bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engaging future healthcare professionals for rural health services in South Africa: students, graduates and managers perceptions
Authors: Gumede Dumsani M. , Taylor Myra , Kvalsvig Jane D. 
Published: March 2021

AbstractBackgroundThe shortage of healthcare professionals (HCP) negatively affects health services in rural areas in many parts of the world, as is the case in South Africa. Innovative programs designed to improve the recruitment strategies for health system in a rural area are essential. They need support with a scholarship and mentorship programme for young people from rural areas to study for health science degrees, with the aim that they would take up a post at the hospital in their community, once qualified.This paper reports the perceptions and experiences of the students and graduates sponsored by the foundation, and those of managers from the facilities where the students were ultimately placed, in order to gauge whether such a programme can make a sustainable contribution to address the shortage of health personnel in rural areas and to what extent this is happening.MethodsThe authors used qualitative methods, combining semi-structured in-depth interviews and focus groups and the data were analyzed thematically.ResultsThe results provide information on students interviewed who appreciated the financial and socio-emotional support that they received. On the other hand, graduates value the availability of jobs in their home community on completion of their studies. The managers reported the success of the programme in increasing the number of healthcare personnel at the hospitals, and the increased range of available medical services. Since the graduates are familiar with the language and culture of their patients the managers considered that they are better able to assist them.ConclusionsThe system was well thought-out and achieved its goal of improving health services in an underdeveloped rural area of South Africa. More could be achieved if other government services in the area were simultaneously improved and if the system were replicated elsewhere. The students and graduates from rural areas are involved on sustaining health services in rural areas while rural managers support the programme and make suggestions for improvement and to promote the program in other regions.
Identification of four key prognostic genes and three potential drugs in human papillomavirus negative head and neck squamous cell carcinoma
Authors: Tian Guocai , Fu You , Zhang Dahe , Li Jiang , Zhang Zhiyuan , Yang Xi 
Published: March 2021

AbstractBackgroundHead and neck squamous cell carcinoma (HNSCC) is a common tumor worldwide with poor prognosis. The pathogenesis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs differs. However, few studies have considered the HPV status when identifying biomarkers for HNSCC. Thus, the identification of biomarkers for HPV-positive and HPV-negative HNSCCs is urgently needed.MethodsThree microarray datasets from Gene Expression Omnibus (GEO) were analyzed, and the differentially expressed genes (DEGs) were obtained. Then, functional enrichment pathway analysis was performed and protein–protein interaction (PPI) networks were constructed. The expression of hub genes at both the mRNA and protein level was determined in Oncomine, The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). In addition, survival analysis of the patient stratified by HPV status and the expression levels of key genes were performed based on TCGA data. The role of AREG, STAG3, CAV1 and C19orf57 in cancer were analyzed through Gene set enrichment analysis (GSEA). The top ten small molecule drugs were identified and the therapeutic value of zonisamide, NVP-AUY922, PP-2 and fostamatinib was further evaluated in six HPV-negative HNSCC cell lines. Finally, the therapeutic value of NVP-AUY922 was tested in vivo based on three HPV-negative HNSCC models, and statistical analysis was performed.ResultsIn total, 47 DEGs were obtained, 11 of which were identified as hub genes. Biological process analysis indicated that the hub genes were associated with the G1/S transition of the mitotic cell cycle. Survival analysis uncovered that the prognostic value of AREG, STAG3, C19orf57 and CAV1 differed between HPV-positive and HPV-negative patients. Gene set enrichment analysis (GSEA) showed the role of AREG, STAG3 and CAV1 in dysregulated pathways of tumor. Ten small molecules were identified as potential drugs specifically for HPV-positive or HPV-negative patients; three—NVP-AUY922, fostamatinib and PP-2—greatly inhibited the proliferation of six HPV-negative HNSCC cell lines in vitro, and NVP-AUY922 inhibited three HPV-negative HNSCC xenografts in vivo.ConclusionsIn conclusion, AREG, STAG3, C19orf57 and CAV1 are key prognostic factors and potential therapeutic targets in HPV-negative HNSCC. NVP-AUY922, fostamatinib and PP-2 may be effective drugs for HPV-negative HNSCC.
Fitness characteristics of the malaria vector Anopheles funestus during an attempted laboratory colonization
Authors: Ngowo Halfan S. , Hape Emmanuel E. , Matthiopoulos Jason , Ferguson Heather M. , Okumu Fredros O. 
Published: March 2021

