bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross‐Sectional and Time Series Momentum Returns and Market States
Authors: Cheema Muhammad A. , Nartea Gilbert V. , Man Yimei 
Published: August 2017

AbstractRecent evidence on momentum returns shows that the time series (TS) strategy outperforms the cross‐sectional (CS) strategy. We present new evidence that this happens only when the market continues in the same state, up or down. In fact, we find that the TS strategy underperforms the CS strategy when the market transitions to a different state. Our results also show that the difference in momentum returns between TS and CS strategies is related to both the net long and net short positions of the TS strategy.
A quantitative evaluation of physical and digital approaches to centre of mass estimation
Authors: Macaulay Sophie , Hutchinson John R. , Bates Karl T. 
Published: August 2017

AbstractCentre of mass is a fundamental anatomical and biomechanical parameter. Knowledge of centre of mass is essential to inform studies investigating locomotion and other behaviours, through its implications for segment movements, and on whole body factors such as posture. Previous studies have estimated centre of mass position for a range of organisms, using various methodologies. However, few studies assess the accuracy of the methods that they employ, and often provide only brief details on their methodologies. As such, no rigorous, detailed comparisons of accuracy and repeatability within and between methods currently exist. This paper therefore seeks to apply three methods common in the literature (suspension, scales and digital modelling) to three ‘calibration objects’ in the form of bricks, as well as three birds to determine centre of mass position. Application to bricks enables conclusions to be drawn on the absolute accuracy of each method, in addition to comparing these results to assess the relative value of these methodologies. Application to birds provided insights into the logistical challenges of applying these methods to biological specimens. For bricks, we found that, provided appropriate repeats were conducted, the scales method yielded the most accurate predictions of centre of mass (within 1.49 mm), closely followed by digital modelling (within 2.39 mm), with results from suspension being the most distant (within 38.5 mm). Scales and digital methods both also displayed low variability between centre of mass estimates, suggesting they can accurately and consistently predict centre of mass position. Our suspension method resulted not only in high margins of error, but also substantial variability, highlighting problems with this method.
Men wielding the plough: Changing patterns of production and reproduction among the Balanta of Guinea‐Bissau
Authors: Temudo Marina Padrão 
Published: August 2017

AbstractThis paper is centred on the fast‐track changes occurring among the Balanta of Guinea‐Bissau—at present, the only ethnic group in West Africa still able to produce a mangrove swamp rice surplus with a manual plough—in their traditionally intensive farming system and their social organization, and on the consequences that these changes have had for gender relations, especially with regard to married women's spatial mobility, sexual and economic independence, and access to land, labour, and capital. In doing so, the paper contributes to old debates about the relationship between means of production and gendered power dynamics in contexts where African societies based on domestic modes of production progressively embrace the market economy. The Balanta case offers a new layer of complexity to this debate due to their long‐term resistance to westernization and market integration, their particular conjugal relations, and the paradoxical way in which women have been losing their traditional rights.
Transdifferentiation of myoblasts into osteoblasts – possible use for bone therapy
Authors: Lin Daphne P L , Carnagarin Revathy , Dharmarajan Arun , Dass Crispin R 
Published: August 2017

Abstract

Objectives
Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful.

Key findings
The potent osteoinductive effects of the bone morphogenetic protein-2 are largely implicated in the transdifferentiation of myoblast to osteoblast. Bone morphogenetic protein-2-induced activation of the Smad1 protein ultimately results in JunB synthesis, the first transcriptional step in myoblast dedifferentiation. The upregulation of the activating protein-1 binding activity triggers the transcription of the runt-related transcription factor 2 gene, a transcription factor that plays a major role in osteoblast differentiation.

Summary
This potential transdifferentiation treatment may be utilised for dental implants, fracture healing, osteoporosis and bone repair post-destruction by bone tumours.
Floating solid cellulose nanofibre nanofoams for sustained release of the poorly soluble model drug furosemide
Authors: Svagan Anna Justina , Müllertz Anette , Löbmann Korbinian 
Published: August 2017

Abstract

Objectives
This study aimed to prepare a furosemide-loaded sustained release cellulose nanofibre (CNF)-based nanofoams with buoyancy.

