bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood pressure after PREeclampsia/HELLP by SELF monitoring (BP-PRESELF): rationale and design of a multicenter randomized controlled trial
Authors: Muijsers Hella E. C. , van der Heijden Olivier W. H. , de Boer Karin , van Bijsterveldt Chantal , Buijs Ciska , Pagels Jens , Tönnies Peter , Heiden Susanne , Roeleveld Nel , Maas Angela H. E. M.
Published: March 2020

Background

Hypertensive disorders of pregnancy (HDP), such as preeclampsia (PE) or the Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome are associated with elevated cardiovascular disease (CVD) risks, but standardized prevention guidelines after such pregnancies are lacking. Hypertension is the first emerging risk factor after PE/HELLP pregnancies and is a major risk factor for CVD. Hypertension before the age of 55 years may lead to various manifestations of end-organ damage at relatively young age. Therefore, timely treatment of elevated blood pressure is mandatory, but many of these high-risk women have long-term undetected and untreated hypertension before adequate treatment is initiated.

Aim

The aim of our study is to assess whether home blood pressure monitoring (HBPM) in women with a previous PE/HELLP pregnancy is a valuable tool for the early detection of hypertension.

Methods

Women with a history of both early and late PE/HELLP syndrome aged 40–60 years are invited to participate. Patients with a history of CVD, known hypertension and/or use of antihypertensive medication are excluded. Women are randomized between HPBM or ‘usual care’. The primary outcome is feasibility and usability of HBPM after 1 year of follow-up.

Secondary outcomes will be the effectiveness of HPBM to detect hypertension, the efficacy of BP treatment, quality of life, health-related symptoms, work ability, and life-style behaviour.

The results of this study will provide better strategies for timely detection and prevention of hypertension in women after PE/HELLP.

Trial registration

ClinicalTrials.gov, NCT03228082. Registered June 15, 2017.
Why girls get married early in Sarawak, Malaysia - an exploratory qualitative study
Authors: Kohno Ayako , Dahlui Maznah , Nik Farid Nik Daliana , Safii Razitasham , Nakayama Takeo
Published: March 2020

Background

Child marriage, a marriage that involves someone under the age of 18 years, is a long-standing social issue in Sarawak state, Malaysia. The state has taken several measures to improve situations of inequity for women who get married early; however, the practice is still a common part of the tradition and culture. The aim of this study was to explore the factors leading to child marriage in Sarawak state, Malaysia.

Methods

This was an exploratory qualitative study conducted via semi-structured interviews with twenty-two women who were married when they were younger than 18 years old in Kuching, Sarawak, Malaysia. Participants were recruited through purposive and convenient sampling with the use of data from a reproductive health clinic and recruitment in villages. Thematic analysis was used for data analysis.

Results

Four overarching themes were identified: health risk behaviour, family poverty, early marriage as fate, and family disharmony.

Conclusions

In-depth understanding of the unique factors leading to child marriage locally will facilitate the introduction of new approaches to interventions to eradicate child marriage in Sarawak state, Malaysia.
The association between reproductive health smartphone applications and fertility knowledge of Australian women
Authors: Ford Emmalee A. , Roman Shaun D. , McLaughlin Eileen A. , Beckett Emma L. , Sutherland Jessie M.
Published: March 2020

Background

Previous studies have identified that women living in developed countries have insufficient knowledge of factors which may be contributing to the increasingly high global infertility rates such as maternal age and assisted reproductive technologies. There is a large market of reproductive health smartphone applications, yet little is known about the advantages these apps may confer to users in regards to reproductive health knowledge.

Methods

An anonymous, online survey of women living in Australia aged 18 and above was open March–June 2018, until ≥200 responses were acquired for statistical power. Respondents answered questions regarding knowledge about general fertility and related factors (age, cyclic fertility, smoking, obesity, miscarriage rate, and success of assisted reproductive technologies). Fertility knowledge was compared in respondents who did or did not use apps relating to female reproductive health. Additionally the functions preferred in reproductive health apps was described by app using respondents. Sociodemographic information was also collected, and relevant data within the dataset was subject to multivariable modelling for the outcome of the fertility knowledge questions.

Results

Of the 673 respondents that completed the survey, 43.09% reported using mobile phone applications relating to female reproductive health. On average, respondents answered only three of the six fertility knowledge questions correctly. App using respondents were more likely to score better on one question, related to fertility during the menstrual cycle (p < 0.001). App users most commonly reported using the menstrual tracking function in apps (82.4%), which may account for the increased knowledge of cyclic fertility.

Conclusions

This data provides preliminary evidence toward the usefulness of smartphone applications as a medium for providing information about fertility to women. A limited understanding of one’s own fertility was demonstrated despite being essential for the decision-making of women throughout their reproductive years.
Perspectives of pregnant and postpartum women and obstetric providers to promote healthy lifestyle in pregnancy and after delivery: a qualitative in-depth interview study
Authors: Ayyala Manasa S. , Coughlin Janelle W. , Martin Lindsay , Henderson Janice , Ezekwe Nneamaka , Clark Jeanne M. , Appel Lawrence J. , Bennett Wendy L.
Published: March 2020

Background

Pregnancy provides an opportunity to promote healthy lifestyle behaviors. This study’s aim was to explore the perspectives of pregnant and postpartum women and obstetric providers around behavioral lifestyle changes in pregnancy and postpartum.