AbstractBackgroundThe malaria vectorAnopheles funestusis increasingly recognized as a dominant vector of residual transmission in many African settings. Efforts to better understand its biology and control are significantly impeded by the difficulties of colonizing it under laboratory conditions. To identify key bottlenecks in colonization, this study compared the development and fitness characteristics of wildAn. funestusfrom Tanzania (FUTAZ) and their F1offspring during colonization attempts. The demography and reproductive success of wild FUTAZ offspring were compared to that of individuals from one of the onlyAn. funestusstrains that has been successfully colonized (FUMOZ, from Mozambique) under similar laboratory conditions.MethodsWildAn. funestus(FUTAZ) were collected from three Tanzanian villages and maintained inside an insectary at 70–85% RH, 25–27 °C and 12 h:12 h photoperiod. Eggs from these females were used to establish three replicate F1laboratory generations. Larval development, survival, fecundity, mating success, percentage pupation and wing length were measured in the F1-FUTAZ offspring and compared with wild FUTAZ and FUMOZ mosquitoes.ResultsWild FUTAZ laid fewer eggs (64.1; 95% CI [63.2, 65.0]) than FUMOZ females (76.1; 95% CI [73.3, 79.1]). Survival of F1-FUTAZ larvae under laboratory conditions was low, with an egg-to-pupae conversion rate of only 5.9% compared to 27.4% in FUMOZ. The median lifespan of F1-FUTAZ females (32 days) and males (33 days) was lower than FUMOZ (52 and 49 for females and males respectively). The proportion of female F1-FUTAZ inseminated under laboratory conditions (9%) was considerably lower than either FUMOZ (72%) or wild-caught FUTAZ females (92%). This resulted in nearly zero viable F2-FUTAZ eggs produced. Wild FUTAZ wings appear to be larger compared to the lab reared F1-FUTAZ and FUMOZ.ConclusionsThis study indicates that poor larval survival, mating success, low fecundity and shorter survival under laboratory conditions all contribute to difficulties in colonizing ofAn. funestus. Future studies should focus on enhancing these aspects ofAn. funestusfitness in the laboratory, with the biggest barrier likely to be poor mating.
Rapid diagnostic test negative Plasmodium falciparum malaria in a traveller returning from Ethiopia
Authors: Schlabe Stefan , Reiter-Owona Ingrid , Nordmann Tamara , Dolscheid-Pommerich Ramona , Tannich Egbert , Hoerauf Achim , Rockstroh Jürgen 
Published: March 2021

Abstract
Background
Plasmodium falciparum strains with mutations/deletions of the genes encoding the histidine-rich proteins 2/3 (pfhrp2/3) have emerged during the last 10 years leading to false-negative results in HRP2-based rapid diagnostic tests (RDTs). This can lead to unrecognized infections in individuals and to setbacks in malaria control in endemic countries where RDTs are the backbone of malaria diagnostics and control.

Case description
Here the detection of a pfhrp2/3-negative P. falciparum infection acquired in Ethiopia by a 63-year old female traveller is presented. After onset of symptoms during travel, she was first tested negative for malaria, most probably by RDT, at a local hospital in Harar, Ethiopia. Falciparum malaria was finally diagnosed microscopically upon her return to Germany, over 4 weeks after infection. At a parasite density of approximately 5387 parasites/µl, two different high-quality RDTs: Palutop + 4 OPTIMA, NADALRMalaria PF/pan Ag 4 Species, did not respond at their respective P. falciparum test lines. pfhrp2/3 deletion was confirmed by multiplex-PCR. The patient recovered after a complete course of atovaquone and proguanil. According to the travel route, malaria was acquired most likely in the Awash region, Central Ethiopia. This is the first case of imported P. falciparum with confirmed pfhrp2/3 deletion from Ethiopia.

Conclusion
HRP2-negative P. falciparum strains may not be recognized by the presently available HRP2-based RDTs. When malaria is suspected, confirmation by microscopy and/or qPCR is necessary in order to detect falciparum malaria, which requires immediate treatment. This case of imported P. falciparum, non-reactive to HRP2-based RDT, possibly underlines the necessity for standardized, nationwide investigations in Ethiopia and should alert clinicians from non-endemic countries to the possibility of false-negative RDT results which may increase in returning travellers with potentially life-threatening infections.
Dietary patterns and associations with biomarkers of inflammation in adults: a systematic review of observational studies
Authors: Hart Michael J. , Torres Susan J. , McNaughton Sarah A. , Milte Catherine M. 
Published: March 2021

