bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the potential impact of Attractive Targeted Sugar Baits (ATSBs) as a new vector control tool for Plasmodium falciparum malaria
Authors: Fraser Keith J. , Mwandigha Lazaro , Traore Sekou F. , Traore Mohamed M. , Doumbia Seydou , Junnila Amy , Revay Edita , Beier John C. , Marshall John M. , Ghani Azra C. , Müller Gunter 
Published: March 2021

Abstract
Background
Attractive targeted sugar baits (ATSBs) are a promising new tool for malaria control as they can target outdoor-feeding mosquito populations, in contrast to current vector control tools which predominantly target indoor-feeding mosquitoes.

Methods
It was sought to estimate the potential impact of these new tools on Plasmodium falciparum malaria prevalence in African settings by combining data from a recent entomological field trial of ATSBs undertaken in Mali with mathematical models of malaria transmission. The key parameter determining impact on the mosquito population is the excess mortality due to ATSBs, which is estimated from the observed reduction in mosquito catch numbers. A mathematical model capturing the life cycle of P. falciparum malaria in mosquitoes and humans and incorporating the excess mortality was used to estimate the potential epidemiological effect of ATSBs.

Results
The entomological study showed a significant reduction of ~ 57% (95% CI 33–72%) in mosquito catch numbers, and a larger reduction of ~ 89% (95% CI 75–100%) in the entomological inoculation rate due to the fact that, in the presence of ATSBs, most mosquitoes do not live long enough to transmit malaria. The excess mortality due to ATSBs was estimated to be lower (mean 0.09 per mosquito per day, seasonal range 0.07–0.11 per day) than the bait feeding rate obtained from one-day staining tests (mean 0.34 per mosquito per day, seasonal range 0.28–0.38 per day).

Conclusions
From epidemiological modelling, it was predicted that ATSBs could result in large reductions (> 30% annually) in prevalence and clinical incidence of malaria, even in regions with an existing high malaria burden. These results suggest that this new tool could provide a promising addition to existing vector control tools and result in significant reductions in malaria burden across a range of malaria-endemic settings.
Temporal evolution of sulfadoxine-pyrimethamine resistance genotypes and genetic diversity in response to a decade of increased interventions against Plasmodium falciparum in northern Ghana
Authors: Amenga-Etego Lucas N. , Asoala Victor , Agongo Godfred , Jacob Christopher , Goncalves Sonia , Awandare Gordon A. , Rockett Kirk A. , Kwiatkowski Dominic 
Published: March 2021

Abstract
Background
Anti-malarial drug resistance remains a key concern for the global fight against malaria. In Ghana sulfadoxine-pyrimethamine (SP) is used for intermittent preventive treatment of malaria in pregnancy and combined with amodiaquine for Seasonal Malaria Chemoprevention (SMC) during the high malaria season. Thus, surveillance of molecular markers of SP resistance is important to guide decision-making for these interventions in Ghana.

Methods
A total of 4469 samples from uncomplicated malaria patients collected from 2009 to 2018 was submitted to the Wellcome Trust Sanger Institute, UK for DNA sequencing using MiSeq. Genotypes were successfully translated into haplotypes in 2694 and 846 mono infections respectively for pfdhfr and pfdhps genes and the combined pfhdfr/pfdhps genes across all years.

Results
At the pfdhfr locus, a consistently high (> 60%) prevalence of parasites carrying triple mutants (IRNI) were detected from 2009 to 2018. Two double mutant haplotypes (NRNI and ICNI) were found, with haplotype NRNI having a much higher prevalence (average 13.8%) than ICNI (average 3.2%) across all years. Six pfdhps haplotypes were detected. Of these, prevalence of five fluctuated in a downward trend over time from 2009 to 2018, except a pfdhps double mutant (AGKAA), which increased consistently from 2.5% in 2009 to 78.2% in 2018. Across both genes, pfdhfr/pfdhps combined triple (NRNI + AAKAA) mutants were only detected in 2009, 2014, 2015 and 2018, prevalence of which fluctuated between 3.5 and 5.5%. The combined quadruple (IRNI + AAKAA) genotype increased in prevalence from 19.3% in 2009 to 87.5% in 2011 before fluctuating downwards to 19.6% in 2018 with an average prevalence of 37.4% within the nine years. Prevalence of parasites carrying the quintuple (IRNI + AGKAA or SGEAA) mutant haplotypes, which are highly refractory to SP increased over time from 14.0% in 2009 to 89.0% in 2016 before decreasing to 78.9 and 76.6% in 2017 and 2018 respectively. Though quintuple mutants are rising in prevalence in both malaria seasons, together these combined genotypes vary significantly within season but not between seasons.

