bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro‐to‐In Vivo Extrapolation of Transporter Inhibition Data for Drugs Approved by the US Food and Drug Administration in 2018
Authors: Yu Jingjing , Ragueneau‐Majlessi Isabelle 
Published: January 2020

A systematic analysis of the inhibition transporter data available in New Drug Applications of drugs approved by the US Food and Drug Administration (FDA) in 2018 (N = 42) was performed. In vitro‐to‐in vivo predictions using basic models were available for the nine transporters currently recommended for evaluation. Overall, 29 parents and 16 metabolites showed in vitro inhibition of at least one transporter, with the largest number of drugs found to be inhibitors of P‐gp followed by BCRP. The most represented therapeutic areas were oncology drugs and anti‐infective agents, each comprising 31%. Among drugs with prediction values greater than the FDA recommended cutoffs and further evaluated in vivo, 56% showed positive clinical interactions (area under the concentration‐time curve ratio (AUCRs) ≥ 1.25). Although all the observed or simulated inhibitions were weak (AUCRs < 2), seven of the nine interactions (involving five drugs) resulted in labeling recommendations. Interestingly, more than half of the drugs with predictions greater than the cutoffs had no further evaluations, highlighting that current basic models represent a useful, simple first step to evaluate the clinical relevance of in vitro findings, but that multiple other factors are considered when deciding the need for clinical studies. Four drugs had prediction values less than the cutoffs but had clinical evaluations or physiologically‐based pharmacokinetic simulations available. Consistent with the predictions, all of them were confirmed not to inhibit these transporters in vivo (AUCRs of 0.94–1.09). Overall, based on the clinical evaluations available, drugs approved in 2018 were found to have a relatively limited impact on drug transporters, with all victim AUCRs < 2.
Twenty years with diabetes and amputations: a retrospective population‐based cohort study
Authors: Røikjer J. , Jensen M. H. , Vestergaard P. , Sørensen A. M. , Laursen H. V. B. , Ejskjær N. 
Published: January 2020

AbstractAimTo investigate the trends in non‐traumatic lower limb amputation in people with and without diabetes.MethodsFrom the Danish National Patient Register, all people with either type 1 or type 2 diabetes (n = 462 743) as well as a group of people without diabetes from the general population (n = 1 388 886) were identified and separated into three groups based on diabetes type. Among these, 17 265 amputations were identified between 1997 and 2017 and stratified into trans‐femoral amputations, trans‐tibial amputations and amputations below the ankle using surgical codes. Annual changes were described using least‐squares linear regression.ResultsThe yearly mean decrease in incidence rate of amputation per 1000 person‐years was −0.032 [95% CI: −0.062, −0.001], −0.022 [−0.032, −0.012] and −0.006 [−0.009, −0.003] for trans−femoral amputation, −0.072 [−0.093, −0.052], −0.090 [−0.102, −0.078] and −0.015 [−0.016, −0.013] for trans‐tibial amputation, and −0.055 [−0.080, −0.020], −0.075 [−0.090, −0.060] and −0.011 [−0.014, −0.007] for amputation below the ankle in people with type 1 diabetes, people with type 2 diabetes and people without diabetes, respectively.ConclusionsOver recent decades, the incidence of amputation has decreased significantly in people with diabetes and in the general population without diabetes.
Public investment efficiency and sectoral economic growth in Pakistan
Authors: Qazi Masood Ahmed , Ammad Syed 
Published: January 2020

AbstractMotivationThe issue of the effect of public investment on private investment and consequently on growth is much debated in economic literature. On the one hand the classical school believes that increment in public spending reduces economic growth by crowding out private investment, whereas Keynesians, on the other hand, consider government spending a key variable for economic growth.PurposeLike other developing economies Pakistan is also facing a high budget deficit which curtails public spending. This study estimates the relative effects of public investment in physical (infrastructure and energy) and social (health and education) sectors on output by estimating long term marginal productivity.Approach and MethodsThis study used the vector autoregressive/vector error correction model (VAR/VECM) technique to measure the effect of public investment on output, private investment and employment; separate VAR models are estimated for each sector and each type of public spending. Further, in order to attain these uncorrelated residuals, Cholesky decomposition is used and the resulting accumulated impulse response measures the cumulative response of all variables due to change in policy variable i.e. public investment.FindingsThis study indicates that public investments have a crowding in effect in 49 cases, while in 21 cases there is crowding out, 34 cases indicate labour absorption effect, while 36 cases show labour substitutions and 52 cases show a positive output effect, while in 18 cases output effects are negative. Overall, these results indicate that all types of public investments are growth stimulating through both crowding‐in and labour absorption effects.Policy ImplicationsThe overwhelming results illuminate that public investment had attracted private investment in Pakistan in the past and therefore to attract private investment in future, the government of Pakistan should increase public investment. This lesson can also be substantiated from the experience of several developing countries, particularly India. In India, the last 20 years have seen very high public investment despite high fiscal deficit, which has led to very high economic growth.
Development of e‐portfolio in undergraduate clinical dentistry: How trainees select and reflect on evidence
Authors: Greviana Nadia , Mustika Rita , Soemantri Diantha 
Published: January 2020

