bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Model‐Informed Drug Development in Pediatric Drug Development, Regulatory Evaluation, and Labeling
Authors: Bi Youwei , Liu Jiang , Li Lingjue , Yu Jingyu , Bhattaram Atul , Bewernitz Michael , Li Ruo‐jing , Liu Chao , Earp Justin , Ma Lian , Zhuang Luning , Yang Yuching , Zhang Xinyuan , Zhu Hao , Wang Yaning
Published: September 2019

The unique challenges in pediatric drug development require efficient and innovative tools. Model‐informed drug development (MIDD) offers many powerful tools that have been frequently applied in pediatric drug development. MIDD refers to the application of quantitative models to integrate and leverage existing knowledge to bridge knowledge gaps and facilitate development and decision‐making processes. This article discusses the current practices and visions of applying MIDD in pediatric drug development, regulatory evaluation, and labeling, with detailed examples. The application of MIDD in pediatric drug development can be broadly classified into 3 categories: leveraging knowledge for bridging the gap, dose selection and optimization, and informing clinical trial design. In particular, MIDD can provide evidence for the assumption of exposure‐response similarity in bridging existing knowledge from reference to target population, support the dose selection and optimization based on the “exposure‐matching” principle in the pediatric population, and increase the efficiency and success rate of pediatric trials. In addition, the role of physiologically based pharmacokinetics in drug‐drug interaction in children and adolescents and in utilizing ontogeny data to predict pharmacokinetics in neonates and infants has also been illustrated. Moving forward, MIDD should be incorporated into all pediatric drug development programs at every stage to inform clinical trial design and dose selection, with both its strengths and limitations clearly laid out. The accumulated experience and knowledge of MIDD has and will continue to drive regulatory policy development and refinement, which will ultimately improve the consistency and efficiency of pediatric drug development.
Industry Perspective on Using MIDD for Pediatric Studies Requiring Integration of Ontogeny
Authors: Corriol‐Rohou Solange , Cheung S. Y. Amy
Published: September 2019

Joining the Food and Drug Administration/University of Maryland Center of Excellence in Regulatory Science and Innovation Workshop to discuss and identify solutions to optimize pediatric drug development and, in particular, to address the question as to whether we are ready to incorporate pediatric ontogeny into modeling was the opportunity to share learnings, confront ideas, and present examples of studies performed in industry and academia. This was not only the opportunity to reflect on the experience and the knowledge so far within the current regulatory framework but also to look at the future and explore new and future approaches as well as best practices with the use of modeling and simulation and extrapolation as part of pediatric development.
Synthesis of chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities
Authors: Aremu Oluwole S. , Singh Parvesh , Singh Moganavelli , Mocktar Chunderika , Koorbanally Neil A.
Published: September 2019

Chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones were produced by reacting malononitrile, barbituric acid, and aromatic aldehydes together with a DABCO catalyst in an aqueous one‐pot reaction. This is the first report of these compounds being synthesized with DABCO as a catalyst, which produced the compounds in yields in excess of 90%. The 2,4‐difluoro derivative (11) was novel. The structures of the synthesized compounds were elucidated by means of 1H, 13C, and 2D NMR spectroscopy. Compound 2 (2‐Cl derivative) had MBC values of <200μM against both Staphylococcus aureus and MRSA, and the 2‐nitro derivative 5 had an MBC of 191μM against the Gram–ve Escherichia coli. The synthesized compounds were also tested for their anticancer activity against a HeLa cell line, where all the compounds showed better activity (IC50 values between 129μM and 340μM) than 5‐fluorouracil, a commonly known anticancer drug.
Synthesis, in vitro urease inhibitory activity and molecular docking of 3,5‐disubstituted thiadiazine‐2‐thiones
Authors: Shah Muhammad Ishaq Ali , Khan Rasool , Arfan Mohammad , Wadood Abdul , Ghufran Mehreen
Published: September 2019

A series of 3,5‐disubstituted‐tetrahydro‐thiadiazine‐2‐thione (1‐16) have been synthesized, characterized by elemental analysis, infrared (IR), UV‐visible, 1H NMR, 13C NMR, and MS spectroscopic techniques, and screened against jack bean urease. Among 16 compounds, compounds (1), (2), (3), (4), (6), (7), and (9) demonstrated excellent urease inhibitory activity with IC50 values (9.8 ± 0.5, 11.0 ± 0.6, 16.0 ± 1.5, 17.2 ± 0.5, 15.4 ± 0.5, 19.7 ± 0.4, and 15.8 ± 0.2μM), respectively, even better than the standard thiourea (IC50 = 21 ± 0.01μM). However, compound (8) shows an almost same level of inhibition (IC50 = 22.9 ± 0.3μM), as like standard. In this work, we reported for the first time urease inhibitory activity of thiadiazine thiones and its molecular docking studies.
Growing Up Malala: Is Today's Educated Girl Tomorrow's Neoliberal Woman?
Authors: Boutilier Sophia
Published: September 2019

Malala Yousafzai is spreading her message: education for women and girls. She speaks at a time when education and gender equality are celebrated as keys to poverty alleviation and development. At the same time, current neoliberal economic policies are hurting women and girls. How is this wider context reflected in the education agenda? Using content analysis, I compare documents from the United Nations, UNESCO and the World Bank to outline their approaches to gender equality through education. The data illustrate the narrowing of women's agency to market terms and an emphasis on local contexts at the expense of macroeconomic structures. © 2019 John Wiley & Sons, Ltd.
Absolute quantification of dystrophin protein in human muscle biopsies using parallel reaction monitoring (PRM)
Authors: Canessa Emily H. , Goswami Mansi V. , Alayi Tchilabalo D. , Hoffman Eric P. , Hathout Yetrib
Published: September 2019

