bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1, open‐label, dose‐escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma
Authors: Dunn Tamara J. , Dinner Shira , Price Elizabeth , Coutré Steven E. , Gotlib Jason , Hao Ying , Berube Caroline , Medeiros Bruno C. , Liedtke Michaela 
Published: April 2016

SummaryPralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used. Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m2 and intravenous bortezomib at a dose of 1·3 mg/m2 on days 1, 8 and 15 of each 4‐week cycle. Eleven patients were enrolled and completed a median of two cycles. The maximum tolerated dose was 20 mg/m2. Two patients experienced dose‐limiting toxicity of mucositis. The most frequent non‐haematological toxicities were fatigue (55%) and mucositis (45%). There were three serious adverse events in three patients: rash, sepsis and hypotension. One patient (9%) had a very good partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and two (18%) had progressive disease. The median duration of response was 4 months, the median time to next treatment was 3·4 months and the median time to progression was 4 months. Pralatrexate, in combination with bortezomib, was generally safe and demonstrated modest activity in relapsed or refractory multiple myeloma. Clinicaltrials.gov identifier: NCT01114282.
Protein phosphatase 4 plays dual roles during cell proliferation
Authors: Huang Xiuqing , Liu Jin , Shen Tao , Meng Xiangyu , Dou Lin , Lin Yajun , Li Jian 
Published: April 2016

AbstractObjectivesProtein phosphatase 4 (PP4) has been reported to be indispensable for cell proliferation and survival. Deletion of PP4 has been shown to induce abnormal and even lethal events in growth and development both in lower eukaryotes and in mammals. However, until now, effects of PP4 up‐regulation have remained unclear.Materials and methodsTo test effects of PP4 on cell proliferation, cell cycle and morphology in HepG2 cells, it was down‐regulated using PP4 siRNA or its activity was inhibited using PP4RL (a PP4 phosphatase‐dead mutant) adenoviruses. Alternatively, PP4 was up‐regulated using PP4 adenoviruses. Next, we used a functional proteomic approach to identify proteins that may interact with PP4. Furthermore, we performed rescue experiments to verify the possible mechanisms.ResultsTo our surprise, we found that both up‐regulation and inhibition of PP4 inhibited cell proliferation. Unlike PP4 inhibition, PP4 up‐regulation induced prominent arrest at the prometaphase/metaphase transition by causing defects in chromosome alignment and spindle assembly. Moreover, we identified scaffold attachment factor A (SAF‐A) (an important protein required for kinetochore‐microtubule attachment that participates in the prometaphase/metaphase transition), to be a novel protein that interacts with PP4, using a proteomic approach. Thus, mutual regulatory mechanisms exist between PP4 and SAF‐A. Interactions between PP4 and SAF‐A played a role in prometaphase/metaphase transition.ConclusionsOur data demonstrate a novel regulatory mechanism involving PP4 in cell proliferation.
Speech discrimination in 11‐month‐old bilingual and monolingual infants: a magnetoencephalography study
Authors: Ferjan Ramírez Naja , Ramírez Rey R. , Clarke Maggie , Taulu Samu , Kuhl Patricia K. 
Published: April 2016

AbstractLanguage experience shapes infants' abilities to process speech sounds, with universal phonetic discrimination abilities narrowing in the second half of the first year. Brain measures reveal a corresponding change in neural discrimination as the infant brain becomes selectively sensitive to its native language(s). Whether and how bilingual experience alters the transition to native language specific phonetic discrimination is important both theoretically and from a practical standpoint. Using whole head magnetoencephalography (MEG), we examined brain responses to Spanish and English syllables in Spanish‐English bilingual and English monolingual 11‐month‐old infants. Monolingual infants showed sensitivity to English, while bilingual infants were sensitive to both languages. Neural responses indicate that the dual sensitivity of the bilingual brain is achieved by a slower transition from acoustic to phonetic sound analysis, an adaptive and advantageous response to increased variability in language input. Bilingual neural responses extend into the prefrontal and orbitofrontal cortex, which may be related to their previously described bilingual advantage in executive function skills. A video abstract of this article can be viewed at:https://youtu.be/TAYhj‐gekqw
Modelling the cost‐effectiveness of adopting risk‐stratified approaches to extended screening intervals in the national diabetic retinopathy screening programme in Scotland
Authors: Scotland G. , McKeigue P. , Philip S. , Leese G. P. , Olson J. A. , Looker H. C. , Colhoun H. M. , Javanbakht M. 
Published: April 2016

