bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives of residential aged care facilities' staff on the identification and recording of residents' medication‐related goals of care
Authors: Sawan Mouna , Kouladjian O’Donnell Lisa , Hilmer Sarah N.
Published: August 2019

Objective

This study primarily aims to explore residential aged care facility (RACF) staff views on the utility of a computerised clinical decision support system (CCDSS) that incorporates validated goal‐directed deprescribing tools and guides to identify residents' goals for medications.

Methods

A qualitative study was conducted in four RACFs. Semi‐structured interviews or focus groups were conducted with 19 participants, representing various types of clinical and care staff.

Results

According to staff, the use of a CCDSS was useful as it facilitated resident (including people with dementia), and caregiver engagement to obtain comprehensive information about the residents' goals and medication concerns. Staff perceptions of the increased workload and that some residents and caregivers would have limited involvement in discussions were barriers to the adoption of a CCDSS.

Conclusion

Integration of a CCDSS into practice, accompanied with staff training and education, has the potential to improve goal‐directed pharmaceutical care.
Effect of CXCL12/CXCR4 on migration of decidua‐derived mesenchymal stem cells from pregnancies with preeclampsia
Authors: Lei Guo‐Qin , Wu Zhi‐Yu , Jiang Wen‐Bin , Luo Jie , Xu Huan , Luo Shi‐Fu , Peng Zhu‐Yun , Wang Wan , Chen Ming , Yu Li‐Li
Published: August 2019

Problem

Systemic immuno‐inflammatory response caused by maternal immune imbalance is central to the pathogenesis of preeclampsia (PE). We hypothesized that changes in the number of decidual mesenchymal stem cells (dMSCs) may be associated with maternal immune imbalance. We aimed to evaluate the expression of CXCL12/CXCR4 axis in patients with PE and its influence on the migration behavior of dMSCs, to further clarify the pathogenesis of PE.

Method of study

Fourteen women with PE and 11 controls were included. DMSCs were extracted from decidual tissue by type II collagenase digestion and adherence. ELISA and immunohistochemistry analysis were used to measure serum and tissue levels of CXCL12. Q‐PCR and Western blotting were used to detect CXCR4 expression on dMSCs, whereas transwell assay was used to measure the migration ability of dMSCs.

Results

Decidual mesenchymal stem cells from women with PE showed higher expressions of CXCR4 and HIF‐1α than the dMSCs of controls did. Tissues from women with PE showed the highest CXCL12 levels in the decidua, followed by the placenta and umbilical cord, whereas tissues from controls showed the highest CXCL2 levels in the umbilical cord, followed by the placenta and decidua. dMSCs from women with PE showed possibly higher migration ability than that of dMSCs from controls, under the induction of CXCL12, whereas dMSCs showed a decreasing trend in hypoxic than in normoxic environment.

Conclusion

Decidual mesenchymal stem cells from women with PE can migrate to the decidua layer with the concentration gradient of CXCL12, which may play a role in the occurrence and development of PE.
Data‐adaptive longitudinal model selection in causal inference with collaborative targeted minimum loss‐based estimation
Authors: Schnitzer Mireille E. , Sango Joel , Ferreira Guerra Steve , van der Laan Mark J.
Published: August 2019

Causal inference methods have been developed for longitudinal observational study designs where confounding is thought to occur over time. In particular, one may estimate and contrast the population mean counterfactual outcome under specific exposure patterns. In such contexts, confounders of the longitudinal treatment‐outcome association are generally identified using domain‐specific knowledge. However, this may leave an analyst with a large set of potential confounders that may hinder estimation. Previous approaches to data‐adaptive model selection for this type of causal parameter were limited to the single time‐point setting. We develop a longitudinal extension of a collaborative targeted minimum loss‐based estimation (C‐TMLE) algorithm that can be applied to perform variable selection in the models for the probability of treatment with the goal of improving the estimation of the population mean counterfactual outcome under a fixed exposure pattern. We investigate the properties of this method through a simulation study, comparing it to G‐Computation and inverse probability of treatment weighting. We then apply the method in a real‐data example to evaluate the safety of trimester‐specific exposure to inhaled corticosteroids during pregnancy in women with mild asthma. The data for this study were obtained from the linkage of electronic health databases in the province of Quebec, Canada. The C‐TMLE covariate selection approach allowed for a reduction of the set of potential confounders, which included baseline and longitudinal variables.
MAGEL2‐related disorders: A study and case series
Authors: Patak Jameson , Gilfert James , Byler Melissa , Neerukonda Vamsee , Thiffault Isabelle , Cross Laura , Amudhavalli Shivarajan , Pacio‐Miguez Marta , Palomares‐Bralo Maria , Garcia‐Minaur Sixto , Santos‐Simarro Fernando , Powis Zoe , Alcaraz Wendy , Tang Sha , Jurgens Julie , Barry Brenda , England Eleina , Engle Elizabeth , Hess Jonathon , Lebel Robert R.
Published: August 2019

