bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic utility of sub‐maximum cardiopulmonary exercise testing in the ambulatory setting for heart failure with preserved ejection fraction
Authors: Oakland Hannah T. , Joseph Phillip , Elassal Ahmed , Cullinan Marjorie , Heerdt Paul M. , Singh Inderjit
Published: November 2020

Pulmonary hypertension is commonly associated with heart failure with preserved ejection fraction. In heart failure with preserved ejection fraction, the elevated left‐sided filling pressures result in isolated post‐capillary pulmonary hypertension or combined pre‐ and post‐capillary pulmonary hypertension. Although right heart catheterization is the gold standard for diagnosis, it is an invasive test with associated risks. The ability of sub‐maximum cardiopulmonary exercise test as an adjunct diagnostic tool in pulmonary hypertension‐associated heart failure with preserved ejection fraction is not known. Forty‐six patients with heart failure with preserved ejection fraction and pulmonary hypertension (27 patients with combined pre‐ and post‐capillary pulmonary hypertension and 19 patients with isolated post‐capillary pulmonary hypertension) underwent sub‐maximum cardiopulmonary exercise test followed by right heart catheterization. The study also included 18 age‐ and gender‐matched control subjects. Several sub‐maximum gas exchange parameters were examined to determine the ability of sub‐maximum cardiopulmonary exercise test to distinguish between isolated post‐capillary pulmonary hypertension and combined pre‐ and post‐capillary pulmonary hypertension. Conventional echocardiogram measures did not distinguish between isolated post‐capillary pulmonary hypertension and combined pre‐ and post‐capillary pulmonary hypertension. Compared to isolated post‐capillary pulmonary hypertension, combined pre‐ and post‐capillary pulmonary hypertension had greater ventilatory equivalent for carbon dioxide (VE/VCO2) slope, reduced delta end‐tidal CO2 change during exercise, reduced oxygen uptake efficiency slope, and reduced gas exchange determined pulmonary vascular capacitance. The latter was significantly associated with right heart catheterization determined pulmonary artery compliance (r = 0.5; p = 0.0004). On univariate analysis, sub‐maximum VE/VCO2, delta end‐tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance emerged as independent predictors of the extrapolated maximum oxygen uptake (%predicted) (β‐coefficient values of –7.32, 95% CI: –13.3 – (–1.32), p = 0.01; 8.01, 95% CI: 1.96–14.05, p = 0.01; 8.78, 95% CI: 2.26–15.29, p = 0.01, respectively). Sub‐maximum gas exchange parameters obtained during cardiopulmonary exercise test in an ambulatory setting allows for discrimination between isolated post‐capillary pulmonary hypertension and combined pre‐ and post‐capillary pulmonary hypertension. Additionally, sub‐maximum cardiopulmonary exercise test derived VE/VCO2, delta end‐tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance influences aerobic capacity in heart failure with preserved ejection fraction.
Risk of translocated soft-tissue sarcoma recurrence using perforator propeller flap: Case report and literature review
Authors: Tiengo Cesare , Sonda Regina , Messana Francesco , Masciopinto Giuseppe , Trovarelli Giulia , Berizzi Antonio , Ruggeri Pietro , Bassetto Franco
Published: November 2020

Tumor seeding after intra-abdominal and head and neck cancer surgery is a well-known entity. The risk of disseminating cancerous cells during surgery is also described for soft-tissue sarcoma of the extremities. Nonetheless, after reconstructive surgery using flaps, the risk of recurrence at the donor site is extremely rare. Up to this date, the literature describes only three cases, but none of them reported a translocated recurrence after a reconstruction with a propeller flap. Here, we report a case of high-grade pleomorphic sarcoma of the knee, which recurred at the proximal edge of a propeller flap 28 months after the first excision surgery. The reasons for such local recurrences are not clear and previous works have advocated different theories: direct contamination by tumor cells, physical manipulation of the tumor and creation of surgical wounds with tumor supportive properties. Although these particular cases of recurrence are exceedingly rare, certain precautionary meticulous surgical techniques and a thorough preoperative planning are pivotal to avoid the contamination of “clean” areas during the first excision surgery.
Cortical brain activity in transfemoral or knee-disarticulation prosthesis users performing single- and dual-task walking activities
Authors: Möller Saffran , Ramstrand Nerrolyn , Hagberg Kerstin , Rusaw David
Published: November 2020

Introduction

Walking with a prosthesis while performing secondary tasks increases demand on cognitive resources, compromising balance and gait. This study investigated effects of a secondary task on patterns of brain activity and temporospatial gait parameters in individuals using a prosthesis with or without a microprocessor-controlled prosthetic knee(MPK) and controls.

Methods

A cross-sectional study with repeated measures was performed. Twenty-nine individuals with amputations and 16 controls were recruited. Functional near-infrared spectroscopy was used to evaluate changes in oxygenated and de-oxygenated haemoglobin in the prefrontal cortex and temporospatial variables during single-and dual-task walking.