AbstractAimsTo assess the cost‐effectiveness of adopting risk‐stratified approaches to extended screening intervals in the national diabetic retinopathy screening programme in Scotland.MethodsA continuous‐time hidden Markov model was fitted to national longitudinal screening data to derive transition probabilities between observed non‐referable and referable retinopathy states. These were incorporated in a decision model simulating progression, costs and visual acuity outcomes for a synthetic cohort with a covariate distribution matching that of the Scottish diabetic screening population. The cost‐effectiveness of adopting extended (2–year) screening for groups with no observed retinopathy was then assessed over a 30–year time horizon.ResultsIndividuals with a current grade of no retinopathy on two consecutive screening episodes face the lowest risk of progressing to referable disease. For the cohort as a whole, the incremental cost per quality‐adjusted life year gained for annual vs. biennial screening ranged from approximately £74 000 (for those with no retinopathy and a prior observed grade of mild or observable background retinopathy) to approximately £232 000 per quality‐adjusted life year gained (for those with no retinopathy on two consecutive screening episodes). The corresponding incremental cost‐effectiveness ratios in the subgroup with Type 1 diabetes were substantially lower; approximately £22 000 to £85 000 per quality‐adjusted life year gained, respectively.ConclusionsBiennial screening for individuals with diabetes who have no retinopathy is likely to deliver significant savings for a very small increase in the risk of adverse visual acuity and quality of life outcomes. There is greater uncertainty regarding the long‐term cost‐effectiveness of adopting biennial screening in younger people with Type 1 diabetes.
Survey of student attitudes towards digital simulation technologies at a dental school in China
Authors: Ren Q. , Wang Y. , Zheng Q. , Ye L. , Zhou X. D. , Zhang L. L. 
Published: April 2016

AbstractIntroductionDigital simulation technologies have become widespread in healthcare education, especially in dentistry; these technologies include digital X‐ray images, digital microscopes, virtual pathology slides and other types of simulation. This study aimed to assess students’ attitudes towards digital simulation technologies at a large, top‐ranked dental school in China, as well as find out how students compare the digital technologies with traditional training methods.MethodsIn April 2015, a custom‐designed questionnaire was distributed to a total of 389 students who had received digital technology and simulation‐based training in West China Dental School during 2012–2014.ResultsResults of a cross‐sectional survey show that most students accept digital simulation technology; they report that the technology is stimulating and facilitates self‐directed and self‐paced learning.ConclusionThese findings, together with the objective advantages of digital technology, suggest that digital simulation training offers significant potential for dental education, highlighting the need for further research and more widespread implementation.
Integration of ultrasound imaging into pre‐clinical dental education
Authors: Kondrashova T. , De Wan D. , Briones M. U. , Kondrashov P. 
Published: April 2016

