bluuebunny/crossref_metadata_2025 huggingface dataset:
The neutron star mass and radius of Aql X‐1 from quiescent X‐ray emissions
Authors: Luo Y. , Li Z.
Published: March 2019

We report the quiescent spectra of neutron star (NS) in Aql X‐1 from XMM‐Newton and Chandra. The NS atmosphere model, NSATMOS, is applied to fit the quiescent spectra. The Monte Carlo Markov Chain algorithm is used to constrain the NS mass and radius in Aql X‐1. We find that the absolute flux calibration between XMM‐Newton and Chandra for Aql X‐1 is in good agreement with each other. The NS mass and radius of Aql X‐1 are obtained.
Magnetic field effect on the decay process of a neutral scalar boson to charged fermions
Authors: Piccinelli G. , Jaber‐Urquiza J. , Sánchez A.
Published: March 2019

The effect of a homogeneous weak magnetic field on the decay process of a neutral scalar particle to a pair of charged fermions is studied. The decay rate is calculated through the imaginary part of the self‐energy of the scalar particle interacting with the charged fermions, at one loop. The weak field approximation can be performed in different ways, depending on the hierarchy of scales. Here, we explore the regime where the progenitor particle has a high transverse momentum and we find that the process is favored by the increase of the magnetic field. We compare our results with recent findings for a different kinematical regime and briefly discuss the possible physical reasons for the different behaviors. The phenomenon can be relevant in early universe events or in high‐energy collisions.
Dirac and Majorana field operators with self/antiself charge‐conjugate states
Authors: Dvoeglazov V. V.
Published: March 2019

We discuss relations between Dirac and Majorana‐like field operators with self/antiself charge‐conjugate states. The connections with recent models of several authors were found.
Concluding remarks to the IWARA 2018
Authors: Horvath J. E.
Published: March 2019

We provide a summary and comments on the articles presented at the IWARA 2018 event.
Genesis of placental sequestration in malaria and possible targets for drugs for placental malaria
Authors: Clark Robert L.
Published: March 2019

Malaria during pregnancy results in intrauterine growth restriction, fetal anemia, and infant mortality. Women are more susceptible to malaria during pregnancy due to malaria‐induced inflammation and the sequestration of infected red blood cells in the placenta, which bind to the chondroitin sulfate portion of syndecan‐1 on the syncytiotrophoblast and in the intervillous space. Syndecan‐1 is a dimeric proteoglycan with an extracellular ectodomain that is cleaved from the transmembrane domain (referred to as “shedding”) by matrix metalloproteinases (MMPs), likely the secreted MMP‐9. The ectodomain includes four binding sites for chondroitin sulfate, which are proximal to the transmembrane domain, and six distal binding sites primarily for heparan sulfate. This “shedding” of syndecan‐1 is inhibited by the presence of the heparan sulfate chains, which can be removed by heparanase. The intervillous space contains fibrin strands and syndecan‐1 ectodomains free of heparan sulfate. The following is proposed as the sequence of events that leads to and is primarily responsible for sequestration in the intervillous space of the placenta. Inflammation associated with malaria triggers increased heparanase activity that degrades the heparan sulfate on the membrane‐bound syndecan‐1. Inflammation also upregulates MMP‐9 and the removal of heparan sulfate gives MMP‐9 access to cleave syndecan‐1, thereby releasing dimeric syndecan‐1 ectodomains with at least four chondroitin sulfate chains attached. These multivalent ectodomains bind infected RBCs together leading to their aggregation and entrapment in intervillous fibrin. This mechanism suggests possible new targets for anti‐placental malaria drugs such as the inhibition of MMP‐9. Doxycycline is an antimalarial drug which inhibits MMP‐9.
Multi‐physics modeling to study the influence of tissue compression and cold stress on enhancing breast tumor detection using microwave radiometry
Authors: Akki Rachana S. , Sugumar Sathya Priya , Venkata Krishnamurthy C. , Arunachalam Kavitha
Published: March 2019

The influence of tissue compression and external thermal modulation on passive detection of breast tumors using medical microwave radiometry was investigated using multi‐physics numerical modeling. A three‐dimensional numerical model of the pendant breast with 10 and 6 mm diameter tumors at varying depths (15 mm, 30 mm) was analyzed at thermodynamic equilibrium using a circular waveguide as the receive antenna. The contrast in the brightness temperature, ΔTB, between the unhealthy and healthy breasts was found to be significantly more for breast compression alone, compared to thermal modulation of the tissue surface, irrespective of tissue composition, tumor size, and depth. The study also concludes that small deep‐seated tumor with very low metabolic activity that is not detectable by a radiometer with 0.1 °C sensitivity could be detected under breast compression and short duration cold stress. Thus, detection of deep‐seated breast tumors can be significantly improved under controlled tissue compression with an optional cold stress. Bioelectromagnetics. © 2019 Bioelectromagnetics Society.
How We Forgot Who Discovered DNA: Why It Matters How You Communicate Your Results
Authors: Dahm Ralf , Banerjee Mita
Published: March 2019

