bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stigmatization, psychological and emotional trauma among frontline health care workers treated for COVID-19 in Lagos State, Nigeria: a qualitative study
Authors: Kwaghe Ayi Vandi , Ilesanmi Olayinka Stephen , Amede Peter Okpeh , Okediran James Olatunde , Utulu Rowland , Balogun Muhammad Shakir 
Published: August 2021

Abstract
Background
COVID-19 pandemic has resulted in global health and economic crisis. We investigated the experiences of frontline health care workers recovering from COVID-19 in Lagos State Nigeria.

Methods
We conducted a qualitative study among frontline health workers recovering from COVID-19 in Lagos State, Nigeria. We interviewed 12 respondents before achieving data saturation. We used a checklist to guide the interview according to the phenomenon under study. Data obtained were analyzed using Colaizzi’s phenomenological method.

Results
The study was summarized under five themes: knowledge of COVID-19, exposure, reactions, challenges and recommendations. The respondents were quite knowledgeable on COVID-19, their reactions when informed of their status were denial, anxiety, distress, disorientation, crying for fear of stigmatization, while some were psychologically prepared. Reactions from colleagues, family and friends were encouraging and provided solace for them with a few colleagues and families that had negative reactions. Challenges include anosmia, movement restriction, loneliness, worries about the state of their families, nondisclosure of status to family members, non-conducive isolation centre with limited space, insomnia, stigmatization by health workers at the isolation centre, extended duration of stay, delay in the release of test results and use of ambulance for evacuation to the isolation centres. Coping strategies were watching movies, phone calls, use of social media, listening to music, attending webinars, working on projects and reading spiritual books. Recommendations were early laboratory testing of samples and conveying of results, increase testing capacity, the need of health care workers to be more compassionate, better method of evacuation of people that tested positive to COVID-19, aside the use of ambulance that increases the likelihood of stigmatization and standard guideline for the case management of people recovering from COVID-19 in Lagos state.

Conclusions
Respondents felt stigmatized and psychologically and morally traumatized. Isolation is a difficult experience and some negative emotions as expressed by previous studies were experienced by the respondents. There is need for increased testing capacity, timely results dissemination, early evacuation and creation of more isolation centres in Lagos State due to the rising number of cases and shortage of bed space.
Demand for malaria rapid diagnostic test, health care-seeking behaviour, and drug use among rural community members with fever or malaria-like illness in Ebonyi state, Nigeria: a cross-sectional household survey
Authors: Omale Ugwu I. , Oka Onyinyechukwu U. , Okeke Ifeyinwa M. , Azuogu Benedict N. , Alo Chihurumnanya , Madubueze Ugochukwu C. , Eze Irene I. , Okeke Kingsley C. , Utulu Rowland , Akpan Uduak E. , Iloke Chijioke V. , Nnubia Anthonia O. , Ibemesi Desi O. , Nnabu Chukwuka R. , Anene Ogechukwu C. 
Published: August 2021

Abstract
Background
A good understanding of the demand for malaria rapid diagnostic test (MRDT), malaria health care-seeking behavior, and drug use among community members is crucial to malaria control efforts. The aim of this study was to assess the demand (use and/or request) for MRDT, health care-seeking behavior, and drug use, as well as associated factors, among rural community members (both children and adults) with fever or malaria-like illness in Ebonyi state, Nigeria.

Methods
A cross-sectional household survey was conducted between October 1st and November 7th, 2018, in 18 rural geographical clusters. Data was collected using a structured interviewer-administered questionnaire. Descriptive analysis was done using summary statistics. Associated factors (socio-demographic, knowledge and opinion level) were assessed using bivariate and multivariate binomial logistic regressions while the overall effects of these factors were assessed using the “postestimation test” command in Stata.

Results
A total of 1310 children under 5 years of age and 2329 children ages 5 years and above and adults (excluding pregnant women) (3639 overall) participated in the study. Among the 1310 children under 5 years of age: 521 (39.8%) received MRDT of which the caregivers of 82 (15.7%) requested for the MRDT; 931 (71.1%) sought care with public/private sector providers (excluding traditional practitioners/drug hawkers) the same/next day; 495 (37.8%) sought care at government primary health centres, 744 (56.8%) sought care with the patent medicine vendors (PMVs); 136 (10.4%) sought care with traditional practitioners; 1020 (77.9%) took ACTs (=88.2%, 1020/1156 of those who took anti-malarial drugs). Generally, lower values were respectively recorded among the 2329 children ages 5 years and above and adults (excluding pregnant women). The most important overarching predictor of the demand for MRDT and care-seeking behaviour was the knowledge and opinion level of respondent female heads of households about malaria and malaria diagnosis.

