bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure and anti-inflammatory and anaphylactic effects of andrographlide sulphonate E in Xiyanping, a traditional Chinese medicine injection
Authors: Yang Qian-Wen , Li Qiao , Zhang Jie , Xu Qian , Yang Xin , Li Zhi-Yong , Xu Hui 
Published: October 2018

Abstract

Objectives
Andrographlide sulphonate E, namely sodium 9-dehydro-17-hydro-andrographolide-19-yl sulphate, was one of the major ingredients of Xiyanping injection. The present study aimed to demonstrate its suitability as a reference standard for use of quality control of this traditional Chinese medicine preparation made from andrographlide that has been widely used to treat various infectious diseases.

Methods
The stable crystals were prepared for unambiguous elucidation of the chemical structure by comprehensive spectral and thermal analysis. The anti-inflammatory effects were investigated using in vitro and in vivo methods, and the potential allergenic risk related with safety was evaluated by in silico molecular docking analysis.

Key findings
The dihydrated sulphonate derivative could be present as orthorhombic crystals with stable three-dimensional supramolecular structure, providing it the favourable physico-chemical stability as reference substance. It exhibited potent anti-inflammatory activity both in vitro and in vivo, suggesting the potency responsible for clinic efficacy of Xiyanping. Molecular docking further demonstrated its low risk of allergic reaction, as well as the proposed mechanism of anaphylactic effect of andrographolide analogues.

Conclusions
Dihydrated sodium 9-dehydro-17-hydro-andrographolide-19-yl sulphate may be the ideal reference standard for use in quality control of Xiyanping.
Introduction to a special feature issue – New insights into plant volatiles
Authors: Kessler André 
Published: October 2018

This article is an Editorial on the special feature issue ‘New insights into plant volatiles’, which is published in this issue and which includes the following articles: Ameye et al., pp. 666–683; Sharifi et al. pp. 684–691; Moreira et al., pp. 703–713; Pichersky & Raguso, pp. 692–702; Chen et al., pp. 714–725; Danner et al., pp. 726–738; Junker et al., pp. 739–749; Rering et al., pp. 750–759; Eberl et al., pp. 760–772; Fernández‐Martínez et al., pp. 773–784; Glenny et al., pp. 785–798 and Visakorpi et al., pp. 799–810.
Role of pyrimidine salvage pathway in the maintenance of organellar and nuclear genome integrity
Authors: Pedroza‐García José‐Antonio , Nájera‐Martínez Manuela , Mazubert Christelle , Aguilera‐Alvarado Paulina , Drouin‐Wahbi Jeannine , Sánchez‐Nieto Sobeida , Gualberto José M. , Raynaud Cécile , Plasencia Javier 
Published: October 2018

SummaryNucleotide biosynthesis proceeds through a de novo pathway and a salvage route. In the salvage route, free bases and/or nucleosides are recycled to generate the corresponding nucleotides. Thymidine kinase (TK) is the first enzyme in the salvage pathway to recycle thymidine nucleosides as it phosphorylates thymidine to yield thymidine monophosphate. The Arabidopsis genome contains two TK genes −TK1a and TK1b− that show similar expression patterns during development. In this work, we studied the respective roles of the two genes during early development and in response to genotoxic agents targeting the organellar or the nuclear genome. We found that the pyrimidine salvage pathway is crucial for chloroplast development and genome replication, as well as for the maintenance of its integrity, and is thus likely to play a crucial role during the transition from heterotrophy to autotrophy after germination. Interestingly, defects in TK activity could be partially compensated by supplementation of the medium with sugar, and this effect resulted from both the availability of a carbon source and the activation of the nucleotide de novo synthesis pathway, providing evidence for a compensation mechanism between two routes of nucleotide biosynthesis that depend on nutrient availability. Finally, we found differential roles of the TK1a and TK1b genes during the plant response to genotoxic stress, suggesting that different pools of nucleotides exist within the cells and are required to respond to different types of DNA damage. Altogether, our results highlight the importance of the pyrimidine salvage pathway, both during plant development and in response to genotoxic stress.
Exercise training reduces the insulin‐sensitizing effect of a single bout of exercise in human skeletal muscle
Authors: Steenberg Dorte E. , Jørgensen Nichlas B. , Birk Jesper B. , Sjøberg Kim A. , Kiens Bente , Richter Erik A. , Wojtaszewski Jørgen F.P. 
Published: October 2018

