bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health benefits of resveratrol: Evidence from clinical studies
Authors: Singh Akhand Pratap , Singh Rachna , Verma Sumit Singh , Rai Vipin , Kaschula Catherine H. , Maiti Pralay , Gupta Subash Chandra 
Published: February 2019

AbstractResveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor‐κB, Notch, 5′‐AMP‐activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator‐activated receptor‐γ coactivator 1α, insulin‐like growth factor 1, insulin‐like growth factor‐binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch‐like ECH–associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.
Technical Note: Optimization of spot and trimmer position during dynamically collimated proton therapy
Authors: Smith Blake R. , Hyer Daniel E. , Flynn Ryan T. , Culberson Wesley S. 
Published: February 2019

PurposeTo demonstrate a novel theoretical optimization design which considers beam spot and trimmer positioning in addition to beamlet weighting for dynamically collimated proton therapy (DCPT) treatments. Prior to this, the previous methods of plan optimization used to study this emerging technology relied upon an intuitive selection criterion to fix the trimmers blades for a uniform grid of beam spots before determining the individual beamlet weights. To evaluate the potential benefit from this new optimization design, a treatment planning optimization study was performed in order to compare the algorithm’s functionality against the existing methods of plan optimization.Materials and methodsA direct parameter optimization (DPO) method was developed to determine beam spot and trimmer positions cohesively with beamlet weighting for DCPT treatment plans. Gradients were numerically determined from applying small adjustments to the aforementioned parameters and quantifying the resulting impact on an objective function. This technique was compared to the conventional trimmer selection algorithm (TSA) which does not optimize spot position concurrently with trimmer position. Both planning methods were used to optimize a set of brain treatment plans, and the resulting dose distributions were compared with dose–volume histogram quantities in addition to target coverage, homogeneity, and conformity metrics.ResultsAn overall improvement to the target conformity and healthy tissue sparing was achieved with DPO over TSA while maintaining an equivalent planning target volume (PTV) coverage index for the three brain patients evaluated in this study. On average, the conformity index improved by 5.5% when utilizing DPO. A similar improvement in reducing the dose to several organs at risk was also noted.ConclusionBoth the TSA and DPO planning methods can achieve highly conformal treatments with the dynamic collimation system (DCS) technology. However, an improvement in the target conformity and healthy tissue sparing was achieved by simultaneously optimizing beam spot position, trimmer location, and beamlet weights using DPO in comparison to the TSA technique.
LET response variability of Gafchromic EBT3 film from a Co calibration in clinical proton beam qualities
Authors: Smith Blake R. , Pankuch Mark , Hammer Clifford G. , DeWerd Larry A. , Culberson Wesley S. 
Published: February 2019

PurposeTo establish a method of accurate dosimetry required to quantify the expected linear energy transfer (LET) quenching effect of EBT3 film used to benchmark the dose distribution for a given treatment field and specified measurement depth. In order to facilitate this technique, a full analysis of film calibration which considers LET variability at the plane of measurement and as a function of proton beam quality is demonstrated. Additionally, the corresponding uncertainty from the process was quantified for several measurement scenarios.Materials and methodsThe net change in optical density (OD) from a single version of Gafchromic EBT3 film was measured using an Epson flatbed scanner and NIST‐traceable OD filters. Film OD response was characterized with respect to the known dose to water at the point of measurement for both a NIST‐traceable beam at the UWADCL and several clinical single‐energy and spread‐out Bragg peak (SOBP) proton beam qualities at the Northwestern Medicine Chicago Proton Center. Increasing proton LET environments were acquired by placing film at increasing depths of Gammex HE Solid Water® whose water‐equivalent thickness was characterized prior to measurement.ResultsA strong LET dependence was observed near the Bragg peak (BP) consistent with previous studies performed with earlier versions of EBT3 film. The influence of range straggling on the film's LET response appears to have a uniform effect toward the BP regardless of the nominal beam energy. Proximal to this depth, the film's response decreased with decreasing energy at the same dose‐average LET. The opposite trend was observed for depths past the BP. Changes in the SOBP energy modulation showed a linear relationship between the film's relative response and dose‐averaged LET. Relative effectiveness factors (RE) were observed to range between 2%–7% depending on the width of the SOBP and depth of the film. Using the field‐specific calibration technique, a total k = 1 uncertainty in the absorbed dose to water was estimated to range from 4.68%–5.21%.ConclusionWhile EBT3 film's strong LET dependence is a common problem in proton beam dosimetry, this work has shown that the LET dependence can be taken into account by carefully considering the depth and energy modulation across the film using field‐specific corrections. RE factors were determined with a combined k = 1 uncertainty of 3.57% for SOBP environments and between 3.17%–4.69% for uniform, monoenergetic fields proximal to the distal 80% of the BP.
Genome‐wide analysis of DNA methylation in endometriosis using Illumina Human Methylation 450 K BeadChips
Authors: Wang Lixian , Zhao Jian , Li Yan , Wang Zihe , Kang Shan 
Published: February 2019

