bluuebunny/crossref_metadata_2025_split huggingface dataset:
FokI‐dCas9 mediates high‐fidelity genome editing in pigs
Authors: Fisicaro Nella , Salvaris Evelyn J. , Philip Gayle K. , Wakefield Matthew J. , Nottle Mark B. , Hawthorne Wayne J. , Cowan Peter J. 
Published: August 2019

AbstractGene editing using clustered regularly interspaced short palindromic repeats/Cas9 has great potential for improving the compatibility of porcine organs with human recipients. However, the risk of detrimental off‐target mutations in gene‐edited pigs remains largely undefined. We have previously generated GGTA1 knock‐in pigs for xenotransplantation using FokI‐dCas9, a variant of Cas9 that is reported to reduce the frequency of off‐target mutagenesis. In this study, we used whole genome sequencing (WGS) and optimized bioinformatic analysis to assess the fidelity of FokI‐dCas9 editing in the generation of these pigs. Genomic DNA was isolated from porcine cells before and after gene editing and sequenced by WGS. The genomic sequences were analyzed using GRIDSS variant‐calling software to detect putative structural variations (SVs), which were validated by PCR of DNA from knock‐in and wild‐type pigs. Platypus variant‐calling software was used to detect single‐nucleotide variations (SNVs) and small insertions/deletions (indels). GRIDSS analysis confirmed the precise integration of one copy of the knock‐in construct in the gene‐edited cells. Three additional SVs were detected by GRIDSS: deletions in intergenic regions in chromosome 6 and the X chromosome and a duplication of part of the CALD1 gene on chromosome 18. These mutations were not associated with plausible off‐target sites, and were not detected in a second line of knock‐in pigs generated using the same pair of guide RNAs, suggesting that they were the result of background mutation rather than off‐target activity. Platypus identified 1375 SNVs/indels after quality filtering, but none of these were located in proximity to potential off‐target sites, indicating that they were probably also spontaneous mutations. This is the first WGS analysis of pigs generated from FokI‐dCas9‐edited cells. Our results demonstrate that FokI‐dCas9 is capable of high‐fidelity gene editing with negligible off‐target or undesired on‐target mutagenesis.
Effects of isomaltulose ingestion on postexercise hydration state and heat loss responses in young men
Authors: Amano Tatsuro , Sugiyama Yuki , Okumura Junya , Fujii Naoto , Kenny Glen P. , Nishiyasu Takeshi , Inoue Yoshimitsu , Kondo Narihiko , Sasagawa Katsumi , Enoki Yasuaki , Maejima Daisuke 
Published: August 2019

New Findings
What is the central question of this study?
What are the effects of isomaltulose, an ingredient in carbohydrate–electrolyte beverages to maintain glycaemia and attenuate the risk of dehydration during exercise heat stress, on postexercise rehydration and physiological heat loss responses?

What is the main finding and its importance?
Consumption of a 6.5% isomaltulose–electrolyte beverage following exercise heat stress restored hydration following a 2 h recovery as compared to a 2% solution or water only. While the 6.5% isomaltulose–electrolytes increased plasma volume and plasma osmolality, which are known to modulate postexercise heat loss, sweating and cutaneous vascular responses did not differ between conditions. Consequently, ingestion beverages containing 6.5% isomaltulose–electrolytes enhanced postexercise rehydration without affecting heat loss responses.

