bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of the varied profiles of Plasmodium falciparum infections among infants living in Kintampo, Ghana
Authors: Botwe Akua Kyerewaa , Oppong Felix Boakye , Gyaase Stephaney , Owusu-Agyei Seth , Asghar Muhammad , Asante Kwaku Poku , Färnert Anna , Osier Faith 
Published: May 2021

Abstract
Background
Understanding why some infants tolerate infections, remaining asymptomatic while others succumb to repeated symptomatic malaria is beneficial for studies of naturally acquired immunity and can guide control interventions. This study compared demographic, host and maternal factors associated with being either parasite negative or having asymptomatic infections versus developing symptomatic malaria in the first year of life.

Methods
A birth cohort (n = 1264) was monitored longitudinally over two years for malaria infections in Kintampo, Ghana. Symptomatic and asymptomatic infections were detected actively through monthly home visits, complemented by passive case detection. Light microscopy was used to detect parasitaemia. Based on data from a minimum of eight monthly visits within the first year of life, infants were classified into one of four groups: “parasite negative”, “only-asymptomatic”, “only-symptomatic” or “alternating” i.e., sometimes symptomatic and other times asymptomatic. The host and maternal characteristics and demographic factors in relation to these four groups were compared.

Results
The parasite negative group formed 36% of the cohort, whilst the only-symptomatic were 35%. The alternating group were 22% and the only-asymptomatic were 7% of the cohort. There were significant associations between residence, socio-economic status (SES), parity, IPTp doses, delivery place of infant and having or not having malaria parasites. Maternal factors such as early commencement and frequency of ante-natal care (ANC) were significantly higher in the parasite negative group compared to all others. ITN use in pregnancy increased the odds of infant having only asymptomatic infections (“protected against disease”). Placental malaria was more common in the groups of infants with symptomatic malaria. Urban residence was significantly higher in the parasite negative group, while birth in the malaria transmission season were significantly more common in the alternating and parasite negative groups. Risk factors for infants with symptomatic malaria included low SES, birth in private maternity homes, sickle cell normal variant, lower MUAC, reported intake of anti-malarials and increased morbidity before the first microscopic infection was detected.

Conclusion
Strengthening ANC by encouraging early and regular attendance, the use of IPTp, maternal bed nets and improving the nourishment of infants help reduce the frequency of symptomatic malaria over the first year of life.
Genetic diversity and genetic relatedness in Plasmodium falciparum parasite population in individuals with uncomplicated malaria based on microsatellite typing in Eastern and Western regions of Uganda, 2019–2020
Authors: Agaba Bosco B. , Anderson Karen , Gresty Karryn , Prosser Christiane , Smith David , Nankabirwa Joaniter I. , Nsobya Sam , Yeka Adoke , Namubiru Rhoda , Arinaitwe Emmanuel , Mbaka Paul , Kissa John , Lim Chae Seung , Karamagi Charles , Nakayaga Joan K. , Kamya Moses R. , Cheng Qin 
Published: May 2021

Abstract
Background
Genetic diversity and parasite relatedness are essential parameters for assessing impact of interventions and understanding transmission dynamics of malaria parasites, however data on its status in Plasmodium falciparum populations in Uganda is limited. Microsatellite markers and DNA sequencing were used to determine diversity and molecular characterization of P. falciparum parasite populations in Uganda.

Methods
A total of 147 P. falciparum genomic DNA samples collected from cross-sectional surveys in symptomatic individuals of 2–10 years were characterized by genotyping of seven highly polymorphic neutral microsatellite markers (n = 85) and genetic sequencing of the Histidine Rich Protein 2 (pfhrp2) gene (n = 62). ArcGIS was used to map the geographical distribution of isolates while statistical testing was done using Student's t-test or Wilcoxon's rank-sum test and Fisher’s exact test as appropriate at P ≤ 0.05.

