bluuebunny/crossref_metadata_2025_split huggingface dataset:
The vasopressin−memory hypothesis: a citation network analysis of a debate
Authors: Leng Gareth , Leng Rhodri Ivor , Maclean Stewart 
Published: May 2019

AbstractThe 1970s saw a growing interest in the vasopressin−memory hypothesis, proposed by David de Wied and his collaborators in Utrecht. This rose to a peak in the 1980s that saw a flurry of papers published from diverse sources critical of the experimental foundations of this idea. In subsequent years, interest in this hypothesis declined markedly as shortcomings were recognized. Here, we study this debate using citation network analysis to identify the influential papers in this debate and the citation links between them. The issues raised have contemporary relevance to the current controversy about the interpretation of studies using intranasal oxytocin.
Stereotactic body radiation therapy for refractory ventricular tachycardia secondary to cardiac lipoma: A case report
Authors: Zeng Li‐Jun , Huang Li‐Hong , Tan Hong , Zhang Hou‐Cai , Mei Ju , Shi Hai‐Feng , Jiang Chen‐Yang , Tan Chen , Zheng Jian‐Wei , Liu Xing‐Peng 
Published: May 2019

AbstractWe present the case of a 29‐year‐old man who developed ventricular tachycardia (VT) secondary to a cardiac lipoma located adjacent to the interventricular groove, which could not be fully resected. Antiarrhythmic drugs and endocardial and epicardial ablation failed to prevent VT recurrence. Finally, noninvasive stereotactic body radiation therapy (SBRT) targeting the lipoma was performed, with a total dose of 24 Gy delivered in three fractions. The number of VT episodes was reduced from 189/24 h before SBRT to 0 after the procedure. At 4‐month follow‐up, there were no signs of therapy‐related complications. Our experience suggests that SBRT could emerge as a viable treatment option for patients with cardiac tumors who develop refractory ventricular arrhythmias.
High‐efficient and precise base editing of C•G to T•A in the allotetraploid cotton (Gossypium hirsutum) genome using a modified CRISPR/Cas9 system
Authors: Qin Lei , Li Jianying , Wang Qiongqiong , Xu Zhongping , Sun Lin , Alariqi Muna , Manghwar Hakim , Wang Guanyin , Li Bo , Ding Xiao , Rui Hangping , Huang Huimei , Lu Tianliang , Lindsey Keith , Daniell Henry , Zhang Xianlong , Jin Shuangxia 
Published: May 2019

SummaryThe base‐editing technique using CRISPR/nCas9 (Cas9 nickase) or dCas9 (deactivated Cas9) fused with cytidine deaminase is a powerful tool to create point mutations. In this study, a novel G. hirsutum‐Base Editor 3 (GhBE3) base‐editing system has been developed to create single‐base mutations in the allotetraploid genome of cotton (Gossypium hirsutum). A cytidine deaminase sequence (APOBEC) fused with nCas9 and uracil glycosylase inhibitor (UGI) was inserted into our CRISPR/Cas9 plasmid (pRGEB32‐GhU6.7). Three target sites were chosen for two target genes, GhCLA and GhPEBP, to test the efficiency and accuracy of GhBE3. The editing efficiency ranged from 26.67 to 57.78% at the three target sites. Targeted deep sequencing revealed that the C→T substitution efficiency within an ‘editing window’, approximately six‐nucleotide windows of −17 to −12 bp from the PAM sequence, was up to 18.63% of the total sequences. The 27 most likely off‐target sites predicted by CRISPR‐P and Cas‐OFFinder tools were analysed by targeted deep sequencing, and it was found that rare C→T substitutions (average < 0.1%) were detected in the editing windows of these sites. Furthermore, whole‐genome sequencing analyses on two GhCLA‐edited and one wild‐type plants with about 100× depth showed that no bona fide off‐target mutations were detectable from 1500 predicted potential off‐target sites across the genome. In addition, the edited bases were inherited to T1 progeny. These results demonstrate that GhBE3 has high specificity and accuracy for the generation of targeted point mutations in allotetraploid cotton.
Bacteria from four phylogroups of the Pseudomonas syringae complex can cause bacterial canker of apricot
Authors: Parisi L. , Morgaint B. , Blanco‐Garcia J. , Guilbaud C. , Chandeysson C. , Bourgeay J. F. , Moronvalle A. , Brun L. , Brachet M. L. , Morris C. E. 
Published: May 2019

