bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated model for customer equity estimation based on brand equity
Authors: Qorbani Zahra , Koosha Hamidreza , Bagheri Mohsen
Published: September 2020

Brand equity (BE) and customer equity (CE) are the two crucial and closely linked concepts in marketing research. This research outlines a new conceptual framework to explore the relationship between the critical elements of BE and CE. Furthermore, using marketing activities, the study quantifies the effect of these activities on CE. The value of CE is computed based on a customer lifetime value (CLV) model in which linear, logistic, and beta regression are used to predict BE, customer acquisition, and customer share of wallet, respectively. We conducted an empirical analysis through questionnaires in an elevator company. The results reveal that brand knowledge and brand differentiation positively relate to customer acquisition. Also, for both existing customers and prospects, brand differentiation plays an important role in the share of wallet. The findings also show that marketing activities have a positive and significant impact on brand knowledge and brand differentiation, and consequently, through the mediating role of BE between marketing activities and CE, on customer acquisition and share of wallet.
Can the youth materialism scale be used across different countries and cultures?
Authors: Zawadzka Anna Maria , Nairn Agnes , Lowrey Tina M , Hudders Liselot , Bakir Aysen , Rogers Andrew , Cauberghe Verolien , Gentina Elodie , Li Hua , Spotswood Fiona
Published: September 2020

As global material wealth rises and young people are heavily exposed to advertising across a range of channels, including rapidly developing social media where material goods are flaunted as symbols of a happy and successful lifestyle, materialism levels across the world seem likely to rise. Given consistent research showing the correlation between materialism and low well-being, this gives cause for concern. However, no studies have so far tested whether current measures of youth materialism are generalizable across different countries and cultures. Our article fills this gap by exploring through a range of internal and external validity tests whether the popular Youth Materialism Scale (YMS) can be used with confidence across China, France, Belgium, Poland, the United Kingdom, and the United States. We show that a 5-item version of YMS is invariant across the countries (internal validity) and that it broadly correlates in expected ways with six different theoretically related constructs: Self-Esteem, Life Satisfaction, Attitude to Advertising, Parental Support, TV Use, and Internet Use (external validity). We believe that researchers and policy makers can confidently use this 5-item version of the scale in international contexts.
circUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis
Authors: Yu Jinling , Shen Weida , Xu Jinping , Gong Bo , Gao Beimin , Zhu Jiangfan
Published: September 2020

We previously showed that microRNA-182 (miR-182) might promote cell proliferation and migration in triple-negative breast cancer (TNBC). This study aimed to investigate circular RNAs (circRNAs) that interact with miR-182 and play important roles in TNBC. Thirty patients with TNBC were enrolled. One pair of tumor and adjacent tissue samples (control) were submitted for circRNA sequencing to establish the expression profile of circRNAs. Concomitantly, circRNAs aberrantly expressed between TNBC and control groups were identified, and these differentially expressed circRNAs (DEcircRNAs) were subjected to Gene Ontology and KEGG pathway enrichment analyses, as well as prediction of interactions with miRNAs. The expression levels of 5 circRNAs interacting with miR-182 were validated using qRT-PCR. Associations between the expression of circUSP42 and clinicopathological features and prognosis were evaluated. A total of 825 upregulated and 1127 downregulated DEcircRNAs were identified between tumor and control groups. Upregulated DEcircRNAs were significantly involved in proteoglycans in cancer, and endocytosis. Downregulated DEcircRNAs were involved in the pathway of resistance to EGFR tyrosine kinase inhibitors. Prediction of circRNA-miRNA interactions showed that hsa_circ_0002032, chr6:131973682-132047340+, hsa_circ_0005982, hsa_circ_0007823 (circUSP42), and hsa_circ_0001777 might act as miRNA sponges for miR-182. qRT-PCR showed consistent results with circRNA sequencing data ( P < 0.05). Downregulation of circUSP42 was significantly associated with lymph node metastasis ( P = 0.005) and advanced clinical stage ( P = 0.032). Furthermore, Kaplan-Meier plots showed that low expression of circUSP42 was closely associated with poor outcome (log-rank test, P < 0.001). Our data suggested that dysregulation of circUSP42 might contribute to the development and progression of TNBC.
A Novel Technique of Endoscopic Vein Harvesting With Preserved Perivascular Tissue
Authors: Yoshino Kunihiko , Abe Kohei , Suzuki Koyu , Tamaki Rihito , Mituishi Atusyuki , Yamasaki Manabu , Misumi Hiroyasu
Published: September 2020

The no-touch saphenous vein harvesting technique is considered to be the ideal procedure to achieve the best quality of vein, whereas the endoscopic vein harvesting (EVH) technique is considered to be ideal for decreasing wound complications. We developed a new technique of EVH with perivascular tissue preservation. This procedure was performed by dissecting the immediate anterior and posterior perivascular connective tissues of the saphenous vein followed by cutting approximately 1 cm laterally from the saphenous vein with the use of a harvester (MAQUET Getinge Group, Getinge AB, Göteborg, Sweden). Histopathological examination revealed preserved perivascular tissue and intimal folding.
Proximal Anastomotic Device Malfunction: Salvage Using Alternative Option
Authors: Dulam Vipin , McCarthy Jim , Guvakov Dmitri , Kashem Mohammed A. , Toyoda Yoshiya , Keshavamurthy Suresh
Published: September 2020

Embolic stroke is a major complication of cardiac surgery and there have been multiple methods developed to reduce this risk. Recent technology has produced 2 primary devices for producing a bloodless and clampless field to perform aortocoronary graft anastomosis. We present a case with a Class V aorta, deployment failure of one device after aortic punch, and salvage of the aortotomy with the other device.
Gender Concept, Work Pressure, and Work–Family Conflict
Authors: Wang H. M. , Ma A. L. , Guo T. T.
Published: September 2020

Based on the data of the 2015 China General Social Survey (CGSS), this article empirically analyzed the influence of gender concept, work pressure, and work flexibility on work–family conflict (work interfering family (WIF) and family interfering work (FIW)) from three perspectives (gender, age, and urban and rural areas in China) and tested its significance. The empirical results show that individuals holding the concept of gender inequality produced lower WIF and FIW, which only exists between sexual relations, older working people, and urban and rural areas. Multicultural exchange and integration only made it easier for working people under the age of 30 to accept the concept of gender equality, but it increased their WIF and FIW. Second, with the development of the economy and society of China, the work pressure of workers is the most important factor causing WIF and FIW. Lastly, in order to cope with the pressure of employment and the cost of living, it is difficult to ease the conflict between work and family.
Manufacturing a ring spun slub yarn using multi-channel drafting technique
Authors: Cui Peng , Xue Yuan , Liu Yuexing
Published: September 2020

In this paper, we propose a novel method for manufacturing a ring-spun slub yarn through multi-channel drafting using a computer numerically controlled (CNC) ring spinning frame. Through controlling the speeds of the feeding rollers, the apron rollers and the spindle, we can manipulate the blending ratio, linear density and twist of the spun yarn online, offering more degrees of freedom to configure fibers in the spun yarn. Furthermore, we develop a digital control system in conjunction with a CNC ring spinning machine, in which each CNC ring spinning machine serves as a drone machine that receives commands from a central computer. A self-developed management platform is designed to help the client manage these drone machines via online regulation. At last, a series of experiments are conducted to examine the impact of manufacturing parameters on the structures and properties of slub yarn. We found that the descriptive parameters that affect the breaking force of the slub yarn samples are the slub length, slub distance, slub multiplier, and roving ratio. The parameters that affect the breaking elongation are obtained as the slub length, slub distance, slub multiplier, and twist coefficient.
Dynamical wear prediction along meshing path in mixed lubrication of spiral bevel gears
Authors: Pei Xin , Huang Lu , Pu Wei , Wei Pengchong
Published: September 2020

Surfaces of gears under combined rolling and sliding motions may suffer a complicated wear process due to the transient time-varying effect along the meshing path. In this paper, a methodology for predicting the wear of tooth surfaces is developed for the spiral bevel gears. In the wear model, the machined surface roughness, mixed lubrication, friction, flash temperature and the dynamic behavior of gears are all considered. Tooth-Contact-Analysis (TCA) method is used to get the time-varying parameters of meshing points along the meshing path. By simulating real movement process, the material is removed according to the Arrhenius equation. First, the distribution of pressure and film thickness is obtained by solving the mixed EHL model. After that, the flash temperature can be computed by the point heat source integration method with the obtained pressure, film thickness and velocity vector. The material removal is based on surface temperature and sliding distance. The numerical results are compared to the ball-on-disk experiments to demonstrate the reasonableness of the present wear model. And it shows that the angle difference between velocity vectors has strong influences on the wear profile. Furthermore, the mechanism of surface wear evolution is investigated systematically in spiral bevel gears. The difference of the wear track between the pinion and gear surfaces is observed. Besides, in the meshing process of tooth surface, the wear along the meshing path is uneven, which appears to be much greater at the engaging-in and engaging-out areas. There is a position with maximum wear rate in the meshing process, and the position is affected by the load and speed.
Making memories: Chinese foodscapes, medicinal foods, and generational eating
Authors: Chen Nancy N
Published: September 2020

The availability and abundance of foods in 21st century China have dramatically expanded over the past three decades. Despite the proximity of memories of food insecurity—the intergenerational preparation and sharing of meals continue to mark social identity and belonging. This article explores how contemporary Chinese foodways and medicinal recipes connect with past times as well as convey cultural memory. Two case studies will animate this analysis. The first part of the article will examine the Cuisine Museum in Hangzhou where past coexists with present and future as attendees view displays of specific dishes and grand tables followed by consuming sumptuous meals recreated at the adjoining restaurant. The second half will explore the realms of medicinal foods and recipes that reflect longstanding notions of health that are being promoted in contemporary China. Altogether, these arenas suggest that foodscapes, particularly medicinal foods, offer key assemblages of food memory, time, and wellbeing.
‘Putting heart’ into history and memory: Dialogues with Maya-Tseltal philosopher, Xuno López Intzin
Authors: Hernández Castillo R Aída
Published: September 2020

In this article, the author shares her dialogues with the Maya-Tseltal scholar Xuno López Intzin, to open an analytical window to Non-Western conceptions of memory and time. It focuses on the cyclical conceptualization of time, and the embodied experience of history and memory of Maya peoples in the Chiapas Highlands. This Mayan perspective is explained by Xuno López Intzin, in an analytical dialogue with the author, who questions her own linear ethnohistorial perspectives. It aims to contribute to the decolonization of memory studies by giving an academic platform to this subaltern, nonlinear conception of time and history.
Model-based evaluation of the cost effectiveness of 3 versus 6 months’ adjuvant chemotherapy in high-risk stage II colon cancer patients
Authors: Jongeneel Gabrielle , Greuter Marjolein J. E. , van Erning Felice N. , Koopman Miriam , Vink Geraldine R. , Punt Cornelis J. A. , Coupé Veerle M. H.
Published: September 2020

Background:

Our aim was to evaluate the cost effectiveness of 3 months’ adjuvant chemotherapy versus 6 months in high-risk (T4 stage + microsatellite stable) stage II colon cancer (CC) patients.

Methods:

Using the validated PATTERN Markov cohort model, which simulates the disease progression of stage II CC patients from diagnosis to death, we first evaluated a reference strategy in which high-risk patients were treated with chemotherapy for 6 months. In the second strategy, treatment duration was shortened to 3 months. Both strategies were evaluated for CAPOX (capecitabine plus oxaliplatin) and FOLFOX (fluorouracil, leucovorin and oxaliplatin). Based on trial data, we assumed that shortened treatment duration compared with a 6-month regimen was equally effective for CAPOX and less effective for FOLFOX. Adverse events were highest in the 6-month strategy. Analyses were conducted from a societal perspective using a lifelong time horizon. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Incremental net monetary benefit (iNMB) was calculated using a willingness-to-pay value of €50,000/QALY.

Results:

For CAPOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €41,257 pp. The 3-month strategy resulted in an equal number of CC deaths, but higher QALYs (6.80 pp) and lower costs (€37,645 pp), leading to a iNMB of €8454 per person for 3 months versus 6 months. For FOLFOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €47,135 pp. The 3-month strategy resulted in more CC deaths (393), lower QALYs (6.19 pp) and lower costs (€44,389 pp). An iNMB of −€23,189 was found for 3 months versus 6 months.

Conclusion:

Our findings indicate that 3 months’ adjuvant chemotherapy should be considered as standard of care in high-risk stage II CC patients for CAPOX, but not for FOLFOX.
Recruitment of Shoulder Complex and Torso Stabilizer Muscles With Rowing Exercises Using a Suspension Strap Training System
Authors: Youdas James W. , Kleis Mary , Krueger Erik T. , Thompson Stephen , Walker Whitney A. , Hollman John H.
Published: September 2020

Background:

Suspension training systems, which use body weight resistance under unstable conditions, may be effective for muscle strengthening in persons with scapular dyskinesis or subacromial impingement syndrome.

Hypothesis:

Greater arm, scapular, and trunk muscle recruitment will occur during horizontal abduction row exercises.

Study Design:

Descriptive laboratory study.

Level of Evidence:

Level 5.

Methods:

Surface electromyography data were collected from 28 participants (14 men, 14 women). A total of 13 right-sided muscles were studied at a sampling frequency of 1000 Hz. Maximal voluntary isometric contractions (MVICs) were established. Participants completed 3 repetitions per exercise in random order. We compared muscle recruitment during 3 rowing exercises: low row, high row, and horizontal abduction row. Data were compared with repeated-measures analyses of variance and post hoc Bonferroni corrections.

Results:

For high row and horizontal abduction row conditions, the upper, middle, and lower trapezius and posterior deltoid demonstrated >60% MVIC magnitudes of recruitment, and the upper erector spinae demonstrated 40% to 60% MVIC magnitudes of recruitment, respectively. In contrast, in the low row exercise, 40% to 60% MVIC magnitudes of recruitment were observed only in the middle trapezius, latissimus dorsi, and posterior deltoid.

Conclusion:

With the suspension system, high row and horizontal abduction row exercises promote muscle strengthening (>50% MVIC) in the upper, middle, and lower fibers of the trapezius, posterior deltoid, and upper erector spinae.

Clinical Relevance:

Rowing exercises performed with suspension straps may be recommended for muscle strengthening in patients with scapular dyskinesis and subacromial impingement syndrome as well as for healthy persons in need of enhanced scapular muscle performance.
Being the Voice of Reason Within Your School Community During a Pandemic and Beyond
Authors: Webb Kimberly
Published: September 2020

The voice of a school nurse can be the voice of reason for a school community during a global health crisis. This article briefly examines how school nurses can best use their voices to be both sources of support and agents working against the spread of misinformation. Components of impactful communications will be explored, along with multiple modes of communication. At all times, and especially during unusual health events such as a pandemic, school nurses must create messages that are clear, evidence based, and empathetic toward the school community.
Virtual echocardiography screening tool to differentiate hemodynamic profiles in pulmonary hypertension
Authors: Vaidya Anjali , Golbus Jessica R. , Vedage Natasha A. , Mazurek Jeremy , Raza Farhan , Forfia Paul R.
Published: September 2020

This study validated a novel virtual echocardiography screening tool (VEST), which utilized routinely reported echocardiography parameters to predict hemodynamic profiles in pulmonary hypertension (PH) and identify PH due to pulmonary vascular disease (PHPVD). Direct echocardiography imaging review has been shown to predict hemodynamic profiles in PH; however, routine use often overemphasizes Doppler‐estimated pulmonary artery systolic pressure (PASPDE), which lacks discriminatory power among hemodynamically varied PH subgroups. In patients with PH of varying subtypes at a tertiary referral center, reported echocardiographic findings needed for VEST, including left atrial size, E:e’ and systolic interventricular septal flattening, were obtained. Receiver operating characteristic analyses assessed the predictive performance of VEST vs. PASPDE in identifying PHPVD, which was later confirmed by right heart catheterization. VEST demonstrated far superior discriminatory power than PASPDE in identifying PHPVD. A positive score was 80.0% sensitive and 75.6% specific for PHPVD with an area under the curve of 0.81. PASPDE exhibited poorer discriminatory power with an area under the curve of 0.56. VEST’s strong discriminatory ability remained unchanged when validated in a second cohort from another tertiary center. We demonstrated that this novel VEST using three routine parameters that can be easily extracted from standard echocardiographic reports can successfully capture PH patients with a high likelihood of PHPVD. During the Covid‐19 pandemic, when right heart catheterization and timely access to experts at accredited PH centers may have limited widespread availability, this may assist physicians to rapidly and remotely evaluate PH patients to ensure timely and appropriate care.
Regional development in Amazonas, Peru: science-society interactions for sustainability
Authors: Mick Carola , Fernández María E. , Alvarado Chuqui Cástula , Amasifuen Guerra Carlos A. , Kleiche-Dray Mina , López Minchán Ana Paula , Silva López Jhonsy Omar
Published: September 2020

Scientific-technological knowledge maintains the anthropocentric power-pattern and exploitive attitude with regard to nature, but sustainability science asks for an integration of territorial and decontextualized knowledge systems. Visual participatory methodologies involving diverse local stakeholder facilitate dialogue on environmental and sustainability issues. Inspired by visual ethnography and mediated discourse analysis, the present article uses semiological analysis to reconstruct the depicted narratives on the nature-society system in drawings representing “regional development”. The drawings were elaborated in a series of participatory workshops involving university faculty and students, regional government and non-governmental organizations and farmers from local communities in the northern Amazonian region of Peru. The analysis reveals a prevailing anthropo and technology centered, “colonial” conception of the nature-society system, and a marginalization of alternative narratives. Beyond confirming the potential for visual participatory methods to enhance multi-stakeholder dialogue, it demonstrates how semiological analysis can be used to deepen an understanding of the cultural, organizational and technological constraints facing critical, trans-disciplinary efforts to decolonize the technology-centered, anthropocentric mainstream worldview of nature and society.
Dual-energy CT parameters in correlation to MRI-based apparent diffusion coefficient: evaluation in rectal cancer after radiochemotherapy
Authors: Sauter Andreas P , Kössinger Antonia , Beck Stefanie , Deniffel Dominik , Dapper Hendrik , Combs Stephanie E , Rummeny Ernst J , Pfeiffer Daniela
Published: September 2020

Background

Rectal cancer (RC) is a frequent malignancy for which magnetic resonance imaging (MRI) is the most common and accurate imaging. Iodine concentration (IC) can be quantified with spectral dual-layer computed tomography CT (DL-CT), which could improve imaging of RC, especially for evaluation of response to radiochemotherapy (RCT).

Purpose

To compare a DL-CT system to MRI as the non-invasive imaging gold standard for imaging of RC to evaluate the possibility of a response evaluation with DL-CT.

Material and Methods

Eleven patients who received DL-CT as well as MRI before and after RCT of RC were retrospectively included into this study. For each examination, a region of interest (ROI) was placed within the tumor. For MRI, the mean apparent diffusion coefficient (ADC) was assessed. For DL-CT, IC, z-effective, and Hounsfield Units (HU) were measured. IC, z-effective, and HU were normalized to the aorta. ADC was correlated to absolute and relative normalized IC, z-effective, and HU with Spearman’s ρ. Differences before and after treatment were tested with Wilcoxon signed-rank test.

Results

HU, IC, and Z-effective values in DL-CT images decreased significantly after RCT ( P<0.01 for each comparison). The mean ADC increased significantly after RCT. Spearman’s ρ of the absolute IC difference and the absolute ADC (both before and after RCT) is high and significant (ρ = 0.73; P = 0.01), whereas the ρ-value for z-effective (ρ = 0.56) or HU (ρ = 0.45) to ADC was lower and non-significant.

Conclusion

Response evaluation of RC after RCT could be possible with DL-CT via the measurement of IC.
Usher syndrome: clinical features, molecular genetics and advancing therapeutics
Authors: Toms Maria , Pagarkar Waheeda , Moosajee Mariya
Published: September 2020

Usher syndrome has three subtypes, each being clinically and genetically heterogeneous characterised by sensorineural hearing loss and retinitis pigmentosa (RP), with or without vestibular dysfunction. It is the most common cause of deaf–blindness worldwide with a prevalence of between 4 and 17 in 100 000. To date, 10 causative genes have been identified for Usher syndrome, with MYO7A accounting for >50% of type 1 and USH2A contributing to approximately 80% of type 2 Usher syndrome. Variants in these genes can also cause non-syndromic RP and deafness. Genotype–phenotype correlations have been described for several of the Usher genes. Hearing loss is managed with hearing aids and cochlear implants, which has made a significant improvement in quality of life for patients. While there is currently no available approved treatment for the RP, various therapeutic strategies are in development or in clinical trials for Usher syndrome, including gene replacement, gene editing, antisense oligonucleotides and small molecule drugs.
Engaging with Grand Challenges: An Institutional Logics Perspective
Authors: Gümüsay Ali Aslan , Claus Laura , Amis John
Published: September 2020

The institutional logics perspective has the explanatory power and potential to further contribute to our understanding of some of the most pressing societal concerns of our time. In this article, we develop the logics perspective along four analytical dimensions – macro-level positioning, contextuality, temporality and value plurality – which, we argue, can be leveraged to research and address grand challenges. We elaborate the currency of these dimensions in the context of the grand challenge of climate change. In doing so, we demonstrate the overall value of a logics perspective for engaging grand challenges.
Origin of orthopyroxene-bearing felsic gneiss from the perspective of ultrahigh-temperature metamorphism: an example from the Chilka Lake migmatite complex, Eastern Ghats Belt, India
Authors: Bose Sankar , Das Kaushik , Torimoto Junji , Dunkley Daniel
Published: September 2020

Orthopyroxene-bearing felsic gneiss occurs as foliation-parallel layers and bands together with aluminous granulite, mafic granulite, and quartzofeldspathic granulite in the Chilka Lake migmatite complex of the Proterozoic Eastern Ghats Belt, India. The rock was classified previously as charnockite which underwent granulite-facies metamorphism. Field and textural features of this rock show evidence of the partial melting of a biotite-bearing greywacke protolith. Orthopyroxene with/without garnet and cordierite were produced with K-feldspar as peritectic phases of incongruent melting of presumed metaluminous sediments. Fluid-inclusion data suggest the presence of high-density CO2-rich fluids during peak metamorphism, which are similar to those found in associated aluminous granulite. Whole-rock major and trace element data show wide variability of the source materials whereas REE distributions show enriched LREE and flat HREE patterns. Zircon grains from representative samples show the presence of inherited cores having spot dates (SHRIMP) in the range c. 1790–3270 Ma. The overgrowth on zircon was formed predominantly during c. 780–730 Ma and sporadically during c. 550–520 Ma. Some neoblastic zircons with c. 780–730 Ma ages are also present. U-rich dark zones surrounding cores appear partially metamictised, but spot ages from this zone vary within c. 1000–900 Ma. The <1000 Ma ages represent metamorphism that mirrors the events in associated aluminous granulite. The sources of metaluminous sediments are speculative as the rock compositions are largely modified under granulite-facies metamorphism and partial melting. Considering the accretionary tectonic setting of the Eastern Ghats Belt during the c. 1000–900 Ma time frame, a greywacke-type protolith for the migmatite complex has been proposed.
Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs
Authors: Jouet Agathe , Gaudin Cyril , Badalato Nelly , Allix-Béguec Caroline , Duthoy Stéphanie , Ferré Alice , Diels Maren , Laurent Yannick , Contreras Sandy , Feuerriegel Silke , Niemann Stefan , André Emmanuel , Kaswa Michel K. , Tagliani Elisa , Cabibbe Andrea , Mathys Vanessa , Cirillo Daniela , de Jong Bouke C. , Rigouts Leen , Supply Philip
Published: September 2020

Conventional molecular tests for detectingMycobacterium tuberculosiscomplex (MTBC) drug resistance on clinical samples cover a limited set of mutations. Whole-genome sequencing (WGS) typically requires culture.

Here, we evaluated the Deeplex Myc-TB targeted deep-sequencing assay for prediction of resistance to 13 anti-tuberculous drugs/drug classes, directly applicable on sputum.

With MTBC DNA tests, the limit of detection was 100–1000 genome copies for fixed resistance mutations. Deeplex Myc-TB capturedin silico97.1–99.3% of resistance phenotypes correctly predicted by WGS from 3651 MTBC genomes. On 429 isolates, the assay predicted 92.2% of 2369 first- and second-line phenotypes, with a sensitivity of 95.3% and a specificity of 95.0% (95.4% and 97.1%, respectively, when excluding ethionamide). 83 out of 102 (81.4%) residual discrepancies with phenotypic results involved pyrazinamide, ethambutol and ethionamide, and low-level rifampicin or isoniazid resistance mutations, all notoriously prone to phenotypic testing variability. Only two out of 96 (2.1%) resistance phenotypes undetected by Deeplex Myc-TB had known resistance-associated mutations by WGS analysis outside Deeplex Myc-TB targets. Phenotype predictions from Deeplex Myc-TB analysis directly on 109 sputa from a Djibouti survey matched those of MTBSeq/PhyResSE/Mykrobe, fed with WGS data from subsequent cultures, with a sensitivity of 93.5/98.5/93.1% and a specificity of 98.5/97.2/95.3%, respectively. Most residual discordances involved gene deletions/indels and 3–12% heteroresistant calls undetected by WGS analysis or natural pyrazinamide resistance of globally rare “Mycobacterium canettii” strains then unreported by Deeplex Myc-TB. On 1494 arduous sputa from a Democratic Republic of the Congo survey, 14 902 out of 19 422 (76.7%) possible susceptible or resistance phenotypes could be predicted culture-free.

Deeplex Myc-TB may enable fast, tailored tuberculosis treatment.
Comparison of ciliary beat frequencies at different temperatures in young adults
Authors: Nikolaizik Wilfried , Hahn Jana , Bauck Monika , Weber Stefanie
Published: September 2020

Rationale

Direct visualisation of ciliary beat pattern (CBP) and ciliary beat frequency (CBF) has been recommended as the first-line diagnostic test in patients suspected of having primary ciliary dyskinesia (PCD). However, the test procedure is not yet completely standardised, and centres measure the CBF at different temperatures.

Objectives

It was the aim of the study to compare CBF at different temperatures, to establish normative values, to check for age dependency and to measure the temperature on the nasal mucosa of the participants.

Methods

High-speed video-microscopy analysis with a Sisson-Ammons Video Analysis (SAVA) system was used to determine CBP and CBF in the participants.

Measurements

Nasal brushings were taken and CBF was measured in randomised order at three temperatures: 25°C, 32°C and 37°C.

Main results

In total, 100 healthy young adults (74 female, 26 male), aged 20.2–31.9 years, were included in the study. We found a highly significant difference among the groups: the median CBF was 7.0 Hz at 25°C, 7.6 Hz at 32°C and 8.0 Hz at 37°C. The maximum time periodex vivowas 65 min and did not differ significantly. However, CBF was significantly higher when the cilia were kept at a higher temperature before the measurements were made. We found no correlation between CBF and the age of the participants. The median nasal mucosal temperature in our study participants was 30.2°C (range 24.7–35.8°C) comparable to the 30.2–34.4°C described in the literature.

Conclusions

The most appropriate temperature at which to measure CBF is 32°C. In our study, with 95% confidence for this temperature the CBF was between 6.3 and 9.0 Hz.
Explicit representation of protein activity states significantly improves causal discovery of protein phosphorylation networks
Authors: Liu Jinling , Ma Xiaojun , Cooper Gregory F. , Lu Xinghua
Published: September 2020

Background

Protein phosphorylation networks play an important role in cell signaling. In these networks, phosphorylation of a protein kinase usually leads to its activation, which in turn will phosphorylate its downstream target proteins. A phosphorylation network is essentially a causal network, which can be learned by causal inference algorithms. Prior efforts have applied such algorithms to data measuring protein phosphorylation levels, assuming that the phosphorylation levels represent protein activity states. However, the phosphorylation status of a kinase does not always reflect its activity state, because interventions such as inhibitors or mutations can directly affect its activity state without changing its phosphorylation status. Thus, when cellular systems are subjected to extensive perturbations, the statistical relationships between phosphorylation states of proteins may be disrupted, making it difficult to reconstruct the true protein phosphorylation network. Here, we describe a novel framework to address this challenge.

Results

We have developed a causal discovery framework that explicitly represents the activity state of each protein kinase as an unmeasured variable and developed a novel algorithm called “InferA” to infer the protein activity states, which allows us to incorporate the protein phosphorylation level, pharmacological interventions and prior knowledge. We applied our framework to simulated datasets and to a real-world dataset. The simulation experiments demonstrated that explicit representation of activity states of protein kinases allows one to effectively represent the impact of interventions and thus enabled our framework to accurately recover the ground-truth causal network. Results from the real-world dataset showed that the explicit representation of protein activity states allowed an effective and data-driven integration of the prior knowledge by InferA, which further leads to the recovery of a phosphorylation network that is more consistent with experiment results.

Conclusions

Explicit representation of the protein activity states by our novel framework significantly enhances causal discovery of protein phosphorylation networks.
Global variation of risk thresholds for initiating statins for primary prevention of cardiovascular disease: a benefit-harm balance modelling study
Authors: Yebyo Henock G. , Zappacosta Sofia , Aschmann Hélène E. , Haile Sarah R. , Puhan Milo A.
Published: September 2020

Background

We previously showed that the 10-year cardiovascular disease (CVD) risk threshold to initiate statins for primary prevention depends on the baseline CVD risk, age, sex, and the incidence of statin-related harm outcome and competing risk for non-CVD death. As these factors appear to vary across countries, we aimed in this study to determine country-specific thresholds and provide guidelines a quantitative benefit-harm assessment method for local adaptation.

Methods

For each of the 186 countries included, we replicated the benefit-harm balance analysis using an exponential model to determine the thresholds to initiate statin use for populations aged 40 to 75 years, with no history of CVD. The analyses took data inputs from a priori studies, including statin effect estimates (network meta-analysis), patient preferences (survey), and baseline incidence of harm outcomes and competing risk for non-CVD (global burden of disease study). We estimated the risk thresholds above which the benefits of statins were more likely to outweigh the harms using a stochastic approach to account for statistical uncertainty of the input parameters.

Results

The 5thand 95thpercentiles of the 10-year risk thresholds above which the benefits of statins outweigh the harms across 186 countries ranged between 14 and 20% in men and 19–24% in women, depending on age (i.e., 90% of the country-specific thresholds were in the ranges stated). The median risk thresholds varied from 14 to 18.5% in men and 19 to 22% in women. The between-country variability of the thresholds was slightly attenuated when further adjusted for age resulting, for example, in a 5thand 95thpercentiles of 14–16% for ages 40–44 years and 17–21% for ages 70–74 years in men. Some countries, especially the islands of the Western Pacific Region, had higher thresholds to achieve net benefit of statins at 25–36% 10-year CVD risks.

Conclusions

This extensive benefit-harm analysis modeling shows that a single CVD risk threshold, irrespective of age, sex and country, is not appropriate to initiate statin use globally. Instead, countries need to carefully determine thresholds, considering the national or subnational contexts, to optimize benefits of statins while minimizing related harms and economic burden.
Effect of cholesterol re-supplementation and atorvastatin on plaque composition in the thoracic aorta of New Zealand white rabbits
Authors: Bonaterra G. A. , Bender K. , Wilhelm B. , Schwarzbach H. , Metz S. , Kelber O. , Weiser D. , Metz J. , Kinscherf R.
Published: September 2020

Background

Effects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date.

Methods

A group of rabbits received standard chow (SC) for 6 weeks (“negative control”; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified.

Results

After CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1+) and apoptotic (TUNEL+; TP53+), antigen-presenting (HLA-DR+) or oxidatively stressed (SOD2+) cells.

Conclusions

In rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.
Prevalence and characteristics of older adults with a persistent death wish without severe illness: a large cross-sectional survey
Authors: Hartog Iris D. , Zomers Margot L. , van Thiel Ghislaine J. M. W. , Leget Carlo , Sachs Alfred P. E. , Uiterwaal Cuno S. P. M. , van den Berg Vera , van Wijngaarden Els
Published: September 2020

Background

Some older persons develop a persistent death wish without being severely ill, often referred to as “completed life” or “tiredness of life”. In the Netherlands and Belgium, the question whether these persons should have legal options for euthanasia or physician-assisted suicide (EAS) is intensely debated. Our main aim was to investigate the prevalence and characteristics of older adults with a persistent death wish without severe illness, as the lack of this knowledge is a crucial problem in de debate.

Methods

We conducted a survey among a representative sample of 32,477 Dutch citizens aged 55+, comprising questions about health, existential issues and the nature of the death wish. Descriptive statistics were used to describe the group with a persistent death wish and no severe illness (PDW-NSI) and several subgroups.

Results

A total of 21,294 respondents completed the questionnaire (response rate 65.6%). We identified 267 respondents (1.25%) as having a persistent death wish and no severe illness (PDW-NSI). PDW-NSI did not only occur among the oldest old. Although qualifying themselves as “not severely ill”, those with PDW-NSI reported considerable health problems. A substantial minority of the PDW-NSI-group reported having had a death wish their whole lives. Within the group PDW-NSI 155 (0.73%) respondents had an active death wish, of which 36 (0.17% of the total response) reported a wish to actually end their lives. Thus, a death wish did not always equal a wish to actually end one’s life. Moreover, the death wishes were often ambiguous. For example, almost half of the PDW-NSI-group (49.1%) indicated finding life worthwhile at this moment.

Conclusions

The identified characteristics challenge the dominant “completed life” or “tiredness of life” image of healthy persons over the age of 75 who, overseeing their lives, reasonably decide they would prefer to die. The results also show that death wishes without severe illness are often ambiguous and do not necessarily signify a wish to end one’s life. It is of great importance to acknowledge these nuances and variety in the debate and in clinical practice, to be able to adequately recognize the persons involved and tailor to their needs.
Enterobacter cloacae colonisation and infection in a neonatal intensive care unit: retrospective investigation of preventive measures implemented after a multiclonal outbreak
Authors: Ferry Alexandrine , Plaisant Frank , Ginevra Christophe , Dumont Yann , Grando Jacqueline , Claris Olivier , Vandenesch François , Butin Marine
Published: September 2020

Background

Enterobacter cloacae species is responsible for nosocomial outbreaks in vulnerable patients in neonatal intensive care units (NICU). The environment can constitute the reservoir and source of infection in NICUs. Herein we report the impact of preventive measures implemented after an Enterobacter cloacae outbreak inside a NICU.

Methods

This retrospective study was conducted in one level 3 NICU in Lyon, France, over a 6 year-period (2012–2018). After an outbreak of Enterobacter cloacae infections in hospitalized neonates in 2013, several measures were implemented including intensive biocleaning and education of medical staff. Clinical and microbiological characteristics of infected patients and evolution of colonization/infection with Enterobacter spp. in this NICU were retrieved. Moreover, whole genome sequencing was performed on 6 outbreak strains.

Results

Enterobacter spp. was isolated in 469 patients and 30 patients developed an infection including 2 meningitis and 12 fatal cases. Preventive measures and education of medical staff were not associated with a significant decrease in patient colonisation but led to a persistent decreased use of cephalosporin in the NICU. Infection strains were genetically diverse, supporting the hypothesis of multiple hygiene defects rather than the diffusion of a single clone.

Conclusions

Grouped cases of infections inside one setting are not necessarily related to a single-clone outbreak and could reveal other environmental and organisational problematics. The fight against implementation and transmission of Enterobacter spp. in NICUs remains a major challenge.
Influences on NHS Health Check behaviours: a systematic review
Authors: Atkins Lou , Stefanidou Chryssa , Chadborn Tim , Thompson Katherine , Michie Susan , Lorencatto Fabi
Published: September 2020

Background

National Health Service Health Checks were introduced in 2009 to reduce cardiovascular disease (CVD) risks and events. Since then, national evaluations have highlighted the need to maximise the programme’s impact by improving coverage and outputs. To address these challenges it is important to understand the extent to which positive behaviours are influenced across the NHS Health Check pathway and encourage the promotion or minimisation of behavioural facilitators and barriers respectively. This study applied behavioural science frameworks to: i) identify behaviours and actors relevant to uptake, delivery and follow up of NHS Health Checks and influences on these behaviours and; ii) signpost to example intervention content.

Methods

A systematic review of studies reporting behaviours related to NHS Health Check-related behaviours of patients, health care professionals (HCPs) and commissioners. Influences on behaviours were coded using theory-based models: COM-B and Theoretical Domains Framework (TDF). Potential intervention types and behaviour change techniques (BCTs) were suggested to target key influences.

Results

We identified 37 studies reporting nine behaviours and influences for eight of these. The most frequently identified influences were physical opportunity including HCPs having space and time to deliver NHS Health Checks and patients having money to adhere to recommendations to change diet and physical activity. Other key influences were motivational, such as beliefs about consequences about the value of NHS Health Checks and behaviour change, and social, such as influences of others on behaviour change. The following techniques are suggested for websites or smartphone apps: Adding objects to the environment, e.g. provide HCPs with electronic schedules to guide timely delivery of Health Checks to target physical opportunity, Social support (unspecified), e.g. include text suggesting patients to ask a colleague to agree in advance to join them in taking the ‘healthy option’ lunch at work; Information about health consequences, e.g. quotes and/or videos from patients talking about the health benefits of changes they have made.

Conclusions

Through the application of behavioural science we identified key behaviours and their influences which informed recommendations for intervention content. To ascertain the extent to which this reflects existing interventions we recommend a review of relevant evidence.
Community health workers impact on maternal and child health outcomes in rural South Africa – a non-randomized two-group comparison study
Authors: le Roux Karl W. , Almirol Ellen , Rezvan Panteha Hayati , le Roux Ingrid M. , Mbewu Nokwanele , Dippenaar Elaine , Stansert-Katzen Linnea , Baker Venetia , Tomlinson Mark , Rotheram-Borus M. J.
Published: September 2020

Background

Home visits by paraprofessional community health workers (CHWs) has been shown to improve maternal and child health outcomes in research studies in many countries. Yet, when these are scaled or replicated, efficacy disappears. An effective CHW home visiting program in peri-urban Cape Town found maternal and child health benefits over the 5 years point but this study examines if these benefits occur in deeply rural communities.

Methods

A non-randomized, two-group comparison study evaluated the impact of CHW in the rural Eastern Cape from August 2014 to May 2017, with 1310 mother-infant pairs recruited in pregnancy and 89% were reassessed at 6 months post-birth.

Results

Home visiting had limited, but important effects on child health, maternal wellbeing and health behaviors. Mothers reported fewer depressive symptoms, attended more antenatal visits and had better baby-feeding practices. Intervention mothers were significantly more likely to exclusively breastfeed for 6 months (OR: 1.8; 95% CI: 1.1, 2.9), had lower odds of mixing formula with baby porridge (regarded as detrimental) (OR: 0.4; 95% CI: 0.2, 0.8) and were less likely to consult traditional healers. Mothers living with HIV were more adherent with co-trimoxazole prophylaxis (p < 0.01). Intervention-group children were significantly less likely to be wasted (OR: 0.5; 95% CI 0.3–0.9) and had significantly fewer symptoms of common childhood illnesses in the preceding two weeks (OR: 0.8; 95% CI: 0.7,0.9).

Conclusion

The impact of CHWs in a rural area was less pronounced than in peri-urban areas. CHWs are likely to need enhanced support and supervision in the challenging rural context.