Results
Overall, 75.5% (95% CI 61.1–85.8) and 24.5% (95% CI14.2–38.9) of parasites examined were of multiclonal (mixed genotype) and single clone infections, respectively. Multiclonal infections occurred more frequently in the Eastern region 73.7% (95% CI 48.8–89.1), P < 0.05. Overall, multiplicity of infection (MOI) was 1.9 (95% CI 1.7–2.1), P = 0.01 that was similar between age groups (1.8 vs 1.9), P = 0.60 and regions (1.9 vs 1.8), P = 0.43 for the < 5 and ≥ 5 years and Eastern and Western regions, respectively. Genomic sequencing of the pfhrp2 exon2 revealed a high level of genetic diversity reflected in 96.8% (60/62) unique sequence types. Repeat type AHHAAAHHATD and HRP2 sequence Type C were more frequent in RDT−/PCR + samples (1.9% vs 1.5%) and (13% vs 8%), P < 0.05 respectively. Genetic relatedness analysis revealed small clusters of gene deleted parasites in Uganda, but no clustering with Eritrean parasites.

Conclusion
High level of genetic diversity of P. falciparum parasites reflected in the frequency of multiclonal infections, multiplicity of infection and variability of the pfhrp2 gene observed in this study is consistent with the high malaria transmission intensity in these settings. Parasite genetic analysis suggested spontaneous emergence and clonal expansion of pfhrp2 deleted parasites that require close monitoring to inform national malaria diagnosis and case management policies.
Luteolin transforms the polarity of bone marrow-derived macrophages to regulate the cytokine storm
Authors: Wang Shuxia , Xu Shuhang , Zhou Jing , Zhang Li , Mao Xiaodong , Yao Xiaoming , Liu Chao 
Published: May 2021

Abstract
Background
Macrophages are indispensable regulators of inflammatory responses. Macrophage polarisation and their secreted inflammatory factors have an association with the outcome of inflammation. Luteolin, a flavonoid abundant in plants, has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarisation of bone marrow-derived macrophages (BMDMs) to suppress inflammation is still unclear. This study aimed to observe the effects of luteolin on the polarity of BMDMs derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism by which luteolin regulates the BMDM polarity.

Methods
M1-polarised BMDMs were induced by lipopolysaccharide (LPS) + interferon (IFN)-γ and M2-polarisation were stimulated with interleukin (IL)-4. BMDM morphology and phagocytosis were observed by laser confocal microscopy; levels of BMDM differentiation and cluster of differentiation (CD)11c or CD206 on the membrane surface were assessed by flow cytometry (FCM); mRNA and protein levels of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; and the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting.

Results
The isolated mouse bone marrow cells were successfully differentiated into BMDMs, LPS + IFN-γ induced BMDM M1-phenotype polarisation, and IL-4 induced M2-phenotype polarisation. After M1-polarised BMDMs were treated with luteolin, the phagocytosis of M1-polarized BMDMs was reduced, and the M1-type pro-inflammatory factors including IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD86 were downregulated while the M2-type anti-inflammatory factors including IL-10, IL-13, found in inflammatory zone (FIZZ)1, Arginase (Arg)1 and CD206 were upregulated. Additionally, the expression of M1-type surface marker CD11c decreased. Nevertheless, the M2-type marker CD206 increased; and the levels of inflammatory signalling proteins phosphorylated signal transducer and activator of transcription (p-STAT)1 and p-STAT6 were attenuated and enhanced, respectively.

Conclusions
Our study suggests that luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin holds promise as an anti-inflammatory and immunomodulatory agent.
Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic prussian blue analogues boycott atherosclerosis
Authors: Zhang Yan , Yin Yifei , Zhang Wei , Li Hongyan , Wang Taixia , Yin Haohao , Sun Liping , Su Chunxia , Zhang Kun , Xu Huixiong 
Published: May 2021

