bluuebunny/crossref_metadata_2025 huggingface dataset:
Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo
Authors: Tarumoto Yusuke , Lin Shan , Wang Jinhua , Milazzo Joseph P. , Xu Yali , Lu Bin , Yang Zhaolin , Wei Yiliang , Polyanskaya Sofya , Wunderlich Mark , Gray Nathanael S. , Stegmaier Kimberly , Vakoc Christopher R.
Published: November 2019

Transcription factors are important drivers in acute myeloid leukemia (AML), but they are notoriously difficult to target. The authors demonstrate that inhibition of salt-inducible kinase (SIK3) inhibits AML cell proliferation in cells dependent on the transcription factor MEF2C, identifying a small molecule that can disrupt a leukemogenic transcription factor pathway.
Annot: a Django-based sample, reagent, and experiment metadata tracking system
Authors: Bucher Elmar , Claunch Cheryl J. , Hee Derrick , Smith Rebecca L. , Devlin Kaylyn , Thompson Wallace , Korkola James E. , Heiser Laura M.
Published: November 2019

Background

In biological experiments, comprehensive experimental metadata tracking – which comprises experiment, reagent, and protocol annotation with controlled vocabulary from established ontologies – remains a challenge, especially when the experiment involves multiple laboratory scientists who execute different steps of the protocol. Here we describe Annot, a novel web application designed to provide a flexible solution for this task.

Results

Annot enforces the use of controlled vocabulary for sample and reagent annotation while enabling robust investigation, study, and protocol tracking. The cornerstone of Annot’s implementation is a json syntax-compatible file format, which can capture detailed metadata for all aspects of complex biological experiments. Data stored in this json file format can easily be ported into spreadsheet or data frame files that can be loaded into R (https://www.r-project.org/) or Pandas, Python’s data analysis library (https://pandas.pydata.org/). Annot is implemented in Python3 and utilizes the Django web framework, Postgresql, Nginx, and Debian. It is deployed via Docker and supports all major browsers.

Conclusions

Annot offers a robust solution to annotate samples, reagents, and experimental protocols for established assays where multiple laboratory scientists are involved. Further, it provides a framework to store and retrieve metadata for data analysis and integration, and therefore ensures that data generated in different experiments can be integrated and jointly analyzed. This type of solution to metadata tracking can enhance the utility of large-scale datasets, which we demonstrate here with a large-scale microenvironment microarray study.
Fibrin γ/γ' influences the secretion of fibrinolytic components and clot structure
Authors: Cantero Miriam , Rojas Héctor , Anglés-Cano Eduardo , Marchi Rita
Published: November 2019

Background

In healthy subjects fibrinogen γ/γ‘ circulates at 8–15% of the total plasma fibrinogen concentration. Elevated levels of this variant have been associated with arterial thrombosis, and its diminution with venous thrombosis. The aims of the present work were to analyze the structure of the fibrin network formed on the top of human dermal microvascular endothelial cells (HMEC-1) at different fibrinogen γ/γ‘ concentrations, as well as its influence on the secretion of fibrinolytic components.

The kinetics of fibrin polymerization on top of HMEC-1 cells with 3, 10, and 30% fibrinogen γ/γ‘ was followed at 350 nm. The secretion of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI 1) by HMEC-1 were measured in the supernatant and cell lysates, after incubation with 1 nM thrombin, fibrin with 3, and 30% fibrinogen γ/γ‘, using commercial kits. The influence of fibrinogen γ/γ‘ on fibrin structure on the surface of the HMEC-1 was followed with laser scanning confocal microscopy (LSCM).