Pathogenic MAGEL2 variants result in the phenotypes of Chitayat‐Hall syndrome (CHS), Schaaf‐Yang syndrome (SYS) and Prader‐Willi syndrome (PWS). We present five patients with mutations in MAGEL2, including the first patient reported with a missense variant, adding to the limited literature. Further, we performed a systematic review of the CHS and SYS literature, assess the overlap between CHS, SYS and PWS, and analyze genotype‐phenotype correlations among them. We conclude that there is neither a clinical nor etiological difference between CHS and SYS, and propose that the two syndromes simply be referred to as MAGEL2‐related disorders.
Potential of automatic diagnosis system with linked color imaging for diagnosis of Helicobacter pylori infection
Authors: Yasuda Takeshi , Hiroyasu Tomoyuki , Hiwa Satoru , Okada Yuto , Hayashi Sadanari , Nakahata Yuki , Yasuda Yuriko , Omatsu Tatsushi , Obora Akihiro , Kojima Takao , Ichikawa Hiroshi , Yagi Nobuaki
Published: August 2019

Background and Aim

It is necessary to establish universal methods for endoscopic diagnosis of Helicobacter pylori (HP) infection, such as computer‐aided diagnosis. In the present study, we propose a multistage diagnosis algorithm for HP infection.

Methods

The aims of this study are to: (i) to construct an interpretable automatic diagnostic system using a support vector machine for HP infection; and (ii) to compare the diagnosis capability of our artificial intelligence (AI) system with that of endoscopists. Presence of an HP infection determined through linked color imaging (LCI) was learned through machine learning. Trained classifiers automatically diagnosed HP‐positive and ‐negative patients examined using LCI. We retrospectively analyzed the new images from 105 consecutive patients; 42 were HP positive, 46 were post‐eradication, and 17 were uninfected. Five endoscopic images per case taken from different areas were read into the AI system, and used in the HP diagnosis.

Results

Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the diagnosis of HP infection using the AI system were 87.6%, 90.4%, 85.7%, 80.9%, and 93.1%, respectively. Accuracy of the AI system was higher than that of an inexperienced doctor, but there was no significant difference between the diagnosis of experienced physicians and the AI system.

Conclusions

The AI system can diagnose an HP infection with significant accuracy. There remains room for improvement, particularly for the diagnosis of post‐eradication patients. By learning more images and considering a diagnosis algorithm for post‐eradication patients, our new AI system will provide diagnostic support, particularly to inexperienced physicians.
Stronger dung removal in forests compared with grassland is driven by trait composition and biomass of dung beetles
Authors: Buse Jörn , Entling Martin H.
Published: August 2019

1. Ecosystem processes depend on the biomass of the involved organisms, but their functional diversity may play an additional role. In particular, the exclusion of key functional groups through habitat disturbance may lead to the breakdown of ecosystem functions. Dung removal is an important process contributing to nutrient cycling and thus productivity in grazed ecosystems.

2. This study investigated the role of different functional groups of dung beetles in dung removal in different habitats within a wood‐pasture in two different seasons. An experimental setting with 12 blocks and 108 dung pads was used to investigate short‐term dung removal over 1 week of exposure.

3. Dung removal was most strongly affected by habitat type, with almost 40% lower levels in grassland than in adjacent forest and forest gaps. Of all assemblage characteristics, total biomass of tunneller species was the strongest predictor of dung removal, whereas functional diversity showed no significant effect. In accordance with the dung removal pattern at habitat type level, densities of large tunnellers were suppressed in grassland compared with forest.

4. It is concluded that dung removal is habitat‐specific and large tunnellers play a disproportionate role in this important ecosystem function in temperate forests.
Ecological memory of daily carbon exchange across the globe and its importance in drylands
Authors: Liu Yao , Schwalm Christopher R. , Samuels‐Crow Kimberly E. , Ogle Kiona
Published: August 2019

How do antecedent (past) conditions influence land‐carbon dynamics after those conditions no longer persist? In particular, quantifying such memory effects associated with the influence of past environmental (exogenous) and biological (endogenous) conditions is crucial for understanding and predicting the carbon cycle. Here we show, using data from 42 eddy covariance sites across six major biomes, that ecological memory—decomposed into environmental and biological memory components—of daily net carbon exchange (NEE) is critical for understanding the land‐carbon metabolism, especially in drylands for which memory explains ~ 32% of the variation in NEE. The strong environmental memory in drylands was primarily driven by short‐ and long‐term moisture status. Moreover, the strength of environmental memory scales with increasing water stress. This universal scaling relationship, emerging within and among major biomes, suggests a potential adaptive response to water limitation. Our findings underscore the necessity of considering ecological memory in experiments, observations and modelling.
“I Don't Want to Make the Same Mistakes”: Relationship Education Among Low‐Income Single Adults
Authors: Bradford Kay , Spuhler Bryan , Higginbotham Brian J. , Laxman Daniel , Morgan Courtney Nielsen
Published: August 2019

Objective

To examine, through the lens of symbolic interactionism, the experiences and initial outcomes of low‐income single adults who received relationship education.

Background

As relationship education reaches more low‐income participants, research is needed to examine how it reaches such audiences and how it works. We used mixed‐methods to examine processes and learning outcomes among these participants.

Method

Focus‐group interview data (n = 10) and short‐response qualitative data (n = 188) were analyzed phenomenologically. Quantitative data (n = 165) were collected to examine changes in participants' perceived knowledge about healthy relationships using a random‐intercept, multilevel regression model.

Results

The two qualitative analyses yielded four themes, three of which overlapped: participant motivation based on past relationship mistakes, reported and anticipated change, and self‐assessment. The quantitative analyses showed a statistically significant increase in perceived knowledge about relationship skills and healthy partner selection. Participants also placed greater importance on a potential partner's past relationship patterns, relationship behaviors, and attitudes.

