bluuebunny/crossref_metadata_2025_split huggingface dataset:
KASP: a genotyping method to rapid identification of resistance in Plasmodium falciparum
Authors: Alvarez-Fernandez Ana , Bernal María J. , Fradejas Isabel , Martin Ramírez Alexandra , Md Yusuf Noor Azian , Lanza Marta , Hisam Shamilah , Pérez de Ayala Ana , Rubio José M. 
Published: January 2021

Abstract
Background
The emergence and spread of anti-malarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known anti-malarials. This anti-malarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorphisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programmes. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum.

Methods
Three SNPs involved in most cases of resistance to the most widespread anti-malarial treatments have been analysed by PCR plus sequencing and by KASP (C580Y of the Kelch13 gene, Y86N of the Pfmdr1 gene and M133I of the Pfcytb gene). A total of 113 P. falciparum positive samples and 24 negative samples, previously analysed by PCR and sequencing, were selected for this assay. Likewise, the samples were genotyped for the MSP-1 and MSP-2 genes, and the Multiplicity of Infection (MOI) and parasitaemia were measured to observe their possible influence on the KASP method.

Results
The KASP results showed the same expected mutations and wild type genotypes as the reference method, with few exceptions that correlated with very low parasitaemia samples. In addition, two cases of heterozygotes that had not been detected by sequencing were found. No correlation was found between the MOI or parasitaemia and the KASP values of the sample. The reproducibility of the technique shows no oscillations between repetitions in any of the three SNPs analysed.

Conclusions
The KASP assays developed in this study were efficient and versatile for the determination of the Plasmodium genotypes related to resistance. The method is simple, fast, reproducible with low cost in personnel, material and equipment and scalable, being able to core KASP arrays, including numerous SNPs, to complete the main pattern of mutations associated to P. falciparum resistance.
Radiofrequency ablation combined with conductive fluid-based dopants (saline normal and colloidal gold): computer modeling and ex vivo experiments
Authors: Castro-López Dora Luz , Berjano Enrique , Romero-Mendez Ricardo 
Published: January 2021

Abstract
Background
The volume of the coagulation zones created during radiofrequency ablation (RFA) is limited by the appearance of roll-off. Doping the tissue with conductive fluids, e.g., gold nanoparticles (AuNPs) could enlarge these zones by delaying roll-off. Our goal was to characterize the electrical conductivity of a substrate doped with AuNPs in a computer modeling study and ex vivo experiments to investigate their effect on coagulation zone volumes.

Methods
The electrical conductivity of substrates doped with normal saline or AuNPs was assessed experimentally on agar phantoms. The computer models, built and solved on COMSOL Multiphysics, consisted of a cylindrical domain mimicking liver tissue and a spherical domain mimicking a doped zone with 2, 3 and 4 cm diameters. Ex vivo experiments were conducted on bovine liver fragments under three different conditions: non-doped tissue (ND Group), 2 mL of 0.9% NaCl (NaCl Group), and 2 mL of AuNPs 0.1 wt% (AuNPs Group).

Results
The theoretical analysis showed that adding normal saline or colloidal gold in concentrations lower than 10% only modifies the electrical conductivity of the doped substrate with practically no change in the thermal characteristics. The computer results showed a relationship between doped zone size and electrode length regarding the created coagulation zone. There was good agreement between the ex vivo and computational results in terms of transverse diameter of the coagulation zone.

Conclusions
Both the computer and ex vivo experiments showed that doping with AuNPs can enlarge the coagulation zone, especially the transverse diameter and hence enhance sphericity.
Comparison of out-of-pocket expenditure and catastrophic health expenditure for severe disease by the health security system: based on end-stage renal disease in South Korea
Authors: Shin Sun Mi , Lee Hee Woo 
Published: January 2021

Abstract
Background
Korea’s health security system named the National Health Insurance and Medical Aid has revolutionized the nation’s mandatory health insurance and continues to reduce excessive copayments. However, few studies have examined healthcare utilization and expenditure by the health security system for severe diseases. This study looked at reverse discrimination regarding end-stage renal disease by the National Health Insurance and Medical Aid.

Methods
A total of 305 subjects were diagnosed with end-stage renal disease in the Korea Health Panel from 2008 to 2013. Chi-square, t-test, and ANCOVA were conducted to identify the healthcare utilization rate, out-of-pocket expenditure, and the prevalence of catastrophic expenditure. Mixed effect panel analysis was used to evaluate total out-of-pocket expenditure by the National Health Insurance and Medical Aid over a 6-year period.

Results
There were no significant differences in the healthcare utilization rate for emergency room visits, admissions, or outpatient department visits between the National Health Insurance and Medical Aid because these healthcare services were essential for individuals with serious diseases, such as end-stage renal disease. Meanwhile, each out-of-pocket expenditure for an admission and the outpatient department by the National Health Insurance was 2.6 and 3.1 times higher than that of Medical Aid (P < 0.05). The total out-of-pocket expenditure, including that for emergency room visits, admission, outpatient department visits, and prescribed drugs, was 2.9 times higher for the National Health Insurance than Medical Aid (P < 0.001). Over a 6-year period, in terms of total of out-of-pocket expenditure, subjects with the National Health Insurance spent more than those with Medical Aid (P < 0.01). If the total household income decile was less than the median and subjects were covered by the National Health Insurance, the catastrophic health expenditure rate was 92.2%, but it was only 58.8% for Medical Aid (P < 0.001).

Conclusion
Individuals with serious diseases, such as end-stage renal disease, can be faced with reverse discrimination depending on the type of insurance that is provided by the health security system. It is necessary to consider individuals who have National Health Insurance but are still poor.
A critical narrative inquiry to understand the impacts of an overdose prevention site on the lives of site users
Authors: Oudshoorn Abe , Sangster Bouck Michelle , McCann Melissa , Zendo Shamiram , Berman Helene , Banninga Jordan , Le Ber Marlene Janzen , Zendo Zayya 
Published: January 2021

Abstract
Background
Globally, communities are struggling to gain support for harm reduction strategies being implemented to address the impacts of substance use. A key part of this discussion is understanding and engaging with people who use drugs to help shape community harm reduction strategies. This study focused on how an overdose prevention site has influenced the lives of people who use drugs.

Methods
A critical narrative method was utilized, centred on photo-narratives. Twenty-seven individuals accessing an overdose prevention site were recruited to participate in preliminary interviews. Sixteen participants subsequently took photographs to describe the impact of the site and participated in a second round of interviews. Through independent coding and several rounds of team analysis, four themes were proposed to constitute a core narrative encompassing the diverse experiences of participants.

Results
A key message shared by participants was the sense that their lives have improved since accessing the site. The core narrative proposed is presented in a series of four themes or “chapters”: Enduring, Accessing Safety, Connecting and Belonging, and Transforming. The chapters follow a series of transitions, revealing a journey that participants presented through their own eyes: one of moving from utter despair to hope, opportunity, and inclusion. Where at the outset participants were simply trying to survive the challenges of chaotic substance use, through the relationships and services provided at the site they moved towards small or large life transformations.

Conclusions
This study contributes to an enhanced understanding of how caring relationships with staff at the overdose prevention site impacted site users’ sense of self. We propose that caring relationships are an intervention in and of themselves, and that these relationships contribute to transformation that extends far beyond the public health outcomes of disease reduction. The caring relationships at the site can be a starting point for significant social changes. However, the micro-environment that existed within the site needs to extend beyond its walls for true transformative change to take place. The marginalization and stigmatization that people who use drugs experience outside these sites remains a constant barrier to achieving stability in their lives.
Patients’ and clinicians’ perspectives on item importance, scoring, and clinically meaningful differences for the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS)
Authors: Kitchen Helen , Seitz Christian , Trigg Andrew , Aldhouse Natalie , Willgoss Thomas , Schmitz Heinz , Gater Adam , Gerlinger Christoph , Haberland Claudia 
Published: January 2021

Abstract
Background
The Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS) are patient-reported outcome measures developed to evaluate efficacy in clinical trials and clinical practice. The ESD is a daily electronic diary assessing symptom severity; the EIS is a weekly electronic diary assessing symptom impact. This study explored the importance of symptoms (ESD items) and impacts (EIS domains), perspectives on scoring algorithms, and clinically important difference (CID) thresholds to inform clinical trial score interpretation.

Methods
Endometriosis patients in Germany (n = 8) and the US (n = 17), and expert clinicians (n = 4) in Germany, the US, Spain, and Finland participated in semi-structured qualitative interviews comprising structured tasks. Interview transcripts were analyzed using thematic analysis techniques.

Results
Quality and severity of endometriosis-associated pelvic pain varied considerably among patients; some experienced pelvic pain daily, others during menstrual bleeding (dysmenorrhea) only. Patients and clinicians ranked “worst pelvic pain” as the most meaningful pain concept assessed by the ESD, followed by constant and short-term pelvic pain. Preferences for summarizing daily pain scores over the 28-day menstrual cycle depended on individuals’ experience of pain: patients experiencing pain daily preferred scores summarizing data for all 28 days; patients primarily experiencing pain during selected days, and their treating clinicians preferred scores based on the most severe pain days. Initial CID exploration for the “worst pelvic pain” 0–10 numerical rating scale (0–10 NRS) revealed that, for most patients, a 2- or 3-point reduction was considered meaningful, depending on baseline severity. Patients and clinicians ranked “emotional well-being” and “limitations in physical activities” as the most important EIS domains.

Conclusions
This study informs the use of the ESD and EIS as clinically relevant measures of endometriosis symptoms and their impact. Findings from the ESD highlight the importance of individual-patient assessment of pain experience and identify “worst pelvic pain” as the most meaningful symptom assessed. Aggregating scores over the 28-day menstrual cycle may inform meaningful endpoints for clinical trials. Diverse EIS concepts (e.g. impact on emotional well-being and physical activities) are meaningful to patients and clinicians, emphasizing the importance of evaluating the impact on both to comprehensively assess treatment efficacy and decisions.

Trial registration

Not applicable. Qualitative, non-interventional study; registration not required.
Lifestyle-related behaviors and health-related quality of life among children and adolescents in China
Authors: Qin Zhenzhen , Wang Na , Ware Robert S. , Sha Yugen , Xu Fei 
Published: January 2021

Abstract
Purpose
To investigate associations of five typical lifestyle-related behavioral risk factors (insufficient physical activity, prolonged screen viewing, deprived sleeping, consumption of fast food and sugar-sweetened beverage) with health-related quality of life (HRQoL) among school students in China.

Methods
Students aged 9–17 years (grades 4–12) were randomly selected from primary and high schools in Nanjing, China, to participate in this cross-sectional study in 2018. The outcome variable, HRQoL, was assessed using the Child Health Utility 9D (CHU9D) instrument and scored from 0 (worst) to 1 (best). Physical activity (including screen viewing and sleeping) and dietary intake were measured using a validated Physical Activity Scale and Food Frequency Questionnaire, respectively. Lifestyle-related behaviors were categorized as sufficient/insufficient or no/yes, and their associations with HRQoL were assessed using mixed-effects linear regression models.

Results
Overall, 4388 participants completed the questionnaire (response rate = 97.6%). Students with insufficient physical activity [mean difference (MD) = − 0.03; 95% confidence interval (CI) = − 0.04, − 0.01], prolonged screen time (MD = − 0.06; 95% CI = − 0.07, − 0.04), insufficient sleeping time (MD = − 0.04; 95% CI = − 0.07, − 0.02), consumption of sugar-sweetened beverage (MD = − 0.02; 95% CI = − 0.03, − 0.01) or fast food intake (MD = − 0.03; 95% CI = − 0.04, − 0.02) reported significantly lower HRQoL scores. When considered additively, each additional lifestyle-related risk factor was associated with an average decrease of 0.03 units (95% CI: − 0.03, − 0.02) CHU9D score.

Conclusions
For Chinese students, HRQoL was positively associated with physical activity and sleep duration, but negatively with screen time and consumption of sugar-sweetened beverage and fast food. Moreover, lifestyle-related behaviors may have an additive effect on HRQoL.
Response shift in health-related quality of life measures in the presence of formative indicators
Authors: Testa Silvia , Di Cuonzo Daniela , Ritorto Giuliana , Fanchini Laura , Bustreo Sara , Racca Patrizia , Rosato Rosalba 
Published: January 2021

Abstract
Background
Response shift (RS) has been defined as a change in the meaning of an individual’s self-evaluation that needs to be accounted for when assessing longitudinal changes in health-related quality of life (HRQoL). RS detection through structural equation modeling is accomplished by adopting Oort’s procedure based on a measurement model in which the observed variables are defined as reflective indicators of the HRQoL latent variable; that is, the latent variable causes the variation in the reflective indicators. This study aims to propose a procedure that assesses RS when formative indicators are used in measuring HRQoL; in this last case, the latent variable is considered to be a function of some formative indicators. A secondary aim is to compare the new procedure with Oort’s procedure to highlight similarities and differences.

Methods
The data were retrieved from a consecutive series of 258 patients newly diagnosed with colorectal cancer and undergoing chemotherapy and/or surgery. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QOL-C30) was administered twice, once before and once six months after treatment. Structural equation modeling was used to evaluate RS and true change with the newly proposed method (in which fatigue and pain were defined as formative indicators) and with Oort’s procedure (in which fatigue and pain were defined as reflective indicators).

Results
According to the new procedure, there was no measurement bias, and on average, patients’ quality of life improved by 3.53 points (on a scale ranging from 0 to 100) at the 6-month follow-up. With Oort’s procedure, the loading of the pain indicator was not invariant across the two time points, suggesting the presence of reprioritization, whereas the estimation of true change was very similar to the previous one: 3.87.

Conclusions
RS and true change in HRQoL can be evaluated in the presence of formative indicators. Defining a measurement model by formative or reflective indicators can lead to different results.
Human T-cell leukaemia virus type 1 associated pulmonary disease: clinical and pathological features of an under-recognised complication of HTLV-1 infection
Authors: Einsiedel Lloyd , Chiong Fabian , Jersmann Hubertus , Taylor Graham P. 
Published: January 2021

AbstractThe lung is one of several organs that can be affected by HTLV-1 mediated inflammation. Pulmonary inflammation associated with HTLV-1 infection involves the interstitium, airways and alveoli, resulting in several clinical entities including interstitial pneumonias, bronchiolitis and alveolitis, depending on which structures are most affected. Augmentation of the inflammatory effects of HTLV-1 infected lymphocytes by recruitment of other inflammatory cells in a positive feedback loop is likely to underlie the pathogenesis of HTLV-1 associated pulmonary disease, as has been proposed for HTLV-1 associated myelopathy. In contrast to the conclusions of early case series, HTLV-1 associated pulmonary disease can be associated with significant parenchymal damage, which may progress to bronchiectasis where this involves the airways. Based on our current understanding of HTLV-1 associated pulmonary disease, diagnostic criteria are proposed.
Shoulder kinematics plus contextual target information enable control of multiple distal joints of a simulated prosthetic arm and hand
Authors: Mick Sébastien , Segas Effie , Dure Lucas , Halgand Christophe , Benois-Pineau Jenny , Loeb Gerald E. , Cattaert Daniel , de Rugy Aymar 
Published: January 2021

Abstract
Background
Prosthetic restoration of reach and grasp function after a trans-humeral amputation requires control of multiple distal degrees of freedom in elbow, wrist and fingers. However, such a high level of amputation reduces the amount of available myoelectric and kinematic information from the residual limb.

Methods
To overcome these limits, we added contextual information about the target’s location and orientation such as can now be extracted from gaze tracking by computer vision tools. For the task of picking and placing a bottle in various positions and orientations in a 3D virtual scene, we trained artificial neural networks to predict postures of an intact subject’s elbow, forearm and wrist (4 degrees of freedom) either solely from shoulder kinematics or with additional knowledge of the movement goal. Subjects then performed the same tasks in the virtual scene with distal joints predicted from the context-aware network.

Results
Average movement times of 1.22s were only slightly longer than the naturally controlled movements (0.82 s). When using a kinematic-only network, movement times were much longer (2.31s) and compensatory movements from trunk and shoulder were much larger. Integrating contextual information also gave rise to motor synergies closer to natural joint coordination.

Conclusions
Although notable challenges remain before applying the proposed control scheme to a real-world prosthesis, our study shows that adding contextual information to command signals greatly improves prediction of distal joint angles for prosthetic control.
Serum HBV RNA correlated with intrahepatic cccDNA more strongly than other HBV markers during peg-interferon treatment
Authors: Wang Xiaomei , Chi Xiumei , Wu Ruihong , Xu Hongqin , Gao Xiuzhu , Yu Lei , Liu Longgen , Zhang Mingxiang , Tan Youwen , Niu Junqi , Jin Qinglong 
Published: January 2021

Abstract
Background
Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, in HBeAg-positive patients treated with peg-interferon (peg-IFN), whether HBV RNA is superior to other HBV markers in reflecting cccDNA profile is still unclear.

Methods
Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment. Besides, intrahepatic cccDNA was detected at baseline and week 48 respectively. Then, the individual correlations between HBV RNA, HBcrAg, HBV DNA, HBsAg, and cccDNA were statistically analyzed.

Results
HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. Among all patients, cccDNA correlated better with HBV RNA than with HBcrAg, HBV DNA, and HBsAg at baseline. After 48 weeks peg-IFN treatment, cccDNA still correlated more strongly with HBV RNA than other HBV markers. Further analysis indicated that in patients with HBeAg seroconversion cccDNA strongly correlated with HBV RNA and HBcrAg, whereas not correlate with HBV DNA and HBsAg. While in patients without HBeAg seroconversion, cccDNA highly correlated with HBV RNA and HBV DNA, moderately correlated with HBcrAg, and not correlated with HBsAg.

Conclusion
Compared to HBcrAg, HBV DNA, and HBsAg, serum HBV RNA correlated more strongly with intrahepatic cccDNA levels before and after 48-week peg-IFN treatment. The level of serum HBV RNA may be a superior surrogate marker in reflecting the intrahepatic cccDNA profile in HBeAg-positive patients during peg-IFN treatment.
Trial registration ClinicalTrials, NCT03546530. Registered 1 January 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03546530.