One hundred and fifty years ago, a hopeful young researcher reported a recent discovery he had made. Working in the bowels of a medieval castle in the German city of Tübingen, he had isolated a then entirely new type of molecule. This was the birth of a field that would fundamentally change the course of biology, medicine, and beyond. His discovery: DNA. His name: Friedrich Miescher. In this article, the authors try to find answers to the question why—despite the fact that virtually everyone nowadays knows DNA—hardly anyone remembers the man who discovered it. In the history of science, the discovery of DNA was a seminal moment. Why then did it not enter into public memory? Ground‐breaking discoveries can occur in a historical context that is not ready to appreciate them. But that's not all that decides who is remembered and who is forgotten. Scientific pioneers sometimes fail to publicize their findings in a way that ensures that they receive the attention they merit. As discussed here, their personalities and habits may cause discoveries to be “overwritten” by more recent researchers, resulting in distorted cultural memories no longer reflecting the initial event.
Simultaneous quantification of propofol, ketamine and rocuronium in just 10 μL plasma using liquid chromatography coupled with quadrupole mass spectrometry and its pilot application to a pharmacokinetic study in rats
Authors: Shopova Teodora , Kiefer Daniel , Wolf Beate , Maurer Felix , Sessler Daniel I. , Volk Thomas , Fink Tobias , Kreuer Sascha
Published: March 2019

The combination of propofol, ketamine and rocuronium can be used for anesthesia of ventilated rats. However, reliable pharmacokinetic models of these drugs have yet to be developed in rats, and consequently optimal infusion strategies are also unknown. Development of pharmacokinetic models requires repeated measurements of drug concentrations. In small animals, samples must be tiny to avoid excessing blood extraction. We therefore developed a drug assay system using high‐performance liquid chromatography coupled with quadrupole mass spectrometry that simultaneously determines the concentration of all three drugs in just 10 μL rat plasma. We established a plasma extraction protocol, using acetonitrile as the precipitating reagent. Calibration curves were linear with R2 = 0.99 for each drug. Mean recovery from plasma was 91–93% for propofol, 89–93% for ketamine and 90–92% for rocuronium. The assay proved to be accurate for propofol 4.1–8.3%, ketamine 1.9–7.8% and rocuronium −3.6–4.7% relative error. The assay was also precise; the intra‐day precisions were propofol 2.0–4.0%, ketamine 2.7–2.9% and rocuronium 2.9–3.3% relative standard deviation. Finally, the method was successfully applied to measurement the three drugs in rat plasma samples. Mean plasma concentrations with standard deviations were propofol 2.0 μg/mL ±0.5%, ketamine 3.9 μg/mL ±1.0% and rocuronium 3.2 μg/mL ±0.8% during ventilation.
Plant Fiber Processing Using the Controlled Deformation Dynamic Mixer
Authors: Harvey Daniel H. S. , Mothersdale Thomas , Shchukin Dmitry , Kowalski Adam J
Published: March 2019

The reduced energy consumption required by the controlled deformation dynamic mixer (CDDM) to process plant fibers is highlighted. Trials have been performed using current industrial mixers, and the products created were compared to those produced using the CDDM technology. Increasing pressure leads to a product of higher viscosity, which is more desirable as the fibers have greater structure development and take up more water. This is also observed with the comparison to current mixing technologies, but the energy consumption and pressure required to obtain products of equal viscosities is less when using CDDM technology.
Catalytic Effect of Hydrogen Peroxide in the Electrochemical Treatment of Phenolic Pollutants using a BDD Anode
Authors: Barrera Héctor , Roa‐Morales Gabriela , Balderas‐Hernández Patricia , Barrera‐Díaz Carlos E. , Frontana‐Uribe Bernardo A.
Published: March 2019

Phenolic pollutants are recalcitrant substances that cannot be removed from wastewater using the current treatments. In this study, degradation of phenolic pollutants was studied on the basis of the application of hydrogen peroxide during the electrooxidation process using BDD as anode (EO−H2O2 coupled process). The process was optimized using 4‐chlorophenol (4‐CP) as model compound and later an emerging pollutant, Nonylphenol Ethoxylate‐10 (NP10EO), was degraded using the optimized experimental conditions found. To ascertain treatment effectiveness, experiments with hydrogen peroxide (H2O2), electrooxidation (EO) and EO−H2O2 (coupled process) were carried out. The variables considered in this investigation were pH, current density, quantity of H2O2, and reaction time. It was observed that the coupled process (EO−H2O2) increases degradation efficiency, reaching 81.9 % for 4‐CP and 94.3 % for NP10EO. UV/VIS spectrophotometry, COD and HPLC analysis verified these results. The results of the analysis by cyclic voltammetry after the EO−H2O2 coupled process indicate that pollutants in the solution were efficiently oxidized. It was concluded that small amounts of hydrogen peroxide (250 μL 30 % w/v solution per 1.1 L) are sufficient to attain good results; larger amounts of H2O2 produce inhibitory effects during degradation. The slow cathode (SS) oxidation during the experiments was confirmed by XPS and AFM analysis.
Symmetric Supercapacitors Based on MnOOH‐Coated Nanoporous Carbon toward High Energy‐Storage Performance
Authors: Shi Xiaoze , Zhang Shuai , Chen Xuecheng , Tang Tao , Mijowska Ewa
Published: March 2019

Pseudocapacitors, one of the most efficient types of energy storage devices due to their high specific capacitance, could not provide adequate information for real applications with a half‐cell device. Therefore, this contribution describes the facile synthesis of hybrid materials based on nanoporous carbon (NPC) and MnOOH with outstanding capacitive performance in symmetric devices. Interconnected NPC with large surface area served as a conductive substrate for deposition of tunable amounts of MnOOH. NPC‐MnOOH electrodes can be scanned with a wide voltage window from 0 to 1.6 V without obvious hydrolysis. The two‐electrode supercapacitor NPC‐MnOOH//NPC‐MnOOH with 26.7 wt% of MnOOH shows the highest specific capacitance of 410 F g−1 and a maximum energy density of 33.5 Wh kg−1. It also shows 86 % retention even after 10 000 cycles. The beneficial properties proved the hybrid materials are suitable for a high‐voltage industrial device under optimal conditions.
Configurational analysis by residual dipolar couplings: A critical assessment of diastereomeric differentiabilities
Authors: Immel Stefan , Köck Matthias , Reggelin Michael
Published: March 2019