Pseudomonas syringae is described as a species complex, containing P. syringae‐related species classified into 13 phylogroups and 23 clades. Pseudomonas syringae is one of the main pathogens of fruit trees, affecting nut trees, hazelnut and kiwi, pome and stone fruits. Bacterial canker of apricots is an important disease in regions of production with cold winters and conducive soils. This work characterizes the bacteria able to induce canker in apricots isolated in different French orchards. Bacteria from four phylogroups were able to induce canker. The pathogenicity to apricot was not linked to the pathogenicity to the three herbaceous species and cherry fruits tested, and was not always related to hypersensitive reaction on tobacco and ice nucleation activity. Bacteria pathogenic to apricot belong to phylogroups 01, 02, 03 and 07. The bacteria of phylogroups 01a and 07a (Pseudomonas viridiflava) characterized in this work have not previously been described as pathogenic to apricot.
Short‐term pre‐operative high‐intensity interval training does not improve fitness of colorectal cancer patients
Authors: Boereboom Catherine L. , Blackwell James E. M. , Williams John P. , Phillips Bethan E. , Lund Jonathan N. 
Published: May 2019

BackgroundPre‐operative cardiorespiratory fitness (CRF) in colorectal cancer (CRC) patients has been shown to affect post‐operative outcomes. The aim of this study was to test the feasibility of high‐intensity interval training (HIIT) for improving fitness in pre‐operative CRC patients within the 31‐day cancer waiting‐time targets imposed in the UK.MethodsEighteen CRC patients (13 males, mean age: 67 years (range: 52‐77 years) participated in supervised HIIT on cycle ergometers 3 or 4 times each week prior to surgery. Exercise intensity during 5 × 1‐minute HIIT intervals (interspersed with 90‐second recovery) was 100%‐120% maximum wattage achieved at a baseline cardiopulmonary exercise test (CPET). CPET before and after HIIT was used to assess CRF.ResultsPatients completed a mean of eight HIIT sessions (range 6‐14) over 19 days (SD 7). There was no significant increase in VO2 peak (23.9 ± 7.0 vs 24.2 ± 7.8 mL/kg/min (mean ± SD), P = 0.58) or anaerobic threshold (AT: 14.0 ± 3.4 vs 14.5 ± 4.5 mL/kg/min, P = 0.50) after HIIT. There was a significant reduction in resting systolic blood pressure (152 ± 19 vs 142 ± 19 mm Hg, P = 0.0005) and heart rate at submaximal exercise intensities after HIIT.ConclusionsOur pragmatic HIIT exercise protocol did not improve the pre‐operative fitness of CRC patients within the 31‐day window available in the UK to meet cancer surgical waiting‐time targets.
Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling
Authors: Nie Yaohui , Sato Yoriko , Garner Ron T. , Kargl Christopher , Wang Chao , Kuang Shihuan , Gilpin Christopher J. , Gavin Timothy P. 
Published: May 2019

New Findings
What is the central question of this study?
Capillary rarefaction is found in diabetic and aged muscle, whereas exercise increases skeletal muscle angiogenesis. The association implies a crosstalk between muscle cells and endothelial cells. The underlying mechanisms mediating the crosstalk between these cells remains to be elucidated fully.

What is the main finding and its importance?
Endothelial cell functions are regulated by skeletal muscle cell‐derived exosomes via a vascular endothelial growth factor‐independent pathway. This study reveals a new mechanism mediating the crosstalk between skeletal muscle cells and endothelial cells.