Results

The kinetics of fibrin formation on HMEC-1 with 3 and 10% fibrinogen γ/γ‘ were similar. However, with 30% fibrinogen γ/γ‘ both the slope and final turbity were approximately 50% less. The LSCM images showed the dramatic effects of increasing fibrinogen γ/γ‘ from 3 to 30%. The uPA and PAI 1 concentrations in culture supernatants HMEC-1 cells treated with thrombin or 30% γ/γ‘ fibrin were two-fold increased as compared to basal culture supernatants and 3% γ/γ‘ fibrin-treated HMEC-1. In all stimulatory conditions the intracellular concentration of uPA was higher than in supernatants. In contrast, the intracellular PAI 1 concentration was decreased as compared to that measured in the supernatant, including the basal condition.

Conclusion

A concentration of 30% fibrin γ/γ‘ alter drastically fibrin structure on the cell surface and affects the secretion of uPA and PAI 1 through its capacity to bind thrombin.
Comparative study between Helicobacter pylori and host human genetics in the Dominican Republic
Authors: Ono Takaaki , Cruz Modesto , Jiménez Abreu José A. , Nagashima Hiroyuki , Subsomwong Phawinee , Hosking Celso , Shiota Seiji , Suzuki Rumiko , Yamaoka Yoshio
Published: November 2019

Background

Helicobacter pylori, a bacterium that infects the human stomach, has high genetic diversity. Because its evolution is parallel to human,H. pyloriis used as a tool to trace human migration. However, there are few studies about the relationship between phylogeography ofH. pyloriand its host human.

Methods

We examined bothH. pyloriDNA and the host mitochondrial DNA and Y-chromosome DNA obtained from a total 119 patients in the Dominican Republic, where human demography consists of various ancestries. DNA extracted from culturedH. pyloriwere analyzed by multi locus sequence typing. Mitochondrial DNA and Y-chromosome DNA were evaluated by haplogroup analyses.

Results

H. pyloristrains were divided into 2 populations; 68 strains with African group (hpAfrica1) and 51 strains with European group (hpEurope). In Y-chromosomal haplogroup, European origin was dominant, whereas African origin was dominant both inH. pyloriand in mtDNA haplogroup. These results supported the hypothesis that mother-to-child infection is predominant inH. pyloriinfection. The Amerindian type of mtDNA haplogroup was observed in 11.8% of the patients; however, Amerindian type (hspAmerind) ofH. pyloriwas not observed. Although subpopulation type of most hpAfrica1 strains in Central America and South America were hybrid (hspWAfrica/hpEurope), most Dominican Republic hpAfrica1 strains were similar to those of African continent.

Conclusions

Genetic features ofH. pylori, mtDNA, and Y haplogroups reflect the history of colonial migration and slave trade in the Dominican Republic. Discrepancy betweenH. pyloriand the host human genotypes support the hypothesis that adaptability of hspAmerindH. pyloristrains are weaker than hpEurope strains.H. pyloristrains in the Dominican Republic seem to contain larger proportion of African ancestry compared to other American continent strains.
Genome-wide identification of microsatellite markers from cultivated peanut (Arachis hypogaea L.)
Authors: Lu Qing , Hong Yanbin , Li Shaoxiong , Liu Hao , Li Haifen , Zhang Jianan , Lan Haofa , Liu Haiyan , Li Xingyu , Wen Shijie , Zhou Guiyuan , Varshney Rajeev K. , Jiang Huifang , Chen Xiaoping , Liang Xuanqiang
Published: November 2019

Background

Microsatellites, or simple sequence repeats (SSRs), represent important DNA variations that are widely distributed across the entire plant genome and can be used to develop SSR markers, which can then be used to conduct genetic analyses and molecular breeding. Cultivated peanut (A. hypogaea L.), an important oil crop worldwide, is an allotetraploid (AABB, 2n = 4× = 40) plant species. Because of its complex genome, genomic marker development has been very challenging. However, sequencing of cultivated peanut genome allowed us to develop genomic markers and construct a high-density physical map.