Two independent statistical models for evaluating the certainties of configurational assignments of compounds based on nuclear magnetic resonance (NMR) data are evaluated and compared. Both methods yield weights or probabilities with which two or more structure models (constitutional or configurational isomers or even conformers) could be differentiated based on experimental parameters. Although this paper focusses on the use of residual dipolar couplings (RDCs) for the differentiation of diastereomers, the concept can be expanded to any set of experimental NMR‐derived parameters. It is demonstrated that highly reliable configurational assignments crucially must depend on thorough statistical analysis, which is frequently neglected in the literature.
Discovery, Optimization, and Biological Characterization of 2,3,6‐Trisubstituted Pyridine‐Containing M4 Positive Allosteric Modulators
Authors: Schubert Jeffrey W. , Harrison Scott T. , Mulhearn James , Gomez Robert , Tynebor Robert , Jones Kristen , Bunda Jaime , Hanney Barbara , Wai Jenny Miu‐Chen , Cox Chris , McCauley John A. , Sanders John M. , Magliaro Brian , O'Brien Julie , Pajkovic Natasa , Huszar Agrapides Sarah L. , Taylor Anne , Gotter Anthony , Smith Sean M. , Uslaner Jason , Browne Susan , Risso Stefania , Egbertson Melissa
Published: March 2019

Herein we describe the discovery and optimization of a new series of 2,3‐disubstituted and 2,3,6‐trisubstituted muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs). Iterative libraries enabled rapid exploration of one‐dimensional structure–activity relationships (SAR) and identification of potency‐enhancing heterocycle and N‐alkyl pyrazole substituents. Further optimization led to identification of the potent, receptor‐subtype‐selective, brain‐penetrant tool compound 24 (7‐[3‐[1‐[(1‐fluorocyclopentyl)methyl]pyrazol‐4‐yl]‐6‐methyl‐2‐pyridyl]‐3‐methoxycinnoline). It is efficacious in preclinical assays that are predictive of antipsychotic effects, producing dose‐dependent reversal of amphetamine‐induced hyperlocomotion in rats and mice, but not in M4 knockout mice. Cholinergic‐related adverse effects observed in rats treated with 24 at unbound plasma concentrations more than 3‐fold higher than an efficacious dose in the hyperlocomotion assay were fewer and less severe than those observed in rats treated with the nonselective M4 agonist xanomeline, suggesting a receptor‐subtype‐selective PAM has the potential for an improved safety profile.
Fast NMR Methods for Measuring in the Direct and/or Competition Mode the Dissociation Constants of Chemical Fragments Interacting with a Receptor
Authors: Dalvit Claudio , Parent Annick , Vallée Francois , Mathieu Magali , Rak Alexey
Published: March 2019

Ligand‐based NMR screening represents a powerful method in fragment‐based drug discovery for the identification of chemical matter interacting with the receptor of interest. The large dynamic range of these methods allows the detection of weakly binding ligands. However, the methodology has not been extensively used for quantifying the strength of these interactions. This knowledge is important for ranking fragments according to their binding strength and for prioritizing structure‐based and medicinal chemistry activities. Rapid NMR methods for measuring the dissociation constant in direct and competition modes are presented here. The theory underpinning these methods are presented, along with their application to the measurement of the binding affinities of several ligands of the heat shock protein 90.
Evaluation of Maternal Drug Exposure Following the Administration of Antenatal Corticosteroids During Late Pregnancy Using Physiologically‐Based Pharmacokinetic Modeling
Authors: Ke Alice Ban , Milad Mark A.
Published: March 2019

Betamethasone and dexamethasone are the most widely studied antenatal corticosteroids (ACS) administered to pregnant women, just prior to the birth of a preterm neonate, to accelerate fetal lung maturation. Although betamethasone, predominantly used in developed countries, has been shown to be an effective and safe intervention for reducing neonatal mortality, the choice of ACS and optimal dosing in low and middle income countries (LMICs) remains unclear. This is primarily because the exposure–response relationships have not been established for ACS despite the long history of use. As the first step toward the optimal use of ACS in LMICs, we developed physiologically‐based pharmacokinetic (PBPK) models to describe the kinetics of ACS following i.v., p.o., or i.m. dosing. In vitro data describing the cytochrome P450 3A4 enzyme contribution were incorporated and this was refined using clinical data. The models can be applied prospectively to predict kinetics of ACS in pregnant women receiving various dosing regimens.
Development of an Engineered Photoactive Yellow Protein as a Cross‐Linking Junction for Construction of Photoresponsive Protein‐Polymer Conjugates
Authors: Ui Mihoko , Miyauchi Yusuke , Inoue Masataka , Murakami Makoto , Araki Yasuyuki , Wada Takehiko , Kinbara Kazushi
Published: March 2019

