bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assays for quantification of male and female gametocytes in human blood by qRT-PCR in the absence of pure sex-specific gametocyte standards
Authors: Wang Claire Y. T. , Ballard Emma , Llewellyn Stacey , Marquart Louise , Bousema Teun , McCarthy James S. , Collins Katharine A. 
Published: June 2020

Abstract
Background
Malaria transmission from humans to Anopheles mosquitoes requires the presence of gametocytes in human peripheral circulation, and the dynamics of transmission are determined largely by the density and sex ratio of the gametocytes. Molecular methods are thus employed to measure gametocyte densities, particularly when assessing transmission epidemiology and the efficacy of transmission-blocking interventions. However, accurate quantification of male and female gametocytes with molecular methods requires pure male and female gametocytes as reference standards, which are not widely available.

Methods
qRT-PCR assays were used to quantify levels of sex-specific mRNA transcripts in Plasmodium falciparum female and male gametocytes (pfs25 and pfMGET, respectively) using synthetic complimentary RNA standards and in vitro cultured gametocytes. Assays were validated and assay performance was investigated in blood samples of clinical trial participants using these standards and compared to absolute quantification by droplet digital PCR (ddPCR).

Results
The number of transcript copies per gametocyte were determined to be 279.3 (95% CI 253.5–307.6) for the female-specific transcript pfs25, and 12.5 (95% CI 10.6–14.9) for the male-specific transcript pfMGET. These numbers can be used to convert from transcript copies/mL to gametocyte/mL. The reportable range was determined to be 5.71 × 106 to 5.71 female gametocytes/mL for pfs25, and 1.73 × 107 to 1.73 × 101 male gametocytes/mL for pfMGET. The limit of detection was 3.9 (95% CI 2.5–8.2) female gametocytes/mL for pfs25, and 26.9 (95% CI 19.3–51.7) male gametocytes/mL for PfMGET. Both assays showed minimal intra-assay and inter-assay variability with coefficient of variation < 3%. No cross-reactivity was observed in both assays in uninfected human blood samples. Comparison of results from ddPCR to qRT-PCR assays on clinical blood samples indicated a high-level agreement (ICC = 0.998 for pfs25 and 0.995 for pfMGET).

Conclusions
This study reports the validation of qRT-PCR assays that are able to accurately quantify female and male P. falciparum gametocytes at sub-microscopic densities. The assays showed excellent reproducibility, sensitivity, precision, specificity, and accuracy. The methodology will enable the estimation of gametocyte density in the absence of pure female and male gametocyte standards, and will facilitate clinical trials and epidemiological studies.
A spatially explicit analysis of chronic diseases in small areas: a case study of diabetes in Santiago, Chile
Authors: Crespo Ricardo , Alvarez Claudio , Hernandez Ignacio , García Christian 
Published: June 2020

Abstract
Background
There is a strong spatial correlation between demographics and chronic diseases in urban areas. Thus, most of the public policies aimed at improving prevention plans and optimizing the allocation of resources in health networks should be designed specifically for the socioeconomic reality of the population. One way to tackle this challenge is by exploring within a small geographical area the spatial patterns that link the sociodemographic attributes that characterize a community, its risk of suffering chronic diseases, and the accessibility of health treatment. Due to the inherent complexity of cities, soft clustering methods are recommended to find fuzzy spatial patterns. Our main motivation is to provide health planners with valuable spatial information to support decision-making. For the case study, we chose to investigate diabetes in Santiago, Chile.

Methods
To deal with spatiality, we combine two statistical techniques: spatial microsimulation and a self-organizing map (SOM). Spatial microsimulation allows spatial disaggregation of health indicators data to a small area level. In turn, SOM, unlike classical clustering methods, incorporates a learning component through neural networks, which makes it more appropriate to model complex adaptive systems, such as cities. Thus, while spatial microsimulation generates the data for the analysis, the SOM method finds the relevant socio-economic clusters. We selected age, sex, income, prevalence of diabetes, distance to public health services, and type of health insurance as input variables. We used public surveys as input data.

Results
We found four significant spatial clusters representing 75 percent of the whole population in Santiago. Two clusters correspond to people with low educational levels, low income, high accessibility to public health services, and a high prevalence of diabetes. However, one presents a significantly higher level of diabetes than the other. The second pair of clusters is made up of people with high educational levels, high income, and low prevalence of diabetes. What differentiates both clusters is accessibility to health centers. The average distance to the health centers of one group almost doubles that of the other.