AbstractIsomaltulose is a disaccharide carbohydrate widely used during exercise to maintain glycaemia and hydration. We investigated the effects of ingesting a beverage containing isomaltulose and electrolytes on postexercise hydration state and physiological heat loss responses. In a randomized, single‐blind cross‐over design, 10 young healthy men were hypohydrated by performing up to three 30 min successive moderate‐intensity (50% heart rate reserve) bouts of cycling, each separated by 10 min, while wearing a water‐perfusion suit heated to 45°C. The protocol continued until a 2% reduction in body mass was achieved. Thereafter, participants performed a final 15 min moderate‐intensity exercise bout followed by a 2 h recovery. Following cessation of exercise, participants ingested a beverage consisting of (i) water only (Water), (ii) 2% isomaltulose (CHO‐2%), or (iii) 6.5% isomaltulose (CHO‐6.5%) equal to the volume of 2% body mass loss within the first 30 min of the recovery. Changes in plasma volume (ΔPV) after fluid ingestion were greater for CHO‐6.5% compared with CHO‐2% (120 min postexercise) and Water (90 and 120 min) (all P ≤ 0.040). Plasma osmolality remained elevated with CHO‐6.5% compared with consumption of the other beverages at 30 and 90 min postexercise (all P ≤ 0.050). Urine output tended to be reduced with CHO‐6.5% compared to other fluid conditions (main effect, P = 0.069). Rectal and mean skin temperatures, chest sweat rate and cutaneous perfusion did not differ between conditions (all P > 0.05). In conclusion, compared with CHO‐2% and Water, consuming a beverage consisting of CHO‐6.5% and electrolytes during recovery under heat stress enhances PV recovery without modulating physiological heat loss responses.
The passive leg movement technique for assessing vascular function: defining the distribution of blood flow and the impact of occluding the lower leg
Authors: Shields Katherine L. , Broxterman Ryan M. , Jarrett Catherine L. , Bisconti Angela V. , Park Soung Hun , Richardson Russell S. 
Published: August 2019

New Findings
What is the central question of this study?
What is the distribution of the hyperaemic response to passive leg movement (PLM) in the common (CFA), deep (DFA) and superficial (SFA) femoral arteries? What is the impact of lower leg cuff‐induced blood flow occlusion on this response?

What is the main finding and its importance?
Of the total blood that passed through the CFA, the majority was directed to the DFA and this was unaffected by cuffing. As a small fraction does pass through the SFA to the lower leg, cuffing during PLM should be considered to emphasize the thigh‐specific hyperaemia.

AbstractIt has yet to be quantified how passive leg movement (PLM)‐induced hyperaemia, an index of vascular function, is distributed beyond the common femoral artery (CFA), into the deep femoral (DFA) and the superficial femoral (SFA) arteries, which supply blood to the thigh and lower leg, respectively. Furthermore, the impact of cuffing the lower leg, a common practice, especially with drug infusions during PLM, on the hyperaemic response is, also, unknown. Therefore, PLM was performed with and without cuff‐induced blood flow (BF) occlusion to the lower leg in 10 healthy subjects, with BF assessed by Doppler ultrasound. In terms of BF distribution during PLM, of the 380 ± 191 ml of blood that passed through the CFA, 69 ± 8% was directed to the DFA, while only 31 ± 8% passed through the SFA. Cuff occlusion of the lower leg significantly attenuated the PLM‐induced hyperaemia through the SFA (∼30%), which was reflected by a fall in BF through the CFA (∼20%), but not through the DFA. Additionally, cuff occlusion significantly attenuated the PLM‐induced peak change in BF (BFΔpeak) in the SFA (324 ± 159 to 214 ± 114 ml min−1), which was, again, reflected in the CFA (1019 ± 438 to 833 ± 476 ml min−1), but not in the DFA. Thus, the PLM‐induced hyperaemia predominantly passes through the DFA and this was unaltered by cuffing. However, as a small fraction of the PLM‐induced hyperaemia does pass through the SFA to the lower leg, cuffing the lower leg during PLM should be considered to emphasize thigh‐specific hyperaemia in the PLM assessment of vascular function.
Evidence of adaptation of maternofetal transport of glutamine relative to placental size in normal mice, and in those with fetal growth restriction
Authors: McIntyre Kirsty R. , Hayward Christina E. , Sibley Colin P. , Greenwood Susan L. , Dilworth Mark R. 
Published: August 2019