AbstractEndometriosis is a common chronic gynecologic disorder characterized by the presence and growth of endometrial‐like tissue outside of the uterine cavity. Although the exact etiology remains unclear, epigenetic modifications, such as DNA methylation, are thought to contribute to the pathogenesis of endometriosis. Here, we used the Illumina Human Methylation 450 K BeadChip Array to analyze the genome‐wide DNA methylation profiles of six endometriotic lesions and six eutopic endometria from patients with ovarian endometriosis and six endometria of women without endometriosis. Compared with the eutopic endometria of women with endometriosis, 12,159 differentially methylated CpG sites and 375 differentially methylated promoter regions were identified in endometriotic lesions. GO analyses showed that these putative differentially methylated genes were primarily associated with immune response, inflammatory response, response to steroid hormone stimulus, cell adhesion, negative regulation of apoptosis, and activation of the MAPK activity. In addition, the expression levels of DNMT1, DNMT3A, DNMT3B, and MBD2 in endometriotic lesions and eutopic endometria were significantly decreased compared with control endometria. Our findings suggest that aberrant DNA methylation status in endometriotic lesions may play a significant role in the pathogenesis and progression of endometriosis.
Exogenous Addition of 25‐Hydroxycholesterol Reduces Level of Very Long‐Chain Fatty Acids in X‐Linked Adrenoleukodystrophy
Authors: Jang Jiho , Lee Jung Wuk , Song Jiho , Kim Dong‐Wook , Min Kyung Hoon 
Published: February 2019

AbstractX‐Linked adrenoleukodystrophy (X‐ALD) is a severe metabolic disorder characterized by the accumulation of very long‐chain fatty acids (VLCFAs). Recently, we demonstrated that levels of 25‐hydroxycholesterol (25‐HC) and cholesterol 25‐hydroxylase (CH25H) were found to be elevated in X‐ALD. Herein, we report that the exogenous addition of 25‐HC significantly reduces C26:0 levels in X‐ALD patient‐derived fibroblasts and oligodendrocytes differentiated from induced pluripotent stem cells (iPSCs) derived from X‐ALD patients. Moreover, 25‐HC treatment was found to down‐regulate the expression of ELOVL1, a key enzyme for the synthesis of C26. In addition, activation of liver X receptor (LXR), a molecular target of endogenous 25‐HC, also reduced C26:0 level. The reduction of C26:0 levels by 25‐HC treatment might result, at least partially, from the decrease of ELOVL1 expression as well as the activation of LXR. Our findings could provide a better understanding of the role of 25‐HC in X‐ALD and useful information to find therapeutic agents to treat X‐ALD.
In‐hospital mortality of hematopoietic stem cell transplantation among children with nonmalignancies: A nationwide study in the United States from 2000 to 2012
Authors: Takahashi Takuto , Pereda Maria A. , Bala Natasha , Nagarajan Sairaman 
Published: February 2019