AbstractIntroductionPatients have complex healthcare needs and typically require more than one healthcare discipline to address issues regarding their health. Interprofessional teams of healthcare professionals may be able to address these complex needs and improve patient outcomes by combining resources. To evaluate the feasibility of integrating ultrasound into a dental school curriculum to teach anatomy as part of an interprofessional education experience, the current study surveyed first‐year dental students to determine their perceptions of the integration of ultrasound techniques into the curriculum.Materials and MethodsUltrasound laboratory exercises were developed for first‐year dental students as part of their anatomy course. The exercises were focused on head, neck and abdominal anatomy. To assess student perception of the integration of ultrasound into the dental curriculum, a survey was created specifically for the current study.ResultsBetween 2013 and 2015, two classes of first‐year dental students participated in the ultrasound laboratory exercise and completed the survey (n = 83). Student survey responses suggested ultrasound was a valuable teaching tool because it allowed them to visualise anatomical structures using live imaging. They also agreed that the ultrasound laboratory exercises were an efficient learning tool, but the majority did not believe that they would use ultrasound regularly in their future practice.ConclusionsResults of the current study suggested first‐year dental students were satisfied with the integration of ultrasound techniques into the dental curriculum. Survey results indicated that the students enjoyed the ultrasound laboratory exercise and felt ultrasound was an effective learning tool.
Do tropical rain forest soils have greater nematode diversity than High Arctic tundra? A metagenetic comparison of Malaysia and Svalbard
Authors: Kerfahi Dorsaf , Tripathi Binu M. , Porazinska Dorota L. , Park Jungok , Go Rusea , Adams Jonathan M. 
Published: April 2016

AbstractAimLatitudinal differences in diversity have long fascinated ecologists. It is unclear whether small soil animals such as nematodes show latitudinal differences in diversity. Based on hypotheses concerning the basis for greater tropical diversity, and by analogy with other groups, we predicted (1) greater alpha diversity in the equatorial tropics than the High Arctic, (2) greater beta and gamma diversity in the tropics. We also predicted (3) no species overlap between the tropics and the High Arctic, and (4) lower abundance of root feeding and insect parasitic nematodes in the high Arctic.LocationWe sampled at three sites in equatorial rain forest in Malaysia at 2° N and three sites in High Arctic tundra in Svalbard at 79° N.MethodsIn Malaysia and Svalbard, three sets of 1‐m2 samples were taken, in interrupted grids. Nematodes were extracted using a Baermann funnel. Bulk DNA was amplified by polymerase chain reaction for the 18S rRNA gene, followed by 454‐pyrosequencing.ResultsComparing operational taxonomic unit (OTU)‐based nematode communities (99% sequence similarity), averaged alpha diversity per 1‐m2 quadrat showed no difference between Malaysia and Svalbard. However, the classic beta diversity and gamma diversity of nematodes was higher for Malaysia.Main conclusionsThere was, surprisingly, no difference in the alpha diversity of nematodes between Malaysia and Svalbard. However, for beta and gamma diversity, diversity was higher in Malaysia. There was also considerable OTU overlap between the two regions, suggesting that very broad climatic niches are common in nematode ecology. Plant root feeders and insect parasites were relatively more common in Svalbard. Overall, we found a mixed and complex picture in terms of agreement with what would be predicted on the basis of ecological theory and observations on other groups. While further confirmatory studies would be beneficial, there is a need to incorporate these new findings in the formulation of hypotheses and tests for the underlying causes of latitudinal trends.
Effects of silymarin on biochemical and oxidative stress markers in end‐stage renal disease patients undergoing peritoneal dialysis
Authors: Firuzi Omidreza , Khajehrezaei Soraya , Ezzatzadegan Shahrokh , Nejati Maryam , Jahanshahi Keramat‐Allah , Roozbeh Jamshid 
Published: April 2016

AbstractIntroductionEnd‐stage renal disease (ESRD) patients especially those undergoing dialysis are vulnerable to several complications, in particular those related to oxidative stress. Silymarin is an herbal medicine commonly used as an antioxidant in different pathologies.MethodsTo evaluate the effect of silymarin on biochemical and oxidative stress markers, 50 ESRD patients undergoing peritoneal dialysis were randomly divided into two groups of silymarin (n = 28) and control (n = 22) and received silymarin (140 mg every 8 hours) or placebo for 2 months, respectively. Ferric reducing antioxidant power and total 8‐iso‐prostaglandin F2αwere measured in plasma, while catalase enzyme activity was measured in erythrocytes of both groups before and after treatment.FindingsFerric reducing antioxidant power values after treatment were significantly decreased in silymarin group compared to before treatment values (17.2 ± 2.9 and 15.9 ± 3.1 µM equivalent of quercetin/dL, respectively, P < 0.05). Conversely, catalase levels were increased 17.3% after silymarin consumption, while it was decreased 9.1% in control group. Further, hemoglobin (from 10.94 ± 2.17 to 11.54 ± 2.03 g/dL, P < 0.05) and albumin levels (from 3.48 ± 0.67 to 3.61 ± 0.53 g/dL, P < 0.05) were significantly increased after silymarin administration.DiscussionIt is concluded that silymarin could be regarded as a supplementary therapy for ESRD patients undergoing peritoneal dialysis in order to reduce complications.
Meal replacements as a strategy for weight loss in obese hemodialysis patients
Authors: Lassemillante Annie‐Claude M. , Oliver Veronica , Hickman Ingrid , Murray Eryn , Campbell Katrina L. 
Published: April 2016