Conclusions
In this study, we combined two statistical techniques: spatial microsimulation and selforganising maps to explore the relationship between diabetes and socio-demographics in Santiago, Chile. The results have allowed us to corroborate the importance of the spatial factor in the analysis of chronic diseases as a way of suggesting differentiated solutions to spatially explicit problems. SOM turned out to be a good choice to deal with fuzzy health and socioeconomic data. The method explored and uncovered valuable spatial patterns for health decision-making. In turn, spatial microsimulation.
Unmet supportive care needs and its relation to quality of life among adult acute leukaemia patients in China: a cross-sectional study
Authors: Jie Yan , Wang Ying , Chen Jingyi , Wang Chunfeng , Lin Yingchun , Hu Rong , Wu Yong 
Published: June 2020

Abstract
Background
Patients with acute leukaemia (AL) usually require prolonged periods of hospitalisation. The treatment and clinical symptoms may lead to patients’ supportive care needs (SCNs) not being met and impairs their quality of life (QoL). Studies on QoL and SCNs among AL patients are limited. This study aimed to identify the unmet SCNs and its relation to QoL of adult AL patients in China.

Methods
This multicentre cross-sectional study recruited 346 participants to complete a self-developed questionnaire, detailing demographic information and disease-related variables. A 34-item Supportive Care Needs Survey (SCNS-SF34) was used to identify unmet SCNs, and the Functional Assessment of Cancer Therapy-Leukaemia (FACT-Leu) questionnaire measured patients’ QoL.

Results
Unmet SCN rates for the 34 items ranged from17.6 to 81.7%. Patients’ needs were high for health systems and information, but low in the sexual domain. The results reveal nine factors associated with the unmet SCNs of adult AL patients, including marital status, original residence, age, education, occupation, other diseases, chemotherapy course, disease course, and treatment stage (p < 0.05). The total score of the FACT-Leu negatively correlated with the SCNS-SF34 in the physical/daily living (r = − 0.527, p < 0.01), psychological (r = − 0.688, p < 0.01), sexual (r = − 0.170, p < 0.01), patient care and support (r = − 0.352, p < 0.01), and health systems and information (r = − 0.220, p < 0.01) domains.

Conclusions
Adult AL patients exhibit a high demand for unmet SCNs, especially in the domain of health systems and information. There was a significant association between patients’ unmet SCNs and QoL. Future research should develop tailored interventions to address the unmet SCNs of adult AL patients, to further improve their QoL.
Measurement properties of the musculoskeletal health questionnaire (MSK-HQ): a between country comparison
Authors: Christiansen David Høyrup , McCray Gareth , Winding Trine Nøhr , Andersen Johan Hviid , Nielsen Kent Jacob , Karstens Sven , Hill Jonathan C. 
Published: June 2020

AbstractBackgroundThe Musculoskeletal Health Questionnaire (MSK-HQ) has been developed to measure musculoskeletal health status across musculoskeletal conditions and settings. However, the MSK-HQ needs to be further evaluated across settings and different languages.ObjectiveThe objective of the study was to evaluate and compare measurement properties of the MSK-HQ across Danish (DK) and English (UK) cohorts of patients from primary care physiotherapy services with musculoskeletal pain.MethodsMSK-HQ was translated into Danish according to international guidelines. Measurement invariance was assessed by differential item functioning (DIF) analyses. Test-retest reliability, measurement error, responsiveness and minimal clinically important change (MCIC) were evaluated and compared between DK (n = 153) and UK (n = 166) cohorts.ResultsThe Danish version demonstrated acceptable face and construct validity. Out of the 14 MSK-HQ items, three items showed DIF for language (pain/stiffness at night, understanding condition and confidence in managing symptoms) and three items showed DIF for pain location (walking, washing/dressing and physical activity levels). Intraclass Correlation Coefficients for test-retest were 0.86 (95% CI 0.81 to 0.91) for DK cohort and 0.77 (95% CI 0.49 to 0.90) for the UK cohort. The systematic measurement error was 1.6 and 3.9 points for the DK and UK cohorts respectively, with random measurement error being 8.6 and 9.9 points. Receiver operating characteristic (ROC) curves of the change scores against patients’ own judgment at 12 weeks exceeded 0.70 in both cohorts. Absolute and relative MCIC estimates were 8–10 points and 26% for the DK cohort and 6–8 points and 29% for the UK cohort.ConclusionsThe measurement properties of MSK-HQ were acceptable across countries, but seem more suited for group than individual level evaluation. Researchers and clinicians should be aware that some discrepancy exits and should take the observed measurement error into account when evaluating change in scores over time.
Loss-of-function mutations in KEAP1 drive lung cancer progression via KEAP1/NRF2 pathway activation
Authors: Gong Meiling , Li Yan , Ye Xiaoping , Zhang Linlin , Wang Zhifang , Xu Xiaowen , Shen Yejing , Zheng Cuixia 
Published: June 2020

Abstract
Background and purpose
Targeted therapy and immunotherapy have led to dramatic change in the treatment of lung cancer, however, the overall 5-year survival rate of lung cancer patients is still suboptimal. It is important to exploit new potential of molecularly targeted therapies. High-frequency somatic mutations in KEAP1/NRF2 (27.9%) have been identified in lung squamous cell carcinoma. In this research, we explored the role of KEAP1 somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target lung cancer carrying KEAP1/NRF2 mutations.