AbstractIntroductionSelf‐reflection is a fundamental part of health professional development, especially in the unstructured clinical stage of dentistry, medical and health profession education, since it plays important role in experiential learning. A portfolio—both conventional and digital—records various aspects of knowledge, skills and attitudes over a long period of time to help students develop their professionalism by conducting self‐reflection. This study aims to explore the process of selecting and reflecting on professionalism evidence recorded in e‐portfolios during undergraduate clinical dentistry training.MethodThis pilot study is a qualitative study with a phenomenological design. The selection of respondents was conducted using a maximum variety sampling method. Following a 6‐week pilot programme, a total of six in‐depth interviews and five focus group discussions were conducted with undergraduate students representing different clinical rotations to explore the process conducted by undergraduate clinical dentistry students in e‐portfolio development. The study of documents was also conducted on the respondents' reflective writing from the e‐portfolio back‐end data to explore their self‐reflection skills.ResultThe results of the present study highlighted two different approaches used amongst trainees in developing a reflective e‐portfolio: selective and non‐selective. The observed reflective e‐portfolio utilisation frequency and trainees' self‐reflection skills were low, with several affecting factors identified. These identified factors consisted of external factors, such as the undergraduate clinical dentistry programme curriculum, the hidden curriculum, the availability of feedback, the availability of role models, and features of the e‐portfolio and internal factors, such as understanding the self‐reflection concept, the availability of time and mood, cultural factors, and understanding the content reflected.ConclusionThrough the process of independently selecting and recording learning activities in e‐portfolios as well as repeatedly conducting self‐reflection, trainees can improve their overall reflective abilities. However, producing a systematic approach to forming a reflective learning environment is necessary to aid the implementation of reflective e‐portfolios, especially at the early stage of e‐portfolio implementation.
Reevaluating the role of ferritin in the diagnosis of adult secondary hemophagocytic lymphohistiocytosis
Authors: Naymagon Leonard , Tremblay Douglas , Mascarenhas John 
Published: January 2020

AbstractBackgroundThe standard diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) include hyperferritinemia to >500 ng/mL. This ferritin threshold is based on pediatric data, and evidence for its application among adults with secondary HLH is lacking.Objective and MethodsWe conducted a retrospective study assessing the relationship between extreme hyperferritinemia and adult secondary HLH at our institution. All adult inpatients seen over a 10‐year period, with serum ferritin >5000 ng/mL, were included.ResultsAmong 1055 patients with serum ferritin >5000 ng/mL, there were 69 cases of HLH (HLH prevalence of 6.5%). Mean ferritin among HLH patients was 70 398 ng/mL (SD 122 908), median 40 019 ng/mL (IQR 16 051‐68 326). The prevalence of HLH only reached 50% as serum ferritin approached 90 000 ng/mL. A variety of conditions were contributory to hyperferritinemia, most commonly bacterial sepsis (33%), hematologic malignancy (29%), renal failure (24%), and liver injury (18%). The optimal cutoff ferritin for diagnosis of HLH was 16 000 ng/mL (sensitivity 79.4%, specificity 79.2%, PPV 20.9%, and NPV 98.2%).ConclusionsThe threshold ferritin levels used in diagnostic criteria for adult secondary HLH are too low to be clinically relevant, and efforts should be undertaken to revise them upward. Similar reappraisals should be taken of the other criteria used to diagnose adult HLH.
Mortality and morbidity of patients with treated and untreated epilepsy in New Zealand
Authors: Hamilton Kristen Joy , Chen Zhibin , Tomlin Andrew , Kwan Patrick 
Published: January 2020