Results

Differences in brain activity were observed within the MPK-group and controls without changes in temporospatial parameters. The Trail-Walking test was associated with highest levels of brain activity in both groups. No differences were observed between single- and dual-task walking in the non-MPK-group (p > 0.05). The Non-MPK and the MPK-group recorded higher levels of brain activity than controls during single-task walking and poorer results on temporospatial variables compared to controls.

Conclusions

For the MPK-group and controls, introduction of a secondary task led to an increase in brain activity. This was not seen in the Non-MPK-group. Significant differences in brain activity were observed in the absence of changes in temporospatial parameters.
Comparison Between the Japanese Orthopaedic Association (JOA) Score and Patient-Reported JOA (PRO-JOA) Score to Evaluate Surgical Outcomes of Degenerative Cervical Myelopathy
Authors: Oshima Yasushi , Takeshita Katsushi , Kato So , Doi Toru , Matsubayashi Yoshitaka , Taniguchi Yuki , Nakajima Koji , Oguchi Fumihiko , Okamoto Naoki , Sakamoto Ryuji , Tanaka Sakae
Published: November 2020

Study Design:

A retrospective cohort study.

Objective:

To investigate whether the Japanese Orthopaedic Association (JOA) score can be used for patients with degenerative cervical myelopathy as a patient-reported outcome (PRO) through the JOA written questionnaire.

Methods:

A total of 75 patients who underwent posterior decompression surgery for degenerative cervical myelopathy were reviewed. Patients responded to questionnaires including PRO-JOA, EuroQOL-5D, Neck Disability Index, and Short Form-12 preoperatively and at >12 months postoperatively. Spearman’s rho and Bland-Altman analyses were used to investigate the correlations.

Results:

Preoperative JOA and PRO-JOA scores were 10.8 and 10.6, respectively, with Spearman’s rho of 0.74. Similarly, postoperative JOA and PRO-JOA scores were 13.3 and 12.9, respectively, with Spearman’s rho of 0.68. However, the recovery rates for JOA and PRO-JOA scores were 42% and 27%, respectively, with Spearman’s rho of 0.45. Compared with other PROs, JOA and PRO-JOA scores were moderately correlated. The minimum clinically important difference was 2.5 for JOA score, 3.0 for PRO-JOA score, 42% for JOA recovery rate, and 33% for PRO-JOA recovery rate. Bland-Altman analyses revealed that limits of agreement were −4.3 to 4.7, −3.4 to 4.3, and −75% to 106% for the preoperative score, postoperative score, and recovery rate, respectively.

Conclusion:

PRO-JOA score can also be used as a disease-specific scoring measure instead of JOA score. However, although both measures demonstrate a similar trend as a group analysis, PRO-JOA and JOA scores should be regarded as different outcomes.
Total Hematology Automation
Authors: Palutke Margarita
Published: November 2020

Hitachi and Sysmex corporations combined their efforts to produce an integrated, high through-put laboratory by combining various sections of hematology and chemistry requiring a small fraction of the number of personnel employed.
Do Institutional and Macroeconomic Factors Matter in IT companies M&As? Evidence from India
Authors: Bhasin Niti , Soni Amit , Kar Rabi Narayan
Published: November 2020

The liberalisation of the Indian economy, along with targeted policies of the Indian government for the information technology (IT) sector, has led to tremendous growth in this sector. While there has been substantial foreign investment in India in the IT sector through setting up of subsidiaries, joint ventures and acquisitions, Indian firms have also aggressively invested within and outside India through multiple modes. Among different sectors, the IT sector has been the most dominant in terms of mergers and acquisitions (M&As). This article focuses on host country (macroeconomic and institutional) determinants of M&As undertaken by Indian IT firms. Random effect negative binomial model in panel set up was selected to estimate the models. Four models were estimated as per the availability of data for 35–42 countries and for the period 2000–2015. The results for most of the variables in four models were very similar, reflecting robustness of the methodology. Most of the macroeconomic and institutional factors were found to be important determinants of the M&As by Indian IT companies. However, the economic recession of 2008–2009 was found to significantly reduce the M&A activities by Indian IT companies.
E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies
Authors: Wills Thomas A. , Soneji Samir S. , Choi Kelvin , Jaspers Ilona , Tam Elizabeth K.
Published: November 2020

Background

Use of electronic cigarettes (e-cigarettes) is prevalent among adolescents and young adults, but there has been limited knowledge about health consequences in human populations. We conduct a systematic review and meta-analysis of results on respiratory disorders from studies of general-population samples and consider the mapping of these results to findings about biological processes linked to e-cigarettes in controlled laboratory studies.

Method

We conducted a literature search and meta-analysis of epidemiological studies on the association of e-cigarette use with asthma and with COPD. We discuss findings from laboratory studies about effects of e-cigarettes on four biological processes: cytotoxicity, oxidative stress/inflammation, susceptibility to infection and genetic expression.