Key points
A single bout of exercise is capable of increasing insulin sensitivity in human skeletal muscle. Whether this ability is affected by training status is not clear.
Studies in mice suggest that the AMPK‐TBC1D4 signalling axis is important for the increased insulin‐stimulated glucose uptake after a single bout of exercise.
The present study is the first longitudinal intervention study to show that, although exercise training increases insulin‐stimulated glucose uptake in skeletal muscle at rest, it diminishes the ability of a single bout of exercise to enhance muscle insulin‐stimulated glucose uptake.
The present study provides novel data indicating that AMPK in human skeletal muscle is important for the insulin‐sensitizing effect of a single bout of exercise.
AbstractNot only chronic exercise training, but also a single bout of exercise, increases insulin‐stimulated glucose uptake in skeletal muscle. However, it is not well described how adaptations to exercise training affect the ability of a single bout of exercise to increase insulin sensitivity. Rodent studies suggest that the insulin‐sensitizing effect of a single bout of exercise is AMPK‐dependent (presumably via the α2β2γ3 AMPK complex). Whether this is also the case in humans is unknown. Previous studies have shown that exercise training decreases the expression of the α2β2γ3 AMPK complex and diminishes the activation of this complex during exercise. Thus, we hypothesized that exercise training diminishes the ability of a single bout of exercise to enhance muscle insulin sensitivity. We investigated nine healthy male subjects who performed one‐legged knee‐extensor exercise at the same relative intensity before and after 12 weeks of exercise training. Training increased and expression of mitochondrial proteins in muscle, whereas the expression of AMPKγ3 was decreased. Training also increased whole body and muscle insulin sensitivity. Interestingly, insulin‐stimulated glucose uptake in the acutely exercised leg was not enhanced further by training. Thus, the increase in insulin‐stimulated glucose uptake following a single bout of one‐legged exercise was lower in the trained vs. untrained state. This was associated with reduced signalling via confirmed α2β2γ3 AMPK downstream targets (ACC and TBC1D4). These results suggest that the insulin‐sensitizing effect of a single bout of exercise is also AMPK‐dependent in human skeletal muscle.
Baroreflex functionality in the eye of diffusion tensor imaging
Authors: Tsai Ching‐Yi , Poon Yan‐Yuen , Chan Julie Y. H. , Chan Samuel H. H. 
Published: October 2018

AbstractBy applying diffusion tensor imaging (DTI) as a physiological tool to evaluate changes in functional connectivity between key brainstem nuclei in the baroreflex neural circuits of mice and rats, recent work has revealed several hitherto unidentified phenomena regarding baroreflex functionality. (1) The presence of robust functional connectivity between nucleus tractus solitarii (NTS) and nucleus ambiguus (NA) or rostral ventrolateral medulla (RVLM) offers a holistic view on the moment‐to‐moment modus operandi of the cardiac vagal baroreflex or baroreflex‐mediated sympathetic vasomotor tone. (2) Under pathophysiological conditions (e.g. neurogenic hypertension), the disruption of functional connectivity between key nuclei in the baroreflex circuits is reversible. However, fatality ensues on progression from pathophysiological to pathological conditions (e.g. hepatic encephalopathy) when the functional connectivity between NTS and NA or RVLM is irreversibly severed. (3) The absence of functional connectivity between the NTS and caudal ventrolateral medulla (CVLM) necessitates partial rewiring of the classical neural circuit that includes CVLM as an inhibitory intermediate between the NTS and RVLM. (4) Sustained functional connectivity between the NTS and NA is responsible for the vital period between brain death and the inevitable cardiac death. (5) Reduced functional connectivity between the NTS and RVLM or NA points to inherent anomalous baroreflex functionality in floxed and Cre‐Lox mice. (6) Disrupted NTS‐NA functional connectivity in Flk‐1 (VEGFR2) deficient mice offers an explanation for the hypertensive side‐effect of anti‐vascular endothelial growth factor therapy (anti‐VEGF) therapy. These newly identified baroreflex functionalities revealed by DTI bear clinical and therapeutic implications.
Spectrum of choroidal neovascularisation associated with dome-shaped macula
Authors: Marchese Alessandro , Arrigo Alessandro , Sacconi Riccardo , Querques Lea , Prascina Francesco , Pierro Luisa , Bandello Francesco , Querques Giuseppe 
Published: October 2018

