bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Novasil Clay (Calcium Montmorillonite) in Children Exposed to Aflatoxin in Ejura-Sekyedumase District in Ghana
Authors: Kumi Justice , Appiah-Opong Regina , Rein Dietrich , Egbi Godfred , Aninagyei Enoch , Boye Alex , Omane-Acheampong Desmond 
Published: September 2022

Background. Aflatoxin levels are very high in animals and humans in places where cereals are poorly stored. In this study, Novasil was evaluated for safety and efficacy in children. Methods. Children (200) aged between 2 and 9 years were put into Novasil and placebo group. Participants received either 1.5 g of Novasil or calcium carbonate in their food. Urine samples were analyzed for AFM1 by HPLC, blood samples were assayed for complete blood count and chemistries. Results. Aflatoxin M1 levels in the Novasil treated group, significantly reduced to 60% compared to an increase of urine AFM1 in the placebo group. Hematological parameters did not change except for an increase in hemoglobin level in the Novasil group. Biochemical parameters remained unchanged except calcium ions. Glutathione levels in the Novasil increased, compared group to the placebo group. Conclusion. Novasil is safe, reduce aflatoxin bioavailability in humans while improving GSH antioxidant capacity as well. The trial has been registered with Pan African Clinical Trial Registry ( www.pactr.org ). A WHO registry for clinical trials with a unique identification number PACTR202202797930675.
Tracing the evolutionary history of blood cells to the unicellular ancestor of animals
Authors: Nagahata Yosuke , Masuda Kyoko , Nishimura Yuji , Ikawa Tomokatsu , Kawaoka Shinpei , Kitawaki Toshio , Nannya Yasuhito , Ogawa Seishi , Suga Hiroshi , Satou Yutaka , Takaori-Kondo Akifumi , Kawamoto Hiroshi 
Published: September 2022

Abstract
Blood cells are thought to have emerged as phagocytes in the common ancestor of animals followed by the appearance of novel blood cell lineages such as thrombocytes, erythrocytes, and lymphocytes, during evolution. However, this speculation is not based on genetic evidence and it is still possible to argue that phagocytes in different species have different origins. It also remains to be clarified how the initial blood cells evolved; whether ancient animals have solely developed de novo programs for phagocytes or they have inherited a key program from ancestral unicellular organisms. Here, we traced the evolutionary history of blood cells, and cross-species comparison of gene expression profiles revealed that phagocytes in various animal species and Capsaspora (C.) owczarzaki, a unicellular organism, are transcriptionally similar to each other. We also found that both phagocytes and C. owczarzaki share a common phagocytic program, and that CEBPα is the sole transcription factor highly expressed in both phagocytes and C. owczarzaki. We further showed that the function of CEBPα to drive phagocyte program in nonphagocytic blood cells has been conserved in tunicate, sponge, and C. owczarzaki. We finally showed that, in murine hematopoiesis, repression of CEBPα to maintain nonphagocytic lineages is commonly achieved by polycomb complexes. These findings indicate that the initial blood cells emerged inheriting a unicellular organism program driven by CEBPα and that the program has also been seamlessly inherited in phagocytes of various animal species throughout evolution.
Trimer IgG and neutralising antibody response to COVID-19 mRNA vaccination in individuals with sarcoidosis
Authors: Vagts Christen L. , Chang Yi-Shin , Ascoli Christian , Lee Jessica M. , Huang Kai , Huang Yue , Cherian Ruth A. , Sarup Nandini , Warpecha Samantha R. , Edafetanure-Ibeh Russell , Amin Md-Ruhul , Sultana Tasmin , Ghassemi Mahmood , Sweiss Nadera J. , Novak Richard , Perkins David L. , Finn Patricia W. 
Published: September 2022

Background
Individuals with sarcoidosis are at higher risk for infection owing to underlying disease pathogenesis and need for immunosuppressive treatment. Current knowledge as to how subjects with sarcoidosis respond to different forms of vaccination is limited. We examined quantitative and functional antibody response to COVID-19 vaccination in infection-naive subjects with and without sarcoidosis.

