bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public health implications of heavy metals in foods and drinking water in Ethiopia (2016 to 2020): systematic review
Authors: Mengistu Dechasa Adare 
Published: November 2021

Abstract
Background
Besides their benefits, heavy metals are toxic, persistent, and hazardous to human health, even at their lower concentrations. Consumption of unsafe concentrations of food contaminated with heavy metals may lead to the disruption of numerous biological and biochemical processes in the human body. In developing country including Ethiopia, where untreated or partially treated wastewater is used for agricultural purposes, the problems related to the consumption foods contaminated with heavy metals may poses highest risk to human health. Therefore, this review was aimed to determine the public health implications of heavy metals in foods and drinking water in Ethiopia.

Methods
The articles published from 2016 to 2020 were identified through systematic searches of electronic databases that include MEDLINE/PubMed, EMBASE, CINAH, Google Scholar, WHO, and FAO Libraries. The data was extracted using a predetermined data extraction form using Microsoft Excel, 2016. The methodological quality of the included studies was assessed using mixed methods appraisal tool (MMAT) version 2018 and Joanna Briggs Institute Critical Appraisal tools to determine the relevance of the studies. Finally, the results were evaluated based on the FAO/WHO guidelines for foods and drinking water.

Results
A total of 1019 articles published from 2016 to 2020 were searched from various electronic databases and by manual searching on Google. Following the initial screening, 317 articles were retrieved for evaluation and 49 articles were assessed for eligibility, of which 21 studies were included in the systematic review. The mean concentration of Cr, Cd, Pb, As, Hg, Zn, Cu, Ni, Co, Fe and Mn in fruits and vegetables ranged from 2.068–4.29, 0.86–1.37, 1.90–4.70, 1.01–3.56, 3.43–4.23, 19.18–98.15, 4.39–9.42, 1.037–5.27, 0.19–1.0, 199.5–370.4, 0.26–869 mg/kg, respectively. The mean concentration Cr, Cd, Pb, As, Zn, and Fe in meat and milk ranged from 1.032–2.72, 0.233–0.72, 1.32–3.15, 0.79–2.96, 78.37–467.7, and 505.61–3549.9 mg/kg, respectively. The mean concentration of Cr, Cd, Pb, Zn, and Cu in drinking water ranged 0.0089–0.054, 0.02–0.0237, 0.005–0.369, 0.625–2.137, and 0.176–1.176 ml/L, respectively. The mean concentration of Cr, Cd, Pb, Zn, Cu, Ni, Co, Fe, and Mn in other edible cereals ranged from 0.973–2.165, 0.424–0.55, 0.65–1.70, 70.51–81.58, 14.123–15.98, 1.89–13.8, 1.06–1.59, 67.866–110.3, and 13.686–15.4 mg/kg, respectively.

Conclusion
This systematic review identified heavy metals in foods and drinking water and determined their public health implications. The results of this finding imply that the majority of the studies reported high concentrations of toxic heavy metals in foods and drinking water that are hazardous to human health. Therefore, effective food safety and risk-based food quality assessment are essential to protect the public health.
Hounsfield unit value on CT as a predictor of cage subsidence following stand-alone oblique lumbar interbody fusion for the treatment of degenerative lumbar diseases
Authors: Zhou Jing , Yuan Chao , Liu Chao , Zhou Lei , Wang Jian 
Published: November 2021

Abstract
Background
To investigate the correlation between vertebral Hounsfield unit (HU) values and cage subsidence in patients treated with stand-alone (SA) OLIF.

Methods
A retrospective review of collected data was performed on 76 patients who underwent SA OLIF. We utilized the HU value for lumbar bone mineral density (BMD) obtained on preoperative CT. The vertebral HU values of patients with subsidence were compared to those without subsidence. The correlation between cage subsidence and clinical score was investigated.