Conclusion

Past relationship experiences motivated participants' learning and moved them toward change. Participants increased their relationship knowledge in terms of selection and pacing.

Implications

Relationship education can be offered as an impactful adjunct service to low‐income participants.
The Impact of Direct Cash Payments on Whole Blood Supply
Authors: Becker David M. , Klüter Harald , Niessen-Ruenzi Alexandra , Weber Martin
Published: August 2019

This paper investigates the impact of monetary incentives on whole blood donations. We take advantage of a quasi-natural experiment in Germany, in which one blood donation site changes its payment scheme from remunerated to non-remunerated. All other donation sites maintain their payment schemes. We show that donation volumes drop significantly after the pay drop and do not recuperate. At the same time, donation volumes increase at other paid donation sites, which is partly due to donor migration to these sites. We do not find any impact of the changed payment scheme on blood quality. Our results offer additional insight into the complex question whether it is efficient to ensure blood supply by paying donors a direct monetary compensation.
Utility of a blood volume monitor in the management of anemia in dialysis by computing the total hemoglobin mass
Authors: Alayoud Ahmed , Belarabi Marouane , Labrini Faycal , Badaoui Mohammed , Zajjari Yassir , Maoujoud Omar , Arrayhani Mohammed , El Fillali Karim
Published: August 2019

Introduction

The degree of interdialytic weight gain and ultrafiltration may influence anemia results in dialysis. The purpose of this study is to evaluate the utility of a blood volume monitor (BVM) in the management of renal anemia and its ability to avoid the variability of hematocrit (Hct) and hemoglobin values (Hb) depending on plasma volume through a simple method of monitoring the total hemoglobin mass (MtHb).

Methods

Predialysis blood samples for measurement were drawn at both the midweek treatment and the beginning‐of‐the‐dialysis‐week treatment in 30 patients. The MtHb was calculated as MtHb = Vb × Hb, where Vb is the absolute blood volume determined by online dialysate dilution using an online hemodiafiltration machine incorporating a relative BVM.

Findings

The MtHb and the total red cell volume (VRBC) as measured with the bolus method at the starting of the treatment were 540 ± 148 grams and 1544 ± 339 mL, respectively. There were significant differences between the Hb levels and between the hematocrit levels according to the time of dialysis. However, the MtHb remained constant. There was also an excellent correlation between the Hb measurements by the BVM and the blood sampling method (R = 0.89, P value <0.001).

Conclusion

Our study suggests that BVM could be very useful in the management of anemia in dialysis by computing the total Hb mass in clinical practice and may support better and more appropriate assessments of the factors influencing circulating Hb.
Coining it? Carolingian rulers and the Frankish coinage, ca. 750–900
Authors: Screen Elina
Published: August 2019

The story of the Frankish coinage is generally told from the Carolingian rulers' perspective as the rise and fall of royal control over minting. Increased coin finds have added nuance to this story by giving us new understanding of coin circulation and coin use. Recent studies confirm just how effectively Charlemagne and Louis the Pious controlled the Frankish coinage, which provided them with both political and economic benefits. Between 792/793 and 840, trade accelerated, and the Carolingian empire became increasingly monetised—though the use and availability of coins varied between regions. Tight royal control loosened after 840, when royal coinages became far more variable in quality. Around 880, the royal monopoly on striking coins was broken. From the perspective of traders and other coin users, having access to an acceptable means of exchange was more important than the availability of specifically royal coins. Trade could and did thrive in the world of regional coin circulation before 750 and after 840. Charlemagne and Louis the Pious's close royal control of the coinage, and the empire‐wide circulation of coins in 792/793–840, stand out as exceptional when set against the early medieval norm of regional coin production and circulation in Francia. The article is accompanied by an appendix introducing key resources for Carolingian numismatics.
TIMP3 gene polymorphisms and relation to Ankylosing spondylitis susceptibility in Chinese Han population
Authors: Wu Jiamin , Xiong Zichao , Sun Yao , Song Jiangjiang , Niu Fanglin , Yan Mengdan , Jin Tianbo
Published: August 2019

Background

Ankylosing spondylitis (AS) is a type of chronic progressive inflammatory disease, which often causes significant damage to the patients on the physical function, labour ability and quality of life. The study found that the enzyme system tissue inhibitor of matrix metalloproteinases (TIMPs) was important for the development of AS. The aim of this study was to investigate the association of polymorphisms of TIMP3 gene with AS in Chinese Han population.

Methods

To evaluate the correlation of TIMP3 polymorphisms with AS risk, Agena MassARRAY was used to determine the genotypes of 268 AS patients and 654 controls. The correlation between TIMP3 variants and AS risk was examined by unconditional logistic regression analysis. Haplotype construction and analysis in TIMP3 were also applied to detect the potential association.

Results

We identified that rs11547635 in the TIMP3 gene (odds ratio[OR] = 0.79, 95% confidence intervals [CI]: 0.63–0.98, p = .029) was significantly associated with a decreased risk of AS in the alleles model. Rs715572 AG genotype (OR = 1.57, 95% CI: 1.05–2.34, p = .041) was potentially associated with an increased risk of AS, and also rs715572 in the dominant model (OR = 1.61, 95% CI: 1.10–2.36, p = .013) and log‐additive model (OR = 1.41, 95% CI: 1.07–1.86, p = .016) adjusted by age and gender were significantly correlated with an increased AS risk.