Results

Epidemiological studies, both cross-sectional and longitudinal, show a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates. For asthma (n=15 studies), the pooled adjusted odds ratio (aOR) was 1.39 (95% CI 1.28–1.51); for COPD (n=9 studies) the aOR was 1.49 (95% CI 1.36–1.65). Laboratory studies consistently show an effect of e-cigarettes on biological processes related to respiratory harm and susceptibility to illness, with e-cigarette conditions differing significantly from clean-air controls, although sometimes less than for cigarettes.

Conclusions

The evidence from epidemiological studies meets established criteria for consistency, strength of effect, temporality, and in some cases a dose–response gradient. Biological plausibility is indicated by evidence from multiple laboratory studies. We conclude that e-cigarette use has consequences for asthma and COPD, which is of concern for respirology and public health.
The impact of COVID-19 on patients with asthma
Authors: Izquierdo José Luis , Almonacid Carlos , González Yolanda , Del Rio-Bermudez Carlos , Ancochea Julio , Cárdenas Remedios , Lumbreras Sara , Soriano Joan B.
Published: November 2020

Background

An association between the severity of coronavirus disease 2019 (COVID-19) and the presence of certain chronic conditions has been suggested. However, unlike influenza and other viruses, the disease burden of COVID-19 in patients with asthma has been less evident.

Objective

To understand the impact of COVID-19 in patients with asthma.

Methods

Using big-data analytics and artificial intelligence through the SAVANA Manager clinical platform, we analysed clinical data from patients with asthma from January 1 to May 10, 2020.

Results

Out of 71 182 patients with asthma, 1006 (1.41%) suffered from COVID-19. Compared to asthmatic individuals without COVID-19, patients with asthma and COVID-19 were significantly older (55versus42 years), predominantly female (66%versus59%), smoked more frequently and had higher prevalence of hypertension, dyslipidaemias, diabetes and obesity. Allergy-related factors such as rhinitis and eczema were less common in asthmatic patients with COVID-19 (p<0.001). In addition, higher prevalence of these comorbidities was observed in patients with COVID-19 who required hospital admission. The use of inhaled corticosteroids (ICS) was lower in patients who required hospitalisation due to COVID-19, as compared to non-hospitalised patients (48.3%versus61.5%; OR 0.58, 95% CI 0.44–0.77). Although patients treated with biologics (n=865; 1.21%) showed increased severity and more comorbidities at the ear, nose and throat level, COVID-19-related hospitalisations in these patients were relatively low (0.23%).

Conclusion

Patients with asthma and COVID-19 were older and at increased risk due to comorbidity-related factors. ICS and biologics are generally safe and may be associated with a protective effect against severe COVID-19 infection.
The Transcriptome of Cunninghamia lanceolata male/female cone reveal the association between MIKC MADS-box genes and reproductive organs development
Authors: Wang Dandan , Hao Zhaodong , Long Xiaofei , Wang Zhanjun , Zheng Xueyan , Ye Daiquan , Peng Ye , Wu Weihuang , Hu Xiangyang , Wang Guibin , Zheng Renhua , Shi Jisen , Chen Jinhui
Published: November 2020

Background

Cunninghamia lanceolata(Chinese fir), a member of the conifer family Cupressaceae, is one of the most popular cultivated trees for wood production in China. Continuous research is being performed to improveC. lanceolatabreeding values. Given the high rate of seed abortion (one of the reasons being the failure of ovule and pollen development) inC. lanceolata, the proper formation of female/male cones could theoretically increase the number of offspring in future generations. MIKC MADS-box genes are well-known for their roles in the flower/cone development and comprise the typical/atypical floral development model for both angiosperms and gymnosperms.

Results

We performed a transcriptomic analysis to find genes differentially expressed between female and male cones at a single, carefully determined developmental stage, focusing on the MIKC MADS-box genes. We finally obtained 47 unique MIKC MADS-box genes fromC. lanceolataand divided these genes into separate branches. 27 out of the 47 MIKC MADS-box genes showed differential expression between female and male cones, and most of them were not expressed in leaves. Out of these 27 genes, most B-class genes (AP3/PI) were up-regulated in the male cone, whileTM8genes were up-regulated in the female cone. Then, with no obvious overall preference forAG(class C + D) genes in female/male cones, it seems likely that these genes are involved in the development of both cones. Finally, a small number of genes such asGGM7,SVP,AGL15, that were specifically expressed in female/male cones, making them candidate genes for sex-specific cone development.

Conclusions

Our study identified a number of MIKC MADS-box genes showing differential expression between female and male cones inC. lanceolata, illustrating a potential link of these genes withC. lanceolatacone development. On the basis of this, we postulated a possible cone development model forC. lanceolata. The gene expression library showing differential expression between female and male cones shown here, can be used to discover unknown regulatory networks related to sex-specific cone development in the future.
Characterization of poplar growth-regulating factors and analysis of their function in leaf size control
Authors: Wang Jinnan , Zhou Houjun , Zhao Yanqiu , Sun Pengbo , Tang Fang , Song Xueqin , Lu Meng-Zhu
Published: November 2020

Background

Growth-regulating factors (GRFs) are plant-specific transcription factors that control organ size. Nineteen GRF genes were identified in the Populus trichocarpa genome and one was reported to control leaf size mainly by regulating cell expansion. In this study, we further characterize the roles of the other poplar GRFs in leaf size control in a similar manner.