AbstractBackgroundHematopoietic stem cell transplant (HSCT) can cure or alleviate a wide range of nonmalignant childhood conditions. However, few studies have examined longitudinal national trends of frequency or short‐term complications of HSCT before 2006 when an HSCT became a reportable procedure by US law. By using a US nationally representative database, we conducted nationwide longitudinal analyses on demographics, in‐hospital mortality, and short‐term complications in nonmalignant HSCT from 2000 to 2012.ProcedureWe analyzed 2504 admissions for children < 20 years old who underwent an allogeneic HSCT for a nonmalignant condition by using the Kids' Inpatient Database for the years 2000, 2003, 2006, 2009, and 2012. Changes in in‐hospital mortality and other outcomes were assessed over the study period using weighted analyses, which enabled generation of national estimates in each year.ResultsThe number of admissions for HSCT increased from 334 to 667 from 2000 to 2012, respectively; among them, the use of bone marrow decreased (66.5% to 34.1%, P < 0.001). In‐hospital mortality declined (13.4% to 7.1%, P = 0.04), as did bacteremia (28.7% to 10.1%, P < 0.001) and vascular catheter infections (18.8% to 8.7%, P = 0.006), but cytomegalovirus infections increased (4.9% to 15.9%, P < 0.001), as did adenovirus infections (1.8% to 6.9%, P < 0.001) from 2000 to 2012.ConclusionPopulation‐based analyses demonstrated a substantial expansion of the utilization of HSCT occurred for pediatric nonmalignancies from 2000 to 2012 in the United States, whereas the in‐hospital mortality declined by approximately a half. Further research is needed to identify distinct contributing factors.
Awareness of the passage of time and self‐consciousness: What do meditators report?
Authors: Droit‐Volet Sylvie , Dambrun Michaël 
Published: February 2019

AbstractWhat do humans mean when they say that time passes quickly or slowly? In this article, we try to respond to this question on the basis of our studies on the judgment of the passage of time and its links with the judgment of physical durations. The awareness of the passage of time when consciousness is altered by meditation is also discussed. A dissociation is then made among the “self‐time perspective,” the “self‐duration” (internal duration), and the “world‐duration” (external duration). A link is also established between the self‐time perspective and the “narrative self,” on one hand, and the self‐duration and the “minimal self,” on the other hand, that is confirmed in our qualitative analysis of testimonials of four meditators. The awareness of self‐duration is thus related to the awareness of the embodied self. When the sense of self is altered and the consciousness of the body is lower, then the subjective experience of internal time changes. However, the mechanisms allowing the disappearance of the self with the feeling of being outside time during meditation remains to be elucidated.
Idiopathic Copper Deficiency Myeloneuropathy Resulting in Paraparesis: A Case Report
Authors: Huang Kevin , Lee Debbie , Ingraham Benjamin , Hijaz Tarek A. , Anschel Alan S. 
Published: February 2019

AbstractAtraumatic spinal cord injuries can be due to inflammatory, vascular, and nutritional etiologies. Due to progression from these causes, the identification and initiation of appropriate treatment are of significant importance. This article explores a case of copper deficiency myeloneuropathy in a patient initially thought to have an inflammatory transverse myelitis. The lack of response to antirheumatologic interventions prompted an extensive workup consistent with copper deficiency. This case stresses the importance of evaluating nutritional causes of myeloneuropathy.Level of EvidenceV
Compartmentalized Encapsulation of Two Antibiotics in Porous Nanoparticles: an Efficient Strategy to Treat Intracellular Infections
Authors: Li Xue , Semiramoth Nicolas , Hall Shaun , Tafani Virginie , Josse Jérome , Laurent Frederic , Salzano Giuseppina , Foulkes Daniel , Brodin Priscille , Majlessi Laleh , Ghermani Nour‐Eddine , Maurin Guillaume , Couvreur Patrick , Serre Christian , Bernet‐Camard Marie‐Françoise , Zhang Jiwen , Gref Ruxandra 
Published: February 2019