AbstractBackgroundAs one typical cardiovascular disease, atherosclerosis severely endanger people’ life and cause burden to people health and mentality. It has been extensively accepted that oxidative stress and inflammation closely correlate with the evolution of atherosclerotic plaques, and they directly participate in all stages of atherosclerosis. Regarding this, anti-oxidation or anti-inflammation drugs were developed to enable anti-oxidative therapy and anti-inflammation therapy against atherosclerosis. However, current drugs failed to meet clinical demands.MethodsNanomedicine and nanotechnology hold great potential in addressing the issue. In this report, we engineered a simvastatin (Sim)-loaded theranostic agent based on porous manganese-substituted prussian blue (PMPB) analogues. The biomimetic PMPB carrier could scavenge ROS and mitigate inflammation in vitro and in vivo. Especially after combining with Sim, the composite Sim@PMPB NC was expected to regulate the processes of atherosclerosis. As well, Mn2+release from PMPB was expected to enhance MRI.ResultsThe composite Sim@PMPB NC performed the best in regulating the hallmarks of atherosclerosis with above twofold decreases, typically such as oxidative stress, macrophage infiltration, plaque density, LDL internalization, fibrous cap thickness and foam cell birth, etc.Moreover, H2O2-induced Mn2+release from PMPB NC in atherosclerotic inflammation could enhance MRI for visualizing plaques. Moreover, Sim@PMPB exhibited high biocompatibility according to references and experimental results.ConclusionsThe biomimetic Sim@PMPB theranostic agent successfully stabilized atherosclerotic plaques and alleviated atherosclerosis, and also localized and magnified atherosclerosis, which enabled the monitoring of H2O2-associated atherosclerosis evolution after treatment. As well, Sim@PMPB was biocompatible, thus holding great potential in clinical translation for treating atherosclerosis.Graphic abstract
Development and validation of a guideline on sexual and reproductive health of breast cancer survivors in Iran: a mixed methods study protocol
Authors: Roshandel Solmaz , Lamyian Minoor , Azin Seyed Ali , Haghighat Shahpar , Mohammadi Eesa 
Published: May 2021

Abstract
Background
Sexual and reproductive health problems significantly decrease quality of life in survivors of breast cancer. The best approach is to provide services according to evidence-based guidelines developed based on their practical context. Here, we aim to develop and validate a guideline on the sexual and reproductive health of breast cancer survivors in Iran.

Methods
The guideline will be developed and validated using an exploratory sequential mixed methods approach in three phases: (1) describing sexual and reproductive health needs of survivors of breast cancer in Iran and the health services they receive in this regard, (2) performing a systematic review of existing guidelines, resources, and documents on the sexual and reproductive health of breast cancer survivors worldwide, and (3) developing and validating a guideline on the sexual and reproductive health of women who survived breast cancer in Iran based on the results of phases 1 and 2 through multiple steps.

Discussion
A comprehensive and practical guideline on the sexual and reproductive health of breast cancer survivors in Iran will be developed which will be compatible with their specific needs and culture, considering the limited resources available. This guideline can significantly improve the quality of life in breast cancer survivors in Iran. In addition, the approach we will use here can be utilized to develop guidelines on sexual and reproductive health of female cancer survivors in general.
Comparative analysis of spatial-temporal patterns of human metapneumovirus and respiratory syncytial virus in Africa using genetic data, 2011–2014
Authors: Oketch John W. , Kamau Everlyn , Otieno James R. , Mwema Anthony , Lewa Clement , Isoe Everlyne , Nokes D. James , Agoti Charles N. 
Published: May 2021

Abstract
Background
Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are leading causes of viral severe acute respiratory illnesses in childhood. Both the two viruses belong to the Pneumoviridae family and show overlapping clinical, epidemiological and transmission features. However, it is unknown whether these two viruses have similar geographic spread patterns which may inform designing and evaluating their epidemic control measures.

Methods
We conducted comparative phylogenetic and phylogeographic analyses to explore the spatial-temporal patterns of HMPV and RSV across Africa using 232 HMPV and 842 RSV attachment (G) glycoprotein gene sequences obtained from 5 countries (The Gambia, Zambia, Mali, South Africa, and Kenya) between August 2011 and January 2014.

Results
Phylogeographic analyses found frequently similar patterns of spread of RSV and HMPV. Viral sequences commonly clustered by region, i.e., West Africa (Mali, Gambia), East Africa (Kenya) and Southern Africa (Zambia, South Africa), and similar genotype dominance patterns were observed between neighbouring countries. Both HMPV and RSV country epidemics were characterized by co-circulation of multiple genotypes. Sequences from different African sub-regions (East, West and Southern Africa) fell into separate clusters interspersed with sequences from other countries globally.