Results

The 19 poplar GRF genes were clustered into six groups according to their phylogenetic relationship with Arabidopsis GRFs. Bioinformatic analysis, degradome, and transient transcription assays showed that 18 poplar GRFs were regulated by miR396, with GRF12b the only exception. The functions of PagGRF6b (Pag, Populus alba × P. glandulosa), PagGRF7a, PagGRF12a, and PagGRF12b, representing three different groups, were investigated. The results show that PagGRF6b may have no function on leaf size control, while PagGRF7a functions as a negative regulator of leaf size by regulating cell expansion. By contrast, PagGRF12a and PagGRF12b may function as positive regulators of leaf size control by regulating both cell proliferation and expansion, primarily cell proliferation.

Conclusions

The diversity of poplar GRFs in leaf size control may facilitate the specific, coordinated regulation of poplar leaf development through fine adjustment of cell proliferation and expansion.
Effectiveness of HPV vaccination against the development of high-grade cervical lesions in young Japanese women
Authors: Shiko Yuki , Konno Ryo , Konishi Hiroshi , Sauvaget Catherine , Ohashi Yasuo , Kakizoe Tadao
Published: November 2020

Background

Although more than 10 years have passed since HPV vaccination was implemented, first as an interim programme (Emergent vaccine promotion programme) in November 2010, followed by incorporating into the National Immunization Programme in April, 2013 and suspended in June 2013, limited studies have investigated the HPV vaccine effectiveness against high-grade cervical lesions in Japan.

Methods

We collected the matched data of the results of cervical biopsy and history of vaccination from the Japan Cancer Society database. The subjects were women aged 20 to 29 years screened for cervical cancer between April, 2015 and March, 2017, and with information on HPV vaccination status. We estimated the relative risk of developing high-grade cervical lesions in vaccinated subjects using Poisson regression as compared to unvaccinated subjects.

Results

Among the 34,281 women screened, 3770 (11.0%) were vaccinated. The prevalence of CIN2+ was statistically significantly lower in the vaccinated women as compared to the unvaccinated women (Vaccine Effectiveness (VE) =76%; RR = 0.24, 95% CI:0.10–0.60). High VE against CIN3+ was also observed (91%; RR = 0.09, 95% CI:0.00–0.42).

Conclusion

Women aged 20–29 years who received at least one dose of HPV vaccine had a significantly lower risk of high-grade cervical lesions than those not vaccinated. In Japan, HPV vaccination should be resumed in order to reduce the incidence of cervical cancer.
Proportion of unplanned pregnancies, their determinants and health outcomes of women delivering at a teaching hospital in Sri Lanka
Authors: Ranatunga Iddamalgoda Dissanayakage Jayani Ch , Jayaratne Kapila
Published: November 2020

Background

Unplanned pregnancy is a significant public health issue in both low- and high-income countries. The burden of unplanned pregnancy is reflected in women opting for pregnancy terminations and it can be detrimental to the women and her family as well as the health system and society. Solid data on the proportion of unplanned pregnancies are using more specific tools such as the London Measure of Unplanned Pregnancy (LMUP) needed to address the issue in Sri Lankan contexts. The objective was to describe the proportion of unplanned pregnancies, their determinants and the health outcomes of women delivering at Colombo North Teaching Hospital-Ragama (CNTH).

Methods

A cross-sectional study was carried out among 494 consecutive pregnant women selected by non-probability consecutive sampling who were admitted for the confinement at CNTH. A pre-tested structured interviewer-administered questionnaire was used to collect data on antenatal women and intentionality measured by self-administered six-item LMUP. Maternal and newborn health outcomes were ascertained in each post-partum women before discharge. Data were analyzed with the Mann-Whitney U tests, Kruskal-Wallis tests and spearman rank correlation. We also evaluated the psychometric properties of the Sinhalese version of LMUP.

Results

The response rate was 97.8 and 17.2% of pregnancies ending at birth were unplanned, 12.7% were ambivalent and 70.1% were planned.

Associated factor profile of women with unplanned pregnancies includes; not married women (p = 0.001), educated up to the passing of GCE ordinary level by women (p <  0.001) and spouse (p <  0.001), primiparity (p = 0.002) and inadequate knowledge on emergency contraceptives (p = 0.037). Less planned pregnancies were also significantly associated with anemia (p = 0.004), low mood for last 2 weeks (p <  0.001), having a partner with problematic alcohol consumption (p <  0.001), presence of Gender-Based Violence (GBV) (p < 0.001), poor relationship satisfaction with partner (p < 0.001) and family (p < 0.001). Inadequate pre-pregnancy preparation and antenatal care were associated with an unplanned pregnancy. No differences were found in neonatal outcomes. Sinhalese version of the LMUP scale was found to be accepted, valid and reliable with the Cronbach’s alpha of 0.936.