Methods
Lung cancer cell lines A549 and H460 with loss-of-function mutations in KEAP1 stably transfected with wild-type (WT) KEAP1 or somatic mutations in KEAP1 were used to investigate the functions of somatic mutations in KEAP1. Flow cytometry, plate clone formation experiments, and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines.

Results
The expression of NRF2 and its target genes increased, and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with KEAP1 mutants compared to control cells with a loss-of-function KEAP1 mutation and stably transfected with WT KEAP1 in both in vitro and in vivo studies. The proliferation of A549 cell line trasfected with the R320Q KEAP1 mutant was inhibited more apparent than that of the A549 cell line trasfected with WT KEAP1 after treatment with NRF2 inhibitor ML385.

Conclusion
Somatic mutations of KEAP1 identified from patients with LSCC likely promote tumorigenesis mediated by activation of the KEAP1/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with KEAP1 mutation.
Direct anterior versus posterolateral approaches for clinical outcomes after total hip arthroplasty: a systematic review and meta-analysis
Authors: Chen Wang , Sun Jian-Ning , Zhang Ye , Zhang Yu , Chen Xiang-Yang , Feng Shuo 
Published: June 2020

Abstract
Objective
The main objective of our study was to compare the intraoperative and postoperative outcomes of direct anterior approach (DAA) with posterolateral approaches (PLA).

Methods
We searched Cochrane library, Web of Science, and PubMed for literatures comparing DAA with PLA. On the basis of inclusion and exclusion criteria, relevant literatures were selected. Two members independently screened qualified literatures, evaluated the literature quality, and extracted data information.

Results
Eighteen randomized controlled trials (RCTs) and non-RCTs totaling 34,873 patients (DAA = 9636, PLA = 25237) were contained in this systematic review and meta-analysis. The results showed that DAA were reduced in terms of length of hospital stay (weighted mean difference (WMD) = −0.43, 95% confidence interval (CI) −0.78 to −0.09, P = 0.01), LLD (WMD = −2.00, 95% CI −2.75 to −1.25, P < 0.00001), PE/DVT (WMD = 0.36, 95% CI 0.15 to 0.85, P = 0.02), dislocation (WMD = 0.42, 95% CI 0.30 to 0.59, P < 0.00001) and visual analog scale (VAS) (WMD = −0.57, 95% CI −0.91 to −0.23, P = 0.0009) compared with PLA; however, DAA compared with the PLA was increasing in terms of operative time (WMD = 14.81, 95% CI 7.18 to 22.44, P = 0.0001), intraoperative blood loss (WMD = 105.13, 95% CI 25.35 to 184.90, P = 0.01), fracture (WMD = 1.46, 95% CI 1.00 to 2.11, P = 0.05), and Harris hip score (HHS) (WMD = 1.19, 95% CI 0.77 to 1.61, P < 0.00001).

Conclusions
DAA was preferable effectiveness to PLA in early pain relief and functional recovery; however, PLA has a shorter operation time, intraoperative less blood loss and fracture.

Trial registration
Registration ID, CRD42020151208
Raising rare disease awareness using red flags, role play simulation and patient educators: results of a novel educational workshop on Raynaud phenomenon and systemic sclerosis
Authors: Sanges S. , Farhat M.-M. , Assaraf M. , Galland J. , Rivière E. , Roubille C. , Lambert M. , Yelnik C. , Maillard H. , Sobanski V. , Lefèvre G. , Launay D. , Morell-Dubois S. , Hachulla E. 
Published: June 2020

Abstract
Background
As lack of awareness of rare diseases (RDs) among healthcare professionals results in delayed diagnoses, there is a need for a more efficient approach to RD training during academic education. We designed an experimental workshop that used role-play simulation with patient educators and focused on teaching “red flags” that should raise the suspicion of an RD when faced with a patient with frequently encountered symptoms. Our objective was to report our experience, and to assess the improvement in learners’ knowledge and the satisfaction levels of the participants.

Results
The workshop consisted of 2 simulated consultations that both started with the same frequent symptom (Raynaud phenomenon, RP) but led to different diagnoses: a frequent condition (idiopathic RP) and an RD (systemic sclerosis, SSc). In the second simulated consultation, the role of the patient was played by a patient educator with SSc. By juxtaposing 2 seemingly similar situations, the training particularly highlighted the elements that help differentiate SSc from idiopathic RP.
When answering a clinical case exam about RP and SSc, students that had participated in the workshop had a higher mean mark than those who had not (14 ± 3.7 vs 9.6 ± 5.5 points out of 20, p = 0.001).
Participants mostly felt “very satisfied” with this training (94%), and “more comfortable” about managing idiopathic RP and SSc (100%). They considered the workshop “not very stressful” and “very formative” (both 71%). When asked about the strengths of this training, they mentioned the benefits of being put in an immersive situation, allowing a better acquisition of practical skills and a more interactive exchange with teachers, as well as the confrontation with a real patient, leading to a better retention of semiological findings and associating a relational component with this experience.

