participants with past experience of treating PLP (TPLP, n=7) and the other on practitioners with no past experience (NTPLP, n=16). Two hypothetical case studies were provided and participants were asked for responses on how they would treat these patients. Three rounds were included. Participants were also invited to rate and comment on the finalised protocol. Round 1 data were analysed using content analysis. In subsequent rounds an a priori criterion for defining consensus was set at ≤1.75 IQR. A group median of 5–6 was considered to mean ‘agree’. Results 19 participants completed all Delphi rounds (12 NTPLP, 7 TPLP). 108 NTPLP and 76 TPLP statements were generated and circulated in round 2; 53% of the NTPLP statements and 62% of the TPLP statements met consensus in round 2 and 45% of the NTPLP statements and 44% of the TPLP statements met consensus in round 3. Participants all agreed with the final protocol developed. Conclusions The protocol developed does not claim to be best practice but provides a preliminary consensus from practitioners practising acupuncture for the treatment of PLP.
Fast-food consumption and body mass index in children and adolescents: an international cross-sectional study
Authors: Braithwaite Irene , Stewart Alistair W , Hancox Robert J , Beasley Richard , Murphy Rinki , Mitchell Edwin A ,   the ISAAC Phase Three Study Group
Published: December 2014

ObjectiveTo investigate whether reported fast-food consumption over the previous year is associated with higher childhood or adolescent body mass index (BMI).DesignSecondary analysis from a multicentre, multicountry cross-sectional study (International Study of Asthma and Allergies in Children (ISAAC) Phase Three).Subjects and methodsParents/guardians of children aged 6–7 completed questionnaires which included questions about their children's asthma and allergies, fast-food consumption, height and weight. Adolescents aged 13–14 completed the same questionnaire. The questionnaire asked “In the past 12 months, how often on average did you (your child) eat fast-food/burgers?” The responses were infrequent (never/only occasionally), frequent (once/twice a week) or very frequent (three or more times per week). A general linear mixed model was used to determine the association between BMI and fast-food consumption, adjusting for Gross National Income per capita by country, measurement type (whether heights/weights were reported or measured), age and sex.Results72 900 children (17 countries) and 199 135 adolescents (36 countries) provided data. Frequent and very frequent fast-food consumption was reported in 23% and 4% of children, and 39% and 13% of adolescents, respectively. Children in the frequent and very frequent groups had a BMI that was 0.15 and 0.22 kg/m2higher than those in the infrequent group (p<0.001). Male adolescents in the frequent and very frequent groups had a BMI that was 0.14 and 0.28 kg/m2lower than those in the infrequent group (p<0.001). Female adolescents in the frequent and very frequent groups had a BMI that was 0.19 kg/m2lower than those in the infrequent group (p<0.001).ConclusionsReported fast-food consumption is high in childhood and increases in adolescence. Compared with infrequent fast-food consumption, frequent and very frequent consumption is associated with a higher BMI in children. Owing to residual confounding, reverse causation and likely misreporting, the reverse association observed in adolescents should be interpreted with caution.
Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis
Authors: Anderson Kristen , Stowasser Danielle , Freeman Christopher , Scott Ian 
Published: December 2014