Conclusions
Among the rural community members with fever or malaria-like illness in Ebonyi state, Nigeria, while majority did not receive MRDT or diagnostic testing, and sought care with the PMVs, most took anti-malaria drugs, and mostly ACTs. Interventions are needed to improve the knowledge and opinion of the female heads of households about malaria and malaria diagnosis.
Identification of SOFT syndrome caused by a pathogenic homozygous splicing variant of POC1A: a case report
Authors: Li Guoqiang , Chang Guoying , Wang Chen , Yu Tingting , Li Niu , Huang Xiaodong , Wang Xiumin , Wang Jian , Wang Jiwen , Yao Ruen 
Published: August 2021

Abstract
Background
Pathogenic variants in POC1A led to SOFT syndrome and variant POC1A-related (vPOC1A) syndrome. SOFT syndrome is a rare primordial dwarfism condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis.The main clinical differences between SOFT and vPOC1A syndrome include dyslipidemia with insulin resistance and acanthosis nigricans. To our knowledge, this is the first report of a SOFT syndrome patient diagnosed with a homozygous splicing variant, which could help to extend our understanding of the genotypic and phenotypic information of the disease.

Case presentation
We reported a seven-year-old boy with SOFT syndrome. The patient presented symmetrical short stature and facial features, including prominent forehead, inverted triangular face, epicanthal fold, small teeth and enlarged ears. Laboratory tests displayed mild insulin resistance. Whole-exome sequencing (WES) led to the identification of a homozygous splicing variant (c.981+1G>A) in POC1A gene of the patient, which was inherited from his heterozygous parents confirmed by Sanger sequencing. Further transcriptional experiments of the splicing variant revealed aberrant percentage of exon 9 skipping transcripts.

Conclusions
This is the firstly reported case of a SOFT syndrome patient with a novel homozygous splicing variant and detailed delineation of the aberrant transcript in proband and carrier of the variant in Chinese. Our study enriched mutational spectrum of POC1A which could help in further genetic diagnosis and counselling of SOFT syndrome patients.
Prognostic value of subclinical myocardial necrosis using high-sensitivity cardiac troponin T in patients with prediabetes
Authors: Witkowski Marco , Wu Yuping , Hazen Stanley L. , Tang W. H. Wilson 
Published: August 2021

Abstract
Background
Risk stratification of patients with prediabetes is an unmet clinical need. Here, we examine the utility of subclinical myocardial necrosis assessed by high-sensitivity cardiac troponin T (hs-cTnT) in predicting health outcomes in stable subjects with prediabetes.

Methods
hs-cTnT was analyzed by a high-sensitivity assay (Roche 5th generation) in 2631 stable subjects with prediabetes (HbA1c 5.7–6.4% or fasting glucose 100–125 mg/dL without previous diagnosis of diabetes or glucose-lowering therapy) who underwent elective coronary angiography for cardiac evaluation, and followed for major adverse cardiac events (MACE; death, myocardial infarction, stroke) over 3 years and all-cause mortality over 5 years.

Results
In our study cohort, hs-cTnT was highly prevalent with a median level of 13 ng/L (interquartile range 8.2–21.6 ng/L). Hs-cTnT was independently associated with incident MACE at 3 years (Q4 vs. Q1 adjusted hazard ratio (HR) 2.42 [95% CI 1.69–3.46], P < 0.001) and 5-year mortality (adjusted HR 3.8 [95% CI 2.55–5.67], P < 0.001). This association remained significant in all subsets after adjustment for traditional risk factors and multiple factors known to increase hs-cTnT levels. Moreover, hs-cTnT independently predicted event risk in primary prevention subjects (n = 557, HR 5.46 [95% CI 1.50–19.89), p < 0.01) for MACE; HR 9.53 [95% CI 2.08–43.73] for all-cause mortality) and secondary prevention subjects (n = 2074, HR 1.86 [95% CI 1.31–2.66], P < 0.001 for MACE; and 2.7 [95% CI 1.79–4.08), P < 0.001 for all-cause mortality).