Methods
Dry foams consisting of CNF and the model drug furosemide at concentrations of 21% and 50% (w/w) have been prepared by simply foaming a CNF-drug suspension followed by drying. The resulting foams were characterized towards their morphology, solid state properties and dissolution kinetics.

Key findings
Solid state analysis of the resulting drug-loaded foams revealed that the drug was present as an amorphous sodium furosemide salt and in form of furosemide form I crystals embedded in the CNF foam cell walls. The foams could easily be shaped and were flexible, and during the drug release study, the foam pieces remained intact and were floating on the surface due to their positive buoyancy. Both foams showed a sustained furosemide release compared to a marketed tablet. It was found that the extent of sustained release from both foams was dependent on the drug loading, the dimension of the foam piece, as well as the solid state of the drug.

Conclusions
Furosemide-loaded CNF-based foams with sustained release and buoyancy have been successfully prepared in a simple casting and drying procedure.
Stimulation of human osteoblast cells (MG63) proliferation using decanoic acid and isopropyl amine fractions of Wattakaka volubilis leaves
Authors: Venugopal Elakkiya , Ramadoss Govindarajan , Krishnan Kannan , Eranezhath Sujith Subash , Bhattacharyya Amitava , Rajendran Selvakumar 
Published: August 2017

Abstract

Objectives
This study was carried out to investigate the impact of various isolated phytochemical components present in the Wattakaka volubilis leaves for the growth and proliferation of human osteoblast like cells (MG63).

Key findings
Ethyl acetate was found to be the best solvent for potential extraction of phytocompounds. Further, the MTT assay was carried out to deduce the viability of 44 isolated phytochemicals. Ten phytochemical fractions found to increase the cell growth were subjected to statistical tool namely Plackett–Burman and Central composite design to screen the optimum phytochemical fraction and its dosage. The active phytochemical constituents were analysed and identified as hexadeconoic acid, octadeconoic acid, N,N-diisopropyl(2,2,3,3,3-pentafluoropropyl)amine using GC-MS and HPLC techniques. The impact of optimized concentration was assessed on osteoblast cells. The maximum % cell viability, % DNA and collagen content were found to be 164.44, 159.32 and 3.81, respectively.

Conclusions
The results confirmed that the optimized fraction containing decanoic acid and isopropyl amine at particular concentration stimulated the proliferation of human osteoblast (MG63) cells. Hence, the optimized concentration of this compound from W. volubilis may used for treatment of bone related injuries externally.
Preventing childhood obesity: Early‐life messages from epidemiology
Authors: Robinson S. M. 
Published: August 2017

AbstractThe high rates of overweight and obesity, currently seen in young children, underline the urgent need for preventive strategies in early life, before excess weight is gained. However, alongside such practical considerations, a body of epidemiological evidence now links experience in fetal and early postnatal life to an individual's later risk of obesity – pointing to the importance and role of ‘developmental influences’, such as maternal obesity, excess gestational weight gain and short duration of breastfeeding, in the aetiology of childhood obesity. Differences in early experience are linked to lifelong differences in predisposition to gain weight and, as the associated differences in obesity risk are large, real benefits could be achieved by early intervention. Such messages, regarding the need for efforts to address these early influences to prevent obesity, are now embedded in national and international health policy. Whilst successful prevention initiatives are needed early in life, the most effective strategies may need to be focused even earlier in the life course, in the period before conception. Although the challenges of changing behaviour are considerable, such changes have the potential to impact both on the health of future mothers and future generations.
Dietary energy density: Applying behavioural science to weight management
Authors: Rolls B. J. 
Published: August 2017