Methods
Our prospective cohort study recruited 14 subjects with biopsy-proven sarcoidosis and 27 age–sex matched controls who underwent a two-shot series of the BNT162b2 mRNA vaccine at the University of Illinois at Chicago. Baseline, 4-week and 6-month trimer spike protein IgG and neutralising antibody (nAb) titres were assessed. Correlation and multivariate regression analysis was conducted.

Results
Sarcoidosis subjects had a significant increase in short-term antibody production to a level comparable to controls; however, IgG titres significantly declined back to baseline levels by 6 months. Corresponding neutralising assays revealed robust nAb titres in sarcoidosis subjects that persisted at 6 months. A significant and strong correlation between IgG and nAb titres across all time points was observed in the control group. However within the sarcoidosis group, a significant but weak correlation between antibody levels was found. Overall, IgG levels were poor predictors of nAb titres at short- or long-term time points.

Conclusions
Sarcoidosis subjects exhibit nAb induced by the BNT162b2 mRNA SARS-CoV-2 vaccine at levels comparable to controls that persists at 6 months indicating conferred immunity. Trimer IgG levels are poor predictors of nAb in subjects with sarcoidosis. Studies of further antibody immunoglobulins and subtypes warrant investigation.
Atlas of regulated target genes of transcription factors (ART-TF) in human ES cells
Authors: Sharov Alexei A. , Nakatake Yuhki , Wang Weidong 
Published: September 2022

Abstract
Background
Transcription factors (TFs) play central roles in maintaining “stemness” of embryonic stem (ES) cells and their differentiation into several hundreds of adult cell types. The regulatory competence of TFs is routinely assessed by detecting target genes to which they bind. However, these data do not indicate which target genes are activated, repressed, or not affected by the change of TF abundance. There is a lack of large-scale studies that compare the genome binding of TFs with the expression change of target genes after manipulation of each TF.

Results
In this paper we associated human TFs with their target genes by two criteria: binding to genes, evaluated from published ChIP-seq data (n = 1868); and change of target gene expression shortly after induction of each TF in human ES cells. Lists of direction- and strength-specific regulated target genes are generated for 311 TFs (out of 351 TFs tested) with expected proportion of false positives less than or equal to 0.30, including 63 new TFs not present in four existing databases of target genes. Our lists of direction-specific targets for 152 TFs (80.0%) are larger that in the TRRUST database. In average, 30.9% of genes that respond greater than or equal to twofold to the induction of TFs are regulated targets. Regulated target genes indicate that the majority of TFs are either strong activators or strong repressors, whereas sets of genes that responded greater than or equal to twofold to the induction of TFs did not show strong asymmetry in the direction of expression change. The majority of human TFs (82.1%) regulated their target genes primarily via binding to enhancers. Repression of target genes is more often mediated by promoter-binding than activation of target genes. Enhancer-promoter loops are more abundant among strong activator and repressor TFs.

Conclusions
We developed an atlas of regulated targets of TFs (ART-TF) in human ES cells by combining data on TF binding with data on gene expression change after manipulation of individual TFs. Sets of regulated gene targets were identified with a controlled rate of false positives. This approach contributes to the understanding of biological functions of TFs and organization of gene regulatory networks. This atlas should be a valuable resource for ES cell-based regenerative medicine studies.
Mesenchymal stem cells- derived exosomes inhibit the expression of Aquaporin-5 and EGFR in HCT-116 human colorectal carcinoma cell line
Authors: Mansourabadi Amir Hossein , Aghamajidi Azin , Faraji Fatemeh , Taghizadeh Shirin , Mohamed Khosroshahi Leila , Bahramkiya Mona , Azimi Maryam 
Published: September 2022

Abstract
Background
Aquaporins are channel proteins, form pores in the membrane of biological cells to facilitate the transcellular and transepithelial water movement. The role of Aquaporins in carcinogenesis has become an area of interest. In this study, we aimed to investigate the effects of adipose-derived mesenchymal stem cells secreted exosomes on the expression of aquaporin 5 and EGFR genes in the HCT-116 tumor cell line.