Results

A total of 8,329,496 SSRs were identified, including 3,772,653, 4,414,961, and 141,882 SSRs that were distributed in subgenome A, B, and nine scaffolds, respectively. Based on the flanking sequences of the identified SSRs, a total of 973,984 newly developed SSR markers were developed in subgenome A (462,267), B (489,394), and nine scaffolds (22,323), with an average density of 392.45 markers per Mb. In silico PCR evaluation showed that an average of 88.32% of the SSR markers generated only one in silico-specific product in two tetraploid A. hypogaea varieties, Tifrunner and Shitouqi. A total of 39,599 common SSR markers were identified among the two A. hypogaea varieties and two progenitors, A. duranensis and A. ipaensis. Additionally, an amplification effectiveness of 44.15% was observed by real PCR validation. Moreover, a total of 1276 public SSR loci were integrated with the newly developed SSR markers. Finally, a previously known leaf spot quantitative trait locus (QTL), qLLS_T13_A05_7, was determined to be in a 1.448-Mb region on chromosome A05. In this region, a total of 819 newly developed SSR markers were located and 108 candidate genes were detected.

Conclusions

The availability of these newly developed and public SSR markers both provide a large number of molecular markers that could potentially be used to enhance the process of trait genetic analyses and improve molecular breeding strategies for cultivated peanut.
A novel miniature transposon-like element discovered in the coding sequence of a gene that encodes for 5-formyltetrahydrofolate in wheat
Authors: Domb Katherine , Keidar-Friedman Danielle , Kashkush Khalil
Published: November 2019

Background

Transposable elements (TEs) comprise over 80% of the wheat genome and usually possess unique features for specific super-families and families. However, the role of TEs in wheat evolution and reshaping the wheat genome remains largely unclear.

Results

In this study, we discovered a miniature (307 bp in length) TE-like sequence in exon 6 of a gene that encodes for 5-formyltetrahydrofolate, in two accessions of wild emmer wheat (T. turgidumssp.dicoccoides) and has interfered with the gene translation by creating a shorter reading frame as a result of a stop codon. The sequence that was termedMariam,does not show any structural similarity to known TEs. It does not possess terminal inverted repeats (TIRs) that would allow us to assign this element to one of the TIR DNA super-families, and it does not possess characteristic features of SINE, such as a Pol-III promotor or a poly-A tail.In-silicoanalysis of five publicly available genome drafts ofTriticumandAegilopsspecies revealed thatMariamelement appears in a very low copy number (1–3 insertions) in diploid wheat species and ~ 12 insertions in tetraploid and hexaploidy wheat species. In addition,Mariamelement was found to be unique to wheat, as it was not found in other plant genomes. The dynamic nature ofMariamin the wheat genome was assessed by site-specific PCR analysis and revealed that it retained activity in wild emmer populations in a population-specific manner.

Conclusions

This study provides additional insight into the evolutionary impact of TEs in wheat.
Ghd8 controls rice photoperiod sensitivity by forming a complex that interacts with Ghd7
Authors: Wang Peng , Gong Rong , Yang Ying , Yu Sibin
Published: November 2019

Background

Flowering time is one of the most important agronomic characteristics that ultimately determine yield potential and eco-geographical adaptation in crops.Ghd8andGhd7, two major flowering genes, have similar functions and large pleiotropic effects in controlling the heading date, plant height and grain yield of rice. However, these gene interactions at the genetic and molecular levels have not been determined to date.

Results

In this study, we investigated the genetic interaction betweenGhd8andGhd7by using a set of near-isogenic lines and a panel of natural germplasm accessions in rice. We found thatGhd8affected multiple agronomic traits in a functionalGhd7-dependent manner.Both functionalGhd8andGhd7are pivotal for rice photoperiod sensitivity controlled byHd1andHd3a. GHD8 could form a heterotrimeric complex with HD1 and OsHAP5b to activate the transcription ofGhd7by binding directly to the promoter region ofGhd7, which contains the CCAAT-box motif.