AbstractStudies conducted by behavioural scientists show that the energy density (kcal/g) of food provides effective guidance for healthy food choices to control intake and promote satiety. Energy density depends upon a number of dietary components, especially water (0 kcal/g) and fat (9 kcal/g). Increasing the proportion of water or water‐rich ingredients, such as vegetables or fruit, lowers a food's energy density. A number of studies show that when the energy density of the diet is reduced, both adults and children spontaneously decrease their ad libitum energy intake. Other studies show that consuming a large volume of a low‐energy‐dense food, such as soup, salad or fruit, as a first course preload can enhance satiety and reduce overall energy intake at a meal. Current evidence suggests that energy density influences intake through a complex interplay of cognitive, sensory, gastrointestinal, hormonal and neural influences. Other studies that focus on practical applications show how the strategic incorporation of foods lower in energy density into the diet allows people to eat satisfying portions while improving dietary patterns. This review discusses studies that have led to greater understanding of the importance of energy density for food intake regulation and weight management.
Saturated fats, dairy foods and health: A curious paradox?
Authors: Givens D. I. 
Published: August 2017

AbstractCardiovascular diseases (CVD) remain a major cause of death and morbidity worldwide. Dietary guidelines aim to restrict the intake of saturated fatty acids (SFA) as they are regarded as an important risk factor for CVD due to their association with increased blood cholesterol. As dairy foods are major contributors of dietary SFA, there have been guidelines to reduce consumption of these foods. However, it is now generally accepted that the effects of reducing intake of SFA are dependent on what replaces them in the diet. Reduced CVD risk has been associated with replacement of SFA with cis‐polyunsaturated fatty acids (cis‐PUFA) and/or cis‐monounsaturated fatty acids (cis‐MUFA), with replacement by carbohydrate leading to no reduction or even increased CVD risk. Most studies on the effect of diet/food on CVD risk have used total cholesterol (TC) and/or low‐density lipoprotein cholesterol (LDL‐C) in blood as the marker(s) of risk. However, because of potentially attenuating effects of dairy foods (e.g. effect of protein on blood lipids and blood pressure; food matrix effects on fat bioavailability), a wider range of markers is needed to more fully evaluate disease risk. Nevertheless, whilst prospective evidence shows no increase in CVD risk from high dairy consumption, it is still unclear whether replacing a proportion of SFA in dairy fat with cis‐MUFA will lead to reduced CVD risk. The relatively few randomised controlled trials that have examined this using TC/LDL‐C as risk markers give some indications of reduced CVD risk from consumption of milk and dairy products with modified fatty acid composition, compared with those of normal milk fat composition. The results of ongoing studies will add valuable new evidence on this issue.
Using Population Pharmacokinetic Modeling and Monte Carlo Simulations To Determine whether Standard Doses of Piperacillin in Piperacillin-Tazobactam Regimens Are Adequate for the Management of Febrile Neutropenia
Authors: Sime Fekade Bruck , Hahn Uwe , Warner Morgyn S. , Tiong Ing Soo , Roberts Michael S. , Lipman Jeffrey , Peake Sandra L. , Roberts Jason A. 
Published: August 2017

ABSTRACT

Changes in the pharmacokinetics of piperacillin in febrile neutropenic patients have been reported to result in suboptimal exposures. This study aimed to develop a population pharmacokinetic model for piperacillin and perform dosing simulation to describe optimal dosing regimens for hematological malignancy patients with febrile neutropenia. Concentration-time data were obtained from previous prospective observational pharmacokinetic and interventional therapeutic drug monitoring studies. Nonparametric population pharmacokinetic analysis and Monte Carlo dosing simulations were performed with the Pmetrics package for R. A two-compartment model, with between-subject variability for clearance (CL), adequately described the data from 37 patients (21 males, age of 59 ± 12 years [means ± standard deviations] and weight of 77 ± 16 kg). Parameter estimates were CL of 18.0 ± 4.8 liters/h, volume of distribution of the central compartment of 14.3 ± 7.3 liters, rate constant for piperacillin distribution from the central to peripheral compartment of 1.40 ± 1.35 h
−1
, and rate constant for piperacillin distribution from the peripheral to central compartment of 4.99 ± 7.81 h
−1
. High creatinine clearance (CL
CR
) was associated with reduced probability of target attainment (PTA). Extended and continuous infusion regimens achieved a high PTA of >90% for an unbound concentration of piperacillin remaining above the MIC (
fT
>MIC
) of 50%. Only continuous regimens achieved >90% PTA for 100%
fT
>MIC
when CL
CR
was high. The cumulative fraction of response (FTA, for fractional target attainment) was suboptimal (<85%) for conventional regimens for both empirical and directed therapy considering 50% and 100%
fT
>MIC
. FTA was maximized with prolonged infusions. Overall, changes in piperacillin pharmacokinetics and the consequences on therapeutic dosing requirements appear similar to those observed in intensive care patients. Guidelines should address the altered dosing needs of febrile neutropenic patients exhibiting high CL
CR
or with known/presumed infections from high-MIC bacteria.
Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response
Authors: Lucas-Hourani Marianne , Dauzonne Daniel , Munier-Lehmann Hélène , Khiar Samira , Nisole Sébastien , Dairou Julien , Helynck Olivier , Afonso Philippe V. , Tangy Frédéric , Vidalain Pierre-Olivier 
Published: August 2017