ObjectiveTo synthesise qualitative studies that explore prescribers’ perceived barriers and enablers to minimising potentially inappropriate medications (PIMs) chronically prescribed in adults.DesignA qualitative systematic review was undertaken by searching PubMed, EMBASE, Scopus, PsycINFO, CINAHL and INFORMIT from inception to March 2014, combined with an extensive manual search of reference lists and related citations. A quality checklist was used to assess the transparency of the reporting of included studies and the potential for bias. Thematic synthesis identified common subthemes and descriptive themes across studies from which an analytical construct was developed. Study characteristics were examined to explain differences in findings.SettingAll healthcare settings.ParticipantsMedical and non-medical prescribers of medicines to adults.OutcomesPrescribers’ perspectives on factors which shape their behaviour towards continuing or discontinuing PIMs in adults.Results21 studies were included; most explored primary care physicians’ perspectives on managing older, community-based adults. Barriers and enablers to minimising PIMs emerged within four analytical themes: problem awareness; inertia secondary to lower perceived value proposition for ceasing versus continuing PIMs; self-efficacy in regard to personal ability to alter prescribing; and feasibility of altering prescribing in routine care environments given external constraints. The first three themes are intrinsic to the prescriber (eg, beliefs, attitudes, knowledge, skills, behaviour) and the fourth is extrinsic (eg, patient, work setting, health system and cultural factors). The PIMs examined and practice setting influenced the themes reported.ConclusionsA multitude of highly interdependent factors shape prescribers’ behaviour towards continuing or discontinuing PIMs. A full understanding of prescriber barriers and enablers to changing prescribing behaviour is critical to the development of targeted interventions aimed at deprescribing PIMs and reducing the risk of iatrogenic harm.
Does high intelligence improve prognosis? The association of intelligence with recurrence and mortality among Swedish men with coronary heart disease
Authors: Sörberg Wallin Alma , Falkstedt Daniel , Allebeck Peter , Melin Bo , Janszky Imre , Hemmingsson Tomas 
Published: December 2014

BackgroundLower intelligence early in life is associated with increased risks for coronary heart disease (CHD) and mortality. Intelligence level might affect compliance to treatment but its prognostic importance in patients with CHD is unknown.MethodsA cohort of 1923 Swedish men with a measure of intelligence from mandatory military conscription in 1969–1970 at age 18–20, who were diagnosed with CHD 1991–2007, were followed to the end of 2008. Primary outcome: recurrent CHD event. Secondary outcome: case fatality from the first event, cardiovascular and all-cause mortality. National registers provided information on CHD events, comorbidity, mortality and socioeconomic factors.ResultsThe fully adjusted HRs for recurrent CHD for medium and low intelligence, compared with high intelligence, were 0.98, (95% CIs 0.83 to 1.16) and 1.09 (0.89 to 1.34), respectively. The risks were increased for cardiovascular and all-cause mortality with lower intelligence, but were attenuated in the fully adjusted models (fully adjusted HRs for cardiovascular mortality 1.92 (0.94 to 3.94) and 1.98 (0.89 to 4.37), respectively; for all-cause mortality 1.63 (1.00 to 2.65) and 1.62 (0.94 to 2.78), respectively). There was no increased risk for case-fatality at the first event (fully adjusted ORs 1.06 (0.73 to 1.55) and 0.97 (0.62 to 1.50), respectively).ConclusionsAlthough we found lower intelligence to be associated with increased mortality in middle-aged men with CHD, there was no evidence for its possible effect on recurrence in CHD.
Hemodynamic–morphological discriminant models for intracranial aneurysm rupture remain stable with increasing sample size
Authors: Xiang Jianping , Yu Jihnhee , Snyder Kenneth V , Levy Elad I , Siddiqui Adnan H , Meng Hui 
Published: December 2014

BackgroundWe previously established three logistic regression models for discriminating intracranial aneurysm rupture status based on morphological and hemodynamic analysis of 119 aneurysms. In this study, we tested if these models would remain stable with increasing sample size, and investigated sample sizes required for various confidence levels (CIs).MethodsWe augmented our previous dataset of 119 aneurysms into a new dataset of 204 samples by collecting an additional 85 consecutive aneurysms, on which we performed flow simulation and calculated morphological and hemodynamic parameters, as done previously. We performed univariate significance tests on these parameters, and multivariate logistic regression on significant parameters. The new regression models were compared against the original models. Receiver operating characteristics analysis was applied to compare the performance of regression models. Furthermore, we performed regression analysis based on bootstrapping resampling statistical simulations to explore how many aneurysm cases were required to generate stable models.ResultsUnivariate tests of the 204 aneurysms generated an identical list of significant morphological and hemodynamic parameters as previously (from the analysis of 119 cases). Furthermore, multivariate regression analysis produced three parsimonious predictive models that were almost identical to the previous ones, with model coefficients that had narrower CIs than the original ones. Bootstrapping showed that 10%, 5%, 2%, and 1% convergence levels of CI required 120, 200, 500, and 900 aneurysms, respectively.ConclusionsOur original hemodynamic–morphological rupture prediction models are stable and improve with increasing sample size. Results from resampling statistical simulations provide guidance for designing future large multi-population studies.
Hypoglossal-Facial Nerve Reconstruction Using a Y-Tube-Conduit Reduces Aberrant Synkinetic Movements of the Orbicularis Oculi and Vibrissal Muscles in Rats
Authors: Kaya Yasemin , Ozsoy Umut , Turhan Murat , Angelov Doychin N. , Sarikcioglu Levent 
Published: December 2014