Conclusions

The results of this study help to elucidate the genetic and molecular bases ofGhd8andGhd7interactions, indicating thatGhd8acts upstream ofGhd7to activate its transcription, which inhibitsHd3aexpression and thus affects flowering time and rice adaptation.
Design of the ZWOT-CASE study: an observational study on the effectiveness of an integrated programme for cardiovascular risk management compared to usual care in general practice
Authors: Marchal Suzanne , Hollander Monika , Schoenmakers Marieke , Schouwink Michiel , Timmer Jorik R. , Bilo Henk J. G. , Schwantje Olof , van ’t Hof Arnoud W. J. , Hoes Arno W.
Published: November 2019

Background

Cardiovascular diseases (CVD) contribute considerably to mortality and morbidity. Prevention of CVD by lifestyle change and medication is important and needs full attention.

In the Netherlands an integrated programme for cardiovascular risk management (CVRM), based on the Chronic Care Model (CCM), has been introduced in primary care in many regions in recent years, but its effects are unknown.

In the ZWOT-CASE study we will assess the effect of integrated care for CVRM in the region of Zwolle on two major cardiovascular risk factors: systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-cholesterol) in patients with or at high risk of CVD.

Methods

This study is a pragmatic observational study comparing integrated care for CVRM with usual care among patients aged 40–80 years with CVD (n = 370) or with a high CVD risk (n = 370) within 26 general practices. After 1 yr follow-up, primary outcomes (SBP and LDL-cholesterol level) are measured. Secondary outcomes include lifestyle habits (smoking, dietary habits, alcohol use, physical activity), risk factor awareness, 10-year risk of cardiovascular morbidity or mortality, health care consumption, patient satisfaction and quality of life.

Conclusion

The ZWOT-CASE study will provide insight in the effects of integrated care for CVRM in general practice in patients with CVD or at high CVD risk.

Trial registration

The ZWOlle Transmural Integrated Care for CArdiovaScular Risk Management Study; ClinicalTrials.gov; Identifier: NCT03428061; date of registration: 09-02-2018; This study has been retrospectively registered.
Tracheobronchitis in ulcerative colitis: a case report of therapeutic response with infliximab and review of the literature
Authors: Horgan Lisa , Mulrennan Siobhain , D’Orsogna Lloyd , McLean-Tooke Andrew
Published: November 2019

Background

The extra-intestinal manifestation of tracheobronchitis is a rare complication of ulcerative colitis (UC). Here, we present a case of UC-related tracheobronchitis wherein the positive clinical effects of infliximab are demonstrated.

Case presentation

We report the case of a 39-year old woman who presented with a chronic productive cough on a distant background of surgically managed ulcerative colitis (UC). Our patient failed to achieve a satisfactory clinical improvement despite treatment with high dose inhaled corticosteroids, oral corticosteroids and azathioprine. Infliximab therapy was commenced and was demonstrated to achieve macroscopic and symptomatic remission of disease.

Conclusions

We present the first case report documenting the benefits of infliximab in UC-related tracheobronchitis.
The clinical significance of myeloid-derived suppressor cells in dengue fever patients
Authors: Guo Peng-Le , Li Ling-Hua , Li Wen-Li , Zhao Jin-Cun , Hu Feng-Yu , Zhang Fu-Chun , Cai Wei-Ping , Tang Xiao-Ping
Published: November 2019

Background

Myeloid-derived suppressor cells (MDSCs) play immunosuppressive roles in cancers and some infectious diseases; however, their role in dengue fever (DF) remains unknown. This study evaluated the clinical significance of MDSCs in DF patients.

Methods

This study comprised 178 non-severe DF patients, 20 non-dengue fever (NDF) controls, and 30 healthy donors. The DF patients were divided into the following five groups based on the fever duration from its onset to the day of sample collection: fever duration of 1–2, 3–4, 5–6, 7–8, and > 9 days. Among these DF patients, 14 were monitored for eight days, and their peripheral blood samples were collected every two days. The mononuclear cells were isolated and analyzed using flow cytometry. The correlation between the MDSCs and clinical and immunological indicators of the DF patients was evaluated using Spearman analysis.