The need for a reliable and accurate method to quantify dystrophin proteins in human skeletal muscle biopsies has become crucial in order to assess the efficacy of dystrophin replacement therapies in Duchenne muscular dystrophy as well as to gain insight into the relationship between dystrophin levels and disease severity in Becker's muscular dystrophy. Current methods to measure dystrophin such as western blot and immunofluorescence, while straightforward and simple, lack precision and sometimes specificity. Here, we standardized a targeted mass spectrometry method to determine the absolute amount of dystrophin in ng/mg of muscle using full‐length 13C6–Arg– and 13C6,15N2–Lys–labeled dystrophin and parallel reaction monitoring (PRM). The method was found to be reproducible with a limit of quantification as low as 30 pg of dystrophin protein per mg of total muscle proteins. The method was then tested to measure levels of dystrophin in muscle biopsies from a healthy donor and from Duchenne and Becker's muscular dystrophy patients.
Anteroposterior Translational Malalignment of Ankle Arthrodesis Alters Foot Biomechanics in Cadaveric Gait Simulation
Authors: Imsdahl Sheri I. , Stender Christina J. , Cook Brian K. , Pangrazzi Garett , Patthanacharoenphon Cameron , Sangeorzan Bruce J. , Ledoux William R.
Published: September 2019

Tibiotalar arthrodesis is a common surgical treatment for end‐stage ankle arthritis. Proper ankle alignment is important as malalignment can lead to complications that may require revision surgery. This study aimed to determine how anteroposterior (AP) translational malalignment of ankle arthrodesis affects distal foot joint kinematics and plantar pressure. Ankle arthrodesis was performed on 10 cadaveric foot specimens using a custom fixture that could fuse the ankle neutrally and induce discrete malalignments (3, 6, and 9 mm) anteriorly and posteriorly. Gait was simulated under each alignment with a robotic gait simulator, and foot bone motion and plantar pressure were quantified. AP translational malalignment did not substantially affect plantar pressure or joint range of motion, but there were several significant differences in joint position throughout stance phase. Differences were seen in five joints (talocalcaneal, talonavicular, calcaneocuboid, fifth tarsometatarsal, and first metatarsophalangeal) and in the position of the first metatarsal relative to the talus. The most extreme effects occurred when the talus was displaced 6 mm or more posteriorly. In vivo, this may lead to aberrant joint loading, which could negatively impact patient outcomes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:450‐458, 2020
The Effect of Glutamine Supplementation on Microbial Invasion in Surgical Infants Requiring Parenteral Nutrition: Results of a Randomized Controlled Trial
Authors: Bishay Mark , Simchowitz Venetia , Harris Kathryn , Macdonald Sarah , De Coppi Paolo , Klein Nigel , Eaton Simon , Pierro Agostino ,   on behalf of the MIGS Trial Group
Published: September 2019

Background

To determine whether parenteral plus enteral glutamine supplementation influences microbial invasion in surgical infants who require parenteral nutrition (PN).

Methods

An prospective double‐blind randomized controlled trial studying surgical infants receiving PN for at least 5 days for congenital or acquired intestinal anomalies (2009–2012) was used. Infants were randomized to receive either glutamine supplementation (parenteral plus enteral; total 400 mg/kg/d) or isonitrogenous control. The primary end point was microbial invasion evaluated after 5 days of supplementation and defined as: (i) positive conventional blood culture, (ii) evidence of microbial DNA in blood (polymerase chain reaction), (iii) plasma endotoxin level ≥50 pg/mL, or (iv) plasma level of lipopolysaccharide binding protein ≥50 ng/mL. Data are given as median (range) and compared by logistic regression.

Results

Sixty infants were randomized and reached the primary end point. Twenty‐five patients had intestinal obstruction, 19 had abdominal wall defects, and 13 had necrotizing enterocolitis. Thirty‐six infants showed evidence of microbial invasion during the study, and 17 of these were not detected by conventional blood culture. There was no significant difference between the 2 groups in the primary outcome; evidence of microbial invasion after 5 days was found in 9/31 (control group) and 8/29 (glutamine group) (odds ratio 0.83 [0.24–2.86; P = 0.77]).

Conclusion

More than half of surgical infants requiring PN showed evidence of microbial invasion. Approximately half of this was not detectable by conventional blood cultures. Parenteral plus enteral glutamine supplementation had no effect on incidence of microbial invasion.
Appraisal of disease‐specific benefits of minimally invasiveness in surgery of breast cancer liver metastases
Authors: Ratti Francesca , Serenari Matteo , Zanello Matteo , Prosperi Enrico , Cipriani Federica , Ercolani Giorgio , Jovine Elio , Cescon Matteo , Aldrighetti Luca
Published: September 2019

Background

The primary endpoint of this study is to analyze short term benefit of laparoscopic approach (minimally invasive liver surgery [MILS]) over the open techniques in patients submitted to surgery for breast cancer liver metastases (BCLM) within a disease‐specific perspective.