Conclusions

A sizeable proportion of pregnancies were unplanned. Teenage pregnancies, non-marital relationships and inadequate knowledge on emergency contraceptives, maternal anemia, low mood, and GBV were modifiable associated factors which could be prevented by evidence-based locally applicable approaches.
Cost-effectiveness analysis of combining traditional Chinese medicine in the treatment of hypertension: compound Apocynum tablets combined with Nifedipine sustained-release tablets vs Nifedipine sustained-release tablets alone
Authors: Xu Qian , Yang Nan , Feng Shuang , Guo Jianfei , Liu Qi-bing , Hu Ming
Published: November 2020

Background

We evaluated the long-term cost-effectiveness of antihypertensive traditional Chinese medicines (TCMs) and to compare the cost-effectiveness of a combined treatment consisting of compound Apocynum tablets and Nifedipine sustained-release tablets with the cost-effectiveness of treatment with Nifedipine sustained-release tablets alone.

Methods

A Markov model was used to simulate the potential incremental cost-effectiveness per quality-adjusted life year (QALY) to be gained from compound Apocynum tablets and Nifedipine sustained-release tablets compared with Nifedipine sustained-release tablets alone. Model parameter estimates were informed by previously published studies. The direct medical costs of outpatients with hypertension were estimated from the health care provider’s perspective. A 5% annual discount rate was applied to both costs and QALYs.

Results

TCMs combined with Nifedipine sustained-release tablets group generated a total 20-year cost of 11,517.94 RMB (US $1739.87), whereas Nifedipine sustained-release tablets alone group resulted in a 20-year cost of 7253.71 RMB (US $1095.73). TCMs combined with Nifedipine sustained-release tablets group resulted in a generation of 12.69 QALYs, whereas Nifedipine sustained-release tablets alone group resulted in 12.50. The incremental cost-utility ratio was 22,443.32 RMB (US $3390.23) per QALY. Considering the threshold of 1 GDP per capita in China in 2018 (US $9764.95), the combination of compound Apocynum tablets and Nifedipine sustained-release tablets was a cost-effective strategy. One-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range.

Conclusions

Combining Traditional Chinese Medicines with chemical medicines is more cost-effective strategy in the treatment of hypertension.
Effects of graded levels of microbial fermented or enzymatically treated dried brewer’s grains on growth, digestive and nutrient transporter genes expression and cost effectiveness in broiler chickens
Authors: Al-Khalaifah Hanan S. , Shahin Sara. E , Omar Anaam E. , Mohammed Haiam A. , Mahmoud Hala. I , Ibrahim Doaa
Published: November 2020

Background

Poultry feed consists mainly of conventional grains and protein supplements, however, using treated unconventional agro-industrial by-products as replacements of corn soybean-based diet can minimize production costs and improve productivity. Therefore, in this study, the effects of fermented or enzymatically treated dried brewer grains (DBG) on growth, expression of digestive enzymes and nutrient transporters genes and the profitability of the rations were evaluated. A total of 1600 one-day-old Ross 308 broiler chicks were randomly distributed in 2 × 4 factorial arrangement (eight treatments with ten replicates, 20 birds/replicate). Experimental diets included two controls; negative control (basal corn-soybean diet;NC) and positive control (basal corn-soybean diet with exogenous enzymes;PC), and six diets in which basal diet was replaced by three levels of fermented DBG (FDBG; 5, 10 or 15%), or enzyme-treated DBG (DBG5, 10 or 15%+Enz), for 38 days.

Results

The results described that feeding FDBG (three levels) or DBG5%+Enz improved (P < 0.05) BW gain and feed efficiency of broilers. Also, feeding FDBG10% yielded the best improvement in weight gain (10%), compared to NC group. Increasing the inclusion levels of DBG either fermented or enzymatically treated up-regulated (p < 0.01) expression of digestive-genes in proventriculus (PGCandPGA5, range 1.4–1.8 fold), pancreas (AMY2A,PNLIP,CELA1, andCCK; range 1.2–2.3 fold) and duodenum (CAT1,CAT2,GLUT1,GLUT2,LAT1,Pep1; range 1.3-3 fold) when compared to NC group. Feeding treated DBG significantly increased (p < 0.05, range 4.5–13.6%) gizzard relative weight compared to NC and PC groups. An additional benefit was lower (p < 0.01) cholesterol content from 66.9 mg/100 mg (NC) to 62.8 mg/100 mg (FDBG5 or 10%) in thigh meat. Furthermore, the least cost feed/kg body gain was achieved in FDBG10% and DBG5%+Enz groups, with approx. 16% reduction compared to NC cost, leading to increasing the income gross margin by 47% and 40% in FDBG10% and DBG5%+Enz groups, respectively.