Results

The count of the peripheral blood MDSCs, especially monocytic MDSCs, of the 178 DF patients were dramatically higher than those of the NDF and healthy controls, and remarkably decreased with the fever duration. Moreover, the MDSC count correlated with some indicators, including the dengue viral load (rho = 0.367, p < .001), body temperature (rho = 0.263, p = .005), prothrombin time (rho = 0.475, p < .001), CD4+ T cell number (rho = − 0.317, p < .001), CD8+ T cell number (rho = − 0.361, p < .001), “programmed cell death protein 1” (PD-1) (rho = − 0.347, p < .001), “T cell immunoglobulin domain and mucin domain-3” (Tim3) (rho = − 0.258, p = .001), interferon-α (IFN-α) (rho = 0.43, p < .001), and “regulated upon activation normal T-cell expressed and secreted” (RANTES) (rho = 0.278, p = .019). Furthermore, the level of arginase-1, but not nitric oxide, was higher in the DF patients than in the healthy controls and was closely related to the number of MDSCs (rho = 0.265, p = .024).

Conclusions

Our study reveals a significant correlation between MDSCs and DF clinical indicators, posing MDSCs as potential target cells for DF treatment.
Changing diagnostic criteria for gestational diabetes in Sweden - a stepped wedge national cluster randomised controlled trial - the CDC4G study protocol
Authors: Fadl Helena , Saeedi Maryam , Montgomery Scott , Magnuson Anders , Schwarcz Erik , Berntorp Kerstin , Sengpiel Verena , Storck-Lindholm Elisabeth , Strevens Helena , Wikström Anna-Karin , Brismar-Wendel Sophia , Persson Martina , Jansson Stefan , Ahlsson Fredrik , Ursing Carina , Ryen Linda , Petersson Kerstin , Wennerholm Ulla-Britt , Hildén Karin , Simmons David
Published: November 2019

Background

The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden (www.cdc4g.se/en) is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches.

Methods

This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January–December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included.

Discussion

The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.

Trial registration

CDC4G is listed on the ISRCTN registry with study ID ISRCTN41918550 (15/12/2017)
Antenatal care use in Ethiopia: a spatial and multilevel analysis
Authors: Tegegne Teketo Kassaw , Chojenta Catherine , Getachew Theodros , Smith Roger , Loxton Deborah
Published: November 2019

Background

Accessibility and utilization of antenatal care (ANC) service varies depending on different geographical locations, sociodemographic characteristics, political and other factors. A geographically linked data analysis using population and health facility data is valuable to map ANC use, and identify inequalities in service access and provision. Thus, this study aimed to assess the spatial patterns of ANC use, and to identify associated factors among pregnant women in Ethiopia.

Method

A secondary data analysis of the 2016 Ethiopia Demographic and Health Survey linked with the 2014 Ethiopian Service Provision Assessment was conducted. A multilevel analysis was carried out using the SAS GLIMMIX procedure. Furthermore, hot spot analysis and spatial regressions were carried out to identify the hot spot areas of and factors associated with the spatial variations in ANC use using ArcGIS and R softwares.

Results

A one-unit increase in the mean score of ANC service availability in a typical region was associated with a five-fold increase in the odds of having more ANC visits. Moreover, every one-kilometre increase in distance to the nearest ANC facility in a typical region was negatively associated with having at least four ANC visits. Twenty-five percent of the variability in having at least four ANC visits was accounted for by region of living. The spatial analysis found that the Southern Nations, Nationalities and Peoples region had high clusters of at least four ANC visits. Furthermore, the coefficients of having the first ANC visit during the first trimester were estimated to have spatial variations in the use of at least four ANC visits.