Conclusions
Despite high prevalence of pfdhfr triple mutants and combined pfdhfr/pfdhps quadruple and quintuple mutants in this setting SP may still be efficacious. These findings are significant as they highlight the need to continuously monitor SP resistance, particularly using deep targeted sequencing to ascertain changing resistance patterns.
Validation of living with chronic illness scale in a type 2 diabetes mellitus population
Authors: Caro-Bautista Jorge , Rodríguez-Blázquez Carmen , Perez-Manchon David , Timonet-Andreu Eva , Carvajal-Carrascal Gloria , Fuentes-Ramírez Alejandra , Corchon Silvia , Aranda-Gallardo Marta , Ambrosio Leire 
Published: March 2021

Abstract
Background
Worldwide, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases and one of those producing greatest impact on patients’ day-to-day quality of life. Our study aim is to validate the “Living with Chronic Illness Scale” for a Spanish-speaking T2DM population.

Methods
In this observational, international, cross-sectional study, 582 persons with T2DM were recruited in primary care and outpatient hospital consultations, in Spain and Colombia, during the period from May 2018 to June 2019. The properties analysed were feasibility/acceptability, internal consistency, reliability, precision and (structural) content-construct validity including confirmatory factor analysis. The COSMIN checklist was used to assess the methodological/psychometric quality of the instrument.

Results
The scale had an adequate internal consistency and test retest reliability (Cronbach’s alpha = 0.90; intraclass correlation coefficient = 0.96, respectively). In addition, the instrument is precise (standard error of measurement = 3.34, with values < ½SD = 8.52) and correlates positively with social support (DUFSS) (rs = 0.56), quality of life (WHOQOL-BREF) (rs = 0.51–0.30) and ssatisfaction with life (SLS-6) (rs = 0.50–0.38). The original 26-items version of the scale did not support totally the confirmatory factor analysis. The COSMIN checklist is favourable for all the properties analysed, although weaknesses are detected for structural validity.

Conclusions
The LW-CI-T2DM is a valid, reliable and accurate instrument for use in clinical practice to determine how a person’s life is affected by the presence of diabetes. This instrument correlates well with the associated constructs of social support, quality of life and satisfaction. Additional research is needed to determine how well the questionnaire structure performs when robust factor analysis methods are applied.
The path linking disease severity and cognitive function with quality of life in Parkinson’s disease: the mediating effect of activities of daily living and depression
Authors: He Yao , Tian Yuling , Han Hongjuan , Cui Jing , Ge Xiaoyan , Qin Yao , Luo Yanhong , Bai Wenlin , Yu Hongmei 
Published: March 2021

Abstract
Background
Research on quality of life (QOL) with Parkinson’s disease (PD) has examined direct influencing factors, not mediators. The study aim was to explore whether PD severity and poor cognitive function may decrease physical and mental QOL by reducing activities of daily living (ADL) and increasing depression in sequence.

Methods
We conducted a cross-sectional questionnaire study of 150 PD hospital patients in China. PD severity, cognitive function, ADL, depression, and QOL were evaluated. We used structural equation modeling to analyze the mediating effects of ADL and depression on the association between PD severity/cognition and the physical health and mental health component summary scores measured by the SF36 quality of life instrument.

Results
There was a significant mediating effect of PD severity on physical health via ADL and depression (95% CI: − 0.669, − 0.026), and a significant direct effect (p < 0.001). The mediating effect of PD severity on mental health via ADL and depression was significant (95% CI: − 2.135, − 0.726), but there was no direct effect (p = 0.548). There was a significant mediating effect of cognitive function on physical health via ADL and depression (95% CI: 0.025, 0.219) and a significant direct effect (p < 0.001). The mediating effect of cognitive function on mental health via ADL and depression was significant (95% CI: 0.256, 0.645), but there was no direct effect (p = 0.313). The physical health models showed a partial mediation, and the mental health models showed a complete mediation, of ADL and depression.

Conclusions
PD severity and cognitive function increase depression by reducing ADL, leading to lower QOL, and directly or indirectly affect physical health and mental health through different pathways.
Volume and accumulation patterns of physical activity and sedentary time: longitudinal changes and tracking from early to late childhood
Authors: Downing Katherine L , Hinkley Trina , Timperio Anna , Salmon Jo , Carver Alison , Cliff Dylan P , Okely Anthony D , Hesketh Kylie D 
Published: March 2021

Abstract
Background
Physical activity (PA) decreases and sedentary time (SED) increases across childhood, with both behaviours tracking. However, no studies have examined how accumulation patterns of PA and SED (i.e., prolonged bouts, frequency of breaks in sedentary time) change and track over time. The aim of this study was to investigate longitudinal changes in and tracking of total volume and accumulation patterns of SED, light-intensity PA (LPA), moderate-intensity PA (MPA), vigorous-intensity PA (VPA) among boys and girls.