Methods and results
Surface antigenic profile of Ad-MSCs was evaluated using specific markers. Exosomes were purified from the Ad-MSc supernatant while the quality and the shape of isolated exosomes were assessed by western blot and transmission electron microscopy (TEM) respectively. HCT-116 cells were co-cultured with MSC-conditioned medium (MSC-CM) and/or with 100 μg/ml of MSC-derived exosomes for 48 h and. Real-time PCR was carried out to determine the expression of aquaporin5 and EGFR in HCT-116. Relative expression levels were calculated using the 2-ΔΔct method.
Our result showed that AQP5 and EGFR mRNA levels were significantly reduced in CM and/or exosomes treated HCT116 compare to the control group (P-value < 0.05).

Conclusion
The current study showed that MSC derived exosomes could inhibit expression of two important molecules involved in tumor progression. Hence it seems MSCs-derived exosomes may hold a hopeful future as drug delivery vehicles which need the furtherer investigation.
Bioinformatics analysis reveals the potential target of rosiglitazone as an antiangiogenic agent for breast cancer therapy
Authors: Hermawan Adam , Putri Herwandhani 
Published: September 2022

AbstractBackgroundSeveral studies have demonstrated the antitumor activity of rosiglitazone (RGZ) in cancer cells, including breast cancer cells. However, the molecular targets of RGZ in the inhibition of angiogenesis in breast cancer cells remain unclear. This study aimed to explore the potential targets of RGZ in inhibiting breast cancer angiogenesis using bioinformatics-based analysis.ResultsVenn diagram analysis revealed 29 TR proteins. KEGG pathway enrichment analysis demonstrated that TR regulated the adipocytokine, AMPK, and PPAR signaling pathways. Oncoprint analysis showed genetic alterations inFABP4(14%),ADIPOQ(2.9%),PPARG(2.8%),PPARGC1A(1.5%),CD36(1.7%), andCREBBP(11%) in patients with breast cancer in a TCGA study. The mRNA levels ofFABP4,ADIPOQ,PPARG,CD36, andPPARGC1Awere significantly lower in patients with breast cancer than in those without breast cancer. Analysis of gene expression using bc-GenExMiner showed that the mRNA levels ofFABP,ADIPOQ,PPARG,CD36, PPARGC1A, andCREBBPwere significantly lower in basal-like and triple-negative breast cancer (TNBC) cells than in non-basal-like and non-TNBC cells. In general, the protein levels of these genes were low, except for that of CREBBP. Patients with breast cancer who had low mRNA levels ofFABP4,ADIPOQ,PPARG, andPPARGC1Ahad lower overall survival rates than those with high mRNA levels, which was supported by the overall survival related to DNA methylation. Correlation analysis of immune cell infiltration with TR showed a correlation between TR and immune cell infiltration, highlighting the potential of RGZ for immunotherapy.ConclusionThis study explored the potential targets of RGZ as antiangiogenic agents in breast cancer therapy and highlighted FABP4, ADIPOQ, PPARG, PPARGC1A, CD36, and CREBBP as potential targets of RGZ. These findings require further validation to explore the potential of RGZ as an antiangiogenic agent.
Drugs utilization profile in England and Wales in the past 15 years: a secular trend analysis
Authors: Naser Abdallah Y. , Alwafi Hassan , Al-Daghastani Tamara , Hemmo Sara Ibrahim , Alrawashdeh Hamzeh Mohammad , Jalal Zahraa , Paudyal Vibhu , Alyamani Nawras , Almaghrabi Murouj , Shamieh Ahmad 
Published: September 2022

Abstract
Background
Medication use assessment has a critical role in promoting the effective and rational use of pharmaceutical medications. There are no studies that have explored the utilization of all medications in England and Wales in the past 15 years without restrictions in the age group being studied or class of medications.