Material and Methods

A group of 30 patients who underwent laparoscopic liver resection for BCLM constituted the Study group (MILS group) and was matched in a ratio of 1:2 with patients who underwent open surgery for BCLM (Open group, constituting the Control group).

Results

MILS approach resulted in a statistically significant lower blood loss (150 vs 300 mL; P < .05). The rate of postoperative complications was similar (13.3% and 16.6% in the MILS and Open groups, respectively). MILS approach was associated with a shorter length of postoperative stay (4 ± 2 days) compared with the Open group (7 ± 3 days), allowing a faster return to adjuvant treatments. Both MILS and open groups showed adequate oncological radicality, with comparable long‐term results.

Conclusion

MILS approach to BCLM represents the optimal instrument to obtain an adequate disease clearance in the selected group of patients candidates to surgery: the type of procedure (minor resections for limited hepatic disease) and characteristics of patients contribute to enhance the feasibility and the benefits of the laparoscopic technique.
A target‐group‐change couple with mass defect filtering strategy to identify the metabolites of “Dogel ebs” in rats plasma, urine and bile
Authors: Dong Xin , Li XiaoNa , Li Na , Zhao HongMei , GuLa A , Zhang Xuan , Zhang Ping , Bao BaoQuan
Published: September 2019

“Dogel ebs” was known as Sophora flavescens Ait., a classical traditional Chinese Mongolian herbal medicine, which had the effects on damp‐heat dysentery, scrofula, and syndrome of accumulated dampness toxicity. Although the chemical constituents have been clarified by our previous studies, the metabolic transformation of “Dogel ebs” in vivo was still unclear. To explore the mechanism of “Dogel ebs,” the metabolites in plasma, bile, and urine samples were investigated. A fast positive and negative ion switching technology was used for the simultaneous determination of flavonoids and alkaloids in “Dogel ebs” in a single run. And a target‐group‐change coupled with mass defect filtering strategy was utilized to analyze the collected data. 89 parent compounds and 82 metabolites were characterized by high‐performance liquid chromatography with quadrupole exactive Orbitrap mass spectrometry. Both phase I and phase II metabolites were observed and the metabolic pathways involved in oxidation, demethylation, acetylation, and glucuronidation. 69 metabolites of “Dogel ebs,” including three hydroxyls bonding xanthohumol, formononetin‐7‐O‐glucuronide, 2′‐hydroxyl‐isoxanthohumol decarboxylation metabolite, oxysophocarpine dehydrogen, 9α‐hydroxysophoramine‐O‐glucuronide, etc. were reported for the first time.
Spatiotemporal railway use by grizzly bears in Canada's Rocky Mountains
Authors: Pollock Sonya Z. , Whittington Jesse , Nielsen Scott E. , St. Clair Colleen C.
Published: September 2019

Railway networks contribute to the direct mortality of wildlife through collisions with trains, which can threaten vulnerable wildlife populations even in protected areas, including grizzly bears (Ursus arctos) in Banff and Yoho National Parks, Canada. Mitigation to reduce bear‐train collisions requires information about how grizzly bears use the railway spatially and temporally and how particular types of use might increase collision vulnerability. We used data from 27 grizzly bears fitted with global positioning system (GPS) collars between 2000 and 2016 to relate railway use by bears via resource selection functions to variables that described land cover, human use, and topography. We used the same suite of explanatory variables to distinguish pairs of 4 types of steps, in which 3 successive GPS points (with 2‐hr fix rates) included ≥1 within 30 m of the rail (hereafter on) and 2 others that defined locations where bears effectively entered the railway (first fix off rail, next 2 on), crossed it (only the middle fix on the rail), continued along the railway (all 3 fixes on), or exited the railway corridor (first 2 on, last off). We compared both sites of higher use and each of these 4 step types to the relative frequency of bear‐train collisions, predicting a positive correlation for continue step types. Relative to available locations, bears were more likely to use the railway close to railroad sidings (sections of twinned track where trains sometimes stop), at intermediate distances from human‐use features (e.g., town sites, highways, trails), in areas with lower values of the compound topographic index (a proxy for wetness; within 500 m), and within 90 m of rugged terrain. Seasonally, bears made greater use of the railway in spring and fall. Among 1,515 sequences of 3 steps, crossing locations comprised >50% and were most distinct from continue locations (about 20%), which occurred in areas with more rugged terrain (within 300 m), closer to railway sidings, in spring and fall, and with steps that were 60% shorter. Contrary to our prediction, past reports of bear‐train collisions were negatively correlated with continue locations and unrelated to overall use or any other movement type. Our results suggest that railway use by bears increased where it provided increased forage or easier travel, particularly in spring and fall, but more work will be needed to determine the mechanistic basis of bear‐train collisions. Meanwhile, mitigation efforts such as habitat alteration or warning systems might target locations where past strikes are concentrated for grizzly bears or other sensitive populations. © 2019 The Wildlife Society.
Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts
Authors: Iwaki Hirotaka , Blauwendraat Cornelis , Leonard Hampton L. , Kim Jonggeol J. , Liu Ganqiang , Maple‐Grødem Jodi , Corvol Jean‐Christophe , Pihlstrøm Lasse , van Nimwegen Marlies , Hutten Samantha J. , Nguyen Khanh‐Dung H. , Rick Jacqueline , Eberly Shirley , Faghri Faraz , Auinger Peggy , Scott Kirsten M. , Wijeyekoon Ruwani , Van Deerlin Vivianna M. , Hernandez Dena G. , Gibbs J. Raphael ,   International Parkinson's Disease Genomics Consortium, Chitrala Kumaraswamy Naidu , Day‐Williams Aaron G. , Brice Alexis , Alves Guido , Noyce Alastair J. , Tysnes Ole‐Bjørn , Evans Jonathan R. , Breen David P. , Estrada Karol , Wegel Claire E. , Danjou Fabrice , Simon David K. , Andreassen Ole , Ravina Bernard , Toft Mathias , Heutink Peter , Bloem Bastiaan R. , Weintraub Daniel , Barker Roger A. , Williams‐Gray Caroline H. , van de Warrenburg Bart P. , Van Hilten Jacobus J. , Scherzer Clemens R. , Singleton Andrew B. , Nalls Mike A.
Published: September 2019