AbstractIntroduction There is currently limited evidence on the use or safety of meal replacements as part of a low– or very–low‐calorie diet in patients with renal insufficiency; however, these are occasionally used under dietetic supervision in clinical practice to achieve the desired weight loss for kidney transplant. This case series reports on the safety and efficacy of a weight loss practice utilizing meal replacements among hemodialysis patients, who needed to lose weight for kidney transplant.Methods Five hemodialysis patients were prescribed a modified low‐calorie diet (950 kcal and 100 g protein per day) comprising three meal replacements (Optifast®), one main meal, and two low‐potassium fruits per day. Dietary requirements and restrictions were met for all participants. Dialysis prescriptions, weight (predialysis and postdialysis), interdialytic weight gain, biochemistry, and medications were monitored during the study period for up to 12 months.Findings Participants were aged between 46 and 61 years, and the median time on the low‐calorie diet was 364 days. Phosphate binders were temporarily ceased for one participant for reasons unrelated to this program and no other safety concerns were recorded. The low‐calorie diet resulted in energy deficits ranging from 1170 kcal to 2160 kcal, and all participants lost weight (median 7% [range 5.2%–11.4%]). The most dramatic weight change appeared to occur by week 12, and declining adherence led to erratic weight change thereafter.Discussion This modified low‐calorie diet was safe and effective to use in this population. Meal replacements are a useful weight loss strategy in hemodialysis patients, therefore, offering an alternative to usual weight loss protocols.
The Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Report on Baseline Characteristics of Participants
Authors: Powers Scott W. , Hershey Andrew D. , Coffey Christopher S. , Chamberlin Leigh A. , Ecklund Dixie J.D. , Sullivan Stephanie M. , Klingner Elizabeth A. , Yankey Jon W. , Kashikar‐Zuck Susmita , Korbee Leslie L. , Costigan Michele L. , Riss Holly H. , Porter Linda L. 
Published: April 2016

ObjectiveTo describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double‐blinded, placebo‐controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study).MethodsChildren and adolescents (age 8–17 years old, inclusive) diagnosed with migraine with or without aura, having headaches at least four times per month were enrolled from 2012 through 2014. The trial involved a baseline period (minimum of 28 days) during which prospective diaries were completed and demographics and headache features obtained.ResultsA total of 488 children and adolescents (mean age 14.0 ± 2.4 years) agreed to participate in the trial, with 361 randomized and 127 not randomized. Randomized subjects had a 5.5 ± 3.1 year history of headaches, with 15.1 ± 7.1 headache days per month (based upon retrospective report at screening visit). Prospective diaries reported 11.5 ± 6.1 headache days per 28 day baseline. Across this 28 day period, reported headache days per week were stable (about 3 headache days per week). Recording of individual headache features by diary (n = 4136 headache days) showed characteristics consistent with migraine (mean duration 10.5 ± 8.1 hours, mean severity 6.0 ± 2.1, 60% throbbing, 55% with activity worsening headaches, 55% with photophobia, and 47% with phonophobia).ConclusionsBaseline data from the CHAMP Study suggested that the randomized sample was representative of the real world population of children and adolescents that present for treatment of migraine. Headaches in children and adolescents recorded during a 28 day prospective baseline period in this multi‐site comparative effectiveness study did not change over the course of the baseline period, even though a clear diagnosis, recommendation for effective acute treatment, and standardized education about healthy habits occurred prior to the diary collection period.
Headache Education in Adult Neurology Residency: A Survey of Program Directors and Chief Residents
Authors: Ahmed Zubair A. , Faulkner Larry R. 
Published: April 2016