Methods
In 2008/09 (T1), children in HAPPY (3-5y; n = 758) in Melbourne, Australia wore ActiGraph GT1M accelerometers to objectively assess SED, LPA, MPA and VPA. This was repeated at age 6-8y (T2; n = 473) and 9-11y (T3; n = 478). Ten pattern variables were computed: bouts of ≥ 5-, ≥ 10-, ≥ 15- and ≥ 20-min for SED, ≥ 1- and ≥ 5-min for LPA, ≥ 1-min for MPA, ≥ 1- and ≥ 5-min for VPA, and breaks in SED (interruptions of > 25 counts 15 s− 1). Longitudinal mixed models examined changes from T1-3, controlling for T1 age. Generalized estimating equations assessed tracking over the three time points, controlling for T1 age and time between measurements. Analyses were stratified by sex.

Results
Total volume and bouts of SED and SED breaks increased, while total volume and bouts of LPA decreased for both sexes. There was a small decrease in total volume of MPA for girls, but time spent in ≥ 1-min bouts increased for both sexes. Total volume of VPA increased for both sexes, with time spent in ≥ 1-min bouts increasing for boys only. All volume and pattern variables tracked moderately for boys, except for all SED bouts ≥ 15-min, LPA bouts ≥ 5-min and MPA bouts ≥ 1-min (which tracked weakly). For girls, total SED and SED bouts ≥ 1-min tracked strongly, total volume of LPA, MPA and VPA, ≥ 5- and ≥ 10-min SED bouts, and ≥ 1-min LPA and MPA bouts tracked moderately, and SED breaks, all SED bouts ≥ 15 min, LPA bouts ≥ 5 min and all VPA bouts tracked weakly.

Conclusions
Patterns of SED and PA change from early to late childhood; with the exception of SED breaks and VPA, changes were detrimental. Total volumes and short bouts tended to track more strongly than longer bouts. Interventions to prevent declines in PA and increases in SED are important from early in life.
KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway
Authors: Zeng Fanchang , Luo Liumei , Li Daoyuan , Guo Juncheng , Guo Min 
Published: March 2021

Abstract
Background
Bladder cancer (BCa) is a common malignancy characterized by high heterogeneity, yet the current treatment modalities are limited. The aim of the present investigation was to unravel the functional role of Karyopherin alpha 2 (KPNA2), a tumor facilitator identified in multiple malignancies, in the progression of BCa.

Methods
BCa tissues and adjacent normal tissues were surgically resected and analyzed from patients with BCa to determine the expression profile of KPNA2 and Chromobox 8 (CBX8) by RT-qPCR, Western blot analysis and immunohistochemistry. The relationship among KPNA2, CBX8 and PR domain zinc finger protein 1 (PRDM1) was explored by co-immunoprecipitation and chromatin-immunoprecipitation. The functions of KPNA2, CBX8 and PRDM1 on BCa cell proliferation, migration and invasion were evaluated. Next, a nude mouse model of BCa was established for validating the roles of KPNA2, CBX8 and PRDM1 in vivo.

Results
KPNA2 and CBX8 were highly expressed in BCa and are in association with dismal oncologic outcomes of patients with BCa. KPNA2 promoted nuclear import of CBX8. CBX8 downregulated PRDM1 by recruiting BCOR in the promoter region of PRDM1. Overexpression of KPNA2 promoted the malignant behaviors of BCa cells, which was counteracted by silencing of CBX8. Overexpressing PRDM1 attenuated the progression of BCa by inhibiting c-FOS expression. The tumor-promoting effects of KPNA2 via the PRDM1/c-FOS pathway were also validated in vivo.

Conclusion
Collectively, our findings attached great importance to the interplay between KPNA2 and CBX8 in BCa in mediating the development and progression of BCa, thus offering a promising candidate target for better BCa patient management.
TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway
Authors: Sun Tianshui , Bi Fangfang , Liu Zhuonan , Yang Qing 
Published: March 2021

Abstract
Background
Ovarian cancer (OV) is the deadliest gynecological cancer. Transmembrane protein 119 (TMEM119) has been reported as oncogene in several human cancers. However, the function of TMEM119 in OV is still poorly known.