AbstractLoss of skeletal muscle capillarization, known as capillary rarefaction, is found in type 2 diabetes, chronic heart failure and healthy ageing and is associated with impaired delivery of substrates to the muscle. However, the interaction and communication of skeletal muscle with endothelial cells in the regulation of capillaries surrounding the muscle remains elusive. Exosomes are a type of secreted extracellular vesicle containing mRNAs, proteins and, especially, microRNAs that exert paracrine and endocrine effects. In this study, we investigated whether skeletal muscle‐derived exosomes (SkM‐Exo) regulate the endothelial cell functions of angiogenesis. We demonstrated that C2C12 myotube‐derived exosomes improved endothelial cell functions, assessed by the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), which were increased by 20, 23 and 40%, respectively, after SkM‐Exo exposure. The SkM‐Exo failed to activate HUVEC vascular endothelial growth factor (VEGF) signalling. The SkM‐Exo increased HUVEC reactive oxygen species and activated the nuclear factor‐κB pathway, suggesting that SkM‐Exo‐induced angiogenesis was mediated by a VEGF‐independent pathway. In addition, several angiogenic microRNAs were packaged in SkM‐Exo, with miR‐130a being particularly enriched and successfully transferred from SkM‐Exo to HUVECs. Delivery of miRNAs into endothelial cells might explain the enhancement of reactive oxygen species production and angiogenesis by SkM‐Exo. The potential angiogenic effect of SkM‐Exo could provide an effective therapy for promoting skeletal muscle angiogenesis in diseases characterized by capillary rarefaction or inadequate angiogenesis.
Issues in the determination of ‘responders’ and ‘non‐responders’ in physiological research
Authors: Atkinson Greg , Williamson Philip , Batterham Alan M. 
Published: May 2019

New Findings
What is the topic for this review?
We discuss the dichotomization of continuous‐level physiological measurements into ‘responders’ and ‘non‐responders’ when interventions/treatments are examined in robust parallel‐group studies.

What advances does it highlight?
Sample responder counts are biased by pre‐to‐post within‐subject variability. Sample differences in counts may be explained wholly by differences in mean response, even without individual response heterogeneity and even if test–retest measurement error informs the choice of response threshold. A less biased and more informative approach uses the SD of individual responses to estimate the chance a new person from the population of interest will be a responder.

AbstractAs a follow‐up to our 2015 review, we cover more issues on the topic of ‘response heterogeneity’, which we define as clinically important individual differences in the physiological responses to the same treatment/intervention that cannot be attributed to random within‐subject variability. We highlight various pitfalls with the common practice of counting the number of ‘responders’, ‘non‐responders’ and ‘adverse responders’ in samples that have been given certain treatments or interventions for research purposes. We focus on the classical parallel‐group randomized controlled trial and assume typical good practice in trial design. We show that sample responder counts are biased because individuals differ in terms of pre‐to‐post within‐subject random variability in the study outcome(s) and not necessarily treatment response. Ironically, sample differences in responder counts may be explained wholly by sample differences in mean response, even if there is no response heterogeneity at all. Sample comparisons of responder counts also have relatively low statistical precision. These problems do not depend on how the response threshold has been selected, e.g. on the basis of a measurement error statistic, and are not rectified fully by the use of confidence intervals for individual responses in the sample. The dichotomization of individual responses in a research sample is fraught with pitfalls. Less biased approaches for estimating the proportion of responders in a population of interest are now available. Importantly, these approaches are based on the SD for true individual responses, directly incorporating information from the control group.
Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth
Authors: Son Jun Seok , Liu Xiangdong , Tian Qiyu , Zhao Liang , Chen Yanting , Hu Yun , Chae Song Ah , de Avila Jeanene M. , Zhu Mei‐Jun , Du Min 
Published: May 2019