Key points
Fetal growth restriction (FGR) is a major risk factor for stillbirth and has significant impact upon lifelong health.
A small, poorly functioning placenta, as evidenced by reduced transport of nutrients to the baby, underpins FGR. It remains unclear how a small but normal placenta differs from the small FGR placenta in terms of ability to transfer nutrients to the fetus.
Placental transport of glutamine and glutamate, key amino acids for fetal growth, was assessed in normal mice and those with FGR.
Glutamine and glutamate transport was greater in the lightest versus heaviest placenta in a litter of normally grown mice. Placentas of mice with FGR had increased transport capacity in mid‐pregnancy, but this adaptation was insufficient in late pregnancy.
Placental adaptations, in terms of increased nutrient transport (per gram) to compensate for small size, appear to achieve appropriate fetal growth in normal pregnancy. Failure of this adaptation might contribute to FGR.
AbstractFetal growth restriction (FGR), a major risk factor for stillbirth, and neonatal and adulthood morbidity, is associated with reduced placental size and decreased placental nutrient transport. In mice, a small, normal placenta increases its nutrient transport, thus compensating for its reduced size and maintaining normal fetal growth. Whether this adaptation occurs for glutamine and glutamate, two key amino acids for placental metabolism and fetal growth, is unknown. Additionally, an assessment of placental transport of glutamine and glutamate between FGR and normal pregnancy is currently lacking. We thus tested the hypothesis that the transport of glutamine and glutamate would be increased (per gram of tissue) in a small normal placenta [C57BL6/J (wild‐type, WT) mice], but that this adaptation fails in the small dysfunctional placenta in FGR [insulin‐like growth factor 2 knockout (P0) mouse model of FGR]. In WT mice, comparing the lightest versus heaviest placenta in a litter, unidirectional maternofetal clearance (Kmf) of 14C‐glutamine and 14C‐glutamate (glutamineKmf and glutamateKmf) was significantly higher at embryonic day (E) 18.5, in line with increased expression of LAT1, a glutamine transporter protein. In P0 mice, glutamineKmf and glutamateKmf were higher (P0 versus wild‐type littermates, WTL) at E15.5. At E18.5, glutamineKmf remained elevated whereas glutamateKmf was similar between groups. In summary, we provide evidence that glutamineKmf and glutamateKmf adapt according to placental size in WT mice. The placenta of the growth‐restricted P0 fetus also elevates transport capacity to compensate for size at E15.5, but this adaptation is insufficient at E18.5; this may contribute to decreased fetal growth.
Longitudinal changes in the ganglion cell-inner plexiform layer thickness in high myopia: a prospective observational study
Authors: Lee Min Woo , Nam Ki Yup , Park Hye Jin , Lim Hyung-Bin , Kim Jung-Yeul 
Published: August 2019

AimTo determine longitudinal changes of the ganglion cell-inner plexiform layer (GC-IPL) thickness in patients with high myopia.MethodsThe subjects were divided into two groups: a high myopia group (axial length ≥26.0 mm) and a normal control group. Both groups were divided into subgroups based on age (decade): 20s, 30s, 40s and 50s. Twenty eyes were included in each subgroup. After the initial visit, GC-IPL thicknesses were measured three more times with at least a 1-year interval between examinations using spectral domain optical coherence tomography. The average GC-IPL thickness was fitted with linear mixed models.ResultsThe average GC-IPL thickness at the first visit was 78.50
±
8.79 µm and 84.29
±
6.12 µm in the high myopia and control groups, respectively. In both groups, the average GC-IPL thickness showed a significant change over time. The rate of GC-IPL reduction in individuals aged in their 50s, 40s, 30s and 20s with high myopia were −0.81 µm/year,–0.51 µm/year, −0.28 µm/year and −0.12 µm/year, respectively, and in controls in their 50s, 40s, 30s and 20s, they were −0.31 µm/year,–0.25 µm/year, −0.12 µm/year and −0.02 µm/year, respectively. Additionally, individuals aged in their 50s showed a statistically significant interaction between group and duration (p<0.001).ConclusionsHighly myopic eyes had thinner GC-IPL and a significantly greater reduction in GC-IPL over 3 years when compared with normal eyes. Additionally, the reduction rate of the GC-IPL thickness was greater in older patients in both groups, which was more prominent in the high myopia group.
Institutionalising participatory health governance: lessons from nine years of the National Health Assembly model in Thailand
Authors: Rajan Dheepa , Mathurapote Nanoot , Putthasri Weerasak , Posayanonda Tipicha , Pinprateep Poldej , de Courcelles Sana , Bichon Rozenn , Ros Emma , Delobre Aurore , Schmets Gerard 
Published: August 2019