ObjectiveThis cross‐sectional study reassesses the status of headache didactics and clinical training in adult neurology residency programs in the United States to determine if program directors and chief residents feel that current training in headache is adequate.BackgroundHeadache is among the most common new complaints to both the neurology and primary care clinic and represents a significant economic burden. However, headache remains both under‐diagnosed and under‐treated. Of those who seek treatment only 28% report they are very satisfied with their management. One possible cause for dissatisfaction is inadequate education of treating physicians. Two studies in 2002 and 2005 that collectively surveyed all 125 adult neurology residency programs concluded that more evidence was needed to evaluate the adequacy of headache education in these programs. A survey of neurology residency department chairs and program directors in 2005 also evaluated the status of headache education in adult neurology training programs and concluded the same.MethodsWe surveyed 133 neurology residency program directors and 213 chief residents. Program directors and chief residents were asked about the amount of headache didactics, amount of clinical exposure to headache, perceived adequacy of current training and if plans existed to increase headache education through didactics or clinical exposure.ResultsSeventy‐two program directors (54%) and 117 chief residents (55%) responded. Twenty‐six percent of programs reported a mandatory headache clinic. Of these, 35% of programs reported <2 weeks of clinic, 54% of programs reported 2‐4 weeks, and 12% of programs reported > 4 weeks of clinic. Fifty‐one percent of program directors felt more than 4 weeks of clinical exposure to headache was needed to adequately prepare neurology residents. Ninety‐six percent of program directors surveyed believed their residents were adequately prepared to diagnose and treat headache disorders. Twenty‐one percent had plans to increase didactic time and 26% planned to incorporate more clinical exposure.ConclusionsDespite a modest increase in headache didactics in neurology residency programs over the last decade, many program directors and chief residents report that their programs do not include what they believe to be adequate educational experiences in headache. Although the overwhelming majority of neurology residency programs reported that residents were adequately prepared to diagnose and treat headache disorders, about a fourth of programs still felt the need to increase the amount of didactic and clinical exposure dedicated toward the management of headache disorders.
Microwave‐assisted extraction in goji berries: effect on composition and bioactivity, evaluated through conventional and nonconventional methodologies
Authors: Carvalho Ana P. , Mendes Marta , Moreira Manuela M. , Cruz Diana , Magalhães Júlia M. C. S. , Barroso M. Fátima , Ramalhosa M. J. , Duarte Abel , Guido Luís , Gomes Ana M. , Matos Cristina Delerue 
Published: April 2016

SummaryThis study aimed to evaluate the effect of microwave‐assisted extraction (MAE) parameters on the composition and bioactivity of goji (Lycium barbarum) extracts. Extracts were obtained under a central composite design combination of experimental conditions, and characterised through HPLC‐DAD; their bioactive capacity was ascertained for antimicrobial and antioxidant capacity, the later by spectrophotometric [2,2‐azinobis (3‐ ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt‐radical scavenging activity assay – 413–748 mg ascorbic acid equivalents/100 g DW and oxygen radical absorbance capacity – 1901–2292 mg trolox equivalents/100 g DW] and electrochemical (DNA‐based sensor – 3571–6602 mg ascorbic acid/100 g DW) methods. The quantitative profile of phenolic compounds was strongly dependent on MAE conditions. Significant correlations were found between the presence of several flavonoids and solvent composition, as well as between phenolic acids with methoxy group and the response to DNA‐based sensor. Results may improve targeted extractions for specific compounds, leading to the achievement of extracts richer in antioxidant capacity, as well as in the tailoring of the biosensor response sensitivity to the composition of the extracts under analysis.