Conclusion

These findings suggested that polymorphisms of the TIMP3 gene may be associated with susceptibility to AS.
A systematic review of the use of simulated patient methodology in pharmacy practice research from 2006 to 2016
Authors: Björnsdottir Ingunn , Granas Anne Gerd , Bradley Amanda , Norris Pauline
Published: August 2019

Objectives

Simulated patient (SP) methodology (mystery shopping) is used increasingly to assess quality of pharmacy services, and evaluate impact of interventions. Our objective was to review papers reporting on the use of SP methodology in pharmacy practice research 2006–2016 in community pharmacies worldwide.

Methods

We searched EMBASE and MEDLINE for papers reporting on the use of mystery shopping in pharmacy settings, using a wide range of terms for SPs, based on previous review. We removed irrelevant papers, duplicates, papers not written in English, and review papers and reviewed remaining papers. Two reviewers carried out data abstraction, using the same tool as the previous review and inserting data into Excel, focusing on how the SP methodology is used.

Key findings

A total of 148 papers from 52 countries from all regions of the world were included in the review. A wide range of terms described the method, and simulated patient was the most common (49 papers). Most studies were cross-sectional (124), and most investigated only community pharmacies (115). The most common aim was to evaluate some aspect of pharmacists’ or other staff's advice and counselling (94). Number of visits is 2-7785. Many papers did not cover details, such as number of visits planned, and carried out, scenario used, training and background of SPs, and ethical approval for the study.

Conclusions

The use of SP methodology has increased substantially in the field of pharmacy over the past decade. This is a useful method in a wide range of countries and settings. Greater detail is required in reporting.
Analyzing the grain‐boundary resistance of oxide‐ion conducting electrolytes: Poisson‐Cahn vs Poisson‐Boltzmann theories
Authors: Tong Xiaorui , Mebane David S. , De Souza Roger A.
Published: August 2019

The diminished conductivity of pristine grain boundaries in oxide‐ion conducting electrolytes, such as (Ce,Gd)O2 and (Zr,Y)O2, is widely interpreted with the Mott‐Schottky space‐charge model, or less frequently, with the Gouy‐Chapman space‐charge model. Although routinely applied to the entire compositional range of solid solutions, from dilute to concentrated, these models, being based on the Poisson‐Boltzmann formalism, are limited in their range of validity to dilute solutions of point defects. Analyzing the grain‐boundary properties of concentrated solid solutions with such models is expected to lead to errors and inconsistencies. In this study, we employ Poisson‐Cahn theory to analyze literature data for the grain‐boundary resistance of CeO2‐Gd2O3 materials as a function of Gd concentration. Poisson‐Cahn theory combines the Cahn‐Hilliard theory of inhomogeneous systems with the Poisson equation of electrostatics and it is valid over the entire compositional range. We treat the realistic case of a restricted equilibrium: Gd accumulation profiles are frozen‐in from sintering temperatures, while the oxygen‐vacancy distributions are in equilibrium at sintering and (much lower) measurement temperatures. Data for the grain‐boundary resistance are also analyzed with the standard analytical expressions from the Mott‐Schottky and Gouy‐Chapman models. Outside the domain of their validity, these expressions are found to perform poorly. In general, we emphasize the importance of treating the interfacial properties of concentrated solid solutions with physically appropriate theories.
Measuring the effects of heat treatment on SiC/SiC ceramic matrix composites using Raman spectroscopy
Authors: Knauf Michael W. , Przybyla Craig P. , Ritchey Andrew J. , Trice Rodney W. , Pipes R. Byron
Published: August 2019

The evolution of residual stresses found within a silicon carbide/silicon carbide (SiC/SiC) ceramic matrix composite through thermal treatments was investigated using Raman microspectroscopy. Constituent stress states were measured before, during, and after exposures ranging from 900 to 1300°C for varying times between 1 and 60 minutes. Silicon carbide particles in the as‐received condition exhibited average hydrostatic tensile stresses of approximately 300 MPa when measured at room temperature before and after heat treatment. The room temperature Raman profile of the silicon matrix was altered in both shape and location with heat treatment cycles due to increasing activation of boron within the silicon lattice as heat treatment temperatures increased. By accounting for boron activation in the silicon–boron system, little to no permanent change of any constituent stresses were observed, and the silicon matrix subsequently exhibited a complimentary average hydrostatic compressive stress of approximately 300 MPa at room temperature, measured before and after heat treatment. This result builds upon previous literature and offers increased insight into boron activation phenomena measured through Raman spectroscopy methods.
Characteristics of early recurrences detected by continuous cardiac monitoring influencing the long‐term outcome after atrial fibrillation ablation
Authors: Forkmann Mathias , Schwab Carolina , Edler Daniela , Vevecka Aneida , Butz Steffi , Haller Bernhard , Brachmann Johannes , Busch Sonia
Published: August 2019

Aims

Early recurrences (ER) of atrial arrhythmias are common after catheter ablation of atrial fibrillation (AF). The significance of these ER is controversial.

Based on data of continuous cardiac monitoring, we sought to investigate the characteristics of ER and their impact on late recurrences (LR) during follow‐up.

Methods

One hundred twenty‐six patients with paroxysmal (49%) or persistent (51%) AF underwent an AF ablation with subsequent implantation of implantable loop recorder. Follow up was 12 months using remote monitoring. All atrial arrhythmia (AF or atrial tachycardia‐AT‐) episodes >30 seconds. within the 3‐month blanking period were considered and the AF burden evaluated every 3 months.