Methods

We conducted a qualitative study with pregnant and postpartum patients recruited from 2 prenatal care clinics at an urban, academic hospital in the United States. In-depth interviews with 23 pregnant or postpartum women and 11 obstetric providers were completed between October 2015–April 2016. Interviews were audio-recorded and transcribed verbatim. We coded transcripts for thematic content and applied the PRECEDE-PROCEED framework for results to directly inform program development.

Results

Six themes highlighted the predisposing, enabling and reinforcing factors that enable and sustain health behavior changes in pregnancy and postpartum: 1) “Motivation to have a healthy baby” during pregnancy and to “have my body back” after delivery, 2) Pre-pregnancy knowledge and experiences about pregnancy and the postpartum period, 3) Prioritizing wellness during pregnancy and postpartum, 4) The power of social support, 5) Accountability, 6) Integration with technology to reinforce behavior change.

Conclusions

In this qualitative study, pregnant and postpartum women and obstetric providers described themes that are aimed at encouraging lifestyle changes to promote healthy weight gain in pregnancy and can directly inform the development of a behavioral weight management intervention for pregnant and postpartum women that is patient-centered and tailored to their needs.
Error-corrected sequencing strategies enable comprehensive detection of leukemic mutations relevant for diagnosis and minimal residual disease monitoring
Authors: Crowgey Erin L. , Mahajan Nitin , Wong Wing Hing , Gopalakrishnapillai Anilkumar , Barwe Sonali P. , Kolb E. Anders , Druley Todd E.
Published: March 2020

Background

Pediatric leukemias have a diverse genomic landscape associated with complex structural variants, including gene fusions, insertions and deletions, and single nucleotide variants. Routine karyotype and fluorescence in situ hybridization (FISH) techniques lack sensitivity for smaller genomic alternations. Next-generation sequencing (NGS) assays are being increasingly utilized for assessment of these various lesions. However, standard NGS lacks quantitative sensitivity for minimal residual disease (MRD) surveillance due to an inherently high error rate.

Methods

Primary bone marrow samples from pediatric leukemia (n = 32) and adult leukemia subjects (n = 5), cell line MV4–11, and an umbilical cord sample were utilized for this study. Samples were sequenced using molecular barcoding with targeted DNA and RNA library enrichment techniques based on anchored multiplexed PCR (AMP®) technology, amplicon based error-corrected sequencing (ECS) or a human cancer transcriptome assay. Computational analyses were performed to quantitatively assess limit of detection (LOD) for various DNA and RNA lesions, which could be systematically used for MRD assays.

Results

Matched leukemia patient samples were analyzed at three time points; diagnosis, end of induction (EOI), and relapse. Similar to flow cytometry for ALL MRD, the LOD for point mutations by these sequencing strategies was ≥0.001. For DNA structural variants, FLT3 internal tandem duplication (ITD) positive cell line and patient samples showed a LOD of ≥0.001 in addition to previously unknown copy number losses in leukemia genes. ECS in RNA identified multiple novel gene fusions, including a SPANT-ABL gene fusion in an ALL patient, which could have been used to alter therapy. Collectively, ECS for RNA demonstrated a quantitative and complex landscape of RNA molecules with 12% of the molecules representing gene fusions, 12% exon duplications, 8% exon deletions, and 68% with retained introns. Droplet digital PCR validation of ECS-RNA confirmed results to single mRNA molecule quantities.

Conclusions

Collectively, these assays enable a highly sensitive, comprehensive, and simultaneous analysis of various clonal leukemic mutations, which can be tracked across disease states (diagnosis, EOI, and relapse) with a high degree of sensitivity. The approaches and results presented here highlight the ability to use NGS for MRD tracking.
Hsa_circ_0137008 suppresses the malignant phenotype in colorectal cancer by acting as a microRNA-338-5p sponge
Authors: Yang Zhanfeng , Zhang Jingjing , Lu Danghui , Sun Yan , Zhao Xinyong , Wang Xiaoqiong , Zhou Wen , He Qunli , Jiang Zhi
Published: March 2020

Background

Circular RNAs (circRNAs) have been shown to play a crucial role in tumorigenesis. In this study, we investigated the function of hsa_circ_0137008 and its underlying molecular mechanism in colorectal cancer (CRC).

Methods

Gene expression was conducted by quantitative real-time PCR or western blot. Functional experiments were performed by cell count kit-8, colony formation assay, wound healing, and transwell assays. Luciferase reporter assay and RNA pull-down assay were performed to investigate the molecular mechanism of hsa_circ_0137008 in CRC. In addition, the xenograft tumor model was applied to determine the role of hsa_circ_0137008 in vivo.

Results

Downregulation of hsa_circ_0137008 was observed in CRC tissues and cell lines. Functionally, overexpression of hsa_circ_0137008 inhibited the proliferation of CRC cells, as indicated by the inhibition of proliferative protein expression (Ki67 and PCNA), reduced cell viability and colony formation ability. Upregulation of hsa_circ_0137008 suppressed the migration, invasion, and epithelial to mesenchymal transition (EMT) of CRC cells. Mechanically, hsa_circ_0137008 negatively regulated the expression of microRNA-338-5p (miR-338-5p). Furthermore, hsa_circ_0137008 abated the miR-338-5p mediated promotion on CRC cell progression. Tumor suppressive function of hsa_circ_0137008 was validated in vivo.