AimsTo investigate the clinical spectrum of choroidal neovascularisation (CNV) in patients with dome-shaped macula with the aid of multimodal imaging.MethodsIn this cross-sectional, retrospective, observational study, we reviewed charts and imaging studies of 144 eyes of 79 consecutive patients with dome-shaped macula evaluated at a tertiary referral centre, including optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICGA). Three masked graders evaluated the prevalence and type of CNV. Primary outcome measures were the diagnostic agreement between OCTA and FA±ICGA, the multimodal imaging characteristics and prevalence of CNV associated with dome-shaped macula.ResultsWe identified 30 eyes with dome-shaped macula complicated by CNV with an estimated prevalence of 20.8% (95% CI 14.2 to 27.4). Twenty-two eyes (73%) showed a type 2 CNV while eight eyes (27%) showed a type 1 CNV. Serous macular detachment was present in 39 eyes (27%) and harboured a CNV in five cases (13%). The overall diagnostic agreement between OCTA and FA±ICGA was excellent (k=0.894, p<0.001), but only the use of both techniques allowed the identification of the whole pool of CNVs.ConclusionEyes with dome-shaped macula may either develop typical myopic CNV (ie, type 2 CNV) or pachychoroid-associated CNV (ie, type 1 CNV), similar to those observed in central serous chorioretinopathy. Accordingly, in case of serous macular detachment complicating dome-shaped macula, the presence of an associated CNV should be considered. When suspecting a CNV associated with dome-shaped macula, the application of both OCTA and FA±ICGA is superior to the use of one technique alone.
Creation of the WHO Indicators of Infant and Young Child Development (IYCD): metadata synthesis across 10 countries
Authors: Lancaster Gillian A , McCray Gareth , Kariger Patricia , Dua Tarun , Titman Andrew , Chandna Jaya , McCoy Dana , Abubakar Amina , Hamadani Jena Derakhshani , Fink Günther , Tofail Fahmida , Gladstone Melissa , Janus Magdalena 
Published: October 2018

BackgroundRenewed global commitment to the improvement of early child development outcomes, as evidenced by the focus of the United Nations Sustainable Development Goal 4, highlights an increased need for reliable and valid measures to evaluate preventive and interventional efforts designed to affect change. Our objective was to create a new tool, applicable across multicultures, to measure development from 0 to 3 years through metadata synthesis.MethodsFourteen cross-sectional data sets were contributed on 21 083 children from 10 low/middle-income countries (LMIC), assessed using seven different tools (caregiver reported or directly assessed). Item groups, measuring similar developmental skills, were identified by item mapping across tools. Logistic regression curves displayed developmental trajectories for item groups across countries and age. Following expert consensus to identify well-performing items across developmental domains, a second mapping exercise was conducted to fill any gaps across the age range. The first version of the tool was constructed. Item response analysis validated our approach by putting all data sets onto a common scale.Results789 individual items were identified across tools in the first mapping and 129 item groups selected for analysis. 70 item groups were then selected through consensus, based on statistical performance and perceived importance, with a further 50 items identified at second mapping. A tool comprising 120 items (23 fine motor, 23 gross motor, 20 receptive language, 24 expressive language, 30 socioemotional) was created. The linked data sets on a common scale showed a curvilinear trajectory of child development, highlighting the validity of our approach through excellent coverage by age and consistency of measurement across contributed tools, a novel finding in itself.ConclusionsWe have created the first version of a prototype tool for measuring children in the early years, developed using novel easy to apply methodology; now it needs to be feasibility tested and piloted across several LMICs.
Corporal punishment bans and physical fighting in adolescents: an ecological study of 88 countries
Authors: Elgar Frank J , Donnelly Peter D , Michaelson Valerie , Gariépy Geneviève , Riehm Kira E , Walsh Sophie D , Pickett William 
Published: October 2018

