bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional regulation of voltage‐gated Ca2+ channels
Authors: González‐Ramírez R. , Felix R. 
Published: April 2017

AbstractThe transcriptional regulation of voltage‐gated Ca2+ (CaV) channels is an emerging research area that promises to improve our understanding of how many relevant physiological events are shaped in the central nervous system, the skeletal muscle and other tissues. Interestingly, a picture of how transcription of CaV channel subunit genes is controlled is evolving with the identification of the promoter regions required for tissue‐specific expression and the identification of transcription factors that control their expression. These promoters share several characteristics that include multiple transcriptional start sites, lack of a TATA box and the presence of elements conferring tissue‐selective expression. Likewise, changes in CaV channel expression occur throughout development, following ischaemia, seizures or chronic drug administration. This review focuses on insights achieved regarding the control of CaV channel gene expression. To further understand the complexities of expression and to increase the possibilities of detecting CaV channel alterations causing human disease, a deeper knowledge on the structure of the 5′ upstream regions of the genes encoding these remarkable proteins will be necessary.
Cyclophosphamide‐based stem cell mobilization in relapsed multiple myeloma patients: A subgroup analysis from the phase III trial ReLApsE
Authors: Baertsch Marc‐Andrea , Schlenzka Jana , Lisenko Katharina , Krzykalla Julia , Becker Natalia , Weisel Katja , Noppeney Richard , Martin Hans , Lindemann Hans W. , Haenel Mathias , Nogai Axel , Scheid Christof , Salwender Hans , Fenk Roland , Graeven Ullrich , Reimer Peter , Schmidt‐Hieber Martin , Goerner Martin , Schmidt‐Wolf Ingo G. H. , Klein Stefan , Ho Anthony D. , Goldschmidt Hartmut , Wuchter Patrick 
Published: April 2017

AbstractObjectiveAnalysis of the efficiency and toxicity of cyclophosphamide‐based stem cell mobilization in patients with relapsed multiple myeloma (RMM).MethodsPeripheral blood stem cells (PBSCs) were mobilized with high dose cyclophosphamide (2 g/m2 daily on days 1 and 2) and G‐CSF plus pre‐emptive/rescue plerixafor in RMM patients (first to third relapse) treated within the ReLApsE trial of the German‐Speaking Myeloma Multicenter Group (GMMG).ResultsMobilization was initiated with high‐dose cyclophosphamide (HD‐CY) and G‐CSF in 30 patients. Fifteen patients received additional pre‐emptive/rescue administration of plerixafor. Stem cell collection was successful (≥2×106 CD34+ cells per kg bw) in 77% (23/30 patients). Patients with prior high‐dose melphalan collected a significantly lower median total number of PBSCs than patients without prior high‐dose melphalan (3.3×106 vs 17×106 CD34+ cells/kg bw). Toxicity of HD‐CY was frequent with 12 serious adverse events (SAE) in 37% of patients (11/30 patients). Infections accounted for the majority of SAE reports. In two patients, SAEs were lethal (septic shock).ConclusionsThese data proof feasibility of PBSC collection at relapse but emphasize the importance of collection and storage of additional PBSC transplants during first‐line treatment when mobilization is more efficient and less toxic.
Long‐term follow‐up of patients with multiple myeloma treated with total body irradiation—Melphalan conditioning
Authors: Munker Reinhold , Baghian Ali , Koleva Yordanka , Andrews Patricia , Matharoo Gunita S. , Wright Ato E. , Saba Nakhle S. , Weiner Roy S. , Safah Hana 
Published: April 2017

AbstractBackground and ObjectivesSince a study published in 2002 showed a survival advantage of melphalan‐only conditioning for stem cell transplantation (HSCT) over melphalan‐total body irradiation (mel‐TBI) in patients with multiple myeloma (MM), most centers abandoned mel‐TBI. Mel‐TBI causes more early toxicity and is more complicated to administer, but we speculated it may result in longer term survival with radiation as an independent treatment modality. Therefore, we analyzed the long‐term outcome of patients with MM who received mel‐TBI as part of conditioning at our center.Patients and MethodsFrom 1995 to 2013, 50 patients with MM underwent autologous HSCT at Tulane University Medical Center using mel‐TBI conditioning. We used Kaplan‐Meier survival analysis and compared our patients with data available from the Louisiana Tumor Registry.ResultsThe mean survival of our patients was 70.98 months from time of transplant and 84.2 months from time of initial diagnosis. No differences were observed according to gender, ethnicity, or age at transplant. The expected median survival in a population‐based registry (matched for age and year of treatment) was 27 months (P<.001).ConclusionsTotal body irradiation in conjunction with melphalan as conditioning is feasible and can lead to long‐term survival. More research is necessary to determine which patients benefit most. Mel‐TBI should also be explored in conjunction with immunotherapy.
Characterization of the first naturally thermostable terpene synthases and development of strategies to improve thermostability in this family of enzymes
Authors: Styles Matthew Q. , Nesbitt Edward A. , Marr Scott , Hutchby Marc , Leak David J. 
Published: April 2017