Results

Within the 3‐months blanking period, 72 patients (57%) experienced an AF/AT recurrence. Survival free from any arrhythmia recurrence during follow‐up was 40% in patients with ER vs 69% in those without ER. AF burden during the blanking period and timing of ER correlated significantly with LR at 12 months (area under curve = 0.74,
P < .0001 and .831,
P < .0001). An AF burden ≥0.5% and ER after 74 days predicted LR (sensitivity 60%, specificity 84.4%; sensitivity 75.6%, specificity 90.3%). In cox regression analysis, AF burden ≥0.5% and ER after 74 days were independently associated with LR.

Conclusion

Continuous cardiac monitoring after AF ablation provides important information regarding early recurrence episodes and their prognostic impact. A cut‐off of 74 days for the blanking period seems to better differentiate patients with a good or a poor long‐term outcome. An AF burden ≥0.5% during the 3 months postablation is predictive for late arrhythmia recurrences.
Comparison of high‐power short‐duration (HPSD) ablation of atrial fibrillation using a contact force‐sensing catheter and conventional technique: Initial results
Authors: Vassallo Fabricio , Cunha Christiano , Serpa Eduardo , Meigre Lucas Luis , Carloni Hermes , Simoes Aloyr , Hespanhol Dalton , Lovatto Carlos Volponi , Batista Walter , Serpa Renato
Published: August 2019

Introduction: Atrial fibrillation (AFib) ablation is alternative treatment to drugs. Literature suggests that use of contact force (CF) catheter with higher power for short periods is effective and safe.

Methods/Results: Retrospectively analyzed 76 patients undergoing the first ablation. Third five patients‐group A: 27 (77%) paroxysmal AFib (PAFib) and 8 (23%) persistent AFib (PersAFib) who underwent ablation at the power of 30 W‐17 mL/minute flow with a CF of 10‐30 g for 30 seconds. Fourty one patients‐group B: 28 (68.3%) PAFib and 13 (31.70%) PersAFib underwent ablation using 45 W on posterior wall with CF of 8/15 g, as well as 50‐W anterior wall with CF of 10/20 g‐35 mL/minute flow for 6 seconds. Pulmonary vein isolation in both groups and ablated. For patients not in the sinus, we performed cardioversion before ablation. No complications. Group A: Left atrial time 110 ± 29 minutes, total 148 ± 33.6 minutes, radiofrequency time (RF) 4558 ± 1998 seconds, X‐ray 8.5 ± 3.5 minutes, and elevation of esophageal temperature (ET) in 26 (74.3%). group B: Left atrial time 70.7 ± 18.5 minutes (
P < .00001), total 106 ± 23 minutes (
P < .00001), RF 1909 ± 675.8 seconds (
P < .00001), X‐ray 8.8 ± 6.6 minutes (
P = .221) and elevation of ET in 21 (51.20% ‐
P = .0578). In 6 and 12 months follow‐up, we had 9 (25.71%) and 11 (31.42%) recurrences in group A and 5 (12.19%) and 7 (17.07%) in group B (
P = .231 at 6 and
P = .14 at 12 months), respectively.

Conclusions: HPSD was safe, useful, and efficient compared with CT, and reduced procedural time and total RF time. HPSD may reduce esophageal injury because of lower heating rate and it may reduce the recurrence of atrial tachyarrythmias.
Synergistic combination of DT‐13 and Topotecan inhibits aerobic glycolysis in human gastric carcinoma BGC‐823 cells via NM IIA/EGFR/HK II axis
Authors: Yu Xiao‐Wen , Wei Dandan , Gao Ying‐Sheng , Du Hong‐Zhi , Yu Bo‐Yang , Li Rui‐Ming , Qian Chang‐Min , Luo Xue‐Jun , Yuan Sheng‐Tao , Wang Jun‐Song , Sun Li
Published: August 2019

DT‐13 combined with topotecan (TPT) showed stronger antitumour effects in mice subcutaneous xenograft model compared with their individual effects in our previous research. Here, we further observed the synergistically effect in mice orthotopic xenograft model. Metabolomics analysis showed DT‐13 combined with TPT alleviated metabolic disorders induced by tumour and synergistically inhibited the activity of the aerobic glycolysis‐related enzymes in vivo and in vitro. Mechanistic studies revealed that the combination treatment promoted epidermal growth factor receptor (EGFR) degradation through non‐muscle myosin IIA (NM IIA)‐induced endocytosis of EGFR, further inhibited the activity of hexokinase II (HK II), and eventually promoted the aerobic glycolysis inhibition activity more efficiently compared with TPT or DT‐13 monotherapy. The combination therapy also inhibited the specific binding of HK II to mitochondria. When using the NM II inhibitor (‐)002Dblebbistatin or MYH‐9 shRNA, the synergistic inhibition effect of DT‐13 and TPT on aerobic glycolysis was eliminated in BGC‐823 cells. Immunohistochemical analysis revealed selective up‐regulation of NM IIA while specific down‐regulation of p‐CREB, EGFR, and HK II by the combination therapy. Collectively, these findings suggested that this regimen has significant clinical implications, warranted further investigation.
Evolution of Escherichia coli in different carbon environments for 2,000 generations
Authors: Choudhury Debika , Saini Supreet
Published: August 2019