The facial nerve is the most frequently damaged nerve in head and neck trauma. Patients undergoing facial nerve reconstruction often complain about disturbing abnormal synkinetic movements of the facial muscles (mass movements, synkinesis) which are thought to result from misguided collateral branching of regenerating motor axons and reinnervation of inappropriate muscles. Here, we examined whether use of an aorta Y-tube conduit during reconstructive surgery after facial nerve injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal (whisking) musculature. The abdominal aorta plus its bifurcation was harvested (N = 12) for Y-tube conduits. Animal groups comprised intact animals (Group 1), those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group 2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y-tube group showed a reduced synkinesis of eyelid and whisker movements compared to HFA alone.
Whole-Exome Sequencing Reveals Frequent Genetic Alterations in BAP1, NF2, CDKN2A, and CUL1 in Malignant Pleural Mesothelioma
Authors: Guo Guangwu , Chmielecki Juliann , Goparaju Chandra , Heguy Adriana , Dolgalev Igor , Carbone Michele , Seepo Sara , Meyerson Matthew , Pass Harvey I. 
Published: December 2014

Abstract
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although previous studies based on candidate gene approaches have identified important common somatic mutations in MPM, these studies have focused on small sets of genes and have provided a limited view of the genetic alterations underlying this disease. Here, we performed whole-exome sequencing on DNA from 22 MPMs and matched blood samples, and identified 517 somatic mutations across 490 mutated genes. Integrative analysis of mutations and somatic copy-number alterations revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM. Cancer Res; 75(2); 264–9. ©2014 AACR.
Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells
Authors: Tsuji Tadahiro , Satoyoshi Rika , Aiba Namiko , Kubo Takanori , Yanagihara Kazuyoshi , Maeda Daichi , Goto Akiteru , Ishikawa Kazuo , Yashiro Masakazu , Tanaka Masamitsu 
Published: December 2014

Abstract
Agr2 is a disulfide isomerase residing in the endoplasmic reticulum (ER), which physiologically regulates protein folding and mediates resistance to ER stress. Agr2 is overexpressed in adenocarcinomas of various organs, where it participates in neoplastic transformation and metastasis, therefore acts as a pro-oncogenic protein. Besides its normal localization in the ER, Agr2 is also found in the serum and urine of cancer patients, although the physiological significance of extracellular Agr2 is poorly understood. In this study, we demonstrated that extracellular Agr2 can activate stromal fibroblasts and promote fibroblast-associated cancer invasion in gastric signet-ring cell carcinoma (SRCC), where Agr2 is highly expressed. Agr2 secreted from SRCC cells was incorporated by the surrounding gastric fibroblasts and promoted invasion by these cells. In turn, activated fibroblasts coordinated the invasive behavior of fibroblasts and cancer cells. Our findings suggested that Agr2 drives progression of gastric SRCC by exerting paracrine effects on fibroblasts in the tumor microenvironment, acting also to increase the growth and resistance of SRCC cells to oxidative and hypoxic stress as cell autonomous effects. Cancer Res; 75(2); 356–66. ©2014 AACR.
AMG 925 Is a Dual FLT3/CDK4 Inhibitor with the Potential to Overcome FLT3 Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Li Cong , Liu Liqin , Liang Lingming , Xia Zhen , Li Zhihong , Wang Xianghong , McGee Lawrence R. , Newhall Katie , Sinclair Angus , Kamb Alexander , Wickramasinghe Dineli , Dai Kang 
Published: December 2014