The terpenoid family of natural products is being targeted for heterologous microbial production as a cheaper and more reliable alternative to extraction from plants. The key enzyme responsible for diversification of terpene structure is the class‐I terpene synthase (TS), and these often require engineering to improve properties such as thermostability, robustness and catalytic activity before they are suitable for industrial use. Improving thermostability typically relies on screening a large number of mutants, as there are no naturally thermostable TSs described upon which to base rational design decisions. We have characterized the first examples of natural TSs exhibiting thermostability, which catalyse the formation of the sesquiterpene τ‐muurolol at temperatures up to 78 °C. We also report an enzyme with a kcat value of 0.95 s−1 at 65 °C, the highest kcat recorded for a bacterial sesquiterpene synthase. In turn, these thermostable enzymes were used as a model to inform the rational engineering of another TS, with the same specificity but low sequence identity to the model. The newly engineered variant displayed increased thermostability and turnover. Given the high structural homology of the class‐I TS domain, this approach could be generally applicable to improving the properties of other enzymes in this class.DatabaseModel data are available in the PMDB database under the accession number PM0080780.
Which interval is most crucial to presentation and survival in gastroesophageal cancer: A systematic review
Authors: Lee Amanda , Khulusi Sam , Watson Roger 
Published: April 2017

AbstractAimThe aim of this study was to identify the most crucial interval to encourage earlier diagnosis in with gastroesophageal cancer and to identify potential factors effecting this interval.BackgroundGastroesophageal malignancy is the eighth most commonly presenting cancer with one of the worst survival rates. Identifying the most crucial period for intervention to inform earlier diagnosis is an important step towards improving survival.DesignMixed methods literature review.Data SourcesCINAHL, MEDLINE and Academic search primer online databases were searched using keywords and inclusion/exclusion criteria. Empirical evidence published between 2000–2016 with a focus on gastroesophageal cancer presentation and survival was reviewed to inform this study.Review methodsTwelve studies were extracted for further review. Selected studies were appraised and presented through Olensen's “delay interval” framework to inform the most crucial interval to survival in gastroesophageal cancer.ResultsThe findings identify the patient interval as the most critical period for encouraging earlier presentation and reducing advanced stage presentation in gastroesophageal cancer. The article also highlighted some methodological limitations to cancer research, such as a lack of consensus in definitions which prevent statistical meta‐analysis of cancer data, survivor bias in gastroesophageal cancer studies and a significant lack of qualitative evidence to reveal patient experience in presenting with this cancer.ConclusionFurther research into the patient interval is required to elicit information on how and why patients present with their cancer symptoms.
A mixed study systematic review of social media in nursing and midwifery education: Protocol
Authors: O'Connor Siobhan , Jolliffe Sarah , Stanmore Emma , Renwick Laoise , Schmitt Terri , Booth Richard 
Published: April 2017