Results
Sixteen patients (21.1%) had at least radiographic evidence of interbody cage subsidence. The average cage subsidence was 2.5 ± 1.3 mm (range 0.9-4.8 mm). There were no significant differences in sex, BMI, preoperative diagnoses, or fused level (p > 0.05); however, there were significant differences between the cage subsidence group and the nonsubsidence group in age, average of the lowest T-score, and average HU value, including for the L1 vertebrae, L1-L4 horizontal plane, and L1-L4 sagittal plane (p < 0.05). The average HU value of the L1-L4 horizontal plane showed a more predictable AUC of 0.909 (95% CI, 0.834–0.984; P < 0.001) compared with the average of the lowest T-score following an AUC of 0.791 (95% CI, 0.674–0.909; P < 0.001). Based on logistic regression analysis, the average HU value of the L1-L4 horizontal plane (OR, 0.912; 95% CI, 0.861–0.966; P = 0.002) was an independent factor influencing cage subsidence.

Conclusions
Patients with lower average HU values of the lumbar vertebrae are at a much higher risk of developing cage subsidence after SA OLIF. Measurement of preoperative HU values on preexisting CT scans could be rapid, simple and feasible.
Long-standing pubic-related groin pain in professional academy soccer players: a prospective cohort study on possible risk factors, rehabilitation and return to play
Authors: Eberbach Helge , Fürst-Meroth David , Kloos Ferdinand , Leible Magnus , Bohsung Valentin , Bode Lisa , Wenning Markus , Hagen Schmal , Bode Gerrit 
Published: November 2021

Abstract
Background
Despite being a common overuse entity in youth soccer, scientific data on risk factors, rehabilitation and return to play for long-standing pubic-related groin pain is still rare. The current prospective cohort study aims to evaluate potential risk-factors, propose a criteria-based conservative rehabilitation protocol and assess return-to-play outcomes among professional youth soccer players suffering from long-standing pubic-related groin pain.

Methods
Male soccer players with long-standing (> 6 weeks) pubic-related groin pain from a professional soccer club’s youth academy were analyzed for possible risk factors such as age, team (U12 - U23), younger/older age group within the team, position and preinjury Functional movement score. All injured players received a conservative, standardized, supervised, criteria-based, 6-level rehabilitation program. Outcome measures included time to return to play, recurrent groin pain in the follow-up period and clinical results at final follow-up two years after their return to play.

Results
A total of 14 out of 189 players developed long-standing pubic-related groin pain in the 2017/2018 season (incidence 7.4%). The average age of the players at the time of the injury was 16.1 ± 1.9 years. Risk factor analysis revealed a significant influence of the age group within the team (p = .007). Only players in the younger age group were affected by long-standing pubic-related groin pain, mainly in the first part of the season. Injured players successfully returned to play after an average period of 135.3 ± 83.9 days. Only one player experienced a recurrence of nonspecific symptoms (7.1%) within the follow-up period. The outcome at the 24-month follow-up was excellent for all 14 players.

Conclusions
Long-standing pubic-related groin pain is an overuse entity with a markedly high prevalence in youth soccer players, resulting in a relevant loss of time in training and match play. In particular, the youngest players in each team are at an elevated risk. Applying a criteria-based rehabilitation protocol resulted in an excellent return-to-play rate, with a very low probability of recurrence.

Trial registration
The trial was retrospectively registered under DRKS00016510 in the German Clinical Trials Register on 19.04.2021.
Screening for mild cognitive impairment in people with obesity: a systematic review
Authors: Karunathilaka Nimantha , Rathnayake Sarath 
Published: November 2021