Background

Several reports have identified different patterns of Parkinson's disease progression in individuals carrying missense variants in GBA or LRRK2 genes. The overall contribution of genetic factors to the severity and progression of Parkinson's disease, however, has not been well studied.

Objectives

To test the association between genetic variants and the clinical features of Parkinson's disease on a genomewide scale.

Methods

We accumulated individual data from 12 longitudinal cohorts in a total of 4093 patients with 22,307 observations for a median of 3.81 years. Genomewide associations were evaluated for 25 cross‐sectional and longitudinal phenotypes. Specific variants of interest, including 90 recently identified disease‐risk variants, were also investigated post hoc for candidate associations with these phenotypes.

Results

Two variants were genomewide significant. Rs382940(T>A), within the intron of SLC44A1, was associated with reaching Hoehn and Yahr stage 3 or higher faster (hazard ratio 2.04 [1.58–2.62]; P value = 3.46E‐8). Rs61863020(G>A), an intergenic variant and expression quantitative trait loci for α‐2A adrenergic receptor, was associated with a lower prevalence of insomnia at baseline (odds ratio 0.63 [0.52–0.75]; P value = 4.74E‐8). In the targeted analysis, we found 9 associations between known Parkinson's risk variants and more severe motor/cognitive symptoms. Also, we replicated previous reports of GBA coding variants (rs2230288: p.E365K; rs75548401: p.T408M) being associated with greater motor and cognitive decline over time, and an APOE E4 tagging variant (rs429358) being associated with greater cognitive deficits in patients.

Conclusions

We identified novel genetic factors associated with heterogeneity of Parkinson's disease. The results can be used for validation or hypothesis tests regarding Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society
A rare case of acquired immunodeficiency associated with myelodysplastic syndrome
Authors: Li Juanjuan , Li Junhui , Li Jianguo , Yao Hailan , Liu Fang , Gusella James F , Shi Xiaodong , Chen Xiaoli
Published: September 2019

Background

Pediatric myelodysplastic syndromes (MDS) display clonal genomic instability that can lead to acquisition of other hematological disorders, usually by loss of heterozygosity. Immunodeficiency caused by uniparental disomy (UPD) has not previously been reported.

Methods

We investigated a 13‐year‐old boy who suffered from recurrent infections and pancytopenia for 1 year. Both the comet assay and chromosome breakage analysis were normal, but the bone marrow showed evidence of dysplasia characteristic of MDS. With his normal sister as donor, he underwent failed hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) followed by successful HSCT with myeloablative conditioning (MAC). We used single nucleotide polymorphism (SNP) array, targeted gene panel, and whole exome sequencing to investigate the etiology of his disease.

Results

The molecular analyses revealed multiple regions of homozygosity, one region encompassing a homozygous missense variant of recombination activating gene 1 (RAG1) which was previously associated with severe immunodeficiency in infancy. This RAG1 mutation was heterozygous in the proband’s fingernail DNA, but was changed to homozygous in the proband’s marrow by somatic acquisition of UPD event. No other pathogenic driver mutation for MDS‐related genes was identified.

Conclusion

The hematological phenotype, somatic genomic instability, and response to HSCT MAC but not HSCT RIC deduced to a diagnosis of MDS type refractory cytopenia of children in this patient. His immunodeficiency was secondary to MDS due to somatic acquisition of homozygosity for known pathogenic RAG1 mutation.
Property Prediction of Organic Donor Molecules for Photovoltaic Applications Using Extremely Randomized Trees
Authors: Paul Arindam , Furmanchuk Alona , Liao Wei‐keng , Choudhary Alok , Agrawal Ankit
Published: September 2019

Organic solar cells are an inexpensive, flexible alternative to traditional silicon‐based solar cells but disadvantaged by low power conversion efficiency due to empirical design and complex manufacturing processes. This process can be accelerated by generating a comprehensive set of potential candidates. However, this would require a laborious trial and error method of modeling all possible polymer configurations. A machine learning model has the potential to accelerate the process of screening potential donor candidates by associating structural features of the compound using molecular fingerprints with their highest occupied molecular orbital energies. In this paper, extremely randomized tree learning models are employed for the prediction of HOMO values for donor compounds, and a web application is developed.1 The proposed models outperform neural networks trained on molecular fingerprints as well as SMILES, as well as other state‐of‐the‐art architectures such as Chemception and Molecular Graph Convolution on two datasets of varying sizes.
A planar miniaturized UWB dual‐polarization multiple‐input‐multiple‐output slot antenna
Authors: Tan Ming‐Tao , Li Xiang , Wei Wang‐He , Tan Wen‐Xue , Zhou Bin , Li Jian‐Qi
Published: September 2019