AbstractAimTo synthesize evidence on the use of social media in nursing and midwifery education.BackgroundSocial media is one type of online platform that is being explored to determine if there is value in using interactive, digital communication tools to support how nurses and midwives learn in a variety of settings.DesignA sequential explanatory synthesis approach will be used for this mixed study review.MethodFive bibliographic databases; PubMed, MEDLINE, CINAHL, Scopus, and ERIC will be searched using a combination of keywords relevant to social networking and social media, nursing and midwifery, and education. The search will not be limited by year of publication. Titles, abstracts, and full papers will be screened by two independent reviewers against inclusion and exclusion criteria, with any disagreements resolved via a third reviewer. Selected studies will undergo quality assessment and data extraction. Data synthesis will occur in three sequential phases, with quantitative and qualitative data analysed separately and then integrated where possible to provide a conceptual framework illustrating learning via social media. Funding for this review was confirmed in May 2016 by Sigma Theta Tau International and the National League for Nursing.DiscussionThe mixed study systematic review will produce the first rigorous synthesis on the use of social media in nursing and midwifery education and will have important implications for educators as well as students. It will also highlight knowledge gaps and make recommendations on the use of this novel technology in higher and continuing education.
Overexpression of microRNA‐138 alleviates human coronary artery endothelial cell injury and inflammatory response by inhibiting the PI3K/Akt/eNOS pathway
Authors: Li Jing‐Bo , Wang Hai‐Yang , Yao Ye , Sun Qing‐Feng , Liu Zong‐Hong , Liu Si‐Qi , Zhuang Jun‐Li , Wang Yun‐Peng , Liu Hong‐Yu 
Published: April 2017

AbstractThis study aimed to investigate the role of miR‐138 in human coronary artery endothelial cell (HCAEC) injury and inflammatory response and the involvement of the PI3K/Akt/eNOS signalling pathway. Oxidized low‐density lipoprotein (OX‐LDL)‐induced HCAEC injury models were established and assigned to blank, miR‐138 mimic, miR‐138 inhibitor, LY294002 (an inhibitor of the PI3K/Akt/eNOS pathway), miR‐138 inhibitor + LY294002 and negative control (NC) groups. qRT‐PCR and Western blotting were performed to detect the miR‐138, PI3K, Akt and eNOS levels and the protein expressions of PI3K, Akt, eNOS, p‐Akt, p‐eNOS, Bcl‐2, Bax and caspase‐3. ELISAs were employed to measure the expressions of TNF‐α, IL‐4, IL‐6, IL‐8, IL‐10 and nitric oxide (NO) and the activities of lactate dehydrogenase (LDH) and eNOS. MTT and flow cytometry were performed to assess the proliferation and apoptosis of HCAECs. Compared to the blank group, PI3K, Akt and eNOS were down‐regulated in the miR‐138 mimic and LY294002 groups but were up‐regulated in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups showed decreased concentrations of TNF‐α, IL‐6, IL‐8 and NO and reduced activities of LDH and eNOS, while opposite trends were observed in the miR‐138 inhibitor group. The concentrations of IL‐4 and IL‐10 increased in the miR‐138 mimic and LY294002 groups but decreased in the miR‐138 inhibitor group. The miR‐138 mimic and LY294002 groups had significantly decreased cell proliferation and increased cell apoptosis compared to the blank group. These findings indicate that up‐regulation of miR‐138 alleviates HCAEC injury and inflammatory response by inhibiting the PI3K/Akt/eNOS signalling pathway.
Network meta‐analysis of studies included in the Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis
Authors: John Mike T. , Michalowicz Bryan S. , Kotsakis Georgios A. , Chu Haitao 
Published: April 2017

AbstractAimThe recent ADA‐commissioned Clinical Practice Guideline on the nonsurgical treatment of chronic periodontitis has provided the most exhaustive library of clinical trials on scaling and root planing (SRP) with or without adjuncts. This network meta‐analysis (NMA) compared the adjuncts against each other.Materials and MethodsA star‐shaped NMA was performed based on 36 indirect comparisons of clinical attachment‐level (CAL) gains among nine adjuncts in 74 studies from the Clinical Practice Guideline.ResultsAll pairwise differences were accompanied by wide confidence intervals, and none of the adjuncts were statistically significantly superior to another. Local doxycycline hyclate and photodynamic therapy with a diode laser had the highest probabilities for ranking first and second, respectively. Publication bias was evident, with fewer than expected studies with small effects. The lack of these studies inflated the treatment effects by an estimated by 20%.ConclusionsAdjuncts improve CAL gain by about a third of a mm over 6–12 months compared with SRP alone, but no significant differences were found among the adjuncts. The patient‐perceived benefit of this gain is unclear because CAL is a physical measure made by the clinician and not a patient‐oriented outcome. Publication bias inflated the observed treatment effects.
Autoantibodies against citrullinated histone H3 in rheumatoid arthritis and periodontitis patients
Authors: Janssen Koen M. J. , de Smit Menke J. , Withaar Coenraad , Brouwer Elisabeth , van Winkelhoff Arie J. , Vissink Arjan , Westra Johanna 
Published: April 2017