Based on a bacterial blue light photoreceptor, photoactive yellow protein (PYP), we have developed a photoresponsive protein module, Hpg5‐PYP, bearing five alkynyl groups as reactive sites. We constructed a yellow‐colored photoresponsive protein–polymer conjugate by using covalently bonded Hpg5‐PYP with poly(N,N‐dimethylacrylamide‐co‐2‐hydroxy‐3‐azidopropyl methacrylate) (DMA‐HAZPMA copolymer). Hpg5‐PYP retained photoreactivity towards blue‐light irradiation in the conjugate, and the conjugate showed a photoresponsive viscosity change upon irradiation with blue light at 25 °C. In contrast, a mixture of Hpg5‐PYP and DMA‐HAZPMA copolymer prepared for reference did not show any dependency of the viscosity on light irradiation, indicating the importance of crosslinking.
Carbamate Synthesis Using a Shelf‐Stable and Renewable C1 Reactant
Authors: Dobi Zoltán , Reddy B. Narendraprasad , Renders Evelien , Van Raemdonck Laurent , Mensch Carl , De Smet Gilles , Chen Chen , Bheeter Charles , Sergeyev Sergey , Herrebout Wouter A. , Maes Bert U. W.
Published: March 2019

4‐Propylcatechol carbonate is a shelf‐stable, renewable C1 reactant. It is easily prepared from renewable 4‐propylcatechol (derived from wood) and dimethyl carbonate (derived from CO2) using a reactive distillation system. In this work, the 4‐propylcatechol carbonate is used for the two‐step synthesis of carbamates under mild reaction conditions. In the first step, 4‐propylcatechol carbonate is treated with an alcohol at 50–80 °C in the presence of a Lewis acid catalyst, such as Zn(OAc)2⋅2 H2O. With liquid alcohols, no solvent is used and with solid alcohols 2‐methyltetrahydrofuran is used as solvent. In the second step, the alkyl 2‐hydroxy‐propylphenyl carbonate intermediates obtained react with amines at room temperature in 2‐methyltetrahydrofuran, forming the target carbamates and the byproduct 4‐propylcatechol, which can be recycled into a carbonate reactant.
Double layers in an inhomogeneous magnetized bi‐ion plasma
Authors: Shan Shaukat Ali , Saleem Hamid
Published: March 2019

A simpler analytical approach is employed to obtain energy integral equation for a pseudo‐particle in a pseudo‐potential, which admits double layer (DL) solutions for the non‐linear low‐frequency electrostatic perturbations in non‐uniform plasma consisting of electrons and two kinds of ions. One of the ion species has field‐aligned shear flow and electrons are superthermal kappa distributed. This theoretical model is applied to the upper ionospheric oxygen‐dominated plasma that has small concentration of protons along with upward flow of oxygen ions. Under suitable boundary conditions, both rarefactive (density dip) and compressive (density hump) DLs are obtained solving energy integral equation using the plasma parameters of ionosphere around altitude of 800 km. The amplitude and width of the DLs depend upon the scale lengths of density and temperature gradients as well as on the ratio of equilibrium densities of oxygen and hydrogen.
Male vocalizations convey information on kinship and inbreeding in a lekking bird
Authors: Cornec Clément , Robert Alexandre , Rybak Fanny , Hingrat Yves
Published: March 2019

Kinship and inbreeding are two major components involved in sexual selection and mating system evolution. However, the mechanisms underlying recognition and discrimination of genetically related or inbred individuals remain unclear. We investigated whether kinship and inbreeding information is related to low‐frequency vocalizations, “booms,” produced by males during their courtship in the lekking houbara bustard (Chlamydotis undulata undulata). Based on a captive breeding program where the pedigree of all males is known, we investigated the similarity of booms’ acoustic parameters among captive males more or less individually inbred and therefore genetically related with each other. In the wild, we investigated the relationship between the spatial distribution of males within leks and the similarity of acoustic parameters of their booms. In the captive population, we found (a) a relationship between the individual inbreeding level of captive males and their vocalization parameters; (b) that kin share similar frequency and temporal characteristics of their vocalizations. In the wild, we found no evidence for spatial structuring of males based on their acoustic parameters, in agreement with previous genetic findings on the absence of kin association within houbara bustard leks. Overall, our results indicate that genetic information potentially related to both the identity and quality of males is contained in their vocalizations.
Correlation between coal and gas outburst risk and adsorption properties of coal seams
Authors: Wang Fakai , Liang Yunpei , Zou Quanle
Published: March 2019

Based on the Langmuir adsorption model, the adsorption constants of eighteen coal samples from the same coal mine with outburst risk, weak outburst risk, and non‐outburst risk were tested by high‐pressure capacity method under different temperature conditions. The results show that the adsorption constantsaandbmonotonically decrease with the increase in temperature. The relationship betweenaand temperature shows three stages: accelerated decreasing stage, decelerated decreasing stage, and stable stage. Thebdecreases with the increase in temperature also shows three stages, namely relative stability, slow decrease, and accelerated decrease. Thea × bfor the outburst coal seam decreases with increasing temperature, which is similar tob. Thea × bfor the weak and non‐outburst coal seams decreases with increasing temperature, which is similar toa. Furthermore, theaof the outburst coal seam decreases with the increase in temperature, and the decrease ofbis the largest. Theaof the weak and non‐outburst coal seams decreases with the increase in temperature, and the magnitude is relatively large. Thebdecreases slightly, with a smaller magnitude. Thea × bof weak outburst seam is smaller than that of non‐outburst seam and is larger than that of outburst seam. The achievements can provide guiding significance for coal and gas outburst prevention and control.
Direct One‐pot Synthesis of Carbon Supported Ag‐Pt Alloy Nanoparticles as High Performance Electrocatalyst for Fuel Cell Application
Authors: Fu T. , Zhang S. , Huang J. , Cai D. , Li J. , Zhao J.
Published: March 2019