AbstractResistance to FLT3 inhibitors is a serious clinical issue in treating acute myelogenous leukemia (AML). AMG 925, a dual FLT3/CDK4 inhibitor, has been developed to overcome this resistance. It is hypothesized that the combined inhibition of FLT3 and CDK4 may reduce occurrence of the FLT3 resistance mutations, and thereby prolong clinical responses. To test this hypothesis, we attempted to isolate AML cell clones resistant to AMG 925 or to FLT3 inhibitors. After a selection of over 8 months with AMG 925, we could only isolate partially resistant clones. No new mutations in FLT3 were found, but a 2- to 3-fold increase in total FLT3 protein was detected and believed to contribute to the partial resistance. In contrast, selection with the FLT3 inhibitors sorafenib or AC220 (Quizartinib), led to a resistance and the appearance of a number of mutations in FLT3 kinase domains, including the known hot spot sites D835 and F691. However, when AC220 was combined with the CDK4 inhibitor PD0332991 (palbociclib) at 0.1 μmol/L or higher, no resistance mutations were obtained, indicating that the CDK4-inhibiting activity of AMG 925 contributed to the failure to develop drug resistance. AMG 925 was shown to potently inhibit the FLT3 inhibitor–resistant mutation D835Y/V. This feature of AMG 925 was also considered to contribute to the lack of resistance mutations to the compound. Together, our data suggest that AMG 925 has the potential to reduce resistance mutations in FLT3 and may prolong clinical responses. Mol Cancer Ther; 14(2); 375–83. ©2014 AACR.
Immunoprevention of Human Papillomavirus–Associated Malignancies
Authors: Wang Joshua W. , Hung Chein-fu , Huh Warner K. , Trimble Cornelia L. , Roden Richard B.S. 
Published: December 2014

AbstractPersistent infection by one of 15 high-risk human papillomavirus (hrHPV) types is a necessary but not sufficient cause of 5% of all human cancers. This provides a remarkable opportunity for cancer prevention via immunization. Since Harald zur Hausen's pioneering identification of hrHPV types 16 and 18, found in approximately 50% and 20% of cervical cancers, respectively, two prophylactic HPV vaccines containing virus-like particles (VLP) of each genotype have been widely licensed. These vaccines are beginning to affect infection and HPV-associated neoplasia rates after immunization campaigns in adolescents. Here, we review recent progress and opportunities to better prevent HPV-associated cancers, including broadening immune protection to cover all hrHPV types, reducing the cost of HPV vaccines especially for developing countries that have the highest rates of cervical cancer, and immune-based treatment of established HPV infections. Screening based upon George Papanicolaou's cervical cytology testing, and more recently detection of hrHPV DNA/RNA, followed by ablative treatment of high-grade cervical intraepithelial neoplasia (CIN2/3) have substantially reduced cervical cancer rates, and we examine their interplay with immune-based modalities for the prevention and eventual elimination of cervical cancer and other HPV-related malignancies. Cancer Prev Res; 8(2); 95–104. ©2014 AACR.
A tribo Pisonieae Meisner (Nyctaginaceae) no Brasil
Authors: Antonio Furlan , Giulietti Ana Maria 
Published: December 2014