AbstractBackgroundEvidence indicates that low-grade inflammation is involved in manychronic diseases of ageing. Modifiable lifestyle factors including dietcan affect low-grade inflammation. Dietary patterns allow assessment of the complex interactions of food nutrients and health and may be associated with inflammatory status.This systematic review aimed to summarises current evidence from observational studies for associations between dietary patterns and inflammatory biomarkers in the general adult population. This review followed the PRISMA guidelines.MethodsWe conducted a systematic search in Embase, CINAHL Complete, Global Health and MEDLINE complete databases. Search terms included terms for diet (“dietary patterns”, “diet scores”) and inflammation (“inflammation“, “c-reactive protein“, “interleukin“).ResultsThe search produced 7161 records. Duplicates were removed leaving 3164 for screening. There were 69 studies included (60 cross-sectional, 9 longitudinal). Papers included studies that were: 1) observational studies; 2) conducted in community-dwelling adults over 18 years of age; 3) assessed dietary patterns; 4) measured specified biomarkers of inflammation and 5) published in English. Dietary patterns were assessed using diet scores (n = 45), data-driven approaches (n = 22), both a data-driven approach and diet score (n = 2). The most frequently assessed biomarkers were CRP (n = 64) and/or IL-6 (n = 22). Cross-sectionally the majority of analyses reported an association between higher diet scores (mostly Mediterranean and anti-inflammatory diet scores) and lower inflammatory markers with 82 significant associations from 133 analyses. Only 22 of 145 cross-sectional analyses using data-driven approaches reported an association between a dietary patterns and lower inflammatory markers; the majority reported no association. Evidence of an association between dietary patterns and inflammatory markers longitudinally is limited, with the majority reporting no association.ConclusionsAdherence to healthy, Mediterranean and anti-inflammatory dietary scores, appear to be associated with lower inflammatory status cross-sectionally. Future research could focus on longitudinal studies using a potential outcomes approach in the data analysis.Trial registrationPROSPERO Registration NumberCRD42019114501.
Prenatal exposure to bisphenol A and autistic- and ADHD-related symptoms in children aged 2 and5 years from the Odense Child Cohort
Authors: Hansen Julie Bang , Bilenberg Niels , Timmermann Clara Amalie Gade , Jensen Richard Christian , Frederiksen Hanne , Andersson Anna-Maria , Kyhl Henriette Boye , Jensen Tina Kold 
Published: March 2021

Abstract
Background
Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive.

Objective
To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children.

Method
In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score.

Results
BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03).

Conclusion
Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.
Extracellular vesicles isolated by size-exclusion chromatography present suitability for RNomics analysis in plasma
Authors: Yang Yang , Wang Yaojie , Wei Sisi , Zhou Chaoxi , Yu Jiarui , Wang Guiying , Wang Wenxi , Zhao Lianmei 
Published: March 2021

Abstract
Background
Extracellular vesicles (EVs), known as cell-derived membranous structures harboring a variety of biomolecules, have been widely used in liquid biopsy. Due to the complex biological composition of plasma, plasma RNA omics analysis (RNomics) is easily affected, thus it is necessary to select an optimal strategy from exiting methods according to the performance for intended application.

Methods
In this study, four different strategies for EVs isolation were performed and compared (i.e. ultracentrifugation (UC), size exclusion chromatography (SEC), and two most frequently-used commercially available isolation kit (ExoQuick and exoEasy). We compared the yield, purity, PCR quantification of RNAs, miRNA-seq analyses and mRNA-seq analyses of RNAs from EVs isolated using four methods.

Results
The results showed that the lowest miRNA binding protein AGO2 (Argonaute-2) and the highest EVs-specific miRNA and lncRNA were observed in EVs obtained through SEC, meanwhile the content of the non-specific miRNA was the lowest. Further RNA-Seq data revealed that RNAs obtained via SEC presented more useful reads for both miRNA and mRNA. Furthermore, the mRNA delivered via SEC tended to have a concentration comparable to the ideal FPKM (Fragments Per Kilobase Million) value.

Conclusions
SEC shall be used as an optimal strategy for the isolation of EVs in plasma RNomics analysis.
Sialadenoma papilliferum: clinicopathologic, Immunohistochemical, molecular analyses of new five cases and review of the literature
Authors: Chen Shuai , Peng Jie , Yuan Chuantao , Sun Lin , Zhang Renya , Sun Yan 
Published: March 2021

Abstract
Background
Sialadenoma papilliferum (SP) is an extremely rare benign neoplasm of salivary glands. To explore and define the clinicopathological features of SP, we retrospectively analyzed 89 cases previously reported and five new cases.