Ag‐Pt alloy material is one of the most potential candidates to improve the catalytic activity of Pt‐based catalyst toward the oxygen reduction reaction (ORR), which can reduce the dosage of the high‐cost metal Pt used in the cathode of fuel cells. But it is hard to synthesis Ag‐Pt alloy with nanosize in an easy and cheap way. In this study, the Ag‐Pt alloy nanoparticles supported on carbon (Ag‐Pt/C) with different Ag at.% were prepared by a facile one‐pot approach with low costs. The XRD, TEM and XPS measurements were applied to verify the alloy structure of Ag‐Pt nanoparticles. These Ag‐Pt/C samples showed enhanced mass activities and catalytic stabilities for the ORR, which was up to two times higher than that of the commercial Pt/C catalyst at 0.9 V (vs. reversible hydrogen electrode). Furthermore, the membrane electrode assembly (MEA) made from the Ag‐Pt/C catalyst also showed a higher power density in H2‐O2 fuel cell test compared to the MEA made from the commercial Pt catalyst. These enhancements are attributed to the higher utilization of Pt and the regulated oxygen adsorption energy of Pt in the surface, which was confirmed using the density function theory calculation.
Effect of Temperature and Solvent on the Structure of Amide Cavitands
Authors: Aroua Safwan , Ray Ankita , Ebert Marc‐Olivier , Yamakoshi Yoko
Published: March 2019

Conformational changes of amide cavitands A–C were investigated at varied temperatures and in several solvents. While cavitands A and B, with comparatively smaller substituents such as Et and iPr, were always in vase conformation in non‐polar solvents such as CDCl3, CD2Cl2, (D8)THF, and C6D6, their thermoswitching (vase to kite) was observed in polar solvents such as (D7)DMF and (D6)DMSO or in the presence of acid (TFA) and H‐bonding inhibitor (TFE). Intra‐ and interannular H‐bonds of A and B were clearly observed by low‐temperature 1H‐NMR spectra in CDCl3. No conformational change of cavitand C with bigger substituent (tBu) was observed under any tested temperature range and in polar or non‐polar solvents; C was always in the kite conformation.
Palestinian managers' views and practices regarding the prevention of home injuries: An explorative qualitative study
Authors: Alrimawi Intima A. , Watson Michael Craig , Hall Carol , ALBashtawy Mohammed , Al‐Yateem Nabeel
Published: March 2019

Background

Unintentional injuries are an important global public health problem. Potentially, some senior managers have a major role to play in the prevention of home injuries.

Aims

To explore senior managers' perceptions and practices regarding the prevention of home injuries among children and the potential factors that might influence such practice in Ramallah District of Palestine.

Method

Qualitative interviews were undertaken using a purposive sampling strategy of 18 senior‐level managers. Thematic analysis was undertaken.

Results

The study revealed that half of the interviewed managers' thought that injury prevention was a priority, and the majority of their institutions had worked on increasing parental awareness regarding injury prevention. Nevertheless, their practice in providing financial and psychological support to the parents was reported less. The participants stated that many factors had interchangeably influenced the practice in injury prevention, including factors related to staff, parents, and environment.

Conclusion

This study highlights the importance of managers' role in injury prevention and draws attention to the numerous obstacles that they face. Attempts to prevent injuries should use a combination of interventions at many levels including: parents, health staff, as well as the wilder governmental, physical.
Serum estradiol level on trigger day impacts clinical pregnancy rate in modified natural frozen embryo transfer cycles
Authors: Ramezanali Fariba , Arabipoor Arezoo , Hafezi Maryam , Salman‐Yazdi Reza , Zolfaghari Zahra , Asharfi Mahnaz
Published: March 2019

Objective

To examine the predictive value of serum estradiol and progesterone on the day of human chorionic gonadotropin (hCG) administration and embryo transfer for clinical pregnancy rate in modified natural‐cycle frozen embryo transfer (NC‐FET).

Methods

In a longitudinal prospective study, all eligible women who underwent NC‐FET cycles with hCG triggering in Royan Institute, Tehran, Iran, from June 1, 2015, to December 31, 2016, were evaluated. Serum estradiol and progesterone levels were measured at menstrual cycle initiation, on day of trigger with hCG, on day of embryo transfer, and in pregnant women every 7 days until the observation of a gestational sac with embryonic heartbeat.

Results

In total, 101 modified natural FET cycles were assessed, and the clinical pregnancy and live birth rates achieved were 34 (33.6%) and 32 (31.6%), respectively. The changes in estradiol level during early pregnancy showed an increase by an average of 200 pg/mL per week. Multivariable logistic regression analysis showed that only the estradiol level on the hCG day was a significant predictive variable for clinical pregnancy following NC‐FET (P=0.04).

Conclusion

Estradiol level on the day of hCG trigger predicted the clinical pregnancy rates after modified NC‐FET; this likely mirrored the developmental competence of the corpus luteum and an appropriate luteal structure‐function.
Performance of FRAX and FRAX-Based Treatment Thresholds in Women Aged 40 Years and Older: The Manitoba BMD Registry
Authors: Crandall Carolyn J , Schousboe John T , Morin Suzanne N , Lix Lisa M , Leslie William
Published: March 2019