Improving health governance is increasingly recognised as a key pillar for achieving universal health coverage (UHC). One good practice example of a participatory health governance platform is the National Health Assembly (NHA) in Thailand. This review of 9 years of the Thai NHA process attempted to understand how it works, given the paucity of such mechanisms worldwide. In addition, an in-depth look at its strengths and weaknesses allowed for reflection on whether the lessons learnt from this participatory governance model can be relevant for other settings.Overall, the power of stakeholder groups coming together has been impressively harnessed in the NHA process. The NHA has helped foster dialogue through understanding and respect for very differing takes on the same issue. The way in which different stakeholders discuss with each other in a real attempt at consensus thus represents a qualitatively improved policy dialogue.Nevertheless, the biggest challenge facing the NHA is ensuring a sustainable link to decision-making and the highest political circles. Modalities are needed to make NHA resolutions high priorities for the health sector.The NHA embodies many core features of a well-prepared deliberative process as defined in the literature (information provision, diverse views, opportunity to discuss freely) as well as key ingredients to enable the public to effectively participate (credibility, legitimacy and power). This offers important lessons for other countries for conducting similar processes. However, more research is necessary to understand how improvements in the deliberative process lead to concrete policy outcomes.
Quasi-experimental study on the effectiveness of a house officer preparatory course for medical graduates on self-perceived confidence and readiness: a study protocol
Authors: Rashid Aneesa Abdul , Shariff Ghazali Sazlina , Mohamad Iliana , Mawardi Maliza , Roslan Dalila , Musa Husna 
Published: August 2019

IntroductionBeing a house officer (HO) is said to be associated with high levels of stress, leading to mental health problems and sometimes to quitting the medical profession altogether. In Malaysia, the number of HOs completing training on time is slowly declining, with increasing annual dropout rates. Feeling incompetent is one of the contributors towards this growing problem. This study aimed to evaluate the effectiveness of a 3-day pre-HO intervention module in addressing participants’ confidence, readiness and psychological well-being in preparation for their HO training.Methods and analysisThe pre-HO intervention is the ‘Medicorp’ module that includes clerkship, experience sharing, hands-on skills training, common clinical cases and introduction of the local healthcare system. This is a pre-post quasi-experimental study lasting 1 year, with three assessment time points—at pretraining, immediately after training and 1 month into the participants’ HO-ship. The study is currently ongoing and involves 208 participants who attended the course in Malaysia. Participants with known psychiatric illness, working HOs and medical students are excluded. A pretested, self-administered questionnaire that includes baseline sociodemography, adaptation of the International Medical University (IMU) Student Competency Survey and the Depression Anxiety Stress Scale has been adopted, and 1 month follow-up will be conducted by telephone. Data will be analysed using SPSS V.24. The primary outcome is change in confidence level, while the secondary outcomes are changes in the readiness and psychological well-being of the participants.Ethics and disseminationThis study protocol has received ethics approval from Ethics Committee for Research Involving Human Subjects Universiti Putra Malaysia and the National Medical Research Registry Malaysia. Written informed consent has been obtained from each participant. Results will be disseminated through journals and conferences, especially those involved in medical education specifically looking into the training of medical doctors.Trial registration numberNCT03510195.
Attitudes of Korean smokers towards smoke-free public places: findings from the longitudinal ITC Korea Survey, 2005–2010
Authors: Park Eunja , Cho Sung-il , Seo Hong Gwan , Kim Yeol , Jung Hyun-Suk , Driezen Pete , Ouimet Janine , Quah Anne C K , Fong Geoffrey T. 
Published: August 2019

ObjectivePrior to December 2012, restaurants in South Korea were required to implement only partial smoking bans. This study documents the changes in Korean smokers’ attitudes towards smoking bans between 2005 and 2010 and explores the effects of anti-smoking advertising as a correlate of support for total smoking bans in public places.DesignLongitudinal cohort study of Korean adult smokers.SettingThe data were derived from three waves (2005, 2008 and 2010) of the International Tobacco Control (ITC) Korea Survey.ParticipantsThe ITC Korea Survey respondents were a probability-based, nationally representative sample of Korean smokers aged 19 and older. The current analysis includes 995 smokers who participated in Wave 1 (2005), 1737 smokers who participated in Wave 2 (2008) and 1560 smokers who participated in Wave 3 (2010).Primary and secondary outcome measuresChanges in respondents’ awareness of secondhand smoke (SHS) harm, attitudes towards smoking bans and personal rules for smoking in private homes and/or vehicles were analysed. Correlates of support for smoking bans in public places were examined using generalised estimating equation regression models.ResultsMore than 80% of Korean smokers are aware of the harms of SHS. The proportion of smokers who support smoke-free restaurants or smoke-free bars increased twofold between 2005 and 2010. Smokers who were aware of the dangers of SHS were more likely to support a total smoking ban in workplaces. Noticing anti-smoking advertising or information was not significantly associated with support for a total smoking ban in public places.ConclusionsKorean smokers became more supportive of smoking bans in public places between 2005 and 2008. These results show that smokers’ attitudes towards smoking bans can change with the implementation of smoke-free policies, even in a country that has a high prevalence of smokers.
Implementing professional behaviour change in teams under pressure: results from phase one of a prospective process evaluation (theImplementing Nutrition Screening in Community Care for Older People(INSCCOPe) project)
Authors: Bracher Mike , Steward Katherine , Wallis Kathy , May Carl R , Aburrow Annemarie , Murphy Jane 
Published: August 2019