AbstractObjectiveTo investigate whether delayed or no treatment was associated with increased mortality and morbidity risks in people with newly diagnosed epilepsy.MethodsWe examined New Zealand hospitalization and antiseizure medication prescription data from 2007‐2015. Mortality and hospital‐diagnosed morbidities were compared between patients immediately treated after epilepsy diagnosis, treated after a delay, or untreated for the duration of follow‐up, adjusted for age, sex, and ethnicity.ResultsThree thousand three hundred sixty‐six patients (54.7% male, median age = 37.5 years) were included and followed up for a median of 3.39 years. A total of 3123 (92.8%) patients were treated immediately, 125 (3.7%) had delayed treatment, and 118 (3.5%) were untreated. Compared to the general New Zealand population, the cohort had a standardized mortality ratio of 4.60 (95% confidence interval [CI] = 4.24‐4.99). Maori patients were less likely to be treated (Holm‐Bonferroni adjusted P = .024) and had higher mortality (hazard ratio [HR] = 1.41, 95% CI = 1.08‐1.83). There was a trend of increased mortality in the untreated or delayed treatment group compared to the immediate treatment group (HR = 1.36, 95% CI = 0.99‐1.87). Hospitalization risk was similar between untreated and immediately treated periods (P = .83). Untreated or delayed treatment patients had higher risk of acute myocardial infarction (HR = 9.64, 95% CI = 1.83‐50.8). Maori patients were more likely to develop liver disease (HR = 4.67, 95% CI = 1.32‐16.4) and alcohol or drug dependence (HR = 2.55, 95% CI = 1.44‐4.51).SignificanceMost epilepsy patients were treated at diagnosis in New Zealand, but Maori patients had lower treatment rates and worse health outcomes. The apparent increased risk of acute myocardial infarction among the untreated or delayed treatment patients warrants further research.
Traffic noise differentially impacts call types in a Japanese treefrog (Buergeria japonica)
Authors: Legett Henry D. , Madden Ryan P. , Aihara Ikkyu , Bernal Ximena E. 
Published: January 2020

AbstractAcoustic noise from automobile traffic impedes communication between signaling animals. To overcome the acoustic interference imposed by anthropogenic noise, species across taxa adjust their signaling behavior to increase signal saliency. As most of the spectral energy of anthropogenic noise is concentrated at low acoustic frequencies, species with lower frequency signals are expected to be more affected. Thus, species with low‐frequency signals are under stronger pressure to adjust their signaling behaviors to avoid auditory masking than species with higher frequency signals. Similarly, for a species with multiple types of signals that differ in spectral characteristics, different signal types are expected to be differentially masked. We investigate how the different call types of a Japanese stream breeding treefrog (Buergeria japonica) are affected by automobile traffic noise. Male B. japonica produce two call types that differ in their spectral elements, a Type I call with lower dominant frequency and a Type II call with higher dominant frequency. In response to acoustic playbacks of traffic noise, B. japonica reduced the duration of their Type I calls, but not Type II calls. In addition, B. japonica increased the call effort of their Type I calls and decreased the call effort of their Type II calls. This result contrasts with prior studies in other taxa, which suggest that signalers may switch to higher frequency signal types in response to traffic noise. Furthermore, the increase in Type I call effort was only a short‐term response to noise, while reduced Type II call effort persisted after the playbacks had ended. Overall, such differential effects on signal types suggest that some social functions will be disrupted more than others. By considering the effects of anthropogenic noise across multiple signal types, these results provide a more in‐depth understanding of the behavioral impacts of anthropogenic noise within a species.
Effects of laser peening on the fatigue strength and defect tolerance of aluminum alloy
Authors: Takahashi Koji , Kogishi Yuta , Shibuya Norihito , Kumeno Fumiaki 
Published: January 2020

