bluuebunny/crossref_metadata_2025_split huggingface dataset:
Miconazole‐tolerant strains of Malassezia pachydermatis generated by culture in medium containing miconazole
Authors: Kano Rui , Kamata Hiroshi 
Published: November 2019

BackgroundTolerance of Malassezia pachydermatis to azole drugs has been reported worldwide, from strains isolated from dogs. Canine Malassezia dermatitis often is treated with shampoos containing 2% miconazole (MCZ) or other topical MCZ products.ObjectivesIn the in vitro study herein, it was investigated whether MCZ‐induced amino acid substitutions in the lanosterol 14‐alpha‐demethylase (ERG11) gene 1 lead to azole tolerance in M. pachydermatis.Methods and materialsToleranced to MCZ was induced in an azole‐susceptible strain of M. pachydermatis (CBS1879T) by culture in medium containing MCZ. Antifungal susceptibility to MCZ, clotrimazole (CTZ) and itraconazole (ITZ) was assessed using the modified broth microdilution (BM) method. To assess the potential mechanism of tolerance in the three MCZ‐resistant strains, ERG11 was sequenced. The interaction between the calcineurin inhibitor tacrolimus and MCZ in the azole‐tolerant isolates also was examined.ResultsThree strains (NUBS19001 to NUBS19003) from CBS1879T cultured in medium containing MCZ exhibited minimum inhibitory concentrations (MICs) of 40 mg/L to MCZ, 5 mg/L to ITZ and >32 mg/L to CTZ, meaning that the isolates were tolerant. The combination of MCZ and tacrolimus exerted an indifferent effect against the MCZ‐tolerant strain. BLAST analysis using the NCBI database showed mutations in the cytochrome p450 encoded by ERG11 in the MCZ‐tolerant strains.ConclusionsIn the present in vitro study, it was shown that MCZ exposure can induce amino acid substitutions in ERG11 and subsequent tolerance of M. pachydermatis to several azoles. Whether topical therapy with azole‐containing products can exert a similar effect in vivo is a question that requires further research.
Theoretical Dynamic Modeling and Validation of Braided Pneumatic Artificial Muscles
Authors: Slightam Jonathon E. , Nagurka Mark L. 
Published: November 2019

Abstract
The high force-to-weight ratios of braided fluidic artificial muscles (AMs) are ideal for human scale and mobile robot applications. Prior modeling efforts focus on the theoretical static characteristics or empirical dynamic models of these actuators when pressurized. This paper develops a comprehensive high fidelity theoretical dynamic model based on first principles for braided pneumatic AMs and presents experimental validation. A novel theoretical model for the nonlinear stiffness is derived to describe the pressure–displacement behavior. The stiffness model, together with friction, damping, and inertia models, forms an equation of motion (EOM) for braided pneumatic AMs. The EOM is coupled with first-order servopneumatic pressure dynamics, resulting in a third-order system model. System model simulations are compared to experimental results of prototypes with nine different geometries. On average, the system model is able to predict the quasi-static displacement within 7% and the dynamic response within 11%. The theoretical model is also benchmarked against a high fidelity curve fit method, with the empirical method showing a 2% improvement in only quasi-static scenarios. The model promises to be useful for mechanical system and model-based control designs.
The role of multiple global change factors in driving soil functions and microbial biodiversity
Authors: Rillig Matthias C. , Ryo Masahiro , Lehmann Anika , Aguilar-Trigueros Carlos A. , Buchert Sabine , Wulf Anja , Iwasaki Aiko , Roy Julien , Yang Gaowen 
Published: November 2019

Many factors influence global changeGlobal environmental change is driven by multiple natural and anthropogenic factors. With a focus on global change as it affects soils, Rilliget al.point out that nearly all published studies consider just one or two factors at a time (see the Perspective by Manning). In a laboratory experiment, they tested 10 drivers of global change both individually and in combination, at levels ranging from 2 to 10 factors. They found that soil properties, processes, and microbial communities could not be predicted from single-effect responses and that multiple factors in combination produced unsuspected responses. They concluded that single-factor studies remain important for uncovering mechanisms but that global change biology needs to embrace more fully the multitude of drivers impinging on ecosystems.Science, this issue p.886; see also p.801
Experiences and challenges of adults living with type 2 diabetes mellitus presenting at the University Teaching Hospital in Lusaka, Zambia
Authors: Mwila Kunda Faith , Bwembya Phoebe Albina , Jacobs Choolwe 
Published: November 2019