ObjectivesTo evaluate the implementation of a new procedure for screening and treatment of malnutrition for older people in community settings and to identify factors promoting or inhibiting its implementation as a routine aspect of care.DesignProspective process evaluation using mixed methods with pre/post-implementation measures.Setting and participantsCommunity teams (nursing and allied health professionals) within a UK National Health Service Community Trust. 73 participants were recruited, of which 32 completed both pre-implemetation and post-implementation surveys.Main outcome measuresNoMAD survey for pre–post-intervention measures; telephone interviews exploring participant experiences and wider organisational/contextual processes.MethodsData prior to implementation of training, baseline (T0—survey and telephone interview) and 2 months following training (T1—follow-up survey). Quantitative data described using frequency tables reporting team type, healthcare provider role group and total study sample; analysis using Wilcoxon rank-sum (subgroup comparison) and Wilcoxon signed-rank (within-group observation point comparison) tests. Qualitative interview data (audio and transcription) analysed through directed content analysis using normalisation process theory.ResultsHigh support for nutrition screening and treatment indicated by participants. Concerns expressed around logistical, organisational and specialist dietetic support. Pre–post-training measures indicated a positive impact of training on knowledge of the new procedure; however, most implementation measures saw no significant changes between time points or between subgroups (training participants vs non-participants). Implementation barriers included the following: high levels of training non-completion; vulnerability to attrition of trained staff; lack of monitoring of post-intervention compliance and lack of access to dietetic support.ConclusionGreater support necessary to support implementation in relation to monitoring of training completion, and organisational support for nutrition screening and treatment activity. Recommended changes to implementation design are as follows: appointment of a key person to support and monitor procedure compliance; adoption of training as an e-learning module within the existing organisational platform to increase participation in changeable working conditions.
Multicentre, prospective observational study of the correlation between the Glasgow Admission Prediction Score and adverse outcomes
Authors: Jones Dominic , Cameron Allan , Lowe David J , Mason Suzanne M , O'Keeffe Colin A , Logan Eilidh 
Published: August 2019

ObjectivesTo assess whether the Glasgow Admission Prediction Score (GAPS) is correlated with hospital length of stay, 6-month hospital readmission and 6-month all-cause mortality. This study represents a 6-month follow-up of patients who were included in an external validation of the GAPS’ ability to predict admission at the point of triage.SettingSampling was conducted between February and May 2016 at two separate emergency departments (EDs) in Sheffield and Glasgow.ParticipantsData were collected prospectively at triage for consecutive adult patients who presented to the ED within sampling times. Any patients who avoided formal triage were excluded from the study. In total, 1420 patients were recruited.Primary outcomesGAPS was calculated following triage and did not influence patient management. Length of hospital stay, hospital readmission and mortality against GAPS were modelled using survival analysis at 6 months.ResultsOf the 1420 patients recruited, 39.6% of these patients were initially admitted to hospital. At 6 months, 30.6% of patients had been readmitted and 5.6% of patients had died. For those admitted at first presentation, the chance of being discharged fell by 4.3% (95% CI 3.2% to 5.3%) per GAPS point increase. Cox regression indicated a 9.2% (95% CI 7.3% to 11.1%) increase in the chance of 6-month hospital readmission per point increase in GAPS. An association between GAPS and 6-month mortality was demonstrated, with a hazard increase of 9.0% (95% CI 6.9% to 11.2%) for every point increase in GAPS.ConclusionA higher GAPS is associated with increased hospital length of stay, 6-month hospital readmission and 6-month all-cause mortality. While GAPS’s primary application may be to predict admission and support clinical decision making, GAPS may provide valuable insight into inpatient resource allocation and bed planning.