AbstractThe effects of laser peening (LP) on the bending fatigue strength of the 7075‐T651 aluminum alloy were investigated. Accordingly, the defect tolerance of the aluminum alloy subjected to LP is discussed on the basis of fracture mechanics. The results indicate that a deeper compressive residual stress was induced by LP compared with the case of shot peening (SP). The fatigue strengths increased when both peening types were used. Semicircular slits with depths less than 0.4 and 0.1 mm were rendered harmless on the basis of the applications of LP and SP, respectively. The apparent threshold stress intensity factor range ΔKth,ap increased by approximately five and two times owing to LP and SP, respectively. The increase of the ΔKth,ap was caused by the compressive residual stress induced by the peening. The Kitagawa‐Takahashi diagram of the laser‐peened specimens shows that the defect tolerance of the aluminum alloy was improved by LP.
Impact of forest plantation on methane emissions from tropical peatland
Authors: Deshmukh Chandra S. , Julius Dony , Evans Chris D. , Nardi  , Susanto Ari P. , Page Susan E. , Gauci Vincent , Laurén Ari , Sabiham Supiandi , Agus Fahmuddin , Asyhari Adibtya , Kurnianto Sofyan , Suardiwerianto Yogi , Desai Ankur R. 
Published: January 2020

AbstractTropical peatlands are a known source of methane (CH4) to the atmosphere, but their contribution to atmospheric CH4 is poorly constrained. Since the 1980s, extensive areas of the peatlands in Southeast Asia have experienced land‐cover change to smallholder agriculture and forest plantations. This land‐cover change generally involves lowering of groundwater level (GWL), as well as modification of vegetation type, both of which potentially influence CH4 emissions. We measured CH4 exchanges at the landscape scale using eddy covariance towers over two land‐cover types in tropical peatland in Sumatra, Indonesia: (a) a natural forest and (b) an Acacia crassicarpa plantation. Annual CH4 exchanges over the natural forest (9.1 ± 0.9 g CH4 m−2 year−1) were around twice as high as those of the Acacia plantation (4.7 ± 1.5 g CH4 m−2 year−1). Results highlight that tropical peatlands are significant CH4 sources, and probably have a greater impact on global atmospheric CH4 concentrations than previously thought. Observations showed a clear diurnal variation in CH4 exchange over the natural forest where the GWL was higher than 40 cm below the ground surface. The diurnal variation in CH4 exchanges was strongly correlated with associated changes in the canopy conductance to water vapor, photosynthetic photon flux density, vapor pressure deficit, and air temperature. The absence of a comparable diurnal pattern in CH4 exchange over the Acacia plantation may be the result of the GWL being consistently below the root zone. Our results, which are among the first eddy covariance CH4 exchange data reported for any tropical peatland, should help to reduce the uncertainty in the estimation of CH4 emissions from a globally important ecosystem, provide a more complete estimate of the impact of land‐cover change on tropical peat, and develop science‐based peatland management practices that help to minimize greenhouse gas emissions.
Copper Isotopic Analysis in Geological and Biological Reference Materials by MC‐ICP‐MS
Authors: Sullivan Kaj , Layton‐Matthews Daniel , Leybourne Matthew , Kidder James , Mester Zoltán , Yang Lu 
Published: January 2020

The characterisation of relative copper isotope amount ratios (δ65Cu) helps constrain a variety of geochemical processes occurring in the geosphere, biosphere and hydrosphere. The accurate and precise determination of δ65Cu in matrix reference materials is crucial in the effort to validate measurement methods. With the goal of expanding the number and variety of available geological and biological materials, we have characterised the δ65Cu values of ten reference materials by MC‐ICP‐MS using C‐SSBIN model for mass bias correction. SGR‐1b (Green River shale), DOLT‐5 (dogfish liver), DORM‐4 (fish protein), TORT‐3 (lobster hepatopancreas), MESS‐4 (marine sediment) and PACS‐3 (marine sediment) have for the first time been characterised for δ65Cu. Additionally, four reference materials (with published δ65Cu values) have been characterised: BHVO‐1 (Hawaiian basalt), BIR‐1 (Icelandic basalt), W‐2a (diabase) and Seronorm™ Trace Elements Serum L‐1 (human serum). The reference materials measured in this study possess complex and varied matrices with copper mass fractions ranging from 1.2 µg g−1 to 497 µg g−1 and δ65Cu values ranging from −0.20‰ to 0.52‰ with a mean expanded uncertainty of ± 0.07‰ (U, k = 2), covering much of the natural copper isotope variability observed in the environment.
DEC1 regulates the rhythmic expression of PPARγ target genes involved in lipid metabolism in white adipose tissue
Authors: Noshiro Mitsuhide , Kawamoto Takeshi , Nakashima Ayumu , Ozaki Noritsugu , Saeki Masayumi , Honda Kiyomasa , Fujimoto Katsumi , Kato Yukio 
Published: January 2020