AbstractObjectiveRecent evidence demonstrates that obesity is associated with developing cognitive impairment. However, evidence related to the assessment of mild cognitive impairment (MCI) in people with obesity is limited. Therefore, this systematic review aimed to examine evidence concerning the screening of MCI in people with obesity from the general population.MethodWe conducted a systematic search of CINHAL, EMBASE, MEDLINE, PsycINFO and PubMed electronic databases for observational studies to assess MCI in people with obesity from the general population. PRISMA guideline was followed. The articles published from January 2011 to July 2021 were included.ResultsDatabase search found 3104 sources. After the screening process, two articles from China and Egypt were included. The main age groups assessed were middle-aged adulthood and older adulthood. There were no studies undertaken in young adults or across the life span. Obesity was assessed by body mass index. MCI was assessed by cognitive screening tools; Mini-mental State Examination and Addenbrooke’s Cognitive Examination. The prevalence of MCI in people with obesity was 18.5 % and 42.9 % in Chinese and Egyptian studies, respectively. Only one study supported a positive association between MCI and obesity.ConclusionsLimited studies were found on screening MCI in people with obesity in the general population. The available evidence was not adequate to explain the overall prevalence, possible associations, and the best tool for assessing MCI in people with obesity. Expanding screening studies for MCI in people with obesity in the general population is essential.
EOESGC: predicting miRNA-disease associations based on embedding of embedding and simplified graph convolutional network
Authors: Pang Shanchen , Zhuang Yu , Wang Xinzeng , Wang Fuyu , Qiao Sibo 
Published: November 2021

AbstractBackgroundA large number of biological studies have shown that miRNAs are inextricably linked to many complex diseases. Studying the miRNA-disease associations could provide us a root cause understanding of the underlying pathogenesis in which promotes the progress of drug development. However, traditional biological experiments are very time-consuming and costly. Therefore, we come up with an efficient models to solve this challenge.ResultsIn this work, we propose a deep learning model called EOESGC to predict potential miRNA-disease associations based on embedding of embedding and simplified convolutional network. Firstly, integrated disease similarity, integrated miRNA similarity, and miRNA-disease association network are used to construct a coupled heterogeneous graph, and the edges with low similarity are removed to simplify the graph structure and ensure the effectiveness of edges. Secondly, the Embedding of embedding model (EOE) is used to learn edge information in the coupled heterogeneous graph. The training rule of the model is that the associated nodes are close to each other and the unassociated nodes are far away from each other. Based on this rule, edge information learned is added into node embedding as supplementary information to enrich node information. Then, node embedding of EOE model training as a new feature of miRNA and disease, and information aggregation is performed by simplified graph convolution model, in which each level of convolution can aggregate multi-hop neighbor information. In this step, we only use the miRNA-disease association network to further simplify the graph structure, thus reducing the computational complexity. Finally, feature embeddings of both miRNA and disease are spliced into the MLP for prediction. On the EOESGC evaluation part, the AUC, AUPR, and F1-score of our model are 0.9658, 0.8543 and 0.8644 by 5-fold cross-validation respectively. Compared with the latest published models, our model shows better results. In addition, we predict the top 20 potential miRNAs for breast cancer and lung cancer, most of which are validated in the dbDEMC and HMDD3.2 databases.ConclusionThe comprehensive experimental results show that EOESGC can effectively identify the potential miRNA-disease associations.
Cell type identification from single-cell transcriptomes in melanoma
Authors: Huo Qiuyan , Yin Yu , Liu Fangfang , Ma Yuying , Wang Liming , Qin Guimin 
Published: November 2021

Abstract
Background
Single-cell sequencing approaches allow gene expression to be measured at the single-cell level, providing opportunities and challenges to study the aetiology of complex diseases, including cancer.

Methods
Based on single-cell gene and lncRNA expression levels, we proposed a computational framework for cell type identification that fully considers cell dropout characteristics. First, we defined the dropout features of the cells and identified the dropout clusters. Second, we constructed a differential co-expression network and identified differential modules. Finally, we identified cell types based on the differential modules.

Results
The method was applied to single-cell melanoma data, and eight cell types were identified. Enrichment analysis of the candidate cell marker genes for the two key cell types showed that both key cell types were closely related to the physiological activities of the major histocompatibility complex (MHC); one key cell type was associated with mitosis-related activities, and the other with pathways related to ten diseases.

