bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome‐wide association study of circulating folate one‐carbon metabolites
Authors: Wang Jun , Asante Isaac , Baron John A. , Figueiredo Jane C. , Haile Robert , Joan Levine A. , Newcomb Polly A. , Templeton Allyson S. , Schumacher Fredrick R. , Louie Stan G. , Casey Graham , Conti David V. 
Published: September 2019

AbstractExperimental, observational, and clinical trials support a critical role of folate one‐carbon metabolism (FOCM) in colorectal cancer (CRC) development. In this report, we focus on understanding the relationship between common genetic variants and metabolites of FOCM. We conducted a genome‐wide association study of FOCM biomarkers among 1,788 unaffected (without CRC) individuals of European ancestry from the Colon Cancer Family Registry. Twelve metabolites, including 5‐methyltetrahydrofolate, vitamin B2 (flavin mononucleotide and riboflavin), vitamin B6 (4‐pyridoxic acid, pyridoxal, and pyridoxamine), total homocysteine, methionine, S‐adenosylmethionine, S‐adenosylhomocysteine, cystathionine, and creatinine were measured from plasma using liquid chromatography‐mass spectrometry (LC‐MS) or LC‐MS/MS. For each individual biomarker, we estimated genotype array‐specific associations followed by a fixed‐effect meta‐analysis. We identified the variant rs35976024 (at 2p11.2 and intronic of ATOH8) associated with total homocysteine (p = 4.9 × 10−8). We found a group of six highly correlated variants on chromosome 15q14 associated with cystathionine (all p < 5 × 10−8), with the most significant variant rs28391580 (p = 2.8 × 10−8). Two variants (rs139435405 and rs149119426) on chromosome 14q13 showed significant (p < 5 × 10−8) associations with S‐adenosylhomocysteine. These three biomarkers with significant associations are closely involved in homocysteine metabolism. Furthermore, when assessing the principal components (PCs) derived from seven individual biomarkers, we identified the variant rs12665366 (at 6p25.3 and intronic of EXOC2) associated with the first PC (p = 2.3 × 10−8). Our data suggest that common genetic variants may play an important role in FOCM, particularly in homocysteine metabolism.
Gene‐based association analysis of survival traits via functional regression‐based mixed effect cox models for related samples
Authors: Chiu Chi‐yang , Zhang Bingsong , Wang Shuqi , Shao Jingyi , Lakhal‐Chaieb M'Hamed Lajmi , Cook Richard J. , Wilson Alexander F. , Bailey‐Wilson Joan E. , Xiong Momiao , Fan Ruzong 
Published: September 2019

AbstractThe importance to integrate survival analysis into genetics and genomics is widely recognized, but only a small number of statisticians have produced relevant work toward this study direction. For unrelated population data, functional regression (FR) models have been developed to test for association between a quantitative/dichotomous/survival trait and genetic variants in a gene region. In major gene association analysis, these models have higher power than sequence kernel association tests. In this paper, we extend this approach to analyze censored traits for family data or related samples using FR based mixed effect Cox models (FamCoxME). The FamCoxME model effect of major gene as fixed mean via functional data analysis techniques, the local gene or polygene variations or both as random, and the correlation of pedigree members by kinship coefficients or genetic relationship matrix or both. The association between the censored trait and the major gene is tested by likelihood ratio tests (FamCoxME FR LRT). Simulation results indicate that the LRT control the type I error rates accurately/conservatively and have good power levels when both local gene or polygene variations are modeled. The proposed methods were applied to analyze a breast cancer data set from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). The FamCoxME provides a new tool for gene‐based analysis of family‐based studies or related samples.
Determination of legal responsibility in shared airway management between anesthesiology and otolaryngology
Authors: Ideker Henry C. , Julakanti Jatin S. , Momin Nishat A. , Chaaban Mohamad R. 
Published: September 2019

AbstractBackgroundMalpractice litigation remains an important point of contention in the United States. Airway management often sees multidisciplinary teams of anesthesiologists and otolaryngologists. This report analyzes lawsuits affecting both teams in airway management.MethodsThe Westlaw legal database (West Publishing Co., St. Paul, MN) was used to search for malpractice cases involving failed airway management, where both anesthesiology and otolaryngology were involved.ResultsAmong the 28 cases analyzed, otolaryngology and anesthesiology were most commonly sued together (46.4%). When sued together, defendants were less likely to win and average award amounts ($4, 558 716) were higher. These cases most commonly occurred in the operating room (78.6%), involved a difficult/improper intubation (39.3%), alleged a failure to follow standard of care (57%), and resulted in death (60.7%).ConclusionThese cases primarily cited failure to follow standard of care and communication failures. Efforts should be directed toward multidisciplinary airway management protocols and effective communication.
Hepatocyte Stress Increases Expression of Yes‐Associated Protein and Transcriptional Coactivator With PDZ‐Binding Motif in Hepatocytes to Promote Parenchymal Inflammation and Fibrosis
Authors: Mooring Meghan , Fowl Brendan H. , Lum Shelly Z.C. , Liu Ye , Yao Kangning , Softic Samir , Kirchner Rory , Bernstein Aaron , Singhi Aatur D. , Jay Daniel G. , Kahn C. Ronald , Camargo Fernando D. , Yimlamai Dean 
Published: September 2019

Background and Aims
Activated hepatocytes are hypothesized to be a major source of signals that drive cirrhosis, but the biochemical pathways that convert hepatocytes into such a state are unclear. We examined the role of the Hippo pathway transcriptional coactivators Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) in hepatocytes to facilitate cell–cell interactions that stimulate liver inflammation and fibrosis.