A planar miniaturized ultra‐wideband (UWB) dual‐polarization multiple‐input‐multiple‐output (MIMO) slot antenna is presented in this article. Two orthogonal microstrip lines are utilized to feed antenna, which can excite both orthogonal modes in two orthogonal‐stepped slots to realize dual‐polarization characteristics. Two orthogonal‐stepped slots are its main radiators. The overall size of the presented antenna is only 32 × 22 × 0.8 mm3. The antenna was built and measured. The measurement of common –10 dB impedance bandwidth reaches 7.56 GHz (110.7%, 3.05‐10.61 GHz). Port isolation is greater than 18 dB over the entire working band. The radiation patterns and gains are stable over the whole working band.
Long‐T2‐suppressed zero echo time imaging with weighted echo subtraction and gradient error correction
Authors: Lee Hyo Min , Weiger Markus , Giehr Caspar , Froidevaux Romain , Brunner David Otto , Rösler Manuela Barbara , Pruessmann Klaas Paul
Published: September 2019

Purpose

To perform direct, selective MRI of short‐T2 tissues using zero echo time (ZTE) imaging with weighted echo subtraction (WSUB).

Methods

Radial imaging was performed at 7T, acquiring both ZTE and gradient echo (GRE) signals created by bipolar gradients. Long‐T2 suppression was achieved by weighted subtraction of ZTE and GRE images. Special attention was given to imperfections of gradient dynamics, to which radial GRE imaging is particularly susceptible. To compensate for gradient errors, matching of gradient history was combined with data correction based on trajectory measurement. The proposed approach was first validated in phantom experiments and then demonstrated in musculoskeletal (MSK) imaging.

Results

Trajectory analysis and phantom imaging demonstrated that gradient imperfections were successfully addressed. Gradient history matching enabled consistency between antiparallel projections as required for deriving zeroth‐order eddy current dynamics. Trajectory measurement provided individual echo times per projection that showed considerable variation between gradient directions. In in vivo imaging of knee, ankle, and tibia, the proposed approach enabled high‐resolution 3D depiction of bone, tendons, and ligaments. Distinct contrast of these structures indicates excellent selectivity of long‐T2 suppression. Clarity of depiction also confirmed sufficient SNR of short‐T2 tissues, achieved by high baseline sensitivity at 7T combined with high SNR efficiency of ZTE acquisition.

Conclusion

Weighted subtraction of ZTE and GRE data reconciles robust long‐T2 suppression with fastest k‐space coverage and high SNR efficiency. This approach enables high‐resolution imaging with excellent selectivity to short‐T2 tissues, which are of major interest in MSK and neuroimaging applications.
Effect of Rhodopseudomonas sphaeroides–Treated Wastewater on Yield, Digestive Enzymes, Antioxidants, Nonspecific Immunity, and Intestinal Microbiota of Common Carp
Authors: Wu Pan , Xie Liying , Wu Xiaozhen , Wang Yanling , Wu Yuan , Li Ning , Zhang Ying , Chen Zhaobo
Published: September 2019

The employment of traditional bait and medicament in freshwater aquaculture causes the frequent occurrence of environmental pollution and disease. Effluent collected after wastewater treatment with Rhodopseudomonas sphaeroides could be reutilized for microbial feed, medicament, and aquaculture water to culture Common Carp Cyprinus carpio. Therefore, a novel integrated system of wastewater treatment and the use of the effluent containing R. sphaeroides, which could improve yield, increase disease resistance, and enhance the quality of aquaculture water for Common Carp culture, was proposed and investigated. Common Carp can grow well in effluent containing R. sphaeroides. The survival rate, yield, and whole-body composition of the fish raised in effluent containing R. sphaeroides were all increased compared with the control group. The biochemical (B vitamin) and other substances in the effluent with R. sphaeroides enhanced the activity of proteases, amylases, lipases, alkaline phosphatase, acid phosphatase, phagocytes, superoxide dismutase, and catalase by up-regulating the expression of their associated genes. Theoretical analysis showed that biochemical molecules regulate the expression of these gene and enzyme activities by acting as a signal that stimulates the active center. Moreover, biochemicals present in R. sphaeroides enhanced the mTOR and NF-kB signaling pathways and improved intestinal microbiota. Furthermore, R. sphaeroides inhibited Aeromonas hydrophila, increasing resistance against fish disease and promoting the growth of intestinal bacteria. Meanwhile, R. sphaeroides in the effluent also improved the aquaculture water quality. This technology would simultaneously save water in aquaculture, reduce water pollution and wastewater discharge, and increase the output and disease resistance of Common Carp.
Uncompromised MRI of knee cartilage while incorporating sensitive sodium MRI
Authors: Brinkhof S. , Ali Haghnejad A. , Ito K. , Markenroth Bloch K. , Klomp D.W.J.
Published: September 2019

Sodium imaging is able to assess changes in ion content, linked to glycosaminoglycan content, which is important to guide orthopeadic procedures such as articular cartilage repair. Sodium imaging is ideally performed using double tuned RF coils, to combine high resolution morphological imaging with biochemical information from sodium imaging to assess ion content. The proton image quality of such coils is often harshly degraded, with up to 50% of SNR or severe acceleration loss as compared to single tuned coils. Reasons are that the number of proton receive channels often severely reduced and double tuning will degrade the intrinsic sensitivity of the RF coil on at least one of the nuclei. However, the aim of this work was to implement a double‐tuned sodium/proton knee coil setup without deterioration of the proton signal whilst being able to achieve acquisition of high SNR sodium images.