Conclusions
In stable prediabetic subjects, the presence of subclinical myocardial necrosis as detected by hs-cTnT portends heightened long-term adverse cardiovascular event risk. Hs-cTnT levels may help to stratify risk and improve clinical decision making in patients with prediabetes.
Trial registration ClinicalTrials.gov Identifier: NCT00590200.
Combining functional metagenomics and glycoanalytics to identify enzymes that facilitate structural characterization of sulfated N-glycans
Authors: Chuzel Léa , Fossa Samantha L. , Boisvert Madison L. , Cajic Samanta , Hennig René , Ganatra Mehul B. , Reichl Udo , Rapp Erdmann , Taron Christopher H. 
Published: August 2021

AbstractBackgroundSulfate modification ofN-glycans is important for several biological functions such as clearance of pituitary hormones or immunoregulation. Yet, the prevalence of thisN-glycan modification and its functions remain largely unexplored. Characterization ofN-glycans bearing sulfate modifications is hampered in part by a lack of enzymes that enable site-specific detection ofN-glycan sulfation. In this study, we used functional metagenomic screening to identify enzymes that act upon sulfated N-acetylglucosamine (GlcNAc). Using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) -based glycoanalysis we proved their ability to act upon GlcNAc-6-SO4onN-glycans.ResultsOur screen identified a sugar-specific sulfatase that specifically removes sulfate from GlcNAc-6-SO4when it is in a terminal position on anN-glycan. Additionally, in the absence of calcium, this sulfatase binds to the sulfated glycan but does not remove the sulfate group, suggesting it could be used for selective isolation of sulfatedN-glycans. Further, we describe isolation of a sulfate-dependent hexosaminidase that removes intact GlcNAc-6-SO4(but not asulfated GlcNAc) from a terminal position onN-glycans. Finally, the use of these enzymes to detect the presence of sulfatedN-glycans by xCGE-LIF is demonstrated.ConclusionThe present study demonstrates the feasibility of using functional metagenomic screening combined with glycoanalytics to discover enzymes that act upon chemical modifications of glycans. The discovered enzymes represent new specificities that can help resolve the presence of GlcNAc-6-SO4inN-glycan structural analyses.
The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis
Authors: Zhao Chengpeng , Ling Xiaoling , Xia Yunxia , Yan Bingxue , Guan Quanlin 
Published: August 2021

AbstractBackgroundPrevious studies have revealed the key functions of N6-methyladenosine (m6A) modification in breast cancer (BC). MALAT1 as a highly m6A modified lncRNA associated with cancer development and metastasis, but the functional relevance of m6A methyltransferase and MALAT1 in BC is still unknown. Here, our study investigated the effects of the novel m6A methyltransferase METTL3 on epithelial-mesenchymal transition (EMT) in BC via the MALAT1/miR-26b/HMGA2 axis.MethodsFirstly, we collected clinical BC samples and cultured BC cells, and detected mRNA and protein levels in the human samples and human cell lines by RT-qPCR and Western blot, respectively. Then, the binding of MALAT1 and miR-26b and the targeting relationship between miR-26b and HMGA2 were examined by dual-luciferase assay. Moreover, the binding of MALAT1 and miR-26b was tested by RNA pull down and RNA immunoprecipitation (RIP) assays. Methylated-RNA immunoprecipitation (Me-RIP) was used to detect the m6A modification level of MALAT1. The interaction of METTL3 and MALAT1 was detected by photoactivatable ribonucleoside-crosslinking immunoprecipitation (PAR-CLIP). Finally, effects on invasion and migration were detected by Transwell.ResultsIn BC, the level of miR-26b was consistently low, while the levels of METTL3, MALAT1 and HMGA2 were high. Further experiments showed that METTL3 up-regulated MALAT1 expression by modulating the m6A modification of MALAT1, and that MALAT1 could promote the expression of HMGA2 by sponging miR-26b. In BC cells, we found that silencing METTL3 could inhibit EMT and tumor cell invasion by suppressing MALAT1. Furthermore, MALAT1 mediated miR-26b to target HMGA2 and promote EMT, migration, and invasion. In summary, METTL3 promoted tumorigenesis of BC via the MALAT1/miR-26b/HMGA2 axis.ConclusionsSilencing METTL3 down-regulate MALAT1 and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.
NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway
Authors: Wu Yun , Lin Ying , Pan Junfan , Tu Xunwei , Xu Yiquan , Li Hongru , Chen Yusheng 
Published: August 2021

Abstract
Background
Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), explore the mechanisms of its progression, and lay the foundation for the search for new biological markers.