Conclusion

These findings highlighted the fact that overexpression of hsa_circ_0137008 inhibited the progression of CRC via sponging miR-338-5p, suggesting that hsa_circ_0137008/miR-338-5p axis is a principal regulator of CRC tumorigenesis.
Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκβ interplay
Authors: Nazmeen Aarifa , Chen Guangping , Ghosh Tamal Kanti , Maiti Smarajit
Published: March 2020

Background

Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Sulfoconjugated estrogen fails to bind estrogen-receptor (ER). High estrogen is a known carcinogen in postmenopausal women. Reports reveal a potential redox-regulation of hSULT1E1/E2-signalling. Further, oxidatively-regulated nuclear-receptor-factor 2 (Nrf2) and NFκβ in relation to hSULT1E1/E2 could be therapeutic-target via cellular redox-modification.

Methods

Here, oxidative stress-regulated SULT1E1-expression was analyzed in human breast carcinoma-tissues and in rat xenografted with human breast-tumor. Tumor and its surrounding tissues were obtained from the district-hospital. Intracellular redox-environment of tumors was screened with some in vitro studies. RT-PCR and western blotting was done for SULT1E1 expression. Immunohistochemistry was performed to analyze SULT1E1/Nrf2/NFκβ localization. Tissue-histoarchitecture/DNA-stability (comet assay) studies were done.

Results

Oxidative-stress induces SULT1E1 via Nrf2/NFκβ cooperatively in tumor-pathogenesis to maintain the required proliferative-state under enriched E2-environment. Higher malondialdehyde/non-protein-soluble-thiol with increased superoxide-dismutase/glutathione-peroxidase/catalase activities was noticed. SULT1E1 expression and E2-level were increased in tumor-tissue compared to their corresponding surrounding-tissues.

Conclusions

It may be concluded that tumors maintain a sustainable oxidative-stress through impaired antioxidants as compared to the surrounding. Liver-tissues from xenografted rat manifested similar E2/antioxidant dysregulations favoring pre-tumorogenic environment.
Costs of insecticide-treated bed net distribution systems in sub-Saharan Africa
Authors: Scates Sara S. , Finn Timothy P. , Wisniewski Janna , Dadi David , Mandike Renata , Khamis Mwinyi , Greer George , Serbantez Naomi , Segbaya Sylvester , Owusu Prince , Mihigo Jules , Gerberg Lilia , Acosta Angela , Koenker Hannah , Yukich Joshua
Published: March 2020

Background

Insecticide-treated nets (ITNs) are one of the most cost-effective measures for preventing malaria. The World Health Organization recommends both large-scale mass distribution campaigns and continuous distributions (CD) as part of a multifaceted strategy to achieve and sustain universal access to ITNs. A combination of these strategies has been effective for scaling up ITN access. For policy makers to make informed decisions on how to efficiently implement CD or combined strategies, information on the costs and cost-effectiveness of these delivery systems is necessary, but relatively few published studies of the cost continuous distribution systems exist.

Methods

To address the gap in continuous distribution cost data, four types of delivery systems—CD through antenatal care services (ANC) and the expanded programme on immunization (EPI) (Ghana, Mali, and mainland Tanzania), CD through schools (Ghana and mainland Tanzania), and a combined community/health facility-based distribution (Zanzibar, Tanzania), as well as mass distributions (Mali)—were costed. Data on costs were collected retrospectively from financial and operational records, stakeholder interviews, and resource use surveys.

Results

Overall, from a full provider perspective, mass distributions and continuous systems delivered ITNs at overlapping economic costs per net distributed (mass distributions: 4.37–4.61 USD, CD channels: 3.56–9.90 USD), with two of the school-based systems and the mass distributions at the lower end of this range. From the perspective of international donors, the costs of the CD systems were, for the most part, less costly than the mass distributions (mass distributions: 4.34–4.55 USD, Ghana and Tanzania 2017 school-based: 3.30–3.69 USD, health facility-based: 3.90–4.55 USD, combined community/health facility 4.55 USD). The 2015 school-based distribution (7.30 USD) and 2016 health facility-based distribution (6.52 USD) programmes in Tanzania were an exception. Mass distributions were more heavily financed by donors, while CD relied more extensively on domestic resource contributions.

Conclusions

These results suggest that CD strategies can continue to deliver nets at a comparable cost to mass distributions, especially from the perspective of the donor.
Low-cost equipment for the evaluation of reach and grasp in post-stroke individuals: a pilot study
Authors: Gomes Camila L. A. , Cacho Roberta O. , Nobrega Viviane T. B. , de A. Confessor Ellen Marjorie , de Farias Eyshila Emanuelle M. , Neto José Leôncio F. , de Araújo Denise S. , de S. Medeiros Ana Loyse , Barreto Rodrigo L. , Cacho Enio W. A.
Published: March 2020

Background

Reach–grasp movements are motor components commonly affected after stroke and directly related to the independence of these individuals. Evaluations of these activities can be performed using clinical instruments and assessed by detailed and costly kinematic analyses. The aim of this study was to develop an analysis of reach–grasp movements in post-stroke patients using a simple, inexpensive, and manageable instrument.