AbstractPreviously, we found that the basic helix‐loop‐helix transcriptional repressor DEC1 interacts with the PPARγ:RXRα heterodimer, a master transcription factor for adipogenesis and lipogenesis, to suppress transcription from PPARγ target genes (Noshiro et al., Genes to Cells, 2018, 23:658‐669). Because the expression of PPARγ and several of its target genes exhibits circadian rhythmicity in white adipose tissue (WAT), we examined the expression profiles of PPARγ target genes in wild‐type and Dec1−/− mice. We found that the expression of PPARγ target genes responsible for lipid metabolism, including the synthesis of triacylglycerol from free fatty acids (FFAs), lipid storage and the lipolysis of triacylglycerol to FFAs, oscillates in a circadian manner in WAT. Moreover, DEC1 deficiency led to a marked increase in the expression of these genes at night (Zeitgeber times 16 and 22), resulting in disruption of circadian rhythms. Serum FFA levels in wild‐type mice also showed circadian oscillations, but these were disrupted by DEC1 deficiency, leading to reduced FFA levels. These results suggest that PPARγ:RXRα and DEC1 cooperatively generate the circadian expression of PPARγ target genes through PPAR‐responsive elements in WAT.
A Pilot Randomized Controlled Trial to Assess the Impact of Motivational Interviewing on Initiating Behavioral Therapy for Migraine
Authors: Minen Mia T. , Sahyoun Gabriella , Gopal Ariana , Levitan Valeriya , Pirraglia Elizabeth , Simon Naomi M. , Halpern Audrey 
Published: January 2020

BackgroundRelaxation, biofeedback, and cognitive behavioral therapy are evidence‐based behavioral therapies for migraine. Despite such efficacy, research shows that only about half of patients initiate behavioral therapy recommended by their headache specialists.ObjectiveMotivational interviewing (MI) is a widely used method to help patients explore and overcome ambivalence to enact positive life changes. We tested the hypothesis that telephone‐based MI would improve initiation, scheduling, and attending behavioral therapy for migraine.MethodsSingle‐blind randomized controlled trial comparing telephone‐based MI to treatment as usual (TAU). Participants were recruited during their appointments with headache specialists at two sites of a New York City medical center. Inclusion criteria: ages from 16 to 80, migraine diagnosis by United Council of Neurologic Subspecialty fellowship trained and/or certified headache specialist, and referral for behavioral therapy for prevention in the appointment of recruitment. Exclusion criteria: having done behavioral therapy for migraine in the past year. Participants in the MI group received up to 5 MI calls. TAU participants were called after 3 months for general follow‐up data. The prespecified primary outcome was scheduling a behavioral therapy appointment, and secondary outcomes were initiating and attending a behavioral therapy appointment.Results76 patients were enrolled and randomized (MI = 36, TAU = 40). At baseline, the mean number of headache days was 12.0 ± 9.0. Self‐reported anxiety was present for 36/52 (69.2%) and depression for 30/52 (57.7%). Follow‐up assessments were completed for 77.6% (59/76, MI = 32, TAU = 27). The mean number of MI calls per participant was 2.69 ± 1.56 [0 to 5]. There was a greater likelihood of those in the MI group to initiating an appointment (22/32, 68.8% vs 11/27, 40.7%, P = .0309). There were no differences in appointment scheduling or attendance. Reasons stated for not initiating behavioral therapy were lack of time, lack of insurance/funding, prioritizing other treatments, and travel plans.ConclusionsBrief telephone‐based MI may improve rates of initiation of behavioral therapy for migraine, but other barriers appear to lessen the impact on scheduling and attending behavioral therapy appointments.
Improved green strength of ceramic bodies through extrusion using hydroxypropyl methylcellulose as binder
Authors: Jiang Guang‐Peng , Tao Dong‐Liang 
Published: January 2020

AbstractDifferent amounts of hydroxypropyl methylcellulose (HPMC) and starch in the form of powder were utilized as binder in the extrusion of silicon nitride green bodies. Their three‐point flexural strength and microstructure of fracture surface are investigated. It is found that HPMC can markedly improve the green strength compared with the use of starch. The bending strength with 10% HPMC addition is 29.3 ± 3.1 MPa, which is approximately 7.5 times that of starch counterpart. The dramatic improvement of strength can be attributed to the rough fiber‐like HPMC particles, which were aligned along the direction of extrusion and were pulled out during bending tests. This work represents a step towards a simple but effective way to extrude high‐strength ceramic green bodies.