Conclusion

There were significant variations in the use of ANC services across the different regions of Ethiopia. Region of living and distance were key drivers of ANC use underscoring the need for increased ANC availability, particularly in the cold spot regions.
Effects and outcomes of septostomy in twin-to-twin transfusion syndrome after fetoscopic laser therapy
Authors: Li Wen-Fang , Chao An-Shine , Chang Shuenn-Dyh , Cheng Po-Jen , Yang Lan-Yan , Chang Yao-Lung
Published: November 2019

Background

To evaluate the incidence and outcomes of septostomy in twin-to-twin transfusion syndrome (TTTS) after fetoscopic laser therapy.

Methods

A retrospective analysis of TTTS postlaser septostomy between 2005 and 2018 was performed. Postlaser septostomy was diagnosed using both (1) a free-floating intertwin membrane flap visible on ultrasound examination and (2) the rapid equalization of amniotic fluid maximum vertical pocket in the donor and recipient amniotic sacs observed after laser therapy. Perinatal survival, neonatal brain image anomaly, gestational age at operation and birth, incidence of premature rupture of membranes (PROM) within 3 weeks after operation, pseudoamniotic band syndrome, and cord entanglement were evaluated.

Results

In the 159 TTTS cases included, 12 had postlaser septostomy. Relative to the group without septostomy, the septostomy group had a lower total fetal survival rate (54.2% vs 73.6%, p = 0.041), an earlier mean gestational age at delivery (27.8 vs 34.4 weeks, p = 0.009), a higher risk of PROMs within 3 weeks after operation (33.3% vs 5.4%, p = 0.004), a higher cord entanglement rate (16.7% vs 0%, p = 0.005), and a higher brain image anomaly rate (23.0% [3/13] vs 5.0% [11/218], p = 0.035). After considering the severe Quintero stages (stage III and IV), postlaser septostomy was the only variable [p = 0.003, odds ratio = 5.1] to predict neonatal brain image anomaly. Postlaser septostomy combined with severe Quintero stages could predict PROMs within 3 weeks after laser therapy [p = 0.001, odds ratio = 14.1 and p = 0.03, odds ratio = 5.4, respectively] and delivery before the gestational age of 28 weeks [p = 0.017, odds ratio = 4.5 and p = 0.034, odds ratio = 2.3, respectively]. The risk of pseudoamniotic band syndrome was not increased by postlaser septostomy in this case series.

Conclusions

Postlaser septostomy in TTTS was associated with poorer fetal survival and more adverse perinatal outcomes even after considering severe Quintero stages before laser therapy. Efforts should be made to prevent septostomy during laser therapy, and septostomy as the primary method to treat TTTS is not advisable.
Association between thyroid-stimulating hormone and maternal hemodynamics in hypertensive disorders of pregnancy: an observational study
Authors: Liu Yu , Gao Bo , Zeng Xin , Yang Jing , Zhang Lei , Xu Ganwei , Jia Ruizhe , Xu Zhengfeng
Published: November 2019

Background

Hypertensive disorders of pregnancy (HDP) are characterized by hemodynamic disturbances. Altered thyroid function is a risk factor for poor outcomes of pregnancy. However, the associations between thyroid function biomarkers and maternal hemodynamics during pregnancy in HDP remain unclear.

Methods

From January 2016 to January 2018, pregnant women diagnosed with HDP admitted to the Nanjing Maternity and Child Health Care Hospital were prospectively enrolled in the third trimester. Normally distributed variables were expressed as mean ± standard deviation and skewed variables were expressed as median (25th percentile, 75th percentile). Correlations between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) and maternal hemodynamic parameters were assessed by Pearson’s correlation coefficient and 95% confidence interval (95%CI). Bonferroni’s correction for multiple correlations was performed. Logistic regression models with odd ratio (OR) and 95%CI were applied to confirm the associations.