Results

A Mann–Whitney test was used to compare paretic and non-paretic limb motor performance. A statistically significant difference was found between the variables of total time (p = 0.02) and speed to reach target 3 (p = 0.04) for task 1, while in task 2 significance was found only in the aspect of speed to reach target 2 (p = 0.04). The correlation between clinical tests and variables of tasks was then performed using Spearman’s rank correlation coefficient. At task 1, when compared with the REACH instrument, the close target sub-item; there was a high positive correlation between the parameters of total time (p = 0.028), target velocity 3 (p = 0.028), and target acceleration 3 (p = 0.028). Another instrument that showed a high positive correlation with the target time 3 (p = 0.01) and target acceleration 3 (p = 0.028) variables was the Box and Block Test. When correlated, the data between the task 2 variables and clinical instruments did not present statistically significant data.

Conclusion

Our instrument—the Temporal Data Acquisition Instrument—TDAI—fulfilled the expected objectives and can be used as an option to evaluate the movements of reach and grasp of upper limb post-stroke, using an easy and fast application, without the need for calibration.

Trial registration Trial Registration: Research Ethics Committee of the Trairi School of Health Sciences—Number 2.625.609, approved on April 13, 2018; Brazilian Registry of Clinical Trials—RBR-4995cr approved on July 4, 2019 retrospectively registered (http://www.ensaiosclinicos.gov.br/rg/RBR-4995cr/)
Dealing with spatial misalignment to model the relationship between deprivation and life expectancy: a model-based geostatistical approach
Authors: Johnson Olatunji , Diggle Peter , Giorgi Emanuele
Published: March 2020

Background 

Life expectancy at birth (LEB), one of the main indicators of human longevity, has often been used to characterise the health status of a population. Understanding its relationships with the deprivation is key to develop policies and evaluate interventions that are aimed at reducing health inequalities. However, methodological challenges in the analysis of LEB data arise from the fact that different Government agencies often provide spatially aggregated information on LEB and the index of multiple deprivation (IMD) at different spatial scales. Our objective is to develop a geostatistical framework that, unlike existing methods of inference, allows to carry out spatially continuous prediction while dealing with spatial misalignment of the areal-level data.

Methods 

We developed a model-based geostatistical approach for the joint analysis of LEB and IMD, when these are available over different partitions of the study region. We model the spatial correlation in LEB and IMD across the areal units using inter-point distances based on a regular grid covering the whole of the study area. The advantages and strengths of the new methodology are illustrated through an analysis of LEB and IMD data from the Liverpool district council.

Results 

We found that the effect of IMD on LEB is stronger in males than in females, explaining about 63.35% of the spatial variation in LEB in the former group and 38.92% in the latter. We also estimate that LEB is about 8.5 years lower between the most and least deprived area of Liverpool for men, and 7.1 years for women. Finally, we find that LEB, both in males and females, is at least 80% likely to be above the England wide average only in some areas falling in the electoral wards of Childwall, Woolton and Church.

Conclusion 

The novel model-based geostatistical framework provides a feasible solution to the spatial misalignment problem. More importantly, the proposed methodology has the following advantages over existing methods used model LEB: (1) it can deliver spatially continuous inferences using spatially aggregated data; (2) it can be applied to any form of misalignment with information provided at a range of spatial scales, from areal-level to pixel-level.
Verification of EZH2 as a druggable target in metastatic uveal melanoma
Authors: Jin Bei , Zhang Ping , Zou Hailin , Ye Huijing , Wang Yun , Zhang Jing , Yang Huasheng , Pan Jingxuan
Published: March 2020

Background

Hepatic metastasis develops in ~ 50% of uveal melanoma (UM) patients with no effective treatments. Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver metastasis remains poorly understood. Given that profound epigenetic evolution may occur in the long journey of circulating tumor cells (CTCs) to distant organs, we hypothesized that EZH2 endowed tumor cells with enhanced malignant features (e.g., stemness and motility) during hepatic metastasis in UM. We aimed to test this hypothesis and explore whether EZH2 was a therapeutic target for hepatic metastatic UM patients.

Methods

Expression of EZH2 in UM was detected by qRT-PCR, Western blotting and immunohistochemistry staining. Proliferation, apoptosis, cancer stem-like cells (CSCs) properties, migration and invasion were evaluated under circumstances of treatment with either EZH2 shRNA or EZH2 inhibitor GSK126. Antitumor activity and frequency of CSCs were determined by xenografted and PDX models with NOD/SCID mice. Hepatic metastasis was evaluated with NOG mice.

Results

We found that EZH2 overexpressed in UM promoted the growth of UM; EZH2 increased the percentage and self-renewal of CSCs by miR-29c-DVL2-β-catenin signaling; EZH2 facilitates migration and invasion of UM cells via RhoGDIγ-Rac1 axis. Targeting EZH2 either by genetics or small molecule inhibitor GSK126 decreased CSCs and motility and abrogated the liver metastasis of UM.