Conclusions

Substitution of corn-soybean based diet with 10% FDBG or 5% DBG+Enz resulted in better growth and higher economic efficiency of broilers chickens.
The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1
Authors: Kolonko Marta , Bystranowska Dominika , Taube Michał , Kozak Maciej , Bostock Mark , Popowicz Grzegorz , Ożyhar Andrzej , Greb-Markiewicz Beata
Published: November 2020

TheDrosophila melanogasterGerm cell-expressed protein (GCE) is a paralog of the juvenile hormone (JH) receptor - Methoprene tolerant protein (MET). Both proteins mediate JH function, preventing precocious differentiation duringD. melanogasterdevelopment. Despite that GCE and MET are often referred to as equivalent JH receptors, their functions are not fully redundant and show tissue specificity. Both proteins belong to the family of bHLH-PAS transcription factors. The similarity of their primary structure is limited to defined bHLH and PAS domains, while their long C-terminal fragments (GCEC, METC) show significant differences and are expected to determine differences in GCE and MET protein activities. In this paper we present the structural characterization of GCEC as a coil-like intrinsically disordered protein (IDP) with highly elongated and asymmetric conformation. In comparison to previously characterized METC, GCEC is less compacted, contains more molecular recognition elements (MoREs) and exhibits a higher propensity for induced folding. The NMR shifts perturbation experiment and pull-down assay clearly demonstrated that the GCEC fragment is sufficient to form an interaction interface with the ligand binding domain (LBD) of the nuclear receptor Fushi Tarazu factor-1 (FTZ-F1). Significantly, these interactions can force GCEC to adopt more fixed structure that can modulate the activity, structure and functions of the full-length receptor. The discussed relation of protein functionality with the structural data of inherently disordered GCEC fragment is a novel look at this protein and contributes to a better understanding of the molecular basis of the functions of the C-terminal fragments of the bHLH-PAS family.
Pain sensitivity in young adults with juvenile idiopathic arthritis: a quantitative sensory testing study
Authors: Arnstad Ellen Dalen , Iversen Johanne Marie , Uglem Martin , Glerup Mia , Romundstad Pål Richard , Sand Trond , Rygg Marite
Published: November 2020

Background

To study for the first-time, pain perception, pain sensitivity, and self-reported pain in young adults with long disease duration of juvenile idiopathic arthritis (JIA) compared with controls.

Methods

Children from Central Norway diagnosed with JIA between 1997 and 2004 were included consecutively in a population-based prospective study. Children with onset 1997–2000 were part of the Nordic JIA cohort. Controls were age- and sex-matched. In 2015–2017, study visits with investigator-blinded quantitative sensory testing (QST) comprising cold and warm detection thresholds (CDT/WDT), cold and heat pain thresholds (CPT/HPT), pressure pain threshold (PPT), and a suprathreshold heat pain test were performed. We constructed separate multilevel models for each variable of detection and pain thresholds with interaction between groups and site adjusted for the effect of age and sex.

Results

Among 96 young adults with JIA, 71% were female, median age was 22.7 years, disease duration was 16.1 years, and 47% had oligoarticular disease. Among 109 controls, 71% were female, and median age was 23.5 years. Participants with JIA had lower pressure pain thresholds (PPTs) (95% CI) compared to controls, upper limb 888 (846,930) versus 1029 (999,1059) kPa and lower limb 702 (670,734) versus 760 (726,794) kPa. Participants with inactive disease had the lowest PPTs and cold pain thresholds (CPTs), compared to those in remission off medication and those with active disease. Minor differences were found regarding CDT/WDT and CPT/HPT in JIA compared to controls. The median (IQR) temperature needed to evoke pain = 6 on a 0–10 numeric rating scale (NRS) in the suprathreshold heat pain tests were lower in JIA than in controls (46 °C (45–47 °C) versus 47 °C (46–48 °C)). We found no associations between self-reported pain and pain thresholds.

Conclusions

Our results indicate for the first time that young adults with long disease duration of JIA may have altered pain perception and sensitivity compared to controls. A clinical implication may be the importance of early treatment to quickly achieve pain-free remission and avoid long-term pain sensitization.
Cerebral amyloid angiopathy aggravates perivascular clearance impairment in an Alzheimer’s disease mouse model
Authors: Kim Shin Heun , Ahn Ji Hoon , Yang Hyunwoo , Lee Peter , Koh Gou Young , Jeong Yong
Published: November 2020

Cerebral amyloid angiopathy (CAA), defined as the accumulation of amyloid-beta (Aβ) on the vascular wall, is a major pathology of Alzheimer’s disease (AD) and has been thought to be caused by the failure of Aβ clearance. Although two types of perivascular clearance mechanisms, intramural periarterial drainage (IPAD) and the perivascular cerebrospinal fluid (CSF) influx, have been identified, the exact contribution of CAA on perivascular clearance is still not well understood. In this study, we investigated the effect of CAA on the structure and function of perivascular clearance systems in the APP/PS1 transgenic mouse model. To investigate the pathological changes accompanied by CAA progression, the key elements of perivascular clearance such as the perivascular basement membrane, vascular smooth muscle cells (vSMCs), and vascular pulsation were evaluated in middle-aged (7–9 months) and old-aged (19–21 months) mice using in vivo imaging and immunofluorescence staining. Changes in IPAD and perivascular CSF influx were identified by ex vivo fluorescence imaging after dextran injection into the parenchyma or cisterna magna. Amyloid deposition on the vascular wall disrupted the integrity and morphology of the arterial basement membrane. With CAA progression, vascular pulsation was augmented, and conversely, vSMC coverage was decreased. These pathological changes were more pronounced in the surface arteries with earlier amyloid accumulation than in penetrating arteries. IPAD and perivascular CSF influx were impaired in the middle-aged APP/PS1 mice and further aggravated in old age, showing severely impaired tracer influx and efflux patterns. Reduced clearance was also observed in old wild-type mice without changing the tracer distribution pattern in the influx and efflux pathway. These findings suggest that CAA is not merely a consequence of perivascular clearance impairment, but rather a contributor to this process, causing changes in arterial function and structure and increasing AD severity.
Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent
Authors: Shen Yang , Yang Yuan-Qi , Liu Chuan , Yang Jie , Zhang Ji-Hang , Jin Jun , Tan Hu , Yuan Fang-Zheng-Yuan , Ke Jing-Bin , He Chun-Yan , Zhang Lai-Ping , Zhang Chen , Yu Jie , Huang Lan
Published: November 2020