A double‐tuned knee coil was constructed as a shielded birdcage optimized for sodium and compromised for proton. To exclude any compromise, the proton part of the birdcage is used for transmit only and interfaced to RF amplifiers that can fully mitigate the reduced efficiency. In addition, a 15 channel single tuned proton receiver coil was embedded within the double‐resonant birdcage to maintain optimal SNR and acceleration for proton imaging. To validate the efficiency of our coil, the designed coil was compared with the state‐of‐the‐art single‐tuned alternative at 7 T. B1+ corrected SNR maps were used to compare both coils on proton performance and g‐factor maps were used to compare both coils on acceleration possibilities. The newly constructed double‐tuned coil was shown to have comparable proton quality and acceleration possibilities to the single‐tuned alternative while also being able to acquire high SNR sodium images.
Assessment of ovarian function in adolescents and young adults after childhood cancer treatment—How accurate are young adult/parent proxy‐reported outcomes?
Authors: George Sobenna A. , Williamson Lewis Rebecca , McKenzie Laurie , Cherven Brooke , Patterson Briana C. , Effinger Karen E. , Mertens Ann C. , Meacham Lillian R.
Published: September 2019

Background

: Providers often rely on self‐reported ovarian function in adolescent and young adult (AYA)‐aged childhood cancer survivors when making clinical decisions. This study described reported menstrual patterns and the agreement between respondent‐reported and biochemical premature ovarian insufficiency (POI) in this population.

Procedure

This was a cross‐sectional study of survivors (or their parent proxy) aged 13‐21.9 years who received gonadotoxic therapy and were enrolled in a longitudinal health survey. Participants reported menstrual regularity, hormone‐replacement therapy (HRT) use, and ovarian dysfunction. Respondent‐reported POI was defined as the survivor taking HRT for ovarian failure or having been told she had ovarian failure. Biochemical POI was defined as follicle‐stimulating hormone (FSH) level ≥40 mIU/mL. The agreement between respondent‐reported and biochemical POI was determined using Cohen's kappa coefficient (κ) and analyzed by demographic and clinical factors.

Results

Among 182 AYA‐aged survivors (72.5% non‐Hispanic White, 46.7% leukemia survivors), 14.8% reported requiring HRT to have menses but 55.5% reported regular menses without HRT use. Among survivors with FSH measurements (n = 130), 17.7% reported POI whereas 18.5% had FSH ≥40 mIU/mL (κ = 0.66, sensitivity 70.8%, specificity 94.3%). The highest agreement between respondent‐reported and biochemical POI was with young adult self‐report (κ = 0.78) and survivors with >5 survivor clinic (κ = 0.83) and/or >5 endocrinologist (κ = 1.00) visits.

Conclusions

The majority of AYA‐aged survivors reported having regular menses without HRT support. The accuracy of respondent‐reported POI increased with repeated survivor clinic or endocrinologist visits, highlighting the importance of continued education. Survivors must be informed about their ovarian function to enable them to advocate for their reproductive health.
Prediction of Residual Stresses in Injection‐Molded Plates Using the Residual Temperature Field Concept
Authors: Estrella‐Guayasamin Marcelo , Figueroa‐López Ulises , Guevara‐Morales Andrea
Published: September 2019

Injection molding is the most widely used technology for precision forming of thermoplastic products. However, high temperature and pressure gradients during solidification can be locked in as residual stresses, resulting in distortion of the product after ejection. Increasing demand for tight dimensional tolerances makes it increasingly important to predict such distortion. In this article, thermal‐induced residual stresses generated during the filling, packing, and cooling stages of injection molding are estimated by implementing the residual temperature field concept to describe the relationship between the thermal history and the frozen‐in strains. Although they are an order of magnitude lower than thermal stresses, it is shown that the approach can be extended to account for pressure‐induced residual stresses, taking advantage of the orthogonal lines already used as integration paths for the residual temperature field. A crystallization model is coupled to the thermal analysis as a heat source to account for its effect on the thermal history of the material. Polymer plates were injection molded under symmetrical and asymmetrical cooling conditions, and the values of deflection were measured using image processing tools. Simulated and experimental results agreed within 7.5%. POLYM. ENG. SCI., 59:2220–2230, 2019. © 2019 Society of Plastics Engineers
Systematic Review of l‐glutamine for Prevention of Vaso‐occlusive Pain Crisis in Patients with Sickle Cell Disease
Authors: Cieri‐Hutcherson Nicole E. , Hutcherson Timothy C. , Conway‐Habes Erin E. , Burns Brianna N. , White Nathan A.
Published: September 2019

l‐glutamine was approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. A vaso‐occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for l‐glutamine in the prevention of VOC and associated pain in patients with SCD. Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on l‐glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered l‐glutamine, reported on outcomes related to VOC or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk‐of‐bias assessments were conducted using the Risk of Bias in Non‐Randomized Studies‐of Interventions (ROBINS‐I) tool and the revised Cochrane risk‐of‐bias tool for randomized studies. Three studies assessing the effect of exogenous l‐glutamine administration in patients with SCD met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving l‐glutamine, although some conflicting results were noted between studies. l‐glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline. l‐glutamine has limited high‐quality evidence supporting its use. Although l‐glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, l‐glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.
Porous microparticles based on methacrylic copolymers and gellan as drug delivery systems
Authors: Vasiliu Silvia , Lungan Maria‐Andreea , Racovita Stefania , Popa Marcel
Published: September 2019