Cellular energetics is thought to have played a key role in dictating all major evolutionary transitions in the history of life on Earth. However, how exactly cellular energetics and metabolism come together to shape evolutionary paths is not well understood. In particular, when an organism is evolved in different energy environments, what are the phenomenological differences in the chosen evolutionary trajectories, is a question that is not well understood. In this context, starting from an Escherichia coli K‐12 strain, we evolve the bacterium in five different carbon environments—glucose, arabinose, xylose, rhamnose and a mixture of these four sugars (in a predefined ratio) for approximately 2,000 generations. At the end of the adaptation period, we quantify and compare the growth dynamics of the strains in a variety of environments. The evolved strains show no specialized adaptation towards growth in the carbon medium in which they were evolved. Rather, in all environments, the evolved strains exhibited a reduced lag phase and an increased growth rate. Sequencing results reveal that these dynamical properties are not introduced via mutations in the precise loci associated with utilization of the sugar in which the bacterium evolved. These phenotypic changes are rather likely introduced via mutations elsewhere on the genome. Data from our experiments indicate that evolution in a defined environment does not alter hierarchy in mixed‐sugar utilization in bacteria.
Novel sulfate tablet PBK‐1701TC versus oral sulfate solution for colon cleansing: A randomized phase 3 trial
Authors: Yang Hyo‐Joon , Park Dong Il , Park Soo‐Kyung , Lee Chang Kyun , Kim Hyo Jong , Oh Shin Ju , Moon Jung Rock , Lee Beom Jae , Koh Jin Sung , Kim Hyun Soo , Park Seon‐Young , Kim Dong Hyun , Chun Jaeyoung , Kang Eun Ae , Kim Jung , Soh Hosim , Eun Chang Soo , Kim You Sun , Jeen Yoon Tae
Published: August 2019

Background and Aim

PBK‐1701TC is a novel sulfate tablet‐based that contains 320 mg of simethicone and delivers 90% of the salt and water delivered by oral sulfate solution (OSS) preparation. This study evaluated the efficacy, safety, and tolerability of PBK‐1701TC compared with OSS in bowel preparation for colonoscopy.

Methods

This randomized, multicenter, phase 3 non‐inferiority trial included adults aged 19 years or older with a body mass index of 19–30 kg/m2 undergoing colonoscopy at five university hospitals in Korea. The primary efficacy endpoint was successful bowel‐cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded central readers. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Tolerability was assessed via participant interview.

Results

Overall, 235 participants were randomized, and 224 were included in the per‐protocol analysis (PBK, 112; OSS, 112). Successful bowel cleansing was achieved for 95.5% (107/112) in the PBK group, which was non‐inferior to the OSS group (98.2%, 110/112) with a difference of −2.7% (one sided 97.5% confidence limit, −8.1%). The participants in the PBK group had fewer intraluminal bubbles (0.9% vs 81.3%, P < 0.001) and reported a lower incidence of nausea and vomiting, with better acceptance, taste, and willingness to repeat the regimen than those in the OSS group (all P < 0.05).

Conclusion

The novel sulfate tablet, PBK‐1701TC, was non‐inferior to OSS with respect to bowel‐cleansing efficacy and exhibited better safety and tolerability in adults undergoing colonoscopy.
Risk factors of neurovascular ageing in women
Authors: Miller Virginia M. , Jayachandran Muthuvel , Barnes Jill N. , Mielke Michelle M. , Kantarci Kejal , Rocca Walter A.
Published: August 2019

Biological sex and changes in sex hormones throughout life influence all aspects of health and disease. In women, changes in sex hormonal status reflect ovarian function, pregnancy and the use of exogenous hormonal treatments. Longitudinal data from defined cohorts of women will help to identify mechanisms by which the hormonal milieu contributes to cerebrovascular ageing, brain structure and ultimately cognition. This review summarises the phenotypes of three cohorts of women identified through the medical records‐linkage system of the Rochester Epidemiology Project and the Mayo Clinic Specialized Center of Research Excellence (SCORE) on Sex Differences: (i) menopausal women with histories of normotensive or hypertensive pregnancies; (ii) women who had bilateral oophorectomy ≤45 years of age; and (iii) women who experienced natural menopause and used menopausal hormone treatments for 4 years. Data from these cohorts will influence the design of follow‐up studies concerning how sex hormonal status affects neurovascular ageing in women.
RP11‐284F21.9 promotes oral squamous cell carcinoma development via the miR‐383‐5p/MAL2 axis
Authors: Shao Bingyi , Fu Xiaohui , Li Xian , Li Yong , Gan Ning
Published: August 2019

Background

Increasing evidence suggests that dysregulated long non‐coding RNAs (lncRNAs) are involved in tumorigenesis and progression. RP11‐284F21.9, one of the temporally expressed S‐phase lncRNAs in cancer cells, was recently identified by nascent RNA capture sequencing.

Methods

Cal‐27, Tca8113, SCC‐9, HB56, and oral squamous cell carcinoma (OSCC) tissues were used in the experiment. RNA extraction, qRT‐PCR, plasmid construction, cell proliferation, EdU labeling, Transwell migration, luciferase reporter, and western blotting were used to investigate the exact role and function of RP11‐284F21.9 in cancer.