Conclusions

These findings validate EZH2 as a druggable target in metastatic UM patients, and may shed light on the understanding and interfering the complicated metastatic process.
MIR22HG acts as a tumor suppressor via TGFβ/SMAD signaling and facilitates immunotherapy in colorectal cancer
Authors: Xu Juan , Shao Tingting , Song Mingxu , Xie Yunjin , Zhou Jialiang , Yin Jiaqi , Ding Na , Zou Haozhe , Li Yongsheng , Zhang Jiwei
Published: March 2020

Background

Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. However, we are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC).

Methods

Differentially expressed lncRNAs in CRC were identified by bioinformatics screen and the level of MIR22HG in CRC and control tissues were determined by qRT-PCR. Cell viability and migration capacities were examined by MTT and transwell assay. Mouse model was used to examine the function and rational immunotherapy of MIR22HG in vivo.

Results

We systematically investigated the expression pattern of lncRNAs and revealed MIR22HG acts as a tumor suppressor in CRC. The expression of MIR22HG was significantly decreased in CRC, which was mainly driven by copy number deletion. Reduced expression of MIR22HG was significantly associated with poor overall survival. Silencing of MIR22HG promoted cell survival, proliferation and tumor metastasis in vitro and in vivo. Mechanistically, MIR22HG exerts its tumor suppressive activity by competitively interacting with SMAD2 and modulating the activity of TGFβ pathway. Decreased MIR22HG promoted the epithelial-mesenchymal transition in CRC. Importantly, we found that MIR22HG expression is significantly correlated with CD8A and overexpression of MIR22HG triggers T cell infiltration, enhancing the clinical benefits of immunotherapy.

Conclusion

MIR22HG acts as a tumor suppressor in CRC. Our data provide mechanistic insights into the regulation of MIR22HG in TGFβ pathway and facilitates immunotherapy in cancer.
Understanding the relationships between mental disorders, self-reported health outcomes and positive mental health: findings from a national survey
Authors: Vaingankar Janhavi Ajit , Chong Siow Ann , Abdin Edimansyah , Siva Kumar Fiona Devi , Chua Boon Yiang , Sambasivam Rajeswari , Shafie Saleha , Jeyagurunathan Anitha , Seow Esmond , Subramaniam Mythily
Published: March 2020

Background

The link between mental illness and mental health is gaining focus in research and practice. This study aimed to investigate the association of mental disorders with positive mental health (PMH), overall health and quality of life. In addition, the role of PMH in mediating the relationships between mental disorders and health outcomes was assessed.

Methods

The study sample comprised 2270 residents aged 18 years and above who participated in a nationally representative, cross-sectional survey estimating the lifetime prevalence of mood, anxiety and alcohol use disorders, and health outcomes (self-reported overall health, quality of life and PMH) in Singapore. The Positive Mental Health Instrument was used to estimate the level of Total PMH among the respondents with and without mental disorders. Associations between mental disorders and health outcomes were assessed through regression models. Path analyses were conducted to investigate mediating role of PMH.

Results

Total PMH (Mean ± SD) was significantly lower among individuals having any of the studied lifetime mental disorders (4.23 ± 0.64 versus 4.50 ± 0.67 among those without these disorders). Although having a mood or anxiety disorder was associated with significantly lower Total PMH even after controlling for socio-demographic characteristics, similar relationship was not observed for alcohol use disorders. History of any mental disorders was also associated with lower overall health and quality of life. Total PMH mediated the relationships between mental disorders and overall health and quality of life by reducing the effect sizes for the associations between mental disorders and these health outcomes.

Conclusions

Mental disorders were associated with poor health outcomes in affected individuals. This study showed that PMH can mediate the relationships between mental disorders and health outcomes, and act as an underlying mechanism to improve overall health and quality of life in individuals with mental disorders. Findings thus highlight the significance of incorporating mental health promotion and interventions in clinical populations.
CDK1 and CDC20 overexpression in patients with colorectal cancer are associated with poor prognosis: evidence from integrated bioinformatics analysis
Authors: Li Jianxin , Wang Yinchun , Wang Xin , Yang Qingqiang
Published: March 2020

Background

Colorectal cancer (CRC) is one of the most common malignancies of the digestive system, which causes severe financial burden worldwide. However, the specific mechanisms involved in CRC are still unclear.

Methods

To identify the significant genes and pathways involved in the initiation and progression of CRC, the microarray dataset GSE126092 was downloaded from Gene Expression Omnibus (GEO) database, and then, the data was analyzed to identify differentially expressed genes (DEGs). Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on these DEGs using the DAVID database, and the protein-protein interaction (PPI) network was constructed using the STRING database and analyzed using the Cytoscape software. Finally, hub genes were screened, and the survival analysis was performed on these hub genes using the Kaplan-Meier curves in the cBioPortal database.

Results

In total, 937 DEGs were obtained, including 316 upregulated genes and 621 downregulated genes. GO analysis revealed that the DEGs were mostly enriched in terms of nuclear division, organelle fission, cell division, and cell cycle process. KEGG pathway analysis showed that the DEGs were mostly enriched in cell cycle, oocyte meiosis, cytokine-cytokine receptor interaction, and cGMP-PKG signaling pathway. The PPI network comprised 608 nodes and 3100 edges, and 4 significant modules and 10 hub genes with the highest degree were identified using the Cytoscape software. Finally, survival analysis showed that overexpression of CDK1 and CDC20 in patients with CRC were statistically associated with worse overall survival.