Conclusion
The spatial clustering patterns of viral sequences and genotype dominance patterns observed in our analysis suggests strong regional links and predominant local transmission. The geographical clustering further suggests independent introduction of HMPV and RSV variants in Africa from the global pool, and local regional diversification.
miR-520c-3p regulates IL-1β-stimulated human chondrocyte apoptosis and cartilage degradation by targeting GAS2
Authors: Peng Le , Deng Ming , Ma Yonggang , Hu Wei , Liang Fan 
Published: May 2021

Abstract
Background
MicroRNAs (miRNAs) have been shown to be associated with osteoarthritis (OA) progression. This study aimed to explore the role of miR-520c-3p in OA progression.

Methods
Expression levels of miR-520c-3p and Growth arrest-specific 2 (GAS2) were detected using quantitative real-time PCR. The proliferation and apoptosis of cells were measured using cell counting kit 8 (CCK8) assay and flow cytometry. Furthermore, the protein levels of apoptosis-related markers, extracellular degradation markers, inflammatory response markers, and GAS2 were tested using quantitative real-time polymerase chain reaction (RT-PCR) and western blot (WB) analysis. In addition, the interaction between miR-520c-3p and GAS2 was examined using dual luciferase reporter assay.

Results
GAS2 was highly expressed, and miR-520c-3p was lowly expressed in OA cartilage tissues. miR-520c-3p could promote the proliferation and inhibit the apoptosis and inflammation of OA chondrocytes. miR-520c-3p could be sponged by GAS2, and its inhibitor could reverse the regulation of GAS2 on the biological functions of OA chondrocytes. GAS2 was a target of miR-520c-3p, which was identified by bioinformatic analysis and dual-luciferase reporter assay. Overexpression of GAS2 could inhibit the proliferation and promoted the apoptosis and inflammation of OA chondrocytes.

Conclusion
Our data showed that miR-520c-3p might regulate the GAS2 to inhibit the progression of OA.
Potential predictors of severe cardiovascular involvement in Marfan syndrome: the emphasized role of genotype–phenotype correlations in improving risk stratification—a literature review
Authors: Stengl Roland , Ágg Bence , Pólos Miklós , Mátyás Gábor , Szabó Gábor , Merkely Béla , Radovits Tamás , Szabolcs Zoltán , Benke Kálmán 
Published: May 2021

Abstract
Background
Marfan syndrome (MFS) is a genetically determined systemic connective tissue disorder, caused by a mutation in the FBN1 gene. In MFS mainly the cardiovascular, musculoskeletal and ocular systems are affected. The most dangerous manifestation of MFS is aortic dissection, which needs to be prevented by a prophylactic aortic root replacement.

Main body
The indication criteria for the prophylactic procedure is currently based on aortic diameter, however aortic dissections below the threshold defined in the guidelines have been reported, highlighting the need for a more accurate risk stratification system to predict the occurrence of aortic complications. The aim of this review is to present the current knowledge on the possible predictors of severe cardiovascular manifestations in MFS patients, demonstrating the wide range of molecular and radiological differences between people with MFS and healthy individuals, and more importantly between MFS patients with and without advanced aortic manifestations. These differences originating from the underlying common molecular pathological processes can be assessed by laboratory (e.g. genetic testing) and imaging techniques to serve as biomarkers of severe aortic involvement. In this review we paid special attention to the rapidly expanding field of genotype–phenotype correlations for aortic features as by collecting and presenting the ever growing number of correlations, future perspectives for risk stratification can be outlined.