Results

RP11‐284F21.9 was upregulated in human OSCC samples and cell lines. RP11‐284F21.9 depletion suppressed the proliferation, migration, and invasion of OSCC cell lines. There was interaction between RP11‐284F21.9, miR‐383‐5p, and MAL2. Increased MAL2 and decreased miR‐383‐5p expression were also detected in OSCC tissues and cell lines. In addition, RP11‐284F21.9 knockdown could reduce MAL2 expression, while miR‐383‐5p inhibitors abolished this repressive effect. RP11‐284F21.9 acted as a competing endogenous RNA (ceRNA) of miR‐383‐5p, leading to MAL2 upregulation, and subsequently promoted OSCC progression.

Conclusion

RP11‐284F21.9/miR‐383‐5p represents a novel and potential therapeutic target for the treatment of OSCC.
Quantitative assessment of the quality of home sleep studies: A computer‐assisted approach
Authors: Maestri Roberto , Robbi Elena , Lovagnini Marta , Taurino Anna Eugenia , Fanfulla Francesco , Pinna Gian Domenico
Published: August 2019

Home monitoring is the most practical means of collecting sleep data in large‐scale research investigations. Because the portion of recording time with poor‐quality data is higher than in attended polysomnography, a quantitative assessment of the quality of each signal should be recommended. Currently, only qualitative or semi‐quantitative assessments are carried out, likely because of the lack of computer‐based applications to carry out this task efficiently. This paper presents an innovative computer‐assisted procedure designed to perform a quantitative quality assessment of standard respiratory signals recorded by Type 2 and Type 3 portable sleep monitors. The proposed system allows to assess the quality (good versus bad) of consecutive 1‐min segments of thoraco‐abdominal movements, oronasal, nasal airflow and oxygen saturation through an automatic classifier. The performance of the classifier was evaluated in a sample of 30 unattended polysomnography recordings, comparing the computer output with the consensus of two expert scorers. The difference (computer versus scorers) in the percentage of good‐quality segments was on average very small, ranging from −3.1% (abdominal movements) to 0.8% (nasal flow), with an average total classification accuracy from 90.2 (oronasal flow) to 94.9 (nasal flow), a Sensitivity from 0.93 (oronasal flow) to 0.98 (nasal flow), and a Specificity from 0.74 (nasal flow) to 0.86 (abdominal movements). In practical applications, the scorer can run a check‐and‐edit procedure, further improving the classification accuracy. Considering a sample of 270 unattended polysomnography recordings (recording time: 545 ± 44 min), the average time taken for the check‐and‐edit procedure of each recording was 6.9 ± 2.1 min for all respiratory signals.
Categorising the broad impacts of continuing professional development: a scoping review
Authors: Allen Louise M , Palermo Claire , Armstrong Elizabeth , Hay Margaret
Published: August 2019

Context

A number of systematic reviews have evaluated the impacts of continuing professional development (CPD). These reviews, due to their focused nature, may fail to capture the full range of impacts of CPD. This scoping review aims to explore the broader impacts of CPD with the intention of developing a categorisation of the types of impact of CPD.

Methods

The authors searched MEDLINE, CINAHL and ERIC databases for studies published between 2007 and 2017 that looked at the impacts of formal CPD programmes for all health professionals. Studies were independently screened for eligibility; one reviewer charted data for all included studies, a sample of 10% was reviewed by a second reviewer. The charted data were analysed using both qualitative and quantitative content analysis.

Results

The search returned 2750 manuscripts; 192 manuscripts describing 191 studies were included in this review. Most articles were from the USA (78 studies, 41%) and included medical doctors in the population (105 studies, 55%). Twelve categories of impact were generated through conventional content analysis: knowledge, practice change, skill, confidence, attitudes, career development, networking, user outcomes, intention to change, organisational change, personal change and scholarly accomplishments. Knowledge was most commonly measured (103 studies, 54%), whereas measurement of scholarly accomplishments was the least common (10 studies, 5%).

Conclusions

Existing evidence takes a narrow view when assessing the impacts of CPD. Emphasis on measuring impacts as knowledge, behaviour, confidence, skills and attitudes may be due to the widely accepted four levels of evaluation from the Kirkpatrick Model or because the majority of studies used quantitative methods. The categories proposed in this review may be used to capture a broader view of the impacts of CPD programmes, contributing to the evidence base for their value and translating into CPD programmes that truly transform health professionals, their careers and their practice.
HtrA‐mediated selective degradation of DNA uptake apparatus accelerates termination of pneumococcal transformation
Authors: Liu Yanni , Zeng Yuna , Huang Yijia , Gu Lixiao , Wang Shaolin , Li Chunhao , Morrison Donald A. , Deng Haiteng , Zhang Jing‐Ren
Published: August 2019

Natural transformation mediates horizontal gene transfer, and thereby promotes exchange of antibiotic resistance and virulence traits among bacteria. Streptococcus pneumoniae, the first known transformable bacterium, rapidly activates and then terminates the transformation state, but it is unclear how the bacterium accomplishes this rapid turn‐around at the protein level. This work determined the transcriptomic and proteomic dynamics during the window of pneumococcal transformation. RNA sequencing revealed a nearly uniform temporal pattern of rapid transcriptional activation and subsequent shutdown for the genes encoding transformation proteins. In contrast, mass spectrometry analysis showed that the majority of transformation proteins were substantially preserved beyond the window of transformation. However, ComEA and ComEC, major components of the DNA uptake apparatus for transformation, were completely degraded at the end of transformation. Further mutagenesis screening revealed that the membrane‐associated serine protease HtrA mediates selective degradation of ComEA and ComEC, strongly suggesting that breakdown of the DNA uptake apparatus by HtrA is an important mechanism for termination of pneumococcal transformation. Finally, our mutagenesis analysis showed that HtrA inhibits natural transformation of Streptococcus mitis and Streptococcus gordonii. Together, this work has revealed that HtrA regulates the level and duration of natural transformation in multiple streptococcal species.
Kant, moral overdemandingness and self‐scrutiny
Authors: Sticker Martin
Published: August 2019