Key points
Maternal exercise improves the metabolic health of maternal mice challenged with a high‐fat diet.
Exercise intervention of obese mothers prevents fetal overgrowth.
Exercise intervention reverses impaired placental vascularization in obese mice.
Maternal exercise activates placental AMP‐activated protein kinase, which was inhibited as a result of maternal obesity.
AbstractMore than one‐third of pregnant women in the USA are obese and maternal obesity (MO) negatively affects fetal development, which predisposes offspring to metabolic diseases. The placenta mediates nutrient delivery to fetuses and its function is impaired as a result of MO. Exercise ameliorates metabolic dysfunction resulting from obesity, although its effect on placental function of obese mothers has not been explored. In the present study, C57BL/6J female mice were randomly assigned into two groups fed either a control or a high‐fat diet (HFD) and then the mice on each diet were further divided into two subgroups with/without exercise. In HFD‐induced obese mice, daily treadmill exercise during pregnancy reduced body weight gain, lowered serum glucose and lipid concentration, and improved insulin sensitivity of maternal mice. Importantly, maternal exercise prevented fetal overgrowth (macrosomia) induced by MO. To further examine the preventive effects of exercise on fetal overgrowth, placental vascularization and nutrient transporters were analysed. Vascular density and the expression of vasculogenic factors were reduced as a result of MO but were recovered by maternal exercise. On the other hand, the contents of nutrient transporters were not substantially altered by MO or exercise, suggesting that the protective effects of exercise in MO‐induced fetal overgrowth were primarily a result of the alteration of placental vascularization and improved maternal metabolism. Furthermore, exercise enhanced downstream insulin signalling and activated AMP‐activated protein kinase in HFD placenta. In sum, maternal exercise prevented fetal overgrowth induced by MO, which was associated with improved maternal metabolism and placental vascularization in obese mothers with exercise.
Mechanism of Chip Segmentation in Orthogonal Cutting of Zr-Based Bulk Metallic Glass
Authors: Maroju Naresh Kumar , Jin Xiaoliang 
Published: May 2019

Abstract
Bulk metallic glasses (BMGs) are a series of metal alloys with an amorphous structure. The deformation of BMGs occurs in localized regions and is highly sensitive to the applied stress, strain rate, and temperature. This paper presents a coupled thermomechanical model to analyze the chip segmentation mechanism due to material shear localization in orthogonal cutting of Zr-BMG. The shear stress variation in the primary shear zone is modeled considering the tool-chip friction and large strain of the material. The constitutive property of BMG corresponding to the inhomogeneous deformation through shear transformation zones is modeled. The oscillations of shear stress, temperature, and free volume are simulated based on the cutting conditions. The predicted chip segmentation frequency is compared with the experimental result under different cutting speeds and uncut chip thicknesses. The developed model provides the fundamental mechanism of material deformation and chip formation in cutting Zr-BMG with an amorphous structure.
Compensation of retinal nerve fibre layer thickness as assessed using optical coherence tomography based on anatomical confounders
Authors: Chua Jacqueline , Schwarzhans Florian , Nguyen Duc Quang , Tham Yih Chung , Sia Josh Tjunrong , Lim Claire , Mathijia Shivani , Cheung Carol , Tin Aung , Fischer Georg , Cheng Ching-Yu , Vass Clemens , Schmetterer Leopold 
Published: May 2019

Background/AimsTo compensate the retinal nerve fibre layer (RNFL) thickness assessed by spectral-domain optical coherence tomography (SD-OCT) for anatomical confounders.MethodsThe Singapore Epidemiology of Eye Diseases is a population-based study, where 2698 eyes (1076 Chinese, 704 Malays and 918 Indians) with high-quality SD-OCT images from individuals without eye diseases were identified. Optic disc and macular cube scans were registered to determine the distance between fovea and optic disc centres (fovea distance) and their respective angle (fovea angle). Retinal vessels were segmented in the projection images and used to calculate the circumpapillary retinal vessel density proﬁle. Compensated RNFL thickness was generated based on optic disc (ratio, orientation and area), fovea (distance and angle), retinal vessel density, refractive error and age. Linear regression models were used to investigate the effects of clinical factors on RNFL thickness.ResultsRetinal vessel density reduced significantly with increasing age (1487±214 µm in 40–49, 1458±208 µm in 50–59, 1429±223 µm in 60–69 and 1415±233 µm in ≥70). Compensation reduced the variability of RNFL thickness, where the effect was greatest for Chinese (10.9%; p<0.001), followed by Malays (6.6%; p=0.075) and then Indians (4.3%; p=0.192). Compensation reduced the age-related RNFL decline by 55% in all participants (β=−3.32 µm vs β=−1.50 µm/10 years; p<0.001). Nearly 62% of the individuals who were initially classified as having abnormally thin RNFL (outside the 99% normal limits) were later reclassified as having normal RNFL.ConclusionsRNFL thickness compensated for anatomical parameters reduced the variability of measurements and may improve glaucoma detection, which needs to be confirmed in future studies.
Economic evaluation of a phase III international randomised controlled trial of very early mobilisation after stroke (AVERT)
Authors: Gao Lan , Sheppard Lauren , Wu Olivia , Churilov Leonid , Mohebbi Mohammadreza , Collier Janice , Bernhardt Julie , Ellery Fiona , Dewey Helen , Moodie Marj 
Published: May 2019