ABSTRACTDe novopyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linkingde novopyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed.
24-Hour Pharmacokinetic Relationships for Vancomycin and Novel Urinary Biomarkers of Acute Kidney Injury
Authors: O'Donnell J. Nicholas , Rhodes Nathaniel J. , Lodise Thomas P. , Prozialeck Walter C. , Miglis Cristina M. , Joshi Medha D. , Venkatesan Natarajan , Pais Gwendolyn , Cluff Cameron , Lamar Peter C. , Briyal Seema , Day John Z. , Gulati Anil , Scheetz Marc H. 
Published: August 2017

ABSTRACT

Vancomycin has been associated with acute kidney injury in preclinical and clinical settings; however, the precise exposure profiles associated with vancomycin-induced acute kidney injury have not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kidney injury using sensitive urinary biomarkers. Male Sprague-Dawley rats received clinical-grade vancomycin or normal saline as an intraperitoneal injection. Total daily doses between 0 and 400 mg/kg of body weight were administered as a single dose or 2 divided doses over a 24-h period. At least five rats were utilized for each dosing protocol. A maximum of 8 plasma samples per rat were obtained, and urine was collected over the 24-h period. Kidney injury molecule-1 (KIM-1), clusterin, osteopontin, cystatin C, and neutrophil gelatinase-associated lipocalin levels were determined using Milliplex multianalyte profiling rat kidney panels. Vancomycin plasma concentrations were determined via a validated high-performance liquid chromatography methodology. Pharmacokinetic analyses were conducted using the Pmetrics package for R. Bayesian maximal
a posteriori
concentrations were generated and utilized to calculate the 24-h area under the concentration-time curve (AUC), the maximum concentration (
C
max
), and the minimum concentration. Spearman's rank correlation coefficient (

r
s

) was used to assess the correlations between exposure parameters, biomarkers, and histopathological damage. Forty-seven rats contributed pharmacokinetic and toxicodynamic data. KIM-1 was the only urinary biomarker that correlated with both composite histopathological damage (

r
s

= 0.348,
P
= 0.017) and proximal tubule damage (

r
s

= 0.342,
P
= 0.019). The vancomycin AUC and
C
max
were most predictive of increases in KIM-1 levels (

r
s

= 0.438 and
P
= 0.002 for AUC and

r
s

= 0.451 and
P
= 0.002 for
C
max
). Novel urinary biomarkers demonstrate that kidney injury can occur within 24 h of vancomycin exposure as a function of either AUC or
C
max
.
Amplification of Antimicrobial Resistance in Gut Flora of Patients Treated with Ceftriaxone
Authors: Meletiadis J. , Turlej-Rogacka A. , Lerner A. , Adler A. , Tacconelli E. , Mouton J. W. 
Published: August 2017