Methods
Western blot and qRT-PCR were used to analyze TMEM119 levels. Transwell assays, wound healing assays, CCK-8 assays and EdU cell proliferation assays were designed to explore the function and potential mechanism of TMEM119 in malignant biological behaviors in OV.

Results
TMEM119 was observed to be overexpressed in OV tissues and associated with poor survival in OV patients. Knockdown and overexpression experiments demonstrated that TMEM119 promoted proliferation, invasion, and migration in OV cells in vitro. TMEM119 mRNA expression was related to the pathways of focal adhesion according to Gene Set Enrichment Analyses and was correlated with the mRNA expression level of platelet-derived growth factor receptor beta (PDGFRB). TMEM119 exerted oncogenic effects partially by regulating the expression of PDGFRB and by activating the PI3K/AKT signaling pathway.

Conclusions
Collectively, our findings highlight the potential role of TMEM119 in the malignant biological behavior of OV, which may serve as a potential biomarker and a therapeutic candidate for OV.
Psychosocial and economic impact of rheumatic diseases on caregivers of Mexican children
Authors: Fortuna-Reyna Brenda de Jesús , Peláez-Ballestas Ingris , García-Rodríguez Fernando , Faugier-Fuentes Enrique , Mendieta-Zerón Samara , Villarreal-Treviño Ana Victoria , Rosiles-De la Garza Sara Georgina , Reyes-Cordero Greta , Jiménez-Hernández Sol , Guadarrama-Orozco Jessica Haydee , de la O-Cavazos Manuel Enrique , Rubio-Pérez Nadina 
Published: March 2021

AbstractBackgroundPediatric rheumatic disease (PRD) patients and their caregivers face a number of challenges, including the consequences of the PRD in patients and the impact on multiple dimensions of the caregivers’ daily lives. The objective of this study is to measure the economic, psychological and social impact that PRD has on the caregivers of Mexican children.MethodsThis is a multicenter, cross-sectional study including primary caregivers of children and adolescents with PRD (JIA, JDM and JSLE) during April and November, 2019. A trained interviewer conducted the CAREGIVERS questionnaire, a specific, 28-item multidimensional tool validated to measure the impact on different dimensions of the lives of caregivers. Sociodemographic, clinical, and healthcare system data were collected for further analysis.ResultsTwo hundred participants were recruited (women 169, 84.5%, aged 38 [IQR 33–44] years); 109 (54.5%) cared for patients with JIA, 28 (14%) JDM and 63 (31.5%) JSLE. The healthcare system was found to be determinant on the impact of the disease. The emotional impact was higher in all the participants, regardless of the specific diagnoses. The social dimension showed significant differences regarding PRD, healthcare system, time to reach the center, presence of disability, active disease, cutaneous and systemic manifestations, treatment and partner. Financial and work impacts were more frequent in those caring for JSLE and less so in those with a partner. Family relationships changed in 81 caregivers (25 [12.5%] worsened and 56 [28%] improved). No variables affecting spirituality were found. For caregivers without a partner, the social networks impact increased.ConclusionThe influence of sociodemographic factors can be devastating on families with children with a PRD. These data will help physicians to identify the areas with the greatest need for intervention to achieve comprehensive care for caregivers and their patients.
Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer’s disease
Authors: Davis Nicola , Mota Bibiana C. , Stead Larissa , Palmer Emily O. C. , Lombardero Laura , Rodríguez-Puertas Rafael , de Paola Vincenzo , Barnes Samuel J. , Sastre Magdalena 
Published: March 2021

Abstract
Background
Astrocytes provide a vital support to neurons in normal and pathological conditions. In Alzheimer’s disease (AD) brains, reactive astrocytes have been found surrounding amyloid plaques, forming an astrocytic scar. However, their role and potential mechanisms whereby they affect neuroinflammation, amyloid pathology, and synaptic density in AD remain unclear.

Methods
To explore the role of astrocytes on Aβ pathology and neuroinflammatory markers, we pharmacologically ablated them in organotypic brain culture slices (OBCSs) from 5XFAD mouse model of AD and wild-type (WT) littermates with the selective astrocytic toxin L-alpha-aminoadipate (L-AAA). To examine the effects on synaptic circuitry, we measured dendritic spine number and size in OBCSs from Thy-1-GFP transgenic mice incubated with synthetic Aβ42 or double transgenics Thy-1-GFP/5XFAD mice treated with LAAA or vehicle for 24 h.