Aim
To explore the medication utilization pattern of dispensed medications in England and Wales in the past 15 years.

Method
A secular trend analysis study using publically available dispensing data on the population level in England and Wales for the duration between 2004 and 2019. Medication dispensing data was extracted from the Prescription Cost Analysis database.

Results
Medication prescriptions rate increased by 42.6% [from 1,345,095.75 (95% CI 1,345,004.25 – 1,345,187.26) in 2004 to 1,918,138.48 (95% CI 1,918,038.38 – 1,918,238.57) in 2019 per 100,000 persons, trend test, p < 0.001]. During the study period, the most common medication prescriptions were for the cardiovascular system, central nervous system, and endocrine system, which accounted for 30.2%, 18.8%, and 9.4%, respectively. The rate of medication prescriptions for skin, immunological products and vaccines, infections, and musculoskeletal and joint diseases decreased by 18.4%, 15.8%, 9.8%, and 5.7%, respectively.

Conclusion
The last two decades have witnessed a remarkable rise in the quantity of medications dispensed in community settings. Utilization of chronic disease medications has increased in the past 15 years, specifically, dispensed medications for the cardiovascular system, central nervous system, and endocrine system. It is necessary to conduct additional cohort studies to investigate the clinical outcomes and prescribing safety of these medications.
Factors that dynamically affect provincial incidences of catastrophic health expenditure among middle-aged and elderly Chinese population-transition of disease financial risk protection from global to local
Authors: Zhang Xiyu , Miao Wenqing , Wu Bing , Lai Yongqiang , Jiao Mingli , Xia Qi , Zhang Chenxi , Tian Wanxin , Song Zhe , Shan Linghan , Hu Lingqin , Han Xinhao , Yin Hui , Cheng Xiaonan , Li Ye , Shi Baoguo , Wu Qunhong 
Published: September 2022

Abstract
Background
The high incidence of catastrophic health expenditure (ICHE) among middle-aged and elderly population is a major deterrent for reducing the financial risk of disease. Current research is predominantly based on the assumption of spatial homogeneity of nationwide population characteristics, ignoring the differences in regional characteristics. Thus, our study aimed to explore the impact of various influencing factors on the ICHE from a spatiotemporal perspective.

Methods
We used data from the China Health and Retirement Longitudinal Study (waves 1 to 4), to conduct a retrospective cohort study across 28 provinces, from 2011 to 2018. We measured regional incidences of catastrophic health expenditure using methods recommended by the World Health Organization. Ordinary least squares (OLS) and geographical and temporal weighted regression (GTWR) were used as the global and local estimation models, respectively. The Fortheringham method was used to test the spatiotemporal non-stationarity.

Results
National ICHE showed a gradual increase from 2011 to 2015, but suddenly decreased from 2015 to 2018, also showing the spatial heterogeneity. And the southwest area and Hebei showed persistently high ICHE (Qinghai even reached the highest value of 27.5% in 2015). Out-of-pocket payment, gross domestic product, PM2.5, ageing, incidence of non-communicable diseases and disabilities, number of nurses, and health insurance coverage in the global estimation passed the significance test, and the GTWR model showed a better model fit (0.769) than the OLS model (0.388). Furthermore, except for health insurance coverage, all seven variables had spatiotemporal non-stationarity among their impacts on ICHE.

Conclusion
In this longitudinal study, we found spatiotemporal non-stationarity among the variable relationships, supporting regional governments’ adoption of regional-target policies. First, after the completion of universal health insurance coverage, the spatiotemporal non-stationarity of the prevalence of non-communicable diseases and disability and ageing should be the focus of the next phase of health insurance design, where improvements to compensation coverage and benefit packages are possible policy instruments. Second, the governance and causes of catastrophic health expenditure need to be laid out from a macro perspective rather than only from the individual/household perspective, especially for the potential impact of economic development, air pollution and nursing resources.
VEGFA promotes the occurrence of PLA2R-associated idiopathic membranous nephropathy by angiogenesis via the PI3K/AKT signalling pathway
Authors: Ke Ben , Huang Jinjing , Duan Zhibing , Shen Wen , Wu Yao , Tu Weiping , Fang Xiangdong 
Published: September 2022

Abstract
Background
The M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) is a common immune-related disease in adults. Vascular endothelial growth factor A (VEGFA) is the key mediator of angiogenesis, which leads to numerous kidney diseases. However, the role of VEGFA in IMN is poorly understood.