AbstractCombinatorial drug therapies emerge among the most promising strategies to treat complex pathologies such as cancer and severe infections. Biocompatible nanoparticles of mesoporous iron carboxylate metal–organic framework (nanoMOFs) are used here to address the challenging aspects related to the coincorporation of two antibiotics. Amoxicillin and potassium clavulanate, a typical example of drugs used in tandem, are efficiently coincorporated with payloads up to 36 wt%. Due to the occurrence of two distinct pore sizes/apertures within the MOF architecture, each drug is able to infiltrate the porous framework and localize within separate compartments. Molecular simulations predict drug loadings and locations consistent with experimental findings. Drug loaded nanoMOFs that are internalized by Staphylococcus aureus infected macrophages are able to colocalize with the pathogen, which in turn leads to an alleviation of bacterial infection. The data also reveal potential antibacterial properties of nanoMOFs alone as well as their ability to deliver a high payload of drugs to fight intracellular bacteria. These results pave the way toward the design of engineered “all‐in‐one” nanocarriers in which both the loaded drugs and their carrier play a role in fighting intracellular infections.
Hair cortisol and stable carbon and nitrogen isotope ratios in barbary macaques (Macaca sylvanus) from Gibraltar
Authors: Schillaci Michael A. , Lintlop Jessica , Sumra Monika , Pizarro Mark , Jones‐Engel Lisa 
Published: February 2019

RationaleProlonged exposure to the stress hormone cortisol can precipitate a catabolic state in animals resulting in a negative nitrogen balance and increased excreted nitrogen, possibly affecting stable nitrogen and carbon isotope ratios in animal tissues. Here we test the hypothesis that stress, as measured by hair cortisol, is a significant contributor to variation in δ15N and δ13C values in hair. The results of the present study have important implications for the use of stable carbon and nitrogen isotope ratios measured in animal and human tissues to make inferences regarding feeding ecology and diet.MethodsSamples containing roughly 10–20 hairs (approx. 4–6 cm long) were collected from 49 free ranging macaque monkeys (Macaca sylvanus) in Gibraltar. Hair samples were analyzed for stable carbon and nitrogen isotopes by continuous‐flow isotope‐ratio mass spectrometry. Cortisol extracted from matched hair samples was measured using gas chromatography/mass spectrometry. Cortisol and stable isotope ratios were compared statistically using nonparametric Kruskal–Wallis and Mann–Whitney U tests, as well as Spearman correlation.ResultsCorrelation analysis revealed that although hair δ15N and δ13C values were significantly correlated with each other, neither was correlated with cortisol concentrations. Cortisol concentrations were not correlated with age‐adjusted body mass index. Age category was correlated with δ13C values but not with δ15N values.ConclusionsThe results of our study suggest that the cumulative stress experienced by these macaques under typical social and environmental conditions is not a significant contributor to variation in δ15N and δ13C values, nor does it have a significant effect on relative body mass.
Fabrication of Porous Mesh‐Like FeCo2S4 Nanosheet Arrays on Ni Foam for High Performance all Solid‐State Supercapacitors and Water Splitting
Authors: Ma Dandan , Lv Minglian , Shen Yu , Zhu Yongqiang , Wang Fumin , Zhang Xubin 
Published: February 2019

AbstractPorous mesh‐like FeCo2S4 nanosheet arrays on Ni foam (NF) have been prepared by a two‐step hydrothermal approach and employed as electrodes for supercapacitors and efficient bifunctional electrocatalysts for water splitting. FeCo2S4/NF exhibits ultrahigh areal capacitance of 7.37 F cm−2 at current density of 5 mA cm−2 and achieves good cycling stability retaining 92% capacitance after 3000 cycles at 10 mA cm−2. Symmetric solid‐state device of FeCo2S4/NF as positive and negative electrodes delivers a remarkable energy density of 19.12 W h kg−1 (434.61 W kg−1). Furthermore, FeCo2S4/NF electrode delivers a low overpotential of 155 mV at a hydrogen evolution reaction (HER) current density of 10 mA cm−2 and shows no obvious attenuation after stability test for 100,000 s in 1 M KOH solution. While a low overpotential of 234 mV at 50 mA cm−2 for oxygen evolution reaction (OER) can be demonstrated in alkaline environment as an anode electrocatalyst. FeCo2S4/NF shows excellent activity toward overall water splitting with 10 mA cm−2 by applying just 1.405 V across the two electrodes. Hence, the porous mesh‐like FeCo2S4 nanosheet arrays on Ni foam are promising electrode materials for supercapacitor application and water splitting.
Rapid and Efficient Synthesis of 11C‐Labeled Benzimidazolones Using [11C]Carbon Dioxide
Authors: Horkka Kaisa , Dahl Kenneth , Bergare Jonas , Elmore Charles S. , Halldin Christer , Schou Magnus 
Published: February 2019