AbstractAimTo determine the presence of citrullinated histones in inflamed periodontal tissue and to determine the presence of anti‐citrullinated histone autoantibodies in sera from patients with rheumatoid arthritis (RA) and periodontitis (PD) patients.MethodsThe presence of citrullinated histone H3, PAD4 and CD68 was determined in 15 periodontal tissue biopsies from PD patients by immunohistochemistry. Sera from 36 healthy controls (HC), 113 PD patients and 84 patients with RA were assessed on presence of autoantibodies against citrullinated histones by Western blot and against citrullinated histone H3 by ELISA.ResultsCitrullinated histone H3, PAD4 and CD68 were present in periodontal tissue from nine (60%), 14 (93%) and 13 (87%) PD patients, respectively. Anti‐citrullinated histone H3 autoantibodies were found in 33 (39%) patients with RA compared to three (8%) HC and 11 (10%) PD patients. Anti‐citrullinated histone H3 levels were higher in anti‐cyclic citrullinated peptide (anti‐CCP)‐positive compared to anti‐CCP‐negative patients with RA (p = .0008) and correlated moderately with anti‐CCP levels (ρ = .22). No associations were found between anti‐citrullinated histone H3 levels and periodontal status or smoking behaviour of patients with RA.ConclusionPD patients are exposed to citrullinated histone H3 in inflamed periodontal tissue. Citrullinated histone H3 is targeted by autoantibodies present in RA sera. This supports a role for periodontitis in generation of antigens targeted by autoantibodies directed against citrullinated proteins.
Open‐label, randomized study comparing basal insulin peglispro and insulin glargine, in combination with oral antihyperglycemic medications, in insulin‐naïve Asian patients with type 2 diabetes
Authors: Hirose Takahisa , Cai Zhihong , Yeo Kwee Poo , Imori Makoto , Ohwaki Kenji , Imaoka Takeshi 
Published: April 2017

AbstractIntroductionThe present phase 3, randomized, open‐label study compared the efficacy and safety of basal insulin peglispro with insulin glargine after 26 weeks of treatment when added to oral antihyperglycemic medications in insulin‐naïve Asian patients with type 2 diabetes.Materials and MethodsThe primary objective was to show non‐inferiority of the change in glycated hemoglobin from baseline to 26 weeks.ResultsAt 26 weeks, insulin peglispro was non‐inferior to glargine, meeting the primary objective. Patients receiving insulin peglispro (n = 192) showed a greater reduction in glycated hemoglobin from baseline compared with glargine (n = 196); −1.6 vs −1.4%, P = 0.005) and in fasting serum glucose (−61.2 vs −54.8 mg/dL, P = 0.02). A significantly higher proportion of patients receiving insulin peglispro achieved glycated hemoglobin <7% (57 vs 44%, P = 0.012). Insulin peglispro patients showed significantly less weight gain from baseline (1.1 vs 1.6 kg, P = 0.03). Relative rates (insulin peglispro/glargine) of total and nocturnal hypoglycemia through 26 weeks were 1.06 (P = 0.67) and 0.7 (P = 0.10), respectively. Significantly more insulin peglispro‐treated patients experienced adverse events compared with glargine‐treated patients (P = 0.042). Alanine aminotransferase and aspartate aminotransferase were significantly increased from baseline with insulin peglispro compared with glargine at week 26 (3.5 vs −4.6 IU/L and 2.8 vs −1.5 IU/L, respectively; P < 0.001). The incidence of injection site reactions was low and did not differ between the treatments.DiscussionInsulin peglispro provided better glycemic control vs glargine with no differences in hypoglycemia and increased aminotransferases in insulin‐naïve Asian patients with type 2 diabetes.
Habitat‐related variation in the plasticity of a UV‐sensitive photoreceptor over a small spatial scale in the palmate newt
Authors: Secondi J. , Martin M. , Goven D. , Mège P. , Sourice S. , Théry M. 
Published: April 2017