ObjectiveTo examine the association between corporal punishment bans and youth violence at an international level.DesignEcological study of low-income to high-income 88 countries.SettingSchool-based health surveys of students.Participants403 604 adolescents.InterventionsNational corporal punishment bans.Primary outcome measureAge-standardised prevalence of frequent physical fighting (ie, 4+ episodes in the previous year) for male and female adolescents in each country.ResultsFrequent fighting was more common in males (9.9%, 95% CI 9.1% to 10.7%) than females (2.8%, 95% CI 2.5% to 3.1%) and varied widely between countries, from 0.9% (95% CI 0.8% to 0.9%) in Costa Rican females to 34.8% (95% CI 34.7 to 35.0) in Samoan males. Compared with 20 countries with no ban, the group of 30 countries with full bans (in schools and in the home) experienced 69% the rate of fighting in males and 42% in females. Thirty-eight countries with partial bans (in schools but not in the home) experienced less fighting in females only (56% the rate found in countries without bans).ConclusionsCountry prohibition of corporal punishment is associated with less youth violence. Whether bans precipitated changes in child discipline or reflected a social milieu that inhibits youth violence remains unclear due to the study design and data limitations. However, these results support the hypothesis that societies that prohibit the use of corporal punishment are less violent for youth to grow up in than societies that have not.
Preferred learning modalities and practice for critical skills: a global survey of paediatric emergency medicine clinicians
Authors: Craig Simon S , Auerbach Marc , Cheek John Alexander , Babl Franz E , Oakley Ed , Nguyen Lucia , Rao Arjun , Dalton Sarah , Lyttle Mark D , Mintegi Santiago , Nagler Joshua , Mistry Rakesh D , Dixon Andrew , Rino Pedro , Kohn-Loncarica Guillermo , Dalziel Stuart R 
Published: October 2018

ObjectiveTo describe senior paediatric emergency clinician perspectives on the optimal frequency of and preferred modalities for practising critical paediatric procedures.MethodsMulticentre multicountry cross-sectional survey of senior paediatric emergency clinicians working in 96 EDs affiliated with the Pediatric Emergency Research Network.Results1332/2446 (54%) clinicians provided information on suggested frequency of practice and preferred learning modalities for 18 critical procedures. Yearly practice was recommended for six procedures (bag valve mask ventilation, cardiopulmonary resuscitation (CPR), endotracheal intubation, laryngeal mask airway insertion, defibrillation/direct current (DC) cardioversion and intraosseous needle insertion) by at least 80% of respondents. 16 procedures were recommended for yearly practice by at least 50% of respondents. Two procedures (venous cutdown and ED thoracotomy) had yearly practice recommended by <40% of respondents. Simulation was the preferred learning modality for CPR, bag valve mask ventilation, DC cardioversion and transcutaneous pacing. Practice in alternative clinical settings (eg, the operating room) was the preferred learning modality for endotracheal intubation and laryngeal mask insertion. Use of models/mannequins for isolated procedural training was the preferred learning modality for all other invasive procedures. Free-text responses suggested the utility of cadaver labs and animal labs for more invasive procedures (thoracotomy, intercostal catheter insertion, open surgical airways, venous cutdown and pericardiocentesis).ConclusionsPaediatric ED clinicians suggest that most paediatric critical procedures should be practised at least annually. The preferred learning modality depends on the skill practised; alternative clinical settings are thought to be most useful for standard airway manoeuvres, while simulation-based experiential learning is applicable for most other procedures.
Extended treatment of venous thromboembolism: a systematic review and network meta-analysis
Authors: Wang Kang-Ling , van Es Nick , Cameron Chris , Castellucci Lana A , Büller Harry R , Carrier Marc 
Published: October 2018