We examined among women aged ≥40 years the performance of the Fracture Risk Assessment Tool (FRAX) and FRAX-based osteoporosis treatment thresholds under the US National Osteoporosis Foundation (NOF) and UK National Osteoporosis Guideline Group (NOGG) guidelines. We used registry data for all women aged ≥40 years in Manitoba, Canada, with baseline bone mineral density (BMD) testing (n = 54,459). Incident major osteoporotic fracture (MOF), hip fracture, and clinical fracture were assessed from population-based health services data (mean follow-up 10.5 years). Age-stratified hazard ratios (HR) were estimated from Cox regression models. We assessed the sensitivity, specificity, positive predictive value (PPV), number needed to screen (NNS), and number needed to treat (NNT) to prevent a fracture (assuming 20% relative risk reduction on treatment) for osteoporosis treatment thresholds under the NOF and NOGG guidelines. Femoral neck T-score and FRAX (with and without BMD) predicted all fracture outcomes at all ages. There was good calibration in FRAX-predicted versus observed 10-year MOF and hip fracture probability. Overall sensitivity (PPV) for incident MOF was 25.7% (24.0%) for femoral neck T-score ≤ –2.5; 20.3% (26.3%) for FRAX (with BMD)-predicted 10-year MOF risk ≥20% (NOF threshold); 27.3% (22.0%) for FRAX-predicted 10-year MOF risk ≥ age-dependent cut-off (NOGG threshold), 59.4% (19.0%) for the NOF treatment algorithm; and 28.5% (18.4%) for the NOGG treatment algorithm. Sensitivity for identifying incident MOF varied by age, ranging from 0.0% to 26.3% in women 40 to 49 years old and from 49.0% to 93.3% in women aged 80+ years. The gradient of risk for fracture prediction from femoral neck T-score and FRAX (with and without BMD) as continuous measures was strong across the age spectrum. The sensitivity and PPV of the strategies based on dichotomous cut-offs are low, especially among women aged 40 to 49 years (who have lowest incidence rates). Threshold-based approaches should be reassessed, particularly in younger women. © 2019 American Society for Bone and Mineral Research.
Parathyroid Hormone Remodels Bone Transitional Vessels and the Leptin Receptor-Positive Pericyte Network in Mice
Authors: Caire Robin , Roche Bernard , Picot Tiphanie , Aanei Carmen-Mariana , He Zhiguo , Campos Lydia , Thomas Mireille , Malaval Luc , Vico Laurence , Lafage-Proust Marie-Hélène
Published: March 2019

Intermittent parathyroid hormone (iPTH) is anti-osteoporotic and affects bone vessels. Transitional capillaries close to the bone surface, which express both endomucin (Edm) and CD31, bear leptin receptor-expressing (LepR) perivascular cells that may differentiate into osteoblasts. Increased numbers of type H endothelial cells (THEC; ie, Edmhi/CD31hi cells assessed by flow cytometry, FACS) are associated with higher bone formation in young mice. We hypothesized that iPTH administration impacts transitional vessels by expanding THECs. Four-month-old C57/Bl6J female mice were injected with PTH 1–84 (100 μg/kg/d) or saline (CT) for 7 or 14 days. We quantified LepR+, CD31+, Edm+ cells and THECs by FACS in hindlimb bone marrow, and Edm/LepR double immunolabelings on tibia cryosections. Additionally, we analyzed bone mRNA expression of 87 angiogenesis-related genes in mice treated with either intermittent or continuous PTH (iPTH/cPTH) or saline (CT) for 7, 14, and 28 days. iPTH dramatically decreased the percentage of THECs by 78% and 90% at days 7 and 14, respectively, and of LepR+ cells at day 14 (–46%) versus CT. Immunolabeling quantification showed that the intracortical Edm+-vessel density increased at day 14 under iPTH. In the bone marrow, perivascular LepR+ cells, connected to each other via a dendrite network, were sparser under iPTH at day 14 (–58%) versus CT. iPTH decreased LepR+ cell coverage of transitional vessels only (–51%), whereas the number of LepR+ cells not attached to vessels increased in the endocortical area only (+ 49%). Transcriptomic analyses showed that iPTH consistently upregulated PEDF, Collagen-18α1, and TIMP-1 mRNA expression compared with CT and cPTH. Finally, iPTH increased immunolabeling of endostatin, a Collagen-18 domain that can be cleaved and become antiangiogenic, in both endocortical (79%) and peritrabecular transitional microvessels at day 14. Our results show that iPTH specifically remodels transitional vessels and suggest that it promotes LepR+ cell mobilization from these vessels close to the bone surface. © 2019 American Society for Bone and Mineral Research.

Abstract
Genetic polymorphisms of long noncoding RNA RP11‐37B2.1 associate with susceptibility of tuberculosis and adverse events of antituberculosis drugs in west China
Authors: Song Jiajia , Liu Tangyuheng , Zhao Zhenzhen , Hu Xuejiao , Wu Qian , Peng Wu , Chen Xuerong , Ying Binwu
Published: March 2019

Background

Little knowledge about the biological functions of RP11‐37B2.1, a newly defined long noncoding RNA (lncRNA) molecule, is currently available. Previous studies have shown rs160441, located in the RP11‐37B2.1 gene, is significantly associated with tuberculosis (TB) in a Ghanaian and the Gambian populations.

Methods

We investigated the influence of single‐nucleotide polymorphisms (SNPs) within lncRNA RP11‐37B2.1 on the risk of TB and the possible correlation with adverse drug reactions (ADRs) from TB treatment in a Western Chinese population. Four SNPs within lncRNA RP11‐37B2.1 were genotyped in 554 TB cases and 561 healthy subjects using the improved multiplex ligation detection reaction method, and the patients were followed up monthly to monitor the development of ADRs.

Results

No significant association between the SNPs of lncRNA RP11‐37B2.1 and TB susceptibility was observed (all P > 0.05). Surprisingly, significant association was observed between two SNPs (rs218916 and rs160441) and thrombocytopenia development during anti‐TB therapy under the dominant model (P = 0.003 and 0.014, respectively).