Conclusions
Through identification and analysis of key melanoma-related cell types, we explored the molecular mechanism of melanoma, providing insight into melanoma research. Moreover, the candidate cell markers for the two key cell types are potential therapeutic targets for melanoma.
Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice
Authors: Zhou Lei , Wu Bo , Yang Jun , Wang Bing , Pan Jing , Xu Donghui , Du Chunling 
Published: November 2021

Abstract
Background
Chronic obstructive pulmonary disease (COPD) remains a prevalent chronic airway inflammatory disease. Circular RNAs (circRNAs) are associated with inflammation regulation; therefore, we examined distinct effects of circRNA FOXO3 (circFOXO3) against pneumonic inflammatory processes in COPD.

Methods
We first quantified and localized circFOXO3 in mouse lung epithelial cell line MLE12 by quantitative reverse-transcription PCR and in situ hybridization. Next, circFOXO3 was suppressed by therapeutic administration of circFOXO3 knockdown lentivirus in mice exposed to air or cigarette smoke (CS) for 12 weeks, and several hallmarks of COPD were evaluated.

Results
We noticed that circFOXO3 is upregulated in CS-exposed lungs and cigarette smoke extract (CSE)-treated murine alveolar epithelial cells. Knockdown of circFOXO3 attenuated the release of CXCL1 and IL-6 as well as inflammatory processes in the lungs of CS-exposed mice. In addition, we identified miR-214-3p as a circFOXO3-targeted microRNA. MiR-214-3p overexpression exerted protective effects against pneumonic inflammation after CS exposure. Silencing of circFOXO3 downregulated IKK-β mRNA (miR-214-3p’s target), resulting in the dysfunction of the NF-κB signaling pathway and attenuation of CSE-induced inflammatory-cytokine expression.

Conclusions
Collectively, these findings reveal a crucial function of circFOXO3 in the pathological remodeling related to CS-induced inflammatory processes. Hence, circFOXO3 might be a good target for the treatment of inflammatory disorders similar to CS-induced lung inflammation.
Anticancer effects of mifepristone on human uveal melanoma cells
Authors: Alvarez Prisca Bustamante , Laskaris Alexander , Goyeneche Alicia A. , Chen Yunxi , Telleria Carlos M. , Burnier Julia V. 
Published: November 2021

Abstract
Background
Uveal melanoma (UM), the most prevalent intraocular tumor in adults, is a highly metastatic and drug resistant lesion. Recent studies have demonstrated cytotoxic and anti-metastatic effects of the antiprogestin and antiglucocorticoid mifepristone (MF) in vitro and in clinical trials involving meningioma, colon, breast, and ovarian cancers. Drug repurposing is a cost-effective approach to bring approved drugs with good safety profiles to the clinic. This current study assessed the cytotoxic effects of MF in human UM cell lines of different genetic backgrounds.

Methods
The effects of incremental concentrations of MF (0, 5, 10, 20, or 40 μM) on a panel of human UM primary (MEL270, 92.1, MP41, and MP46) and metastatic (OMM2.5) cells were evaluated. Cells were incubated with MF for up to 72 h before subsequent assays were conducted. Cellular functionality and viability were assessed by Cell Counting Kit-8, trypan blue exclusion assay, and quantitative label-free IncuCyte live-cell analysis. Cell death was analyzed by binding of Annexin V-FITC and/or PI, caspase-3/7 activity, and DNA fragmentation. Additionally, the release of cell-free DNA was assessed by droplet digital PCR, while the expression of progesterone and glucocorticoid receptors was determined by quantitative real-time reverse transcriptase PCR.

Results
MF treatment reduced cellular proliferation and viability of all UM cell lines studied in a concentration-dependent manner. A reduction in cell growth was observed at lower concentrations of MF, with evidence of cell death at higher concentrations. A significant increase in Annexin V-FITC and PI double positive cells, caspase-3/7 activity, DNA fragmentation, and cell-free DNA release suggests potent cytotoxicity of MF. None of the tested human UM cells expressed the classical progesterone receptor in the absence or presence of MF treatment, suggesting a mechanism independent of the modulation of the cognate nuclear progesterone receptor. In turn, all cells expressed non-classical progesterone receptors and the glucocorticoid receptor.