Nesta revisão taxonômica da tribo Pisonieae (Nyctaginaceae) no Brasil foram utilizadas as técnicas tradicionais em trabalhos taxonômicos, envolvendo a análise de cerca de 3000 espécimes depositados em herbários nacionais e estrangeiros, aliada a coletas e observações de campo. A maioria das espécies da tribo Pisonieae é neotropical, exceto o gênero Pisonia que apresenta distribuição pantropical. Todas as espécies brasileiras são dióicas. Um estudo de morfologia floral comparada mostra as diferenças genéricas em plantas estaminadas, pistiladas e com frutos. Pelas descontinuidades florais apresentadas, considerou-se os gêneros Guapira e Neea como distintos, em oposição ao tratamento sistemático de Heimerl publicado em 1934. São reconhecidas no país 30 espécies incluídas nos gêneros Guapira, Neea e Pisonia: Guapira areolata (Heimerl) Lundell, G. campestris (Netto) Lundell, G. graciliflora (Mart. ex J.A.Schmidt) Lundell, G. hirsuta (Choisy) Lundell, G. laxa (Netto) Furlan, G. nitida (Mart. ex J.A.Schmidt) Lundell, G. noxia (Netto) Lundell, G. obtusata (Jacq.) Little, G. opposita (Vell.) Reitz, G. pernambucensis (Casar.) Lundell, G. venosa (Choisy) Lundell, Neea duckei (Huber) Furlan, N. floribunda Poepp. & Endl., N. hermaphrodita S.Moore, N. hirsuta Poepp. & Endl., N. laxa Poepp. & Endl., N. macrophylla Poepp. & Endl., N. madeirana Standl., N. obovata Spruce ex Heimerl, N. oppositifolia Ruiz & Pav., N. ovalifolia Spruce ex J.A.Schmidt, N.parviflora Poepp. & Endl., N. pendulina Heimerl, N. theifera Oerst., N. uleana (Heimerl) Furlan, N. verticillata Ruiz & Pav., Pisonia aculeata L., P. ambigua Heimerl e P. zapallo Griseb. São apresentadas chaves de identificação para os gêneros e espécies, bem como descrições, ilustrações, mapas de distribuição e comentários taxonômicos para os táxons estudados. Guapira foi delimitado com 12 espécies distribuídas principalmente na região Sudeste do Brasil, enquanto Neea inclui 15 espécies com ocorrência predominante na região Norte do Brasil e em Pisonia foram definidas três espécies concentradas na região Sul do pais. Neste trabalho foram propostas três combinações novas e 56 nomes foram reduzidos a sinonímia, permanecendo 15 nomes como duvidosos e 42 lectótipos são propostos.
Strategy for Identifying Repurposed Drugs for the Treatment of Cerebral Cavernous Malformation
Authors: Gibson Christopher C. , Zhu Weiquan , Davis Chadwick T. , Bowman-Kirigin Jay A. , Chan Aubrey C. , Ling Jing , Walker Ashley E. , Goitre Luca , Delle Monache Simona , Retta Saverio Francesco , Shiu Yan-Ting E. , Grossmann Allie H. , Thomas Kirk R. , Donato Anthony J. , Lesniewski Lisa A. , Whitehead Kevin J. , Li Dean Y. 
Published: December 2014

Background—

Cerebral cavernous malformation (CCM) is a hemorrhagic stroke disease affecting up to 0.5% of North Americans that has no approved nonsurgical treatment. A subset of patients have a hereditary form of the disease due primarily to loss-of-function mutations in
KRIT1, CCM2
, or
PDCD10.
We sought to identify known drugs that could be repurposed to treat CCM.

Methods and Results—

We developed an unbiased screening platform based on both cellular and animal models of loss of function of
CCM2
. Our discovery strategy consisted of 4 steps: an automated immunofluorescence and machine-learning–based primary screen of structural phenotypes in human endothelial cells deficient in CCM2, a secondary screen of functional changes in endothelial stability in these same cells, a rapid in vivo tertiary screen of dermal microvascular leak in mice lacking endothelial
Ccm2
, and finally a quaternary screen of CCM lesion burden in these same mice. We screened 2100 known drugs and bioactive compounds and identified 2 candidates, cholecalciferol (vitamin D
3
) and tempol (a scavenger of superoxide), for further study. Each drug decreased lesion burden in a mouse model of CCM vascular disease by ≈50%.

Conclusions—
By identifying known drugs as potential therapeutics for CCM, we have decreased the time, cost, and risk of bringing treatments to patients. Each drug also prompts additional exploration of biomarkers of CCM disease. We further suggest that the structure-function screening platform presented here may be adapted and scaled to facilitate drug discovery for diverse loss-of-function genetic vascular disease.