Conclusions

Our findings firstly exhibit that rs218916 and rs160441 within lncRNA RP11‐37B2.1 significantly associate with the occurrence of thrombocytopenia and suggest RP11‐37B2.1 genetic variants are potential biosignatures for thrombocytopenia during anti‐TB treatment.
A Phase 1, Open‐Label, Parallel‐Group, Single‐Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment
Authors: Taylor Lesley , Crockett Julie , Tayo Bola , Morrison Gilmour
Published: March 2019

The pharmacokinetics and safety of a single oral dose of 200‐mg plant‐derived pharmaceutical formulation of highly purified cannabidiol (CBD) in oral solution (Epidiolex in the United States; 100 mg/mL) were assessed in subjects with mild to severe hepatic impairment (n =  8 each for mild and moderate, n = 6 for severe) relative to matched subjects with normal hepatic function (n = 8). Blood samples were collected until 48 hours after dosing and evaluated by liquid chromatography and tandem mass spectrometry. Pharmacokinetic parameters (primarily maximum measured plasma concentration, area under the plasma concentration–time curve from time zero to time t, area under the concentration‐time curve from time zero to infinity, time to maximum plasma concentration, and terminal half‐life) of CBD and its major metabolites were derived using non‐compartmental analysis. CBD was rapidly absorbed in all groups independent of hepatic function (median time to maximum plasma concentration, 2‐2.8 hours). Exposure (area under the concentration–time curve from time zero to infinity) to total CBD slightly increased in subjects with mild hepatic impairment (geometric mean ratio [GMR], 1.48; 90% confidence interval [CI], 0.90‐2.41). However, there were clinically relevant increases in subjects with moderate (GMR, 2.45; 90%CI, 1.50‐4.01) and severe (GMR, 5.15; 90%CI, 2.94‐9.00) hepatic impairment, relative to subjects with normal hepatic function. Exposure to the CBD metabolites (6‐hydroxy‐CBD and 7‐hydroxy‐CBD) also increased in subjects with moderate and severe hepatic impairment, but to a lesser extent than the parent drug. The 7‐carboxy‐CBD metabolite exposure was lower in subjects with severe hepatic impairment when compared with subjects with normal liver function. These findings indicate that dose modification is necessary in patients with moderate and severe hepatic impairment, and a lower starting dose and slower titration are necessary based on benefit‐risk. CBD was well tolerated, and there were no serious adverse events reported during the trial.
A Convenient Synthetic Route of Diethyl (4‐Oxo‐chromeno[2,3‐d]pyrimidin‐2(5)‐yl)phosphonates
Authors: Ali Tarik E. , Assiri Mohammed A. , Hassanin Noha M. , Yahia I. S. , Hussien Mai S. A.
Published: March 2019

Novel diethyl (4‐oxo‐3,4‐dihydro‐2H‐chromeno[2,3‐d]pyrimidin‐2‐yl)phosphonate as two enantiomers and diethyl (4‐oxo‐1,5‐dihydro‐4H‐chromeno[2,3‐d]pyrimidin‐5‐yl) phosphonate were obtained in easy procedure via reaction of 2‐imino‐2H‐chromene‐3‐carboxamide, dimethylformamide dimethyl‐acetal, and diethyl phosphite in a simple one pot. Possible reaction mechanisms were proposed. The structures of the obtained products were confirmed by elemental analyses and spectral tools.
Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome
Authors: Cade William Todd , Bohnert Kathryn L. , Peterson Linda R. , Patterson Bruce W. , Bittel Adam J. , Okunade Adewole L. , de las Fuentes Lisa , Steger‐May Karen , Bashir Adil , Schweitzer George G. , Chacko Shaji K. , Wanders Ronald J. , Pacak Christina A. , Byrne Barry J. , Reeds Dominic N.
Published: March 2019

Barth syndrome (BTHS) is a rare X‐linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children/adolescents and young adults with BTHS (n = 29) and children/adolescent and young adult control participants (n = 28, total n = 57) underwent an infusion of 6′6′H2 glucose and U‐13C palmitate and indirect calorimetry during rest, 30‐minutes of moderate exercise (50% ), and recovery. Cardiac function, cardioskeletal mitochondrial energetics, and exercise capacity were examined via echocardiography, 31P magnetic resonance spectroscopy, and peak exercise testing, respectively. The glucose turnover rate was significantly higher in individuals with BTHS during rest (33.2 ± 9.8 vs 27.2 ± 8.1 μmol/kgFFM/min, P < .01) and exercise (34.7 ± 11.2 vs 29.5 ± 8.8 μmol/kgFFM/min, P < .05) and tended to be higher postexercise (33.7 ± 10.2 vs 28.8 ± 8.0 μmol/kgFFM/min, P < .06) compared to controls. Increases in total fat (−3.9 ± 7.5 vs 10.5 ± 8.4 μmol/kgFFM/min, P < .0001) and plasma fatty acid oxidation rates (0.0 ± 1.8 vs 5.1 ± 3.9 μmol/kgFFM/min, P < .0001) from rest to exercise were severely blunted in BTHS compared to controls. Conclusion: An inability to upregulate fat metabolism during moderate intensity exercise appears to be partially compensated by elevations in glucose metabolism. Derangements in fat and glucose metabolism are characteristic of the pathophysiology of BTHS.