Two types of porous microparticles based on glycidyl methacrylate, dimethacrylic monomers (ethylene glycol dimethacrylate, diethylene glycol dimethacrylate and triethylene glycol dimethacrylate) and gellan were prepared by two methods. The first method was aqueous suspension polymerization in the presence of N‐butyl acetate as porogenic agent when the crosslinking and grafting reactions were achieved in a single step. The second method was based on the reaction between hydroxyl groups belonging to gellan and the epoxy groups situated on the surface of porous microparticles based on glycidyl methacrylate and dimethacrylic monomers in basic medium. The microparticles with and without gellan were characterized by Fourier transform infrared spectroscopy, SEM, AFM and TGA. Also, the porous structure was investigated in terms of pore volume, porosity and specific surface. The swelling behaviour in aqueous solution with different pH values as well as sorption studies of cefuroxime sodium salt onto porous microparticles were investigated. The presence of gellan in the structure of the microparticles leads to porous materials characterized by higher specific surface areas (Ssp = 78–140 m2 g–1), higher swelling capacities (Sw = 162%–365%) and higher sorption capacities of the drug (qe = 101–147 mg g–1) compared to microparticles without gellan in their structures (Ssp = 73–85 m2 g–1; Sw = 139%–209%; qe = 70–110 mg g–1). © 2019 Society of Chemical Industry
Catalytic Activity of Ferrates (NiFe2O4, ZnFe2O4 and CoFe2O4) on the Thermal Decomposition of Ammonium Perchlorate
Authors: Zhang Ming , Zhao Fengqi , Yang Yanjing , An Ting , Qu Wengang , Li Hui , Zhang Jiankan , Li Na
Published: September 2019

Three kinds of ferrates (NiFe2O4, ZnFe2O4 and CoFe2O4) were prepared via the facile solvothermal method and characterized using SEM, TEM, XRD, XPS, FT‐IR and BET instruments. The NiFe2O4, CoFe2O4 and ZnFe2O4 particles possess hollow structure with average particle size of 70, 220 and 360 nm, respectively. The catalytic performance of the ferrates for AP thermal decomposition were studied using DSC and TG‐DTG methods, and the decomposition mechanism of AP were suggested. The catalytic effects of different ferrates for AP thermal decomposition were significantly different. The CoFe2O4 has the best catalytic activity, and the high thermal decomposition peak temperature (THDP) and apparent activation energy (Ea) of AP were decreased by 108.99 °C and 37.38 kJ mol−1 in the presence of CoFe2O4 sample. Adding ferrates has no obvious influence on the gas‐phase decomposition products of AP, but has a great influence on the energy barrier of high temperature decomposition of AP. The excellent catalytic activity of CoFe2O4 is mainly attributed to the synergistic interaction between Fe and Co, which is conducive to the thermal decomposition of AP.
Immediate effects of Mulligan's techniques on pain and functional mobility in individuals with knee osteoarthritis: A randomized control trial
Authors: Bhagat Madhura , Neelapala Y.V. Raghava , Gangavelli Ranganath
Published: September 2019

Background and Purpose

Mulligan's mobilization with movement was shown to be effective when implemented in multimodal therapy for knee osteoarthritis. However, no study has evaluated the Mulligan's technique in isolation and compared the relative effectiveness with sham‐controlled interventions. Hence, the present study examined the immediate effects of Mulligan's techniques with sham mobilization on the numerical pain rating scale (NPRS) and timed up and go (TUG) test in individuals with knee osteoarthritis.

Methods

Thirty participants (mean age: 55.3 ± 8.3 years) with symptoms at the knee and radiographic diagnosis of knee osteoarthritis were randomized into sham (n = 15) and intervention (n = 15) groups. The intervention (I) group received Mulligan's mobilization glides that resulted in relative pain relief for three sets of 10 repetitions. For the sham (S) group, the therapist's hand was placed over the joint surfaces mimicking the pain‐relieving glides, without providing the gliding force. The outcome measures NPRS and TUG were recorded by a blinded assessor pre‐ and post‐intervention.

Results

Statistically significant differences were identified between the groups in post‐intervention median (interquartile range) NPRS (I group: 4.00 [2.00–5.00]; S group: 6.00 [4.00–7.00]) and TUG scores (I group: 10.9 [9.43–10.45]; S group: 13.18 [10.38–16.00]) with the intervention group demonstrating better outcomes (p < .05). Within‐group, the post‐intervention scores of NPRS and TUG were significantly lower (p < .05) compared to the pre‐intervention scores in the intervention group. In the sham group, a statistically significant pre–post change was noticed only in the NPRS scores but not in the TUG scores.