Results
Treatment of OBCSs with L-AAA resulted in an increased expression of pro-inflammatory cytokine IL-6 in conditioned media of WTs and 5XFAD slices, associated with changes in microglia morphology but not in density. The profile of inflammatory markers following astrocytic loss was different in WT and transgenic cultures, showing reductions in inflammatory mediators produced in astrocytes only in WT sections. In addition, pharmacological ablation of astrocytes led to an increase in Aβ levels in homogenates of OBCS from 5XFAD mice compared with vehicle controls, with reduced enzymatic degradation of Aβ due to lower neprilysin and insulin-degrading enzyme (IDE) expression. Furthermore, OBSCs from wild-type mice treated with L-AAA and synthetic amyloid presented 56% higher levels of Aβ in culture media compared to sections treated with Aβ alone, concomitant with reduced expression of IDE in culture medium, suggesting that astrocytes contribute to Aβ clearance and degradation. Quantification of hippocampal dendritic spines revealed a reduction in their density following L-AAA treatment in all groups analyzed. In addition, pharmacological ablation of astrocytes resulted in a decrease in spine size in 5XFAD OBCSs but not in OBCSs from WT treated with synthetic Aβ compared to vehicle control.

Conclusions
Astrocytes play a protective role in AD by aiding Aβ clearance and supporting synaptic plasticity.
Neck circumference as an independent predictor for NAFLD among postmenopausal women with normal body mass index
Authors: Shi Jie , Wang Zixuan , Zhang Weiwei , Niu Yixin , Lin Ning , Li Xiaoyong , Zhang Hongmei , Ning Guang , Fan Jiangao , Qin Li , Su Qing , Yang Zhen 
Published: March 2021

Abstract
Background
Neck circumference, a proxy for upper-body subcutaneous fat, is a unique and pathogenic fat depot that confers additional metabolic risk. The purpose of present study was to determine whether neck circumference associates with nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with normal body mass index.

Methods
A cross-sectional survey (n = 2492) and a 3.1-year follow-up investigation (n = 1354) were conducted among Chinese postmenopausal women with normal BMI (18.5 to < 25 kg/m2). Neck circumference was measured horizontally at the lower margin of the laryngeal prominence.

Results
In the cross-sectional analysis, large neck circumference was associated with the presence of NAFLD (odds ratio 2.28; 95% CI 1.74–2.98; highest tertile versus lowest tertile) after adjustment for confounding factors. Among 1354 subjects without the NAFLD at baseline, 429 (31.7%) incident NAFLD cases occurred at 3.1 years. Neck circumference was positively associated with triglycerides, homeostasis model assessment of insulin resistance, C-reactive protein, and negatively associated with high-density lipoprotein cholesterol and adiponectin. Individuals with large baseline neck circumference had a significantly higher risk of NAFLD than those with small neck circumference. The multivariable adjusted hazard ratio was 1.42 (95% CI 1.15–1.97; p for trend = 0.004) for the highest versus the lowest tertile of neck circumference, and was 1.22 (95% CI 1.10–1.41; p = 0.006) per 1-standard deviation increment in neck circumference.

Conclusions
Among postmenopausal women with normal BMI, relatively large neck circumference levels are associated with an increased risk of NAFLD.
Diagnostic pitfall of thyroid fine-needle aspiration induced fibrosis: follicular adenoma mimicking medullary thyroid carcinoma in frozen section
Authors: Moon Woo Sung , Kang Myoung Jae , Youn Hyun Jo , Kim Kyoung Min 
Published: March 2021

Abstract
Background
Fine-needle aspiration (FNA) is a frequently utilized method for the diagnosis of thyroid nodules. Although the technique has clear advantages, the injury caused by the aspiration needle can induce various histological alterations. Herein, we report a case of follicular adenoma showing histological alterations possibly caused by FNA biopsy. Furthermore, the histological appearance of the lesion mimicked those of medullary thyroid carcinoma, particularly in the frozen section.

Case presentation
Ultrasonography of a thyroid nodule in a 39-year-old man revealed a mass (2.2 cm in diameter) in the right thyroid lobe. FNA was performed three times on the mass, and the results of the cytology were atypia of undetermined significance. Thereafter, the patient underwent right hemithyroidectomy. The histological findings of the operative frozen section analysis indicated medullary thyroid carcinoma. However, after evaluation and immunohistochemical staining of the permanent section, the mass was diagnosed as follicular adenoma with extensive fibrosis.

Conclusion
The histological alterations observed in the follicular adenoma are believed to have been caused by injury during the repeated FNA procedures.