AbstractPlastic phenotypes are expected to be favoured in heterogeneous environments compared with stable environments. Sensory systems are interesting to test this theory because they are costly to produce and support, and strong fitness costs are expected if they are not tuned to the local environment. Consistently, the visual system of several species changes with the conditions experienced during early development. However, there is little information on whether the amplitude of the change, that is the reaction norm, differs between visual environments. Given the rapid change of many ecosystems, especially eutrophication for aquatic habitats, it is crucial to determine down to which spatial scale, change in the reaction norm occurs. We addressed this issue by quantifying the between‐habitat variation in the expression of a UV‐sensitive opsin in a newt. In western France, this species breeds in ponds of small forest patches, where water filters out UV, and in agricultural ponds where UV transmission is variable. We raised larvae from both habitats with or without exposure to UV. Opsin expression was reduced in larvae from agricultural habitats when raised without UV, whereas it was low in larvae from forest ponds under all lighting conditions. Thus, the variation in the reaction norm of opsin expression was lower in stable filtering environments and higher in heterogeneous environments. Its variation occurred between habitats across a small spatial scale. We discuss the hypotheses for this pattern and for the maintenance of residual opsin expression in forest populations.
A randomized, single‐blinded trial of a tripeptide/hexapeptide healing regimen following laser resurfacing of the face
Authors: Vanaman Wilson Monique J , Bolton Joanna , Fabi Sabrina Guillen 
Published: April 2017

SummaryBackgroundA topical healing system containing a combination of active ingredients including a tripeptide and hexapeptide (TriHex Technology™) has been found to stimulate neoelastogenesis and neocollagenesis.ObjectiveEvaluate the use of the tripeptide/hexapeptide topical system following fractionated CO2 laser resurfacing compared to a bland ointment and cream.Patients/MethodsIn this single‐blinded, randomized study, 15 female subjects aged 45‐70 years underwent laser resurfacing of the face. Subjects were randomized to use of the tripeptide/hexapeptide system (n=10) or a bland dimethicone‐based ointment and petrolatum‐based cream (n=5) from 3 weeks pre‐ until 12 weeks postprocedure. A blinded investigator graded erythema, edema, crusting, exudation, and healing on postprocedure days 1, 3, 4, 7, 28, and 84. A photodamage/wrinkle scale was completed on days 28 and 84. Subjects performed symptomatology grading on days 1 through 14 and completed self‐assessments at days 28 and 84.ResultsData from 14 subjects were analyzed. Blinded‐investigator‐rated healing was better for the tripeptide/hexapeptide system, reaching statistical significance at day 7. The tripeptide/hexapeptide group demonstrated less erythema and exudation during the first postprocedure week, reaching significance at day 3. On days 1 through 14, subjects using the tripeptide/hexapeptide system reported less tenderness and burning/stinging, also reaching significance on day 3. At day 84, subjects using the tripeptide/hexapeptide system reported higher satisfaction and were more likely to recommend the treatment to others.ConclusionPostresurfacing use of a tripeptide/hexapeptide system proved effective and well‐tolerated. Subject satisfaction was greater among those using this system, which may indicate an improved patient experience following laser resurfacing.
Shortened dental arch and prosthetic effect on oral health‐related quality of life: a systematic review and meta‐analysis
Authors: Fueki K. , Baba K. 
Published: April 2017

SummaryThis systematic review aimed to compare oral health‐related quality of life (OHRQoL) between two tooth replacement strategies – the shortened dental arch (SDA) concept and conventional treatment with removable partial dental prosthesis (RPDP) or implant‐supported fixed partial dental prosthesis (IFPDP) – for distal extension of edentulous space in the posterior area. We retrieved eligible randomised controlled trials (RCTs) and non‐RCTs published between 1980 and November 2016 retrieved from MEDLINE and the Cochrane Central Register of Controlled Trials. The primary outcome was OHRQoL evaluated using validated questionnaires. Two reviewers independently screened and selected the articles, evaluated the risk of bias and determined the standardised weighted mean difference (SWMD) in OHRQoL scores between the two strategies using a random effects model. Two RCTs and one non‐RCT involving 516 participants were included in this review. All studies employed the oral health impact profile (OHIP) for evaluation of OHRQoL. There was no statistically significant difference in OHIP summary scores between SDA and RPDP at 6 (SWMD = 0·24) or 12 (SWMD = 0·40) months post‐treatment. Only one non‐RCT had reported higher OHRQoL with IFPDP than with SDA; however, because of the small sample size, there was no significant difference in OHIP summary scores between the two strategies at 6 (SWMD = −0·59) or 12 (SWMD = −0·67) months post‐treatment. In terms of OHRQoL in partially dentate patients, the SDA concept appears to be as feasible as RPDP restoration. Further clinical trials are required to clarify the effect of IFPDP restoration on OHRQoL.