Results

A total of 163 third-trimester pregnant women with HDP with a mean gestational age of 35.62 ± 2.83 weeks were recruited. The infant birth weight of patients with elevated TSH levels was lower than that of patients with normal TSH levels (2635 ± 867 g vs. 3037 ± 673 g, p = 0.002). Reduced cardiac output (CO) was defined as CO < 3.5 L/min. The infant birth weight of patients with reduced CO was lower than that of patients with normal CO (2250 ± 510 g vs. 2890 ± 774 g, p = 0.002). TSH levels were significantly and negatively correlated with CO (r = − 0.260, 95%CI: − 0.392- -0.103, p < 0.001). FT4 levels were not significantly correlated with any of the maternal hemodynamic parameters (all p > 0.05). TSH level (OR = 1.371, 95%CI: 1.086–1.733, p = 0.008) was confirmed associated with reduced CO in the logistic regression analysis.

Conclusions

Elevated TSH levels are associated with reduced CO in HDP during the third trimester.
Clear cell sarcoma of the kidney in a 62-year-old patient presenting with generalized pruritus
Authors: Zhang Yuxi , Li Jun , Wang Yan
Published: November 2019

Background

Clear cell sarcoma of the kidney (CCSK) is the second most common renal tumor in children following Wilms’ tumor. CCSK is extremely rare in adults, with only 25 adult cases reported in the medical literature.

Case presentation

We reported a 62-year-old man with a right renal mass presenting only with generalized pruritus who underwent radical right nephrectomy. With immunostaining, tumor cells were positive for expressed vimentin, neural cell adhesion molecule (NCAM, CD56), and Ki-67 and focally positive for p53, CD10 and Bcl-2. The histopathological diagnosis was CCSK. Two weeks after the operation, the generalized pruritus ended. One month after the operation, the patient started treatment with a regimen combining doxorubicin, vincristine, cyclophosphamide, and etoposide. At the 20-month follow-up visit, there was no evidence of local recurrence or metastases.

Conclusions

In a patient presenting with generalized pruritus, further evaluation for an underlying malignancy should be considered. It is difficult to distinguish CCSK from undifferentiated renal neoplasms. Immunohistochemistry could help to make exact histopathological diagnoses. The BCL-6 corepressor (BCOR) gene could play a significant role in CCSK tumorigenesis and be a good marker for CCSK diagnosis. Surgery with combination chemotherapy and radiation therapy could be used to treat CCSK in older patients.
β-arrestin-2 up-regulates toll-like receptor 2 signaling and inhibits apoptosis in human endometrial cancer heterotransplants in nude mice
Authors: Hong Fanling , Zhang Yujun , Cheng Wenjin , Sun Xiuli , Wang Jianliu
Published: November 2019

Background

β-arrestin-2(Arr2) functions as an anti-apoptotic factor and affects cell proliferation, but its downstream molecular pathway in endometrial carcinoma (EC) is still unclear. This study aimed to investigate the effects of the stable overexpression of Arr2 on the proliferation and apoptosis of human EC heterotransplants and the expression of associated molecules, including Toll-like receptor 2(TLR2), serine-threonine kinase Akt (Akt), glycogen synthase kinase-3β(GSK3β) and some typical inflammatory cytokines such as NF-κB p56, TNF-α and IL-6 & IL-8.

Methods

Human EC cell line Ishikawa, stably transfected with Arr2 full-length plasmid, was injected subcutaneously into nude mice. They were treated with 0, 10, 20 mg/kg paclitaxel and the volume and weight of the tumor tissue were measured and calculated. The necrotic index were assessed by H&E staining and microscopic observation. The levels of caspase-3, caspase-9, TLR2, NF-κB p56, Akt, GSK3β were measured by western blot, and the levels of TNF-α, IL-6, IL-8 were measured by real-time PCR.

Results

We found that Arr2 overexpression promoted the growth of human EC heterotransplants. Arr2 attenuated the promotion of caspase-3 and caspase-9 by paclitaxel and mediated the increase of TLR2 and several inflammatory cytokines. The levels of Akt and GSK3β were not affected.

Conclusion

Arr2 overexpression was associated with the increase of TLR2 and several inflammatory factors, meanwhile inhibited paclitaxel-induced anti-tumor effect on human