Conclusions

This bioinformatics analysis revealed that CDK1 and CDC20 might be candidate targets for diagnosis and treatment of CRC, which provided valuable clues for CRC.
Chitinase 3 like 1 suppresses the stability and activity of p53 to promote lung tumorigenesis
Authors: Park Kyung-Ran , Yun Hyung-Mun , Yoo Kyeongwon , Ham Young Wan , Han Sang Bae , Hong Jin Tae
Published: March 2020

Background

Chitinase 3 like 1 protein (Chi3L1) is expressed in several cancers, and a few evidences suggest that the secreted Chi3L1 contributes to tumor development. However, the molecular mechanisms of intracellular Chi3L1 are unknown in the lung tumor development.Methods:In the present study, we generated Chi3L1 knockout mice (Chi3L1KO(−/−)) using CRISPR/Cas9 system to investigate the role of Chi3L1 on lung tumorigenesis.

Results

We established lung metastasis induced by i.v. injections of B16F10 in Chi3L1KO(−/−). The lung tumor nodules were significantly reduced in Chi3L1KO(−/−)and protein levels of p53, p21, BAX, and cleaved-caspase 3 were significantly increased in Chi3L1KO(−/−), while protein levels of cyclin E1, CDK2, and phsphorylation of STAT3 were decreased in Chi3L1KO(−/−). Allograft mice inoculated with B16F10 also suppressed tumor growth and increased p53 and its target proteins including p21 and BAX. In addition, knockdown of Chi3L1 in lung cancer cells inhibited lung cancer cell growth and upregulated p53 expression with p21 and BAX, and a decrease in phosphorylation of STAT3. Furthermore, we found that intracellular Chi3L1 physically interacted and colocalized with p53 to inhibit its protein stability and transcriptional activity for target genes related with cell cycle arrest and apoptosis. In lung tumor patient, we clinically found that Chi3L1 expression was upregulated with a decrease in p53 expression, as well as we validated that intracellular Chi3L1 was colocalized, reversely expressed, and physically interacted with p53, which results in suppression of the expression and function of p53 in lung tumor patient.

Conclusions

Our studies suggest that intracellular Chi3L1 plays a critical role in the lung tumorigenesis by regulating its novel target protein, p53 in both an in vitro and in vivo system.
Ascorbate protects liver from metabolic disorder through inhibition of lipogenesis and suppressor of cytokine signaling 3 (SOCS3)
Authors: Xu Yingying , Wu Yuhang , Xiong Yue , Tao Jiawang , Pan Tingcai , Tan Shenglin , Gao Ge , Chen Yan , Abbas Nasir , Getachew Anteneh , Zhuang Yuanqi , You Kai , Yang Fan , Li Yin-xiong
Published: March 2020

Background

Fatty liver is a reversible status, but also an origin stage to develop to other metabolic syndromes, such as diabetes and heart disease that threatens public health worldwide. Ascorbate deficiency is reported to be correlated with increasing risks for metabolic syndromes, but whether ascorbate has a therapeutic effect is unknown. Here, we investigated if ascorbate treatment alone could work on protecting from the development of steatosis and mechanisms beyond.

Methods

Guinea pigs were fed with a chow diet or a high palm oil diet (HPD) respectively. HPD induced animals were administered different concentrations of ascorbate in different time intervals through water. Besides, hepatocyte-like cells derived from human embryonic stem cells and HepG2 cells were treated with palmitic acid (PA) to induce lipid accumulation for molecular mechanism study.

Results

We find that ascorbate rescues HPD and PA induced steatosis and insulin tolerance in vivo and in vitro. We demonstrate that ascorbate changes cellular lipid profiles via inhibits lipogenesis, and inhibits the expression ofSOCS3via STAT3, thus enhances insulin signal transduction. Overexpression ofSOCS3abolishes the ascorbate rescue effects on insulin signal and lipid accumulation in hepatic cells.

Conclusions

Ascorbate ameliorates hepatic steatosis and improves insulin sensitivity through inhibiting lipogenesis andSOCS3.
International cooperation in public health in Martinique: geostrategic utility for cancer surveillance in the Caribbean
Authors: Joachim Clarisse , Almont Thierry , Drame Moustapha , Contaret Cédric , Vestris Mylène , Najioullah Fatiha , Aline-Fardin Aude , Escarmant Patrick , Leduc Nicolas , Grossat Nathalie , Promeyrat Xavier , Bougas Stefanos , Papadopoulou Eva , Vinh-Hung Vincent , Sylvestre Emmanuelle , Veronique-Baudin Jacqueline
Published: March 2020

Background

Cooperation in public health and in oncology in particular, is currently a major issue for the island of Martinique, given its geopolitical position in the Caribbean region. The region of Martinique shares certain public health problems with other countries of the Caribbean, notably in terms of diagnostic and therapeutic management of patients with cancer. We present here a roadmap of cooperation priorities and activities in cancer surveillance and oncology in Martinique.