A severely blunted ability to upregulate fat metabolism during a modest level of physical activity is a defining pathophysiologic characteristic in children, adolescents, and young adults with BTHS.
Large variations in clinical antibiotic activity against Staphylococcus aureus biofilms of periprosthetic joint infection isolates
Authors: Mandell Jonathan B. , Orr Sara , Koch John , Nourie Blake , Ma Dongzhu , Bonar Daniel D. , Shah Neel , Urish Kenneth L.
Published: March 2019

Staphylococcus aureus biofilms have a high tolerance to antibiotics, making the treatment of periprosthetic joint infection (PJI) challenging. From a clinical perspective, bacteria from surgical specimens are cultured in a planktonic state to determine antibiotic sensitivity. However, S. aureus exists primarily as established biofilms in PJI. To address this dichotomy, we developed a prospective registry of total knee and hip arthroplasty PJI S. aureus isolates to quantify the activity of clinically important antibiotics against isolates grown as biofilms. S. aureus planktonic minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were assessed using clinical laboratory standard index assays for 10 antibiotics (cefazolin, clindamycin, vancomycin, rifampin, linezolid, nafcillin, gentamicin, trimethoprim/sulfamethoxazole, doxycycline, and daptomycin). Mature biofilms of each strain were grown in vitro, after which biofilm MIC (MBIC) and biofilm MBC (MBBC) were determined. Overall, isolates grown as biofilms displayed larger variations in antibiotic MICs as compared to planktonic MIC values. Only rifampin, doxycycline, and daptomycin had measurable biofilm MIC values across all S. aureus isolates tested. Biofilm MBC observations complemented biofilm MIC observations; rifampin, doxycycline, and daptomycin were the only antibiotics with measurable biofilm MBC values. 90% of S. aureus biofilms could be killed by rifampin, 50% by doxycycline, and only 15% by daptomycin. Biofilm formation increased bacterial antibiotic tolerance nonspecifically across all antibiotics, in both MSSA and MRSA samples. Rifampin and doxycycline were the most effective antibiotics at killing established S. aureus biofilms. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1604–1609, 2019.
The clinical efficacy of deproteinized bovine bone mineral with 10% collagen in conjunction with localized piezosurgical decortication enhanced orthodontics: A prospective observational study
Authors: Miyamoto Takanari , Lang Melissa , Khan Shakeel , Kumagai Kota , Nunn Martha E.
Published: March 2019

Background

Evidence exists on the clinical efficacy and safety of periodontally accelerated osteogenic orthodontics (PAOO) with “Piezocision”—a minimally invasive, flapless alternative to corticotomy for alveolar bone augmentation. Allograft has been extensively studied for alveolar bone augmentation in Piezocision; however, the use of deproteinized bovine bone mineral with 10% collagen (DBBM‐C) in Piezocision for PAOO has not been investigated.

Methods

This study is a prospective, observational, cohort study of 19 patients of Angle Class I malocclusion with a total of 692 teeth assessed for maintenance of health of the periodontal attachment apparatus. Patient‐centered pain, sensitivity, and satisfaction outcomes, digital photographs and radiographs, and changes in probing depth, clinical attachment level, width of keratinized tissue, percussion sensitivity, pulp vitality tests, radiographic pathology, and root‐crown‐ratio were all recorded.

Results

Overall treatment was significantly faster (5 to 7 days between clear aligner tray changes), periodontal parameters remained stable, and alveolar bone loss was not observed. Visual analog score for healing, sensitivity/duration, bleeding/duration, swelling/duration, appearance, and inflammation, demonstrated no significant differences between DBBM‐C and control (no bone graft) groups. Patient‐centered outcomes revealed high levels of satisfaction with Piezocision. Piezocision‐treated teeth with DBBM‐C tended to exhibit less root resorption, although it was not statistically significant (P = 0.074).

Conclusions

Within the limits of the study, our results show that the use of DBBM‐C with piezosurgically enhanced orthodontics is effective and safe. This study was not designed to demonstrate equivalence with other materials that might be used in Piezocision. To understand whether there is an advantage to using DBBM‐C, additional studies may be required.
Effects of soil water on maize root morphological and physiological responses to phosphorus supply
Authors: Zhan Ai , Chen Xinping , Li Shiqing
Published: March 2019

Water shortage directly constrains plant growth and survival, and indirectly influences plant responses to soil mineral nutrients, especially low‐mobility nutrients such as phosphorus (P). We examined the effects of soil water content on the responses of agronomic and root morphological and physiological traits of maize (Zea mays L. cv. NE15) to P supply. Seven P supply levels (0, 12.5, 25, 50, 75, 100, and 300 mg P kg−1 soil) and two water regimes (well watered, WW; water stress, WS) were employed. Shoot dry weight, root dry weight, and root length were enhanced with the increase of P supply rates, while the root : shoot ratio, specific root length, and transcription levels of four inorganic phosphate (Pi) transporter genes (Pht1;1–4) declined with the increase of P supply rates. Under WS conditions, root dry weight and root length decreased by 4–38% and 6–32%, respectively, compared to the WW treatment, whereas the root : shoot ratio and specific root length increased by 7–33% and 8–28%, respectively. Pi transporter gene transcription was up‐regulated and that of the arbuscular‐mycorrhizal‐induced transporter (Pht1;6) gene was both up‐ and down‐regulated in response to the WS treatment. Comprehensive analysis revealed that interaction between maize root morphological and physiological traits was stimulated as a strategy for efficient P acquisition under WS conditions. This study is the first to use both morphological and physiological traits to describe the impacts of soil water conditions on maize responses to P fertilization. Our results provide valuable information for optimization of P management under different soil water conditions.