Conclusion

Mulligan's techniques were effective in improving pain and functional mobility in individuals with knee osteoarthritis. The underlying mechanisms for observed effects must be examined further, as participants reported pain relief following sham mobilization.
A moving average control chart using a robust scale estimator for process dispersion
Authors: Koukouvinos Christos , Lappa Angeliki
Published: September 2019

Control charts are one of the most powerful tools used to detect and control industrial process deviations in statistical process control. In this paper, a moving average control chart based on a robust scale estimator of standard deviation, namely, the sample median absolute deviation (MAD) statistic, for monitoring process dispersion, is proposed. A simulation study is conducted to evaluate the performance of the proposed moving average median absolute deviation (MA‐MAD) chart, in terms of average run length for various distributions. The results show that the moving average MAD chart performs well in detecting small and moderate shifts in process dispersion, especially when the normality assumption is violated. In addition, this chart is very efficient, especially when the quality characteristic follows a skewed distribution. Numerical and simulated examples are given at the end of the paper.
Prescribed performance control of strict‐feedback systems under actuation saturation and output constraint via event‐triggered approach
Authors: Cao Ye , Wen Changyun , Song Yongduan
Published: September 2019

In this work, we study the performance‐guaranteed event‐triggered control for a class of uncertain nonlinear systems in strict‐feedback form subject to input saturation and output constraint. The prescribed performance (ie, convergence rate, tracking error accuracy) and output constraint are firstly taken into account for nonlinear systems with event‐triggered input. By blending a speed transformation into the barrier Lyapunov function and introducing an intermediate variable to the system, two different event‐triggered control schemes are proposed for systems with and without saturation, respectively. Each scheme has two rules to determine triggering time sequences, one for control signal updating and the other for control signal transmission with the latter being a subsequence of the first. Meanwhile, it is proved that the tracking error converges to a preset compact set around zero at the prescribed decay rate and the output is maintained within a given bound at all times. Simulation verification also confirms the effectiveness of the proposed approach.
Quantifying treatment effects using the personalized chance of longer survival
Authors: Zhao Ying‐Qi , Redman Mary W. , LeBlanc Michael L.
Published: September 2019

The hazard ratio is widely used to measure or to summarize the magnitude of treatment effects, but it is justifiably difficult to interpret in a meaningful way to patients and perhaps for clinicians as well. In addition, it is most meaningful when the hazard functions are approximately proportional over time. We propose a new measure, termed personalized chance of longer survival. The measure, which quantifies the probability of living longer with one treatment over the another, accounts for individualized characteristics to directly address personalized treatment effects. Hence, the measure is patient focused, which can be used to evaluate subgroups easily. We believe it is intuitive to understand and clinically interpretable in the presence of nonproportionality. Furthermore, because it estimates the probability of living longer by some fixed amount of time, it encodes the probabilistic part of treatment effect estimation. We provide nonparametric estimation and inference procedures that can accommodate censored survival outcomes. We conduct extensive simulation studies, which characterize performance of the proposed method, and data from a large randomized Phase III clinical trial (SWOG S0819) are analyzed using the proposed method.
Phosphonate‐functionalized Ionic Liquid: A Novel Electrolyte Additive for Eenhanced Cyclic Stability and Rate Capability of LiCoO2 Cathode at High Voltage
Authors: Ge Jiawen , Liang Hongze , Zhou Mingjiong , Zhao Chuanli , Zheng Zhe , Yan Yinghua , Zhao Lingling , Tang Keqi
Published: September 2019

Phosphonate‐functionalized ionic liquid (PFIL) is employed as a multifunctional additive to the base electrolyte mixture consisting of ethylene carbonate, dimethyl carbonate and LiPF6. Addition of PFIL (5 wt%) significantly improves the cyclic stability and rate capability of LiCoO2 cathode performed between 3.0 and 4.3 V (vs Li/Li+), and decreases the flammability of the base electrolyte as well. Electrochemical studies indicate that PFIL is preferentially oxidized on cathode to form robust cathode electrolyte interface (CEI), which contributes to the enhanced cyclic stability and rate capability. Morphological and surface analysis on the cycled cathodes also reveal that PFIL is a key component for the formation of thin CEI film and retention of structural integrity of cathode material. Comparison experiments verify that chemically linking between ionicity and phosphorus functionality is indispensable for the enhanced performance. Additives of individual nonfunctionalized ionic liquid, neutral phosphonate, or their mixture all fail to improve the electrochemical performances.
Analytical Determination of the Oxazolidinone Antibiotic Linezolid at a Pencil Graphite and Carbon Paste Electrodes
Authors: Aydin Ilknur , Akgun Hilal , Pınar Pınar Talay
Published: September 2019

Electrochemical properties of linezolid, an antibiotic drug, using unmodified renewable pencil graphite and carbon paste electrodes, were investigated from pH 2 to 10 in Britton‐Robinson buffer solution. Experimental studies were examined by square‐wave (SW) and cyclic voltammetry (CV). Firstly, parameters affecting the performance of both electrode, such as electrode activation, support electrolyte selection, pH effect, interval of potentials, scan rates and voltammetric method parameters were investigated in detail by using square wave voltammetry. Linezolid was not reversibly oxidized in supporting electrolytes solutions, yielding well‐defined peaks in the oxidation potential interval. Using the pencil graphite electrode (PGE), a linearity range between peak current and concentration was obtained between 0.01 and 0.2 μg mL−1 (2.96×10−8‐5.93×10−7 M), other one, at carbon paste electrode (CPE), a linearity range between 0.1 and 7.5 μg mL−1 (2.96×10−7‐2.22×10−5 M) was obtained by SWV. The selectivity, sensitivity, precision, and other validation parameters of the developed voltammetric method was evaluated. Lastly, the concentration of linezolid was examined in pharmaceutical and biological samples with standard addition technique.