Main body

The fight against cancer is a key public health priority that features high on the regional health policy for Martinique. In the face of these specific epidemiological conditions, Martinique needs to engage in medical cooperation in the field of oncology within the Caribbean, to improve skills and knowledge in this field, and to promote the creation of bilateral relations that will help to improve cancer management in an international healthcare environment.

Conclusions

These collaborative exchanges will continue throughout 2020 and will lead to the implementation of mutual research projects across a larger population basin, integrating e-health approaches and epidemiological e-cohorts.
Ethnomycological study of edible and medicinal mushrooms in Menge District, Asossa Zone, Benshangul Gumuz Region, Ethiopia
Authors: Sitotaw Rediet , Lulekal Ermias , Abate Dawit
Published: March 2020

Background

Menge District has long been inhabited by people who have a long tradition of using wild mushrooms mainly as food, source of income, and medicine. Extensive utilization of wild edible mushrooms (WEM) coupled with an ever-increasing population growth, deforestation, and agricultural land expansion threatens fungal diversity and WEM in the area. Hence, this study is aimed at documenting and analyzing the ethnomycological knowledge of the people in order to preserve the dwindling WEM wealth and associated indigenous knowledge.

Methods

Ethnomycological data were collected using semi-structured interviews, focus group discussions, participant observations, and walk-in-the-woods methods. Statistical tests were used to compare the indigenous knowledge and practice of wild mushroom among different informant categories using One-way ANOVA and t tests.

Results

A total of 20 ethnomycologically important wild mushroom species belonging to ten genera and six families were identified, of which 15 were reported to be edible in the District. The family Lyophyllaceae was represented by the highest number of species (nine species, 45%) followed by Agaricaceae (seven species, 35%) and each of the remaining four families had single species representation. Significant difference (P < 0.05) was observed on the mean number of WEM reported among different group of respondents. Wild edible mushroom collection habit and practice was significantly (P < 0.05) influenced by gender, age, and literacy level. The output of preference ranking exercise indicated Termitomyces schimperi was ranked first followed by Termitomyces letestui, Termitomyces microcarpus, and Termitomyces eurhizusas as the most preferred edible mushrooms respectively.

Conclusion

The present study shows that Menge District is rich in wild mushroom diversity and associated indigenous knowledge. However, anthropogenic factors together with loss of indigenous knowledge and very poor conservation efforts threaten the survival of economically and ecologically important mushrooms in the area. Thus, complementary in situ and ex situ mushroom conservation strategy is highly recommended.
The fidelity of implementation of recommended care for children with malaria by community health workers in Nigeria
Authors: Adeoti Oluwatomi , Spiegelman Donna , Afonne Chinenye , Falade Catherine O. , Jegede Ayodele S. , Oshiname Frederick O. , Gomes Melba , Ajayi IkeOluwapo O.
Published: March 2020

Background

In the context of task shifting, a promoted approach to healthcare delivery in resource-poor settings, trained community health workers (CHWs) have been shown to be effective in delivering quality care of malaria for febrile under-5 children. While their effectiveness has been documented, the fidelity of implementation (FOI) has not been adequately studied. By understanding and measuring whether an intervention has been performed with fidelity, researchers and practitioners gain a better understanding of how and why an intervention works, and the extent to which outcomes can be improved. The objective of this study was to assess the FOI of a recommended protocol for malaria care by CHWs in a resource-poor setting in Nigeria.

Methods

Thirty-five female CHWs who participated in a 3-day training on home management of malaria among under-5 children were studied. They managed 1,646 children over the implementation period and then underwent evaluation via a one-time hospital-based observation by the trainers. During the evaluation, a pre-tested standard checklist was used to compute performance scores for CHWs; doctors and nurses were selected to serve as the gold standard for comparison. Performance scores (PS) recorded during the evaluation were used to assess adherence and compliance with the recommended treatment protocol.

Results

Of the 4 skill domains assessed, adherence was greatest for compliance with malaria treatment recommendations (94%) and lowest for post-treatment initiation counseling of home-based caregivers (69%). The average overall adherence of 83% was comparable to adherence by gold standard comparators. Mean PS was not found to be significantly associated with CHW demographics. Scores for clinical evaluation among those whose occupation was not healthcare-related were significantly lowered by 0.52 [95% CI (1.05–0.01), p = 0.05]. Compliance with the treatment protocol increased by 23% for every unit increase in total PS (p = 0.07) and doubled for every unit increase in scores for post-treatment initiation counseling of caregivers (p = 0.002).

Conclusions

Studying intervention fidelity stands to identify the shortcomings of implementation and specific areas to target for improvement in future adoption or implementation. This study concludes that future trainings should emphasize clinical evaluation and post-treatment counseling of caregivers by CHWs to ensure the best outcome for children.
Single segment of spleen autotransplantation, after splenectomy for trauma, can restore splenic functions
Authors: Toro Adriana , Parrinello Nunziatina Laura , Schembari Elena , Mannino Maurizio , Corsale Giuseppe , Triolo Anna , Palermo Filippo , Romano Alessandra , Di Raimondo Francesco , Di Carlo Isidoro
Published: March 2020

Background

Splenectomy is sometimes necessary after abdominal trauma, but splenectomized patients are at risk of sepsis due to impaired immunological functions.

To overcome this risk, autotransplantation of the spleen by using a new technique has been proposed, but so far, a demonstration of functionality of the transplanted tissue is lacking.