ObjectiveTo evaluate efficacy and safety of oral anticoagulant regimens and aspirin for extended venous thromboembolism (VTE) treatment.MethodsWe searched MEDLINE, Embase, CENTRAL and conference proceedings for randomised controlled trials studying vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or aspirin for secondary prevention of VTE beyond 3 months. ORs (95% credible intervals) between treatments were estimated using random-effects Bayesian network meta-analysis.ResultsSixteen studies, totaling more than 22 000 patients, were included. Compared with placebo or observation and with aspirin, respectively, the risk of recurrent VTE was lower with standard-intensity VKAs (0.15 (0.08 to 0.24) and 0.23 (0.09 to 0.54)), low-dose factor Xa inhibitors (0.16 (0.06 to 0.38) and 0.25 (0.09 to 0.66)), standard-dose factor Xa inhibitors (0.17 (0.08 to 0.33) and 0.27 (0.11 to 0.65)) and the direct thrombin inhibitor (0.15 (0.04 to 0.37) and 0.23 (0.06 to 0.74)) although the risk of major bleeding was higher with standard-intensity VKAs (4.42 (1.99 to 12.24) and 4.14 (1.17 to 18.86)). Effect estimates were consistent in male patients and those with index pulmonary embolism or with unprovoked VTE and in sensitivity analyses. In addition, compared with placebo or observation, the risk of all-cause mortality was reduced with standard-intensity VKAs (0.44 (0.20 to 0.87)) and low-dose factor Xa inhibitors (0.38 (0.12 to 0.995)).ConclusionsStandard-intensity VKAs and DOACs are more efficacious than aspirin for extended VTE treatment. Despite a higher risk of major bleeding, standard-intensity VKAs was associated with a lower risk of all-cause mortality. Since overall efficacy and safety of standard-intensity VKAs and DOACs are in equipoise, patient factors, costs and patient preferences should be considered when recommending extending anticoagulation treatment.
Severe sociopolitical stressors and preterm births in New York City: 1 September 2015 to 31 August 2017
Authors: Krieger Nancy , Huynh Mary , Li Wenhui , Waterman Pamela D , Van Wye Gretchen 
Published: October 2018

BackgroundSevere stressors can induce preterm birth (PTB; gestation <37 weeks), with such stressors including social and economic threats, interpersonal violence, hate crimes and severe sociopolitical stressors (ie, arising from political leaders’ threatening rhetoric or from political legislation). We analysed temporal changes in risk of PTB among immigrant, Hispanic and Muslim populations targeted in the US 2016 presidential election and its aftermath.MethodsTrend analysis of all singleton births in New York City from 1 September 2015 to 31 August 2017 (n=230 105).ResultsComparing the period before the US presidential nomination (1 September 2015 to 31 July 2016) to the post-inauguration period (1 January 2017 to 31 August 2017), the overall PTB rate increased from 7.0% to 7.3% (relative risk (RR): 1.04; 95% CI 1.00 to 1.07). Among Hispanic women, the highest post-inauguration versus pre-inauguration increase occurred among foreign-born Hispanic women with Mexican or Central American ancestry (RR: 1.15; 95% CI 1.01 to 1.31). The post-inauguration versus pre-inauguration PTB rate also was higher for women from the Middle East/North Africa and from the travel ban countries, although non-significant due to the small number of events.ConclusionSevere sociopolitical stressors may contribute to increases in the risk of PTB among targeted populations.
Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood
Authors: Shalata Adel , Lauhasurayotin Supanun , Leibovitz Zvi , Li Hongbing , Hebert Diane , Dhanraj Santhosh , Hadid Yarin , Mahroum Mohammed , Bajar Jacob , Egenburg Sandro , Arad Ayala , Shohat Mordechai , Haddad Sami , Bakry Hassan , Moshiri Houtan , Scherer Stephen W , Tzur Shay , Dror Yigal 
Published: October 2018

BackgroundDandy-Walker malformation features agenesis/hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of posterior fossa. Although Dandy-Walker malformation is relatively common and several genes were linked to the syndrome, the genetic cause in the majority of cases is unknown.ObjectiveTo identify the mutated gene responsible for Dandy-Walker malformation, kidney disease and bone marrow failure in four patients from two unrelated families.MethodsMedical assessment, sonographic, MRI and pathological studies were used to define phenotype. Chromosomal microarray analysis and whole-exome sequence were performed to unravel the genotype.ResultsWe report four subjects from two unrelated families with homozygous mutations in the Exocyst Complex Component 3-Like-2 gene (EXOC3L2).EXOC3L2 functions in trafficking of post-Golgi vesicles to the plasma membrane. In the first family a missense mutation in a highly conserved amino acid, p.Leu41Gln, was found in three fetuses; all had severe forms of Dandy-Walker malformation that was detectable by prenatal ultrasonography and confirmed by autopsy. In the second family, the affected child carried a nonsense mutation, p.Arg72*, and no detected protein. He had peritrigonal and cerebellar white matter abnormalities with enlargement of the ventricular trigones, developmental delay, pituitary hypoplasia, severe renal dysplasia and bone marrow failure.ConclusionWe propose that biallelic EXOC3L2 mutations lead to a novel syndrome that affects hindbrain development, kidney and possibly the bone marrow.