Conclusions
Data on promising biomarkers of severe aortic complications of MFS have been accumulating steadily. However, more unifying studies are required to further evaluate the applicability of the discussed predictors with the aim of improving the risk stratification and therefore the life expectancy and quality of life of MFS patients.
Legacies of humanitarian neglect: long term experiences of children who returned from the Lord’s Resistance Army in Uganda
Authors: Parker Melissa , Fergus Cristin A. , Brown Charlotte , Atim Dorothy , Ocitti James , Atingo Jackline , Allen Tim 
Published: May 2021

AbstractBackgroundMuch has been written about the short-term challenges facing children returning ‘home’ from rebel fighting groups, but little is known about the longer term day to day realities of return. This article presents findings from the first long-term assessment of the social and economic challenges facing an officially registered group of children who passed through an internationally-financed reception centre after a period of time with the Lord’s Resistance Army (LRA).MethodsRecords from a reception centre were used to trace a random sample of individuals to their current location. Two hundred and thirty in-depth semi-structured interviews were carried out and 40 follow-up interviews between 2013 and 2016.Interviews were informed by long-term ethnographic research in the region. These interviews were subsequently coded and analysed to describe the long-term day to day realities of return.ResultsAt the time of interview, 90% of formerly abducted people returned ‘home’ six or more years ago, and 75% returned nine or more years ago. The majority have managed to access family land for farming, but concerns about what they may have done to survive whilst living with the LRA adversely affects their day-to-day lives. However, some important differences were noted: those men and women who spent less time with the LRA are more likely to live on ancestral land with close relatives; and they are more likely to report experiencing stigma and a spiritual affliction called ‘cen’. In contrast, those who spent the longest time with the LRA are less likely to report these problems, they are mainly living in urban locations and tend to manage slightly better. Children born of war are vulnerable to abuse, irrespective of current residence.ConclusionsResearch findings question the merits of post-conflict reintegration programmes emphasising immediate family reunifications, without follow-up monitoring, social protection, education and skills training. By overlooking the diverse experiences of those who lived and fought with the LRA, and failing to anticipate or respond to the long term socio-political and economic challenges facing children on their return, reception centre processes not only failed to foster social reintegration, but they also inadvertently exacerbated the vulnerability of returning children.
Oleaginous yeasts respond differently to carbon sources present in lignocellulose hydrolysate
Authors: Brandenburg Jule , Blomqvist Johanna , Shapaval Volha , Kohler Achim , Sampels Sabine , Sandgren Mats , Passoth Volkmar 
Published: May 2021

Abstract
Background
Microbial oils, generated from lignocellulosic material, have great potential as renewable and sustainable alternatives to fossil-based fuels and chemicals. By unravelling the diversity of lipid accumulation physiology in different oleaginous yeasts grown on the various carbon sources present in lignocellulose hydrolysate (LH), new targets for optimisation of lipid accumulation can be identified. Monitoring lipid formation over time is essential for understanding lipid accumulation physiology. This study investigated lipid accumulation in a variety of oleaginous ascomycetous and basidiomycetous strains grown in glucose and xylose and followed lipid formation kinetics of selected strains in wheat straw hydrolysate (WSH).

Results
Twenty-nine oleaginous yeast strains were tested for their ability to utilise glucose and xylose, the main sugars present in WSH. Evaluation of sugar consumption and lipid accumulation revealed marked differences in xylose utilisation capacity between the yeast strains, even between those belonging to the same species. Five different promising strains, belonging to the species Lipomyces starkeyi, Rhodotorula glutinis, Rhodotorula babjevae and Rhodotorula toruloides, were grown on undiluted wheat straw hydrolysate and lipid accumulation was followed over time, using Fourier transform-infrared (FTIR) spectroscopy. All five strains were able to grow on undiluted WSH and to accumulate lipids, but to different extents and with different productivities. R. babjevae DVBPG 8058 was the best-performing strain, accumulating 64.8% of cell dry weight (CDW) as lipids. It reached a culture density of 28 g/L CDW in batch cultivation, resulting in a lipid content of 18.1 g/L and yield of 0.24 g lipids per g carbon source. This strain formed lipids from the major carbon sources in hydrolysate, glucose, acetate and xylose. R. glutinis CBS 2367 also consumed these carbon sources, but when assimilating xylose it consumed intracellular lipids simultaneously. Rhodotorula strains contained a higher proportion of polyunsaturated fatty acids than the two tested Lipomyces starkeyi strains.

Conclusions
There is considerable metabolic diversity among oleaginous yeasts, even between closely related species and strains, especially when converting xylose to biomass and lipids. Monitoring the kinetics of lipid accumulation and identifying the molecular basis of this diversity are keys to selecting suitable strains for high lipid production from lignocellulose.