Methods

We therefore evaluated 5 patients who underwent a splenic autotransplant in comparison with 5 splenectomized patients without splenic autotransplant and 7 normal subjects.

Results

We confirmed that the patients not undergoing autotransplantation, when compared to normal subjects, had a higher platelet count, higher percentage of micronucleated reticulocytes (p = 0.002), increased levels of naive B lymphocytes (p = 0.01), a defect of class-switched memory (p = 0.001) and class-unswitched memory B cells (p = 0.002), and increased levels of PD1 on T lymphocytes CD8+ (p = 0.08). In contrast, no significant differences for any of the abovementioned parameters were recorded between patients who underwent spleen autotransplantation and normal subjects.

Conclusion

These findings suggest that splenic autotransplantation is able to restore an adequate hemocatheretic activity as well as recover the immunological deficit after splenectomy.
Ability of adhesion and biofilm formation of pathogens of periprosthetic joint infections on titanium-niobium nitride (TiNbN) ceramic coatings
Authors: Bidossi Alessandro , Bottagisio Marta , De Grandi Roberta , De Vecchi Elena
Published: March 2020

Background

Orthopedic metal implants are notoriously associated with release of metallic ions able to cause biological adverse reactions which might lead to implant loosening and failure. To limit any possible adverse reactions, ceramic coatings for orthopedic metal implants have been introduced. However, information regarding the interaction of these coatings with microbes responsible for periprosthetic joint infections (PJIs) is lacking. Hence, the aim of the present in vitro study is to assess the microbial affinity to a titanium-niobium nitride (TiNbN) coating.

Methods

Adhesion and biofilm formation of clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Cutibacterium acnes were assessed on TiNbN-coated titanium discs in comparison with uncoated titanium and cobalt-chrome alloys discs, with either smooth or rough surfaces. Bacterial adhesion was performed by counting adhered bacteria in the first hours of incubation, and the biofilm formation was performed by means of a spectrophotometric assay and by confocal laser scan microscopy after 72 hours of incubation.

Results

Overall, Staphylococcus aureus and Staphylococcus epidermidis, among the most common bacteria responsible for PJIs, displayed a significantly decreased attachment in the first hours of contact and, when cultured in presence of TiNbN coating, in comparison with CoCrMo. Biofilm formation of the four tested strains was comparable on all alloys.

Conclusions

Although the onset of a PJI is more complex than in an in vitro scenario, these findings suggest that TiNbN-coated orthopedic implants do not increase PJIs risk while ameliorating tribological and surface properties could represent a valid choice to limit possible complications such as metal hypersensitivity.
Laryngeal chondritis as a differential for upper airway diseases in German sheep
Authors: Reineking Wencke , Punsmann Teresa Maria , Wagener Matthias Gerhard , Verspohl Jutta , Ganter Martin , Baumgärtner Wolfgang , Puff Christina
Published: March 2020

Background

Ovine laryngeal chondritis is a rare entity of sheep in the USA, Great Britain, New Zealand and Iceland, but has not been reported in Germany so far. Here, two German cases are reported.

Case presentation

Two rams showed severe and progressive signs of dyspnea. Endoscopically, a severe bilateral swelling of the larynx was identified in both rams. Due to poor prognosis and progression of clinical signs one ram was euthanized, while the other ram died overnight. In both cases, a necrosuppurative laryngitis and chondritis of arytenoid cartilages was found at necropsy. Fusobacterium necrophorum and Streptococcus ovis were isolated from the laryngeal lesion in one animal.

Conclusions

This is the first report of ovine laryngeal chondritis in continental Europe. This entity should be considered a differential diagnosis for upper airway disease in sheep.
Correction to: Injury-related deaths before and during the Islamic State insurgency – Baghdad, Iraq, 2010–2015
Authors: Goers Matthew , Leidman Eva , Sultan Abdul-Salam Saleh , Hassan Ahmed , Bilukha Oleg
Published: March 2020

The original publication of this article [1] contained an incorrect author name.
Genome‐wide meta‐analysis identified novel variant associated with hallux valgus in Caucasians
Authors: Arbeeva Liubov , Yau Michelle , Mitchell Braxton D. , Jackson Rebecca D. , Ryan Kathleen , Golightly Yvonne M. , Hannan Marian T. , Nelson Amanda , Jordan Joanne M. , Hochberg Marc C.
Published: March 2020

Background

Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome‐wide association study (GWAS) conducted in 4409 Caucasians did not identify genome‐wide significant associations with hallux valgus in both gender‐specific and sex‐combined GWAS meta‐analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus.

Methods

A total of 5925 individuals of European Ancestry were categorized into two groups: ‘hallux valgus present’ (n = 2314) or ‘no deformity’ (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex‐specific and sex‐combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed‐effects inverse‐variance meta‐analyses. Functional Mapping and Annotation web‐based platform (FUMA) was used for positional mapping, gene and gene‐set analyses.

Results

We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E‐09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family.

Conclusion

In this report of the largest GWAS of hallux valgus to date, we identified a novel genome‐wide significant locus for hallux valgus. Additional replication and functional follow‐up will be needed to determine the functional role of this locus in hallux valgus biology.