Methods
The clinical features, histopathology, immunohistochemistry and molecular analysis of our cases were further performed and the related literatures were reviewed and analyzed.

Results
Combining 89 cases from the literature with our cases, the hard palate was the most common locations for SP. However, two of our cases were rarely located in the esophageal mucosa. Among all cases, the male gender was more affected, with the average age and median age of 61.8 and 62 years, respectively. Conventional histomorphologically, SP was characterized by complex papillary structures with a biphasic growth pattern of exophytic squamous component and endophytic glandular component. The glandular structures were lined by a double layer of epithelium composed of flattened or cuboidal basal cells and a cuboidal or columnar luminal cells formed papillary infoldings into the ductal lumina. Immunohistochemically, the luminal epithelial configurations showed strong expression of CK7 along the luminal cell membrane, while the basal myoepithelia displayed strong nuclear p63 expression. In both the glandular and squamous tumour components showed BRAF V600E-positive immunostaining and BRAF V600E mutation.

Conclusion
For the first time, we have comprehensively aggregated and analyzed 90 cases sialadenoma papilliferum from almost all previous publications, and further explored the clinicopathological features of SP; concordantly, this study demonstrated that SP shows a papillomatous growth pattern with exophytic and endophytic proliferation of ductal epithelium composed of double-layered cells harboring BRAF V600E mutation. Additionly, adequate treatment for SP is surgical excision, with a favorable prognosis in patients.
Extending the phenotypic spectrum of PRPF8, PRPH2, RP1 and RPGR, and the genotypic spectrum of early-onset severe retinal dystrophy
Authors: Georgiou Michalis , Ali Naser , Yang Elizabeth , Grewal Parampal S. , Rotsos Tryfon , Pontikos Nikolas , Robson Anthony G. , Michaelides Michel 
Published: March 2021

Abstract
Purpose
To present the detailed retinal phenotype of patients with Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy (LCA/EOSRD) caused by sequence variants in four genes, either not (n = 1) or very rarely (n = 3) previously associated with the disease.

Methods
Retrospective case series of LCA/EOSRD from four pedigrees. Chart review of clinical notes, multimodal retinal imaging, electrophysiology, and molecular genetic testing at a single tertiary referral center (Moorfields Eye Hospital, London, UK).

Results
The mean age of presentation was 3 months of age, with disease onset in the first year of life in all cases. Molecular genetic testing revealed the following disease-causing variants: PRPF8 (heterozygous c.5804G > A), PRPH2 (homozygous c.620_627delinsTA, novel variant), RP1 (homozygous c.4147_4151delGGATT, novel variant) and RPGR (heterozygous c.1894_1897delGACA). PRPF8, PRPH2, and RP1 variants have very rarely been reported, either as unique cases or case reports, with limited clinical data presented. RPGR variants have not previously been associated with LCA/EOSRD. Clinical history and detailed retinal imaging are presented.

Conclusions
The reported cases extend the phenotypic spectrum of PRPF8-, PRPH2-, RP1-, and RPGR-associated disease, and the genotypic spectrum of LCA/EOSRD. The study highlights the importance of retinal and functional phenotyping, and the importance of specific genetic diagnosis to potential future therapy.
Facioscapulohumeral muscular dystrophy: genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: an update
Authors: Schätzl Teresa , Kaiser Lars , Deigner Hans-Peter 
Published: March 2021

AbstractWhilst a disease-modifying treatment for Facioscapulohumeral muscular dystrophy (FSHD) does not exist currently, recent advances in complex molecular pathophysiology studies of FSHD have led to possible therapeutic approaches for its targeted treatment. Although the underlying genetics of FSHD have been researched extensively, there remains an incomplete understanding of the pathophysiology of FSHD in relation to the molecules leading toDUX4gene activation and the downstream gene targets ofDUX4that cause its toxic effects. In the context of the local proximity of chromosome 4q to the nuclear envelope, a contraction of the D4Z4 macrosatellite induces lower methylation levels, enabling the ectopic expression ofDUX4. This disrupts numerous signalling pathways that mostly result in cell death, detrimentally affecting skeletal muscle in affected individuals. In this regard different options are currently explored either to suppress the transcription ofDUX4gene, inhibitingDUX4protein from its toxic effects, or to alleviate the symptoms triggered by its numerous targets.