ObjectiveThe study explored the experiences and challenges of adults living with type 2 diabetes mellitus (T2DM) presenting at the University Teaching Hospital (UTH) in Lusaka.Research designA qualitative descriptive study was conducted. The research relied on purposive sampling to select 28 participants for in-depth interviews. Participants were interviewed during clinical visits at UTH.ResultsViews from participants showed that some adults living with T2DM experienced physical and mental illnesses. Participants’ views reflected that their livelihood with T2DM was influenced by family support, poor or non-adherence to treatment guidelines and access to information, education and communication materials. The most important challenges reported were psychosocial and financial.ConclusionThe study concluded that some adults living with T2DM experience a lot of physical sicknesses and their challenges, especially of the psychosocial nature may require professional attention. However, particular attention should be paid to the patient’s self-care and psychosocial therapy. Self-care protocols should be tailored to complement the different types of patients with diabetes and improve their quality of life.Cite Now
Trimethylamine N-oxide and incident atherosclerotic events in high-risk individuals with diabetes: an ACCORD trial post hoc analysis
Authors: Cardona Andrea , O'Brien Aaron , Bernier Matthew C , Somogyi Arpad , Wysocki Vicki H , Smart Suzanne , He Xin , Ambrosio Giuseppe , Hsueh Willa Ann , Raman Subha V 
Published: November 2019

IntroductionType 2 diabetes mellitus (T2D) confers high atherosclerotic cardiovascular disease (ASCVD) risk. The metabolite trimethylamine N-oxide (TMAO) derived via gut flora has been linked to excess ASCVD.Research design and methodsWe analyzed data, biospecimens, and major adverse cardiovascular events (MACEs) from the prospective multicenter randomized Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to assess its value in 330 high-risk individuals with T2D without evident atherosclerotic disease at enrollment.ResultsIncident cardiovascular events occurred in 165 cases; 165 controls matched by age, sex, and treatment arm experienced no incident events during follow-up. Cases and controls (mean age 64.5 years) had similar mean glycated hemoglobin (HbA1c) (8.2%) and mean 10-year ASCVD risk (23.5%); groups also had similar use of statins and antihypertensive medications at baseline and follow-up. Baseline plasma TMAO levels did not differ between groups after adjusting for ASCVD risk score, HbA1c, and estimated glomerular filtration rate, nor did TMAO distinguish patients suffering incident MACE from those who remained event-free.ConclusionsTMAO’s prognostic value for incident ASCVD events may be blunted when applied to individuals with T2D with poor glycemic control and high baseline ASCVD risk. These results behoove further translational investigations of unique mechanisms of ASCVD risk in T2D.
Deficiency of C3a receptor attenuates the development of diabetic nephropathy
Authors: Li Xiao-Qian , Chang Dong-Yuan , Chen Min , Zhao Ming-Hui 
Published: November 2019

ObjectiveDiabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN.Research design and methodsThe expression of C3aR was examined in the renal specimen of patients with DN. Using a C3aR gene knockout mice (C3aR−/−), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a.ResultsCompared with normal controls, the renal expression of C3aR was significantly increased in patients with DN. C3aR−/− diabetic mice developed less severe diabetic renal damage compared with wild-type (WT) diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T-cell adaptive immunity in C3aR−/− diabetic mice compared with WT diabetic mice, and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophage infiltration. In vitro study demonstrated C3a can enhance macrophage-secreted cytokines which could induce inflammatory responses and differentiation of T-cell lineage.ConclusionsC3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T-cell adaptive immunity, possibly by influencing macrophage-secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.
BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa
Authors: Berendsen Mike LT , van Gijzel Sjors WL , Smits Jeroen , de Mast Quirijn , Aaby Peter , Benn Christine S , Netea Mihai G , van der Ven Andre JAM 
Published: November 2019

IntroductionMalaria continues to be a major cause of morbidity and mortality in sub-Saharan Africa (SSA) without effective interventions. Bacillus Calmette-Guérin (BCG) vaccine possesses protective non-specific effects, which extend beyond protection against tuberculosis. This study explores whether BCG is associated with protection against malaria in children under the age of 5 years in SSA.MethodsWe used data from the Demographic Health Survey programme, including 34 206 children from 13 SSA countries. BCG status was taken from vaccination cards when present; if not, mother’s recall was used. Presence of malaria was defined as a positive rapid diagnostic test. Maternally reported presence or absence of fever in the previous 2 weeks defined symptomatic status. Multilevel logistic regression was used to account for the two-stage cluster sampling method.ResultsOf the 34 206 children, 12 325 (36.0%) children were malaria positive and 29 766 (87.0%) were BCG vaccinated. After correction for relevant child, maternal and household factors, BCG vaccination was associated with a lower malaria prevalence (adjusted OR (aOR)=0.94, 95% CI 0.90 to 0.98), especially among children of whom BCG information was retrieved from a vaccination card (aORcard=0.88, 95% CI 0.82 to 0.94). Restricting the analysis to children from regions with suboptimal BCG coverage increased the association (aORcard=0.81, 95% CI 0.73 to 0.89). We observed an increasingly beneficial association with each month of age of the child (aORcard=0.996, 95% CI 0.993 to 0.999). BCG associations were similar for asymptomatic (aORcard=0.86, 95% CI 0.81 to 0.92) and symptomatic (aORcard=0.89, 95% CI 0.78 to 1.01) malaria.ConclusionsBCG vaccination is associated with protection against malaria. This protection is highest in regions with suboptimal BCG coverage. These results indicate a possible role for timely BCG vaccination in the protection of malaria and its elimination by reducing the transmission reservoir. If confirmed in further research, our findings have substantial implications for global efforts to reduce malaria burden.
The patient safety practices of emergency medical teams in disaster zones: a systematic analysis
Authors: El-khani Ussamah , Ashrafian Hutan , Rasheed Shahnawaz , Veen Harald , Darwish Ammar , Nott David , Darzi Ara 
Published: November 2019

IntroductionDisaster zone medical relief has been criticised for poor quality care, lack of standardisation and accountability. Traditional patient safety practices of emergency medical teams (EMTs) in disaster zones were not well understood. Improving the quality of healthcare in disaster zones has gained importance within global health policy. Ascertaining patient safety practices of EMTs in disaster zones may identify areas of practice that can be improved.MethodsA systematic search of OvidSP, Embase and Medline databases; key journals of interest; key grey literature texts; the databases of the WHO, Médecins Sans Frontieres and the International Committee of the Red Cross; and Google Scholar was performed. Descriptive studies, case reports, case series, prospective trials and opinion pieces were included with no limitation on date or language of publication.ResultsThere were 9685 records, evenly distributed between the peer-reviewed and grey literature. Of these, 30 studies and 9 grey literature texts met the inclusion criteria and underwent qualitative synthesis. From these articles, 302 patient safety statements were extracted. Thematic analysis categorised these statements into 84 themes (total frequency 632). The most frequent themes were limb injury (9%), medical records (5.4%), surgery decision-making (4.6%), medicines safety (4.4%) and protocol (4.4%).ConclusionPatient safety practices of EMTs in disaster zones are weighted toward acute clinical care, particularly surgery. The management of non-communicable disease is under-represented. There is widespread recognition of the need to improve medical record-keeping. High-quality data and institutional level patient safety practices are lacking. There is no consensus on disaster zone-specific performance indicators. These deficiencies represent opportunities to improve patient safety in disaster zones.
‘New Medicine Service’: supporting adherence in people starting a new medication for a long-term condition: 26-week follow-up of a pragmatic randomised controlled trial
Authors: Elliott Rachel Ann , Boyd Matthew J , Tanajewski Lukasz , Barber Nick , Gkountouras Georgios , Avery Anthony J , Mehta Rajnikant , Davies James E , Salema Nde-Eshimuni , Craig Christopher , Latif Asam , Waring Justin , Chuter Antony 
Published: November 2019

ObjectiveTo examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks.MethodsPragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged ≥14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective).ResultsUnadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: −£104 (95% CI −£37 to £257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI −0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of −£113.9 (−1159.4, 683.7). The incremental cost-effectiveness ratio was −£2758/QALY (2.5% and 97.5%: −38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of £20 000 per QALY.ConclusionsAt 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high.Trial registration numberNCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494.
Morphine for dyspnoea in chronic obstructive pulmonary disease: a before–after efficacy study
Authors: Matsuda Yoshinobu , Morita Tatsuya , Matsumoto Hirotaka , Hosoi Keita , Kusama Kayo , Kohashi Yasuo , Morishita Hiroshi , Kaku Sawako , Ariyoshi Keisuke , Oyamada Shunsuke , Inoue Yoshikazu , Iwase Satoru , Yamaguchi Takuhiro , Nishikawa Mitsunori 
Published: November 2019

ObjectivesDyspnoea in patients with chronic obstructive pulmonary disease (COPD) is frequent and often persists despite conventional treatment. This study aimed to evaluate the efficacy and safety of oral morphine for dyspnoea in Japanese COPD patients.MethodsWe conducted a multi-institutional, prospective, before–after study of morphine in COPD patients with dyspnoea at rest in seven hospitals. Patients received 12 mg of oral morphine per day (or 8 mg per day if low body weight or renal impairment). Primary outcome was change in the numerical rating scale (NRS) of current dyspnoea in the evening from Day 0 to Day 2. Secondary outcomes included changes in dyspnoea intensity in the evening from Day 0 to Day 1, dyspnoea intensity between the morning from Day 0 to Day 1 and Day 2, vital signs, nausea, somnolence, anorexia and other adverse events (AEs).ResultsA total of 35 patients were enrolled in this study between October 2014 and January 2018. One patient did not receive study treatment. Data from 34 patients was analysed. The NRS of dyspnoea intensity in the evening significantly decreased from 3.9 on Day 0 (95% CI: 3.1 to 4.8) to 2.4 on Day 2 (95% CI: 1.7 to 3.1; p=0.0002). Secondary outcomes significantly improved in a similar manner. There were no apparent changes in the mean scores of the opioid-related AEs and vital signs. One patient experienced grade 3 lung infection not associated with morphine. Other AEs were mild.ConclusionOral morphine is effective in alleviating dyspnoea in Japanese COPD patients.Trial registrationUMIN000015288 (http://www.umin.ac.jp/ctr/index.htm).
The differences of clinicopathologic characteristics among subgroups of reclassified HER2 fluorescence in situ hybridization (FISH) according to the ASCO/CAP 2018 breast cancer HER2 testing guidelines
Authors: Yang Libo , Chen Min , Pu Tianjie , Wu Shuang , Wei Bing , Yang Jieliang , Bu Hong , Zhang Zhang 
Published: November 2019

AimsThe aim of this study is to analyse differences in clinicopathologic features among reclassified human epidermal growth factor receptor-2 (HER2) fluorescencein situhybridization (FISH) results in breast cancers according to 2018 guidelines.MethodsAccording to different ratios ofHER2copy numbers to chromosome 17 centromere numbers (HER2/CEP17) and averageHER2copy numbers, 3795 invasive breast cancers were classified into six groups. Clinicopathologic features were collected and compared among different FISH groups.ResultsThere were no statistically significant differences about HER2 positive rate between 2013 and 2018 guidelines (p=0.518). After re-evaluating these cases according to 2018 guidelines, the cases that converted to a HER2 positive status had clinicopathologic features similar to samples in group 1 (ratio ≥2.0, HER2≥4.0). Compared with group 5 (ratio <2.0,HER2<4.0), the cases in groups 1 had higher histological grade, more frequent occurrence of negative oestrogen receptor and progesterone receptor status and a higher Ki67 index. The samples in group 4 (ratio <2.0, 4.0≤HER2<6.0) showed a higher histological grade and higher Ki67 index than did the samples in group 5 but had a lower histological grade and lower Ki67 index than did the samples in group 1a (ratio ≥2.0,HER2≥6.0).ConclusionDifferent categories of HER2 FISH test results have significant differences in clinicopathologic features. With no equivocal cases in 2018 HER2 guidelines, the clear division of HER2 status is helpful for making treatment recommendations about HER2 targeted therapy.
Audit of the prevalence and investigation of iron deficiency anaemia in patients with heart failure in hospital practice
Authors: Simon Steny , Ioannou Adam , Deoraj Stuart , Metaxa Sofia , Mandal Amit K J , Missouris Constantinos G 
Published: November 2019

AbstractPurpose of the studyIron deficiency anaemia (IDA) is associated with increased morbidity and mortality in heart failure patients. The aim of our audit was to evaluate the current practice in diagnosis and assessment of IDA in patients admitted with heart failure.Study designWe conducted a retrospective audit of patients admitted to our hospital between January 2017 and June 2017 with a diagnosis of heart failure, and obtained data regarding each patient’s demographics and anaemic status. We also conducted a qualitative survey to assess healthcare professionals’ ability to diagnose IDA, and their knowledge of iron replacement in heart failure patients.ResultsOur audit identified 218 heart failure patients, nearly two-thirds (n=138, 63.3%) of which were anaemic. Of the 138 anaemic patients, only 40 had a full haematinic screen compared with 98 who had incomplete investigations (29% vs 71%, p=0.007). Iron studies were the most commonly performed haematinic investigation (n=87, 63%), and over half of these patients were iron deficient (n=49, 56.3%). Only 12 (24.5%) iron deficient patients were prescribed oral iron therapy, while 37 (75.5%) were left without iron replacement (X2=12.8, p=0.0003). Our survey demonstrated a lack of awareness among healthcare professionals with only 19.7% of participants being able to correctly define anaemia and 9.1% being aware of guidelines regarding treatment of IDA.ConclusionMany patients admitted to hospital with heart failure also have a concomitant diagnosis of anaemia. The aetiology of the underlying anaemia is often poorly investigated, and where IDA is identified it is poorly treated.