ObjectivesWhile very early mobilisation (VEM) intervention for stroke patients was shown not to be effective at 3 months, 12 month clinical and economical outcomes remain unknown. The aim was to assess cost-effectiveness of a VEM intervention within a phase III randomised controlled trial (RCT).DesignAn economic evaluation alongside a RCT, and detailed resource use and cost analysis over 12 months post-acute stroke.SettingMulti-country RCT involved 58 stroke centres.Participants2104 patients with acute stroke who were admitted to a stroke unit.InterventionA very early rehabilitation intervention within 24 hours of stroke onsetMethodsCost-utility analyses were undertaken according to pre-specified protocol measuring VEM against usual care (UC) based on 12 month outcomes. The analysis was conducted using both health sector and societal perspectives. Unit costs were sourced from participating countries. Details on resource use (both health and non-health) were sourced from cost case report form. Dichotomised modified Rankin Scale (mRS) scores (0 to 2 vs 3 to 6) and quality adjusted-life years (QALYs) were used to compare the treatment effect of VEM and UC. The base case analysis was performed on an intention-to-treat basis and 95% CI for cost and QALYs were estimated by bootstrapping. Sensitivity analysis were conducted to examine the robustness of base case results.ResultsVEM and UC groups were comparable in the quantity of resource use and cost of each component. There were no differences in the probability of achieving a favourable mRS outcome (0.030, 95% CI −0.022 to 0.082), QALYs (0.013, 95% CI −0.041 to 0.016) and cost (AUD1082, 95% CI -$2520 to $4685 from a health sector perspective or AUD102, 95% CI -$6907 to $7111, from a societal perspective including productivity cost). Sensitivity analysis achieved results with mostly overlapped CIs.ConclusionsVEM and UC were associated with comparable costs, mRS outcome and QALY gains at 12 months. Compared with to UC, VEM is unlikely to be cost-effective. The long-term data collection during the trial also informed resource use and cost of care post-acute stroke across five participating countries.Trial registration numberACTRN12606000185561; Results.
Supporting and improving community health services—a prospective evaluation of ECHO technology in community palliative care nursing teams
Authors: White Clare , McIlfatrick Sonja , Dunwoody Lynn , Watson Max 
Published: May 2019

IntroductionProject ECHO (Extension for Community Healthcare Outcomes) uses teleconferencing technology to support and train healthcare providers (HCPs) remotely, and has improved care across the USA. A 6-month pilot was trialled in a community palliative care nursing setting to determine if ECHO would be effective in the UK in providing education and support to community hospice nurses (CHN).MethodsThe pilot involved weekly 2 hour sessions of teaching and case-based discussions facilitated by hospice staff linking with nine teams of CHN using video conferencing technology. A mixed-methods prospective longitudinal cohort study was used to evaluate the pilot. Each CHN provided demographic data, and completed a written knowledge assessment and a self-efficacy tool before and after the pilot. Two focus groups were also performed after the pilot.Results28 CHNs completed the evaluation. Mean knowledge score improved significantly from 71.3% to 82.7%(p=0.0005) as did overall self-efficacy scores following the ECHO pilot. Pre-ECHO (p=0.036) and Retro-Pretest ECHO (p=0.0005) self-efficacy were significantly lower than post-ECHO. There was no significant difference between Pretest and Retro-Pretest ECHO self-efficacy (p=0.063). 96% recorded gains in learning, and 90% felt that ECHO had improved the care they provided for patients. 83% would recommend ECHO to other HCPs. 70% stated the technology used in ECHO had given them access to education that would have been hard to access due to geography.ConclusionsThis study supports the use of Project ECHO for CHNs in the UK by demonstrating how a 6-month pilot improved knowledge and self-efficacy. As a low-cost high-impact model, ECHO provides an affordable solution to addressing growing need.