Methods
We analyzed overlapping differentially expressed genes (DEGs) from three datasets; a protein–protein interaction (PPI) network was subsequently constructed and analyzed using Cytoscape. We then selected NCAPG for validation because of its poor prognosis and because it has not been sufficiently studied in the context of LUAD. Immunohistochemical analysis was used to detect the expression of NCAPG in LUAD tissues, and the relationships between NCAPG and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to verify the role of NCAPG in LUAD. Finally, we studied the specific mechanism of action of NCAPG in LUAD.

Results
Through comprehensive analysis of the GSE43458, GSE75037, and The Cancer Genome Atlas databases, we identified 517 overlapping DEGs. Among them, NCAPG was identified as a hub gene. Immunohistochemical analysis revealed that NCAPG was strongly associated with the clinical stage, M-classification, and N-classification. Univariate and multivariate Cox regression analyses indicated that NCAPG was a prognostic risk factor for LUAD, while the in vitro experiments showed that NCAPG overexpression promoted proliferation, migration, invasion, and epithelial-mesenchymal transition. Furthermore, knockdown of NCAPG inhibited LUAD progression, both in vitro and in vivo. Mechanistically, NCAPG overexpression increased p-Smad2 and p-Smad3 expressions in the transforming growth factor β (TGF-β) signaling pathway. Additionally, rescue experiments indicated that TGF-β signaling pathway inhibitors could restore the effect of NCAPG overexpression in LUAD cells.

Conclusions
NCAPG may promote proliferation and migration via the TGF-β signaling pathway in LUAD.
NF-kB-dependent activation of STAT3 by H. pylori is suppressed by TFF1
Authors: Soutto Mohammed , Bhat Nadeem , Khalafi Shayan , Zhu Shoumin , Poveda Julio , Garcia-Buitrago Monica , Zaika Alexander , El-Rifai Wael 
Published: August 2021

Abstract
Background
H. pylori infection is the main risk factor for gastric cancer. In this study, we investigated H. pylori-mediated activation of STAT3 and NF-κB in gastric cancer, using in vitro and in vivo models.

Methods
To investigate the activation of NF-κB and STAT3 by H. pylori strains we used in vitro and in vivo mouse models, western blots, immunofluorescence, ChIP Assay, luciferase and quantitative real-time PCR assays.

Results
Following infection with H. pylori in vitro, we found an earlier phosphorylation of NF-kB-p65 (S536), followed by STAT3 (Y705). Immunofluorescence, using in vitro and in vivo models, demonstrated nuclear localization of NF-kB and STAT3, following H. pylori infection. NF-kB and STAT3 luciferase reporter assays confirmed earlier activation of NF-kB followed by STAT3. In vitro and in vivo models demonstrated induction of mRNA expression of IL-6 (p < 0.001), VEGF-α (p < 0.05), IL-17 (p < 0.001), and IL-23 (p < 0.001). Using ChIP, we confirmed co-binding of both NF-kB-p65 and STAT3 on the IL6 promoter. The reconstitution of Trefoil Factor 1 (TFF1) suppressed activation of NF-kB with reduction in IL6 levels and STAT3 activity, in response to H. pylori infection. Using pharmacologic (BAY11-7082) and genetic (IκB super repressor (IκBSR)) inhibitors of NF-kB-p65, we confirmed the requirement of NF-kB-p65 for activation of STAT3, as measured by phosphorylation, transcription activity, and nuclear localization of STAT3 in in vitro and in vivo models.

Conclusion
Our findings suggest the presence of an early autocrine NF-kB-dependent activation of STAT3 in response to H. pylori infection. TFF1 acts as an anti-inflammatory guard against H. pylori-mediated activation of pro-inflammatory networks.
NEK7 promotes gastric cancer progression as a cell proliferation regulator
Authors: Li Yi-Ke , Zhu Xiao-Ran , Zhan Yue , Yuan Wen-Zhen , Jin Wei-Lin 
Published: August 2021

Abstract
Background
Gastric cancer is one of the most common malignant tumors of the digestive system. However, its targeted therapy develops at a slow pace. Thus, exploring the mechanisms of the malignant behavior of gastric cancer cells is crucial to exploit its treatment. Mammalian never-in-mitosis A (NIMA)-related kinases (NEKs) are considered to play a significant role in cancer cell proliferation. However, no study has reported on NIMA family proteins in gastric cancer.