This paper contributes to the debate about how the overdemandingness objection applies to Kant's ethics. I first look at the versions of the overdemandingness objections Kant himself levels against other ethicists and ethical principles and I discuss in what sense he acknowledges overdemandingness as a problem. Then I argue that, according to Kant's own standards, introspection about the moral worthiness of one's actions can constitute forms of moral overdemandingness. Self‐scrutiny and Kant's well‐known claim that we can never be certain that we acted for the right reason jeopardize agents’ deserved happiness. Furthermore, self‐scrutiny can constitute an activity Kant himself criticizes under the labels of “micrology” and “fantastic virtue”. The demandingness of critical self‐scrutiny has not yet received due attention in the overdemandingness debate since this debate is focused on duties we have towards others.
Extensive adipose replacement of the parotid glands: an unusual presentation of sialadenosis. A Case Report and Literature Review
Authors: Guan G. , Won J. , Mei L. , Polonowita A.
Published: August 2019

Sialadenosis is an asymptomatic, bilateral enlargement of salivary glands which most commonly affects the parotid glands. Dental practitioners must be able to differentiate gland enlargement to inflammatory, autoimmune and neoplastic processes to prevent unnecessary management and allow for correct referrals to specialists. Adipose replacement has been recognised as an uncommon feature of sialadenosis that may be linked to several systemic conditions; however, fatty infiltration of the glands to the degree of this case report has been rarely presented. The authors report on an unusual presentation of sialadenosis with extensive adipose replacement in the parotid glands, and review on the current literature for associated causes, clinicopathological features, various diagnostic tools and the appropriate management of sialadenosis.
Reducing cardiovascular disease in a rural community
Authors: Allgood Sallie D. , Leeman Jennifer , Rosemond Cherie A. , Ammerman Alice S. , Samuel‐Hodge Carmen , Cykert Samuel
Published: August 2019

In this case report, we describe the one‐year formative phase of a five‐year study to develop, implement, and test a community health worker (CHW)‐delivered cardiovascular disease (CVD) prevention intervention. The purpose of the formative phase was to engage community partners in the adaptation of an existing evidence‐based CVD prevention intervention to fit the needs and preferences of a rural, predominantly African‐American community. The formative work was guided by a framework for adapting evidence‐based interventions and involved engaging stakeholders in assessing the intervention's fit with the local context and then applying assessment findings to iteratively adapt the intervention's contents, materials, and delivery methods. Findings from the formative work were then applied to develop CHW position descriptions, workflow diagrams, and a training plan. Findings also were applied to adapt intervention materials and protocols to fit the needs of the community. This case report illustrates how community‐engaged formative work can be applied to adapt an evidence‐based intervention to fit community needs and resources.
Different Immigrants, Same Attitudes? Making Sense of the Association Between Two Immigrant Groups
Authors: Tsai Tsung‐han , Tsai Chia‐hung , Huang Chi
Published: August 2019

Objective

Previous studies of public attitudes toward immigration have been set in economically developed areas such as the United States and the countries of Western Europe, implicitly applying the term “immigrants” solely to blue‐collar laborers. In this article, we extend the discussion to Taiwan, a newly democratic and nearly developed country in East Asia.

Methods

Our study investigates public attitudes toward immigrants with different occupations and test predictions derived from both economic and cultural approaches.

Results

From an analysis of the survey data, we find different economic factors for pro‐immigration attitudes toward foreign professionals and laborers.

Conclusions

Specifically, people who have higher incomes are more likely to allow foreign professionals to become citizens, and people with positive assessments of national and individual economic conditions are more likely to favor the inflow of foreign workers. Furthermore, cultural tolerance and a high level of education are correlated to pro‐migration attitudes toward both foreign professionals and laborers.
Resilience: insights from medical educators
Authors: Chan Linda , Dennis Ashley A
Published: August 2019

Background

Educators have unique opportunities to cultivate resilience in themselves and in their learners across the medical education continuum through the formal, informal and hidden curricula. Yet, there is a dearth of research exploring how medical educators conceptualise resilience, and how they foster learner resilience in medical education.

Methods

Thematic framework analysis was conducted on data collected through an online questionnaire, which was part of a larger study exploring resilience in medical educators. Open‐ended questions examined educators’ conceptualisations of resilience and how they reported supporting resilience in their learners. Sociodemographic characteristics were also collected to describe the sample of participants.

Findings

A total of 244 medical educators participated from across the UK. They predominantly conceptualised resilience as an individual process. Participants mostly reported approaches to fostering learner resilience that aligned with the formal and informal curricula. Approaches addressing the hidden curriculum were seldom mentioned.

Discussion

Opportunities exist for faculty development around multidimensional conceptualisations of resilience, and for medical educators to critically reflect on how their concepts of resilience may be influencing their approach to fostering learner resilience. Furthermore, the hidden curriculum could be featured as one of the multifaceted strategies to support resilience in learners.