Abstract[11C]Carbon dioxide is an attractive synthon for the labeling of positron emission tomography (PET) tracers for subsequent use in biomedical research and drug development. In this study, [11C]CO2 was used for direct 11C‐labeling of a set of cyclic aromatic ureas starting from their corresponding ortho‐phenylenediamines, BEMP (2‐tert‐butylimino‐2‐diethylamino‐1,3‐dimethylperhydro‐1,3,2‐diazaphosphorine) as fixation base, and Mitsunobu reagents (DBAD, nBu3P) for the intramolecular cyclization. The procedure is rapid (6 minutes total synthesis time), mild (proceeds at room temperature) and provided a set of 11C‐benzimidazolones in good to excellent radiochemical yields. As a final testament to the utility of this method, the beta‐adrenoceptor PET ligand [11C]CGP12177, was successfully prepared using the optimized conditions.
Potassium Iodide/ Tert‐Butyl Hydroperoxide Mediated Sequential Oxidative Amidation of Ethylarenes – A Direct Approach to α‐Ketoamides and Amides
Authors: Sridhar Arunasalam , Selvaraj Mari 
Published: February 2019

AbstractA highly efficient KI‐TBHP mediated oxidative amidation of ethylarenes into primary, secondary and tertiary α‐ketoamides was developed at an ambient temperature. In addition, oxidative degradation of ethylarenes to primary aromatic amides using KI‐TBHP‐I2 was also demonstrated in an environmentally benign water medium. The merits of this transition metal free transformation includes 52–81% yield, inexpensive catalyst and substrate. The synthetic potential of the protocol was showcased by scale up reaction and functionalization of the α‐ketoamides.
Immobilized Gelatin–λ–Carrageenan on Magnetite Nanoparticles as an Efficient Organocatalyst for Enantioselective Biginelli Reaction
Authors: Jafari‐Chermahini Mohammad Taqi , Tavakol Hossein 
Published: February 2019

AbstractA facile method for preparation of stabilized and functionalized nanoparticles (NPs) from magnetite by successive application of blended natural polymers (gelatin and λ–carrageenan) on Fe3O4 core has been developed. Gelatin plays a privileged role in the catalytic active sites and it is responsible for the enantiomeric induction. λ–carrageenan endowed chemical stability for immobilization of gelatin on Fe3O4 nanoparticles, thereby enhancing its stability and recoverability. The versatility of the modified NPs was proved by their excellent heterogeneous catalytic activity in one–pot, three–component Biginelli cyclocondensation reaction involving an aromatic aldehyde, urea, and ethyl acetoacetate (or Dimedone) to afford optically active corresponding dihydropyrimidinones in acceptable yields. This novel and green protocol has several advantages such as high efficiency, reusability of the catalyst, using inexpensive and available compounds for the catalyst.
Layered Ln(III) Complexes from a Sulfonate‐Based 1,8‐Naphthalimide: Structures, Magnetism and Photophysics
Authors: Carter Anthony B. , Zhang Ningjin , Kühne Irina A. , Keene Tony D. , Powell Annie K. , Kitchen Jonathan A. 
Published: February 2019

AbstractFive lanthanide(III) complexes of N‐(4‐phenylsulfonate)‐1,8‐naphthalimide (L1) are described {[Ln(L1)(DMSO)5(H2O)2](L1)2 ⋅3H2O where Ln(III)=Eu(III) (1), Tb(III) (2), Dy(III) (3), Ho(III) (4) and Er(III) (5)} . A structural, magnetic and photophysical study is reported for these complexes. The complexes feature a 1,8‐naphthalimide based anionic ligand, which is known for extending structure directing properties through π‐based interactions. Within these complexes L1 acts as both a coordinating ligand as well as a non‐coordinating counter‐ion and overall the solid‐state structures adopt layered topologies that are achieved through π‐π interactions between L1 molecules. Complexes of 1 and 2 display the characteristic line‐like emission profiles expected for Eu(III) and Tb(III) whilst the magnetic properties of the Dy(III) containing complex 3 were investigated.