Methods
Bioinformatics analysis was employed to clarify the expression patterns of NEK1–NEK11 and their effects on prognosis. The effects of NEK7 on immune infiltration and NEK7 related pathways were also analyzed. At the cell level, 5-ethynyl-2-deoxyuridine, cell cycle, and Cell Counting Kit-8 assays were utilized to clarify the effect of NEK7 on gastric cancer cell proliferation. A mouse subcutaneous model revealed the regulating effect of NEK7 on gastric cancer cell proliferation in vivo.

Results
Bioinformatics analysis revealed that NEK7 is upregulated in gastric cancer and is related to poor prognosis. NEK7 is also related to T-stage, which is closely associated with cell proliferation. Further analysis showed that NEK7 was correlated with infiltration of multiple immune cells as well as gastric cancer-related pathways. Cell experiments indicated the promoting effect of NEK7 on cell proliferation, while the absence of NEK7 could lead to inhibition of gastric cancer proliferation and G1/S arrest.

Conclusion
NEK7 exerts a regulatory effect on cell proliferation and is closely related to tumor immune infiltration.
Molecular mechanisms of the microRNA-132 during tumor progressions
Authors: Moghbeli Meysam , Zangouei Amir Sadra , Nasrpour Navaii Zahra , Taghehchian Negin 
Published: August 2021

AbstractCancer as one of the leading causes of human deaths has always been one of the main health challenges in the world. Despite recent advances in therapeutic and diagnostic methods, there is still a high mortality rate among cancer patients. Late diagnosis is one of the main reasons for the high ratio of cancer related deaths. Therefore, it is required to introduce novel early detection methods. Various molecular mechanisms are associated with the tumor progression and metastasis. MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) family that has important functions in regulation of the cellular processes such as cell proliferation, apoptosis, and tumor progression. Moreover, they have higher stability in body fluids compared with mRNAs which can be introduced as non-invasive diagnostic markers in cancer patients. MiR-132 has important functions as tumor suppressor or oncogene in different cancers. In the present review, we have summarized all of the studies which have been reported the role of miR-132 during tumor progressions. We categorized the miR-132 target genes based on their cell and molecular functions. Although, it has been reported that the miR-132 mainly functions as a tumor suppressor, it has also oncogenic functions especially in pancreatic tumors. MiR-132 mainly exerts its roles during tumor progressions by regulation of the transcription factors and signaling pathways. Present review clarifies the tumor specific molecular mechanisms of miR-132 to introduce that as an efficient non-invasive diagnostic marker in various cancers.
Assessment of turbulent blood flow and wall shear stress in aortic coarctation using image-based simulations
Authors: Perinajová Romana , Juffermans Joe F. , Mercado Jonhatan Lorenzo , Aben Jean-Paul , Ledoux Leon , Westenberg Jos J. M. , Lamb Hildo J. , Kenjereš Saša 
Published: August 2021

AbstractIn this study, we analyzed turbulent flows through a phantom (a 180$$^{\circ }$$∘bend with narrowing) at peak systole and a patient-specific coarctation of the aorta (CoA), with a pulsating flow, using magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). For MRI, a 4D-flow MRI is performed using a 3T scanner. For CFD, the standard$$k-\epsilon $$k-ϵ, shear stress transport$$k-\omega $$k-ω, and Reynolds stress (RSM) models are applied. A good agreement between measured and simulated velocity is obtained for the phantom, especially for CFD with RSM. The wall shear stress (WSS) shows significant differences between CFD and MRI in absolute values, due to the limited near-wall resolution of MRI. However, normalized WSS shows qualitatively very similar distributions of the local values between MRI and CFD. Finally, a direct comparison between in vivo 4D-flow MRI and CFD with the RSM turbulence model is performed in the CoA. MRI can properly identify regions with locally elevated or suppressed WSS. If the exact values of the WSS are necessary, CFD is the preferred method. For future applications, we recommend the use of the combined MRI/CFD method for analysis and evaluation of the local flow patterns and WSS in the aorta.