Approach and Results
Using a variety of genetic, metabolic, and liver injury models in mice, we manipulated Hippo signaling in hepatocytes and examined its effects in nonparenchymal cells to promote liver inflammation and fibrosis. YAP‐expressing hepatocytes rapidly and potently activate the expression of proteins that promote fibrosis (collagen type I alpha 1 chain, tissue inhibitor of metalloproteinase 1, platelet‐derived growth factor c, transforming growth factor β2) and inflammation (tumor necrosis factor, interleukin 1β). They stimulate expansion of myofibroblasts and immune cells, followed by aggressive liver fibrosis. In contrast, hepatocyte‐specific YAP and YAP/TAZ knockouts exhibit limited myofibroblast expansion, less inflammation, and decreased fibrosis after CCl4 injury despite a similar degree of necrosis as controls. We identified cellular communication network factor 1 (CYR61) as a chemokine that is up‐regulated by hepatocytes during liver injury but is expressed at significantly lower levels in mice with hepatocyte‐specific deletion of YAP or TAZ. Gain‐of‐function and loss‐of‐function experiments with CYR61 in vivo point to it being a key chemokine controlling liver fibrosis and inflammation in the context of YAP/TAZ. There is a direct correlation between levels of YAP/TAZ and CYR61 in liver tissues of patients with high‐grade nonalcoholic steatohepatitis.

Conclusions
Liver injury in mice and humans increases levels of YAP/TAZ/CYR61 in hepatocytes, thus attracting macrophages to the liver to promote inflammation and fibrosis.
Transition‐Metal‐Catalyzed 1,2‐Carboboration of Alkenes: Strategies, Mechanisms, and Stereocontrol
Authors: Liu Zhen , Gao Yang , Zeng Tian , Engle Keary M. 
Published: September 2019

AbstractDuring the past decade, many research groups have described catalytic methods for 1,2‐carboboration, allowing access to structurally complex organoboronates from alkenes. Various transition metals, especially copper, palladium, and nickel, have been widely used in these reactions. This review summarizes advances in this field, with a special focus on the catalytic cycles involved in different metal‐catalyzed carboboration reactions, as well as the regio‐ and stereochemical consequences of the underlying mechanisms. 1,2‐Carboboration of other unsaturated systems, such as alkynes and allenes, is outside of the scope of this review.
Sterilized chitosan‐based composite hydrogels: Physicochemical characterization and in vitro cytotoxicity
Authors: Rodríguez‐Rodríguez Rogelio , Velasquillo‐Martínez Cristina , Knauth Peter , López Zaira , Moreno‐Valtierra Maira , Bravo‐Madrigal Jorge , Jiménez‐Palomar Inés , Luna‐Bárcenas Gabriel , Espinosa‐Andrews Hugo , García‐Carvajal Zaira Y. 
Published: September 2019

AbstractGelatin/chitosan/polyvinyl alcohol hydrogels were fabricated at different polymer ratios using the freeze‐drying and sterilized by steam sterilization. The thermal stability, chemical structure, morphology, surface area, mechanical properties, and biocompatibility of hydrogels were evaluated by simultaneous thermal analysis, Fourier transform infrared spectroscopy, X‐ray diffraction, confocal microscopy, adsorption/desorption of nitrogen, rheometry, and 3‐4,[5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide cell viability assay (MTT assay), respectively. The samples showed a decomposition onset temperature below 253.3 ± 4.8°C, a semicrystalline nature, and a highly porous structure. Hydrogels reached the maximum water uptake in phosphate‐buffered saline after 80 min, showing values from nine to twelve times their dry mass. Also, hydrogels exhibiting a solid‐like behavior ranging from 2,567 ± 467 to 48,705 ± 2,453 Pa at 0.1 rad/s (low frequency). The sterilized hydrogels showed low cytotoxicity (cell viability > 70%) to the HT29‐MTX‐E12 cell line. Sterilized hydrogels by steam sterilization can be good candidates as scaffolds for tissue engineering applications.
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

AbstractThe 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

AbstractJoining 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

AbstractChloro, 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

AbstractA 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

AbstractMalala 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

AbstractThe 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

ABSTRACTTibiotalar 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

AbstractBackgroundTo determine whether parenteral plus enteral glutamine supplementation influences microbial invasion in surgical infants who require parenteral nutrition (PN).MethodsAn 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.ResultsSixty 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]).ConclusionMore 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

AbstractBackgroundThe 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 MethodsA 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).ResultsMILS 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.ConclusionMILS 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.