Methods
In the present study, we downloaded the microarray data GSE115857 from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified with R software. The cytoHubba plug-in were used to identify hub genes from the protein–protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signalling pathway in IMN. CCK8 was performed to assess the cell viability in human vascular endothelial cells (HVECs). Then, passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Animals treated with VEGFA inhibitor bevacizumab (BV), with saline as a positive control. Proteinuria was evaluated by biochemical measurements. Immunohistochemistry and immunofluorescence was used to evaluate relative proteins expression. Electron microscopy was performed to observe the thickness of the glomerular basement membrane (GBM).

Results
We revealed 3 hub genes, including one up-regulated gene VEGFA and two down-regulated genes JUN and FOS, which are closely related to the development of PLA2R-associated IMN. Pathway enrichment analysis found that the biological process induced by VEGFA is associated with PI3K/Akt signalling. GSEA showed that the signalling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. We confirmed the high expression of VEGFA, PI3K, and AKT in IMN renal biopsy samples with immunohistochemistry. In HVECs, we found that BV suppresses cell viability in a time and dose dependent manner. In vivo, we found low dose of BV attenuates proteinuria via inhibiting VEGFA/PI3K/AKT signalling. Meanwhile, low dose of BV alleviates the thickening of the GBM.

Conclusion
VEGFA/PI3K/AKT signalling may play significant roles in the pathogenesis of IMN, which may provide new targets for the treatment of IMN.
The role of informational support from women’s social networks on antenatal care initiation: qualitative evidence from pregnant women in Uganda
Authors: Comfort Alison B. , El Ayadi Alison M. , Camlin Carol S. , Tsai Alexander C. , Nalubwama Hadija , Byamugisha Josaphat , Walker Dilys M. , Moody James , Roberts Tatyana , Senoga Umar , Krezanoski Paul J. , Harper Cynthia C. 
Published: September 2022

Abstract
Background
Early and appropriate use of antenatal care services is critical for reducing maternal and neonatal mortality and morbidity. Yet most women in sub-Saharan Africa, including Uganda, do not seek antenatal care until later during pregnancy. This qualitative study explored pregnant women’s reliance on social ties for information about initiation of antenatal care.

Methods
We conducted semi-structured, in-depth interviews with 30 pregnant women seeking their first antenatal care visit at Kawempe Referral Hospital in Kampala, Uganda. Recruitment was done purposively to obtain variation by parity and whether women currently had a male partner. Study recruitment occurred from August 25th 2020 – October 26th, 2020. We used thematic analysis following a two-stage coding process, with both deductive and inductive codes. Deductive codes followed the key domains of social network and social support theory.

Results
We found that the most important source of information about antenatal care initiation was these women’s mothers. Other sources included their mothers-in-law, female elders including grandmothers, and male partners. Sisters and female friends were less influential information sources about antenatal initiation. One of the primary reasons for relying on their own mothers, mothers-in-law, and elder women was due to these women’s lived experience with pregnancy and childbirth. Trust in the relationship was also an important factor. Some pregnant women were less likely to rely on their sisters or female friends, either due to lack of trust or these women’s lack of experience with pregnancy and childbirth. The advice that pregnant women received from their mothers and others on the ideal timing for antenatal care initiation varied significantly, including examples of misinformation about when to initiate antenatal care. Pregnant women seemed less likely to delay care when more than one social tie encouraged early antenatal care.

Conclusions
Educating women’s social networks, especially their mothers, mothers-in-law, and community elders, about the importance of early antenatal care initiation is a promising avenue for encouraging pregnant women to seek care earlier in pregnancy.