ABSTRACT

Although antibacterial therapy has an impact on human intestinal flora and the emergence of resistant bacteria, its role in the amplification of antimicrobial resistance and the quantitative exposure-effect relationship is not clear. An observational prospective study was conducted to determine whether and how ceftriaxone exposure is related to amplification of resistance in non-intensive care unit (non-ICU) patients. Serial stool samples from 122 extended-spectrum β-lactamase-positive (ESBL
+
) hospitalized patients were analyzed by quantitative real-time PCR to quantify the resistant gene
bla
CTX-M
. Drug exposure was calculated for each patient by using a population pharmacokinetic model. Multi- and univariate regression and classification regression tree (CART) analyses were used to explore relationships between measures of exposure and amplification of
bla
CTX-M
genes. Amplification of
bla
CTX-M
was observed in 0% (0/11) of patients with no treatment and 33% (20/61) of patients treated with ceftriaxone. Stepwise regression analysis showed a significant association between amplification of
bla
CTX-M
and the plasma area under the concentration-time curve from 0 to 24 h for the unbound fraction of the drug (
f
AUC
0–24
), the maximum concentration of drug in serum for the unbound fraction of the drug (
fC
max
), and the duration of ceftriaxone therapy. Using CART analysis, amplification of
bla
CTX-M
was observed in 11/16 (69%) patients treated for >14 days and in 9/40 (23%) patients treated for ≤14 days (
P
= 0.0019). In the latter group, amplification was observed in 5/7 (71%) patients with an
f
AUC
0–24
of ≥222 mg · h/liter and in 4/33 (12%) patients with lower drug exposures (
P
= 0.0033). A similar association was found for an
fC
max
of ≥30 mg/liter (63% versus 13%,
P
= 0.0079). A significant association was found between the amplification of
bla
CTX-M
resistance genes and exposure to ceftriaxone. Both duration of treatment and degree of ceftriaxone exposure have a significant impact on the amplification of resistance genes. (The project described in this paper has been registered at ClinicalTrials.gov under identifier NCT01208519.)
Inhibition of Calcineurin or IMP Dehydrogenase Exerts Moderate to Potent Antiviral Activity against Norovirus Replication
Authors: Dang Wen , Yin Yuebang , Wang Yijin , Wang Wenshi , Su Junhong , Sprengers Dave , van der Laan Luc J. W. , Felczak Krzysztof , Pankiewicz Krzysztof W. , Chang Kyeong-Ok , Koopmans Marion P. G. , Metselaar Herold J. , Peppelenbosch Maikel P. , Pan Qiuwei 
Published: August 2017

ABSTRACT
Norovirus is a major cause of acute gastroenteritis worldwide and has emerged as an important issue of chronic infection in transplantation patients. Since no approved antiviral is available, we evaluated the effects of different immunosuppressants and ribavirin on norovirus and explored their mechanisms of action by using a human norovirus (HuNV) replicon-harboring model and a surrogate murine norovirus (MNV) infectious model. The roles of the corresponding drug targets were investigated by gain- or loss-of-function approaches. We found that the calcineurin inhibitors cyclosporine (CsA) and tacrolimus (FK506) moderately inhibited HuNV replication. Gene silencing of their cellular targets, cyclophilin A, FKBP12, and calcineurin, significantly inhibited HuNV replication. A low concentration, therapeutically speaking, of mycophenolic acid (MPA), an uncompetitive IMP dehydrogenase (IMPDH) inhibitor, potently and rapidly inhibited norovirus replication and ultimately cleared HuNV replicons without inducible resistance following long-term drug exposure. Knockdown of the MPA cellular targets IMPDH1 and IMPDH2 suppressed HuNV replication. Consistent with the nucleotide-synthesizing function of IMPDH, exogenous guanosine counteracted the antinorovirus effects of MPA. Furthermore, the competitive IMPDH inhibitor ribavirin efficiently inhibited norovirus and resulted in an additive effect when combined with immunosuppressants. The results from this study demonstrate that calcineurin phosphatase activity and IMPDH guanine synthase activity are crucial in sustaining norovirus infection; thus, they can be therapeutically targeted. Our results suggest that MPA shall be preferentially considered immunosuppressive medication for transplantation patients at risk of norovirus infection, whereas ribavirin represents as a potential antiviral for both immunocompromised and immunocompetent patients with norovirus gastroenteritis.