Conclusion
This study demonstrates that MF impedes the proliferation of UM cells in a concentration-dependent manner. We report that MF treatment at lower concentrations results in cell growth arrest, while increasing the concentration leads to lethality. MF, which has a good safety profile, could be a reliable adjuvant of a repurposing therapy against UM.
Analysis of the potential for a malaria vaccine to reduce gaps in malaria intervention coverage
Authors: Unwin H. Juliette T. , Mwandigha Lazaro , Winskill Peter , Ghani Azra C. , Hogan Alexandra B. 
Published: November 2021

Abstract
Background
The RTS,S/AS01 malaria vaccine is currently being evaluated in a cluster-randomized pilot implementation programme in three African countries. This study seeks to identify whether vaccination could reach additional children who are at risk from malaria but do not currently have access to, or use, core malaria interventions.

Methods
Using data from household surveys, the overlap between malaria intervention coverage and childhood vaccination (diphtheria-tetanus-pertussis dose 3, DTP3) uptake in 20 African countries with at least one first administrative level unit with Plasmodium falciparum parasite prevalence greater than 10% was calculated. Multilevel logistic regression was used to explore patterns of overlap by demographic and socioeconomic variables. The public health impact of delivering RTS,S/AS01 to those children who do not use an insecticide-treated net (ITN), but who received the DTP3 vaccine, was also estimated.

Results
Uptake of DTP3 was higher than malaria intervention coverage in most countries. Overall, 34% of children did not use ITNs and received DTP3, while 35% of children used ITNs and received DTP3, although this breakdown varied by country. It was estimated that there are 33 million children in these 20 countries who do not use an ITN. Of these, 23 million (70%) received the DTP3 vaccine. Vaccinating those 23 million children who receive DTP3 but do not use an ITN could avert up to an estimated 9.7 million (range 8.5–10.8 million) clinical malaria cases each year, assuming all children who receive DTP3 are administered all four RTS,S doses. An additional 10.8 million (9.5–12.0 million) cases could be averted by vaccinating those 24 million children who receive the DTP3 vaccine and use an ITN. Children who had access to or used an ITN were 9–13% more likely to reside in rural areas compared to those who had neither intervention regardless of vaccination status. Mothers’ education status was a strong predictor of intervention uptake and was positively associated with use of ITNs and vaccination uptake and negatively associated with having access to an ITN but not using it. Wealth was also a strong predictor of intervention coverage.

Conclusions
Childhood vaccination to prevent malaria has the potential to reduce inequity in access to existing malaria interventions and could substantially reduce the childhood malaria burden in sub-Saharan Africa, even in regions with lower existing DTP3 coverage.
Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
Authors: Zurmühl Noelle , Schmitt Anna , Formentini Ulrike , Weiss Johannes , Appel Heike , Debatin Klaus-Michael , Fabricius Dorit 
Published: November 2021

Abstract
Background
Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood.

Methods
This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy.

Results
We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects.

Conclusions
To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.
Quantitative assessment of AD markers using naked eyes: point-of-care testing with paper-based lateral flow immunoassay
Authors: Zhang Liding , Du Xuewei , Su Ying , Niu Shiqi , Li Yanqing , Liang Xiaohan , Luo Haiming 
Published: November 2021

AbstractAβ42is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer’s disease (AD). Because of the heterogeneity and transient nature of Aβ42oligomers (Aβ42Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ42monomers (Aβ42Ms) and Aβ42Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ42ELISA test kits usually mis-detected the elevated Aβ42Os, leading to incomplete analysis and underestimation of soluble Aβ42, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ42monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ42Ms and Aβ42Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ42Ms or/and Aβ42Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment.Graphical Abstract