Background

Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS.

Methods

A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO2) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6–8 h after the ascent.

Results

Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P < 0.001), height (168.4 ± 5.9 vs. 171.3 ± 6.1 cm, P = 0.019), weight (62.0 ± 10.0 vs. 66.7 ± 8.6 kg, P = 0.014) and proportion of smokers (23.4% vs. 51.9%, P = 0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR) =6.32, P < 0.001), SpO2 change upon exercise at low altitude (OR = 0.63, P = 0.002) and systolic BP change after the ascent (OR = 0.96, P = 0.029). Women had larger reduction in SpO2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO2 after exercise was associated with both AMS incidence (P = 0.001) and AMS score (P < 0.001) in men but not in women.

Conclusions

Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women.

Trial registration

Chinese Clinical Trial Registration, ChiCTR1900025728. Registered 6 September 2019.
Evaluating the effectiveness of a multi-faceted inpatient diabetes management program among hospitalised patients with diabetes mellitus
Authors: Kao Shih Ling , Chen Ying , Ning Yilin , Tan Maudrene , Salloway Mark , Khoo Eric Yin Hao , Tai E Shyong , Tan Chuen Seng
Published: November 2020

Background

Diabetes mellitus (DM) is one of the most common chronic diseases. Individuals with DM are more likely to be hospitalised and stay longer than those without DM. Inpatient hypoglycemia and hyperglycemia, which are associated with adverse outcomes, are common, but can be prevented through hospital quality improvement programs.

Methods

We designed a multi-faceted intervention program with the aim of reducing inpatient hypoglycemia and hyperglycemia. This was implemented over seven phases between September 2013 to January 2016, and covered all the non-critical care wards in a tertiary hospital. The program represented a pragmatic approach that leveraged on existing resources and infrastructure within the hospital. We calculated glucometric outcomes in June to August 2016 and compared them with those in June to August 2013 to assess the overall effectiveness of the program. We used regression models with generalised estimating equations to adjust for potential confounders and account for correlations of repeated outcomes within patients and admissions.

Results

We observed significant reductions in patient-days affected by hypoglycemia (any glucose reading < 4 mmol/L: OR = 0.71, 95% CI: 0.61 to 0.83, p <  0.001), and hyperglycemia (any glucose reading > 14 mmol/L: OR = 0.84, 95% CI: 0.71 to 0.99, p = 0.041). Similar findings were observed for admission-level hypoglycemia and hyperglycemia. Further analyses suggested that these reductions started to occur four to 6 months post-implementation.

Conclusions

Our program was associated with sustained improvements in clinically relevant outcomes. Our described intervention could be feasibly implemented by other secondary and tertiary care hospitals by leveraging on existing infrastructure and work force.
Functional evaluation of gene mutations in Long QT Syndrome: strength of evidence from in vitro assays for deciphering variants of uncertain significance
Authors: Hancox Jules C. , Stuart Alan G. , Harmer Stephen C.
Published: November 2020

Background

Genetic screening is now commonplace for patients suspected of having inherited cardiac conditions. Variants of uncertain significance (VUS) in disease-associated genes pose problems for the diagnostician and reliable methods for evaluating VUS function are required. Although function is difficult to interrogate for some genes, heritable channelopathies have established mechanisms that should be amenable to well-validated evaluation techniques.

The cellular electrophysiology techniques of ‘voltage-’ and ‘patch-’ clamp have a long history of successful use and have been central to identifying both the roles of genes involved in different forms of congenital Long QT Syndrome (LQTS) and the mechanisms by which mutations lead to aberrant ion channel function underlying clinical phenotypes. This is particularly evident forKCNQ1,KCNH2andSCN5A, mutations in which underlie > 90% of genotyped LQTS cases (the LQT1-LQT3 subtypes). Recent studies utilizing high throughput (HT) planar patch-clamp recording have shown it to discriminate effectively between rare benign and pathological variants, studied through heterologous expression of recombinant channels. In combination with biochemical methods for evaluating channel trafficking and supported by biophysical modelling, patch clamp also provides detailed mechanistic insight into the functional consequences of identified mutations. Whilst potentially powerful, patient-specific stem-cell derived cardiomyocytes and genetically modified animal models are currently not well-suited to high throughput VUS study.

Conclusion

The widely adopted 2015 American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines for the interpretation of sequence variants include the PS3 criterion for consideration of evidence from well-established in vitro or in vivo assays. The wealth of information on underlying mechanisms of LQT1-LQT3 and recent HT patch clamp data support consideration of patch clamp data together (for LQT1 and LQT2) with information from biochemical trafficking assays as meeting the PS3 criterion of well established assays, able to provide ‘strong’ evidence for functional pathogenicity of identified VUS.
Human reliability analysis of bronchoscope-assisted percutaneous dilatational tracheostomy: implications for simulation-based education
Authors: Lavelle Aoife , White Mary , Griffiths Mark J.D. , Byrne Dara , O’Connor Paul
Published: November 2020

Background

Teaching and assessing clinical procedures requires a clear delineation of the individual steps required to successfully complete the procedure. For decades, human reliability analysis (HRA) has been used to identify the steps required to complete technical procedures in higher risk industries. However, the use of HRA is uncommon in healthcare. HRA has great potential supporting simulation-based education (SBE) in two ways: (1) to support training through the identification of the steps required to complete a clinical procedure; and (2) to support assessment by providing a framework for evaluating performance of a clinical procedure. The goal of this study was to use HRA to identify the steps (and the risk associated with each of these steps) required to complete a bronchoscope-assisted percutaneous dilatational tracheostomy (BPDT). BPDT is a potentially high-risk minimally invasive procedure used to facilitate tracheostomy placement at the bedside or in the operating theatre.

Methods

The subgoals, or steps, required to complete the BPDT procedure were identified using hierarchical task analysis. The Systematic Human Error Reduction and Prediction Approach (SHERPA) was then used to identify potential human errors at each subgoal, the level of risk and how these potential errors could be prevented.

Results

The BPDT procedure was broken down into 395 subgoals, of which 18% were determined to be of high-risk. The most commonly identified remediation strategies for reducing the risk of the procedure included: checklist implementation and audit, statutory and mandatory training modules, simulation training, consultant involvement in all procedures, and fostering a safety-focused hospital culture.

Conclusion

This study provides an approach for how to systematically identify the steps required to complete a clinical procedure for both training and assessment. An understanding of these steps is the foundation of SBE. HRA can identify ‘a correct way’ for teaching learners how to complete a technical procedure, and support teachers to give systematic and structured feedback on performance.
Automated, cassette-based isolation and formulation of high-purity [61Cu]CuCl2 from solid Ni targets
Authors: Svedjehed Johan , Kutyreff Christopher J. , Engle Jonathan W. , Gagnon Katherine
Published: November 2020

Background

A need for improved, cassette-based automation of 61Cu separation from irradiated Ni targets was identified given the growing interest in theranostics, and generally lengthy separation chemistries for 64Cu/64Ni, upon which 61Cu chemistry is often based.

Methods

A method for separating 61Cu from irradiated natNi targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated natNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [61Cu]CuCl2, removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions.

Results

61Cu saturation yields of 190 ± 33 MBq/μA from energetically thick natNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4% with an average radiochemical yield of 90.4 ± 3.2% (N = 5). The isolated activity was collected approximately 65 min post end of bombardment in ~ 2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [61Cu]CuCl2 (N = 5) measured 58Co content of (8.3 ± 0.6) × 10− 5% vs. 61Cu by activity, Ni separation factors ≥ (2.2 ± 1.8) × 106, EoB molar activities 85 ± 23 GBq/μmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively.

Conclusion

High purity 61Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64Cu, as demonstrated with a single proof-of-concept 64Ni target production run.
Adapting implementation science for higher education research: the systematic study of implementing evidence-based practices in college classrooms
Authors: Soicher Raechel N. , Becker-Blease Kathryn A. , Bostwick Keiko C. P.
Published: November 2020

Finding better ways to implement effective teaching and learning strategies in higher education is urgently needed to help address student outcomes such as retention rates, graduation rates, and learning. Psychologists contribute to the science and art of teaching and learning in higher education under many flags, including cognitive psychology, science of learning, educational psychology, scholarship of teaching and learning in psychology, discipline-based educational research in psychology, design-based implementation research, and learning sciences. Productive, rigorous collaboration among researchers and instructors helps. However, translational research and practice-based research alone have not closed the translation gap between the research laboratory and the college classroom. Fortunately, scientists and university faculty can draw on the insights of decades of research on the analogous science-to-practice gap in medicine and public health. Health researchers now add to their toolbox of translational and practice-based research the systematic study of the process of implementation in real work settings directly. In this article, we define implementation science for cognitive psychologists as well as educational psychologists, learning scientists, and others with an interest in use-inspired basic cognitive research, propose a novel model incorporating implementation science for translating cognitive science to classroom practice in higher education, and provide concrete recommendations for how use-inspired basic cognitive science researchers can better understand those factors that affect the uptake of their work with implementation science.