Conclusions
Through the use of innovative educational methods, such as role-play simulation and patient educators, and by focusing on teaching “red flags”, our workshop successfully improved RP and SSc learning in a way that satisfied students. By modifying the workshop’s scenarios, its template can readily be applied to other clinical situations, making it an interesting tool to teach other RDs.
Comparative studies on the histological characteristics of equine nasomaxillary aperture and paranasal sinus mucosa considering topographic and age-related differences
Authors: Schwieder Alexander , Pfarrer Christiane , Ohnesorge Bernhard , Staszyk Carsten , Bienert-Zeit Astrid 
Published: June 2020

AbstractBackgroundHorses may acquire a range of paranasal sinus diseases. Clinical studies show slight differences regarding anatomical regions and age. Histopathological examination of tissue samples could play an important role in the diagnostic process. Therefore, detailed knowledge of the histological appearance of the paranasal sinus mucosa (PSM) and the nasomaxillary aperture mucosa (NAM) is essential. The objective of this study was to determine topographic and age-related differences within the healthy equine PSM. In addition, we aimed to gain detailed knowledge of the histological appearance of the NAM in comparison to the PSM.ResultsThe PSM had an average height of 75.72 ± 44.48 μm with a two-row pseudostratified columnar epithelium of 13.52 ± 4.78 μm. The parameters mucosal height, epithelial height and number of goblet cells revealed significant dependency of the sample site and age group. The maxillary and dorsal conchal sinus showed the highest values for these parameters. In terms of age, younger horses showed a significantly higher total mucosal height in contrast to a significantly lower epithelial height than older horses. Positive correlation was seen between the epithelial height and number of goblet cells. The NAM had an average height of 820.27 ± 653.21 μm. Its pseudostratified epithelium was usually arranged in three rows and had an average height of 44.9 ± 12.78 μm. The number of goblet cells in the NAM was five times higher than in the PSM. Serous glands were found in only 4% of the PSM samples and 100% of the NAM samples.ConclusionsThere are significant histological differences between different paranasal sinus sites and between different groups of age. This may be related to an altered susceptibility for certain pathologies. The striking difference in the histological appearance of the NAM compared to the PSM could be due to an enhanced role in mucociliary clearance. Further studies are necessary to improve the understanding of mucosal function in specific paranasal sinus compartments and mucosal changes generated by different diseases.
Measuring the psychosocial, biological, and cognitive signatures of profound stress in humanitarian settings: impacts, challenges, and strategies in the field
Authors: Panter-Brick Catherine , Eggerman Mark , Ager Alastair , Hadfield Kristin , Dajani Rana 
Published: June 2020

Abstract
Background
Evidence of ‘what works’ in humanitarian programming is important for addressing the disruptive consequences of conflict and forced displacement. However, collecting robust scientific evidence, and ensuring contextual relevance, is challenging. We measured the biological, psychosocial, and cognitive impacts of a structured psychosocial intervention, implemented by Mercy Corps with Syrian refugees and Jordanian host-community youth. In this paper, we present a case analysis of this evaluation study and reflect on the scientific contributions of the work, the challenges experienced in its delivery, and the strategies deployed to address them.

Discussion
We identified challenges with respect to study design, methods, and dissemination: these included the logistics and acceptability of implementing a randomized controlled trial in a humanitarian context, the selection and refinement of culturally-relevant research tools and community-based practices, and the dissemination of results to multiple stakeholders. We demonstrated beneficial and sustained impacts on self-reports of insecurity, stress, and mental health; developed a reliable and culturally-relevant measure of resilience; experimentally tested cognitive skills; and showed that levels of cortisol, a biomarker of chronic stress, reduced by one third in response to intervention. Using stress biomarkers offered proof-of-concept evidence, beyond self-reported data: interventions targeting mental health and psychosocial wellbeing can regulate physiological stress in the body as well as improve self-reported mental health and wellbeing. We built constructive dialogue between local communities, scholars, humanitarian practitioners, and policy-makers.

Conclusions
Our work shows the value of rigorous research in humanitarian settings, emphasizing relevance for local communities and meaningful ways to build research ownership. Findings encourage the adoption of cognitive measures and stress biomarkers alongside self-report surveys in evaluating programme impacts. High-quality scientific research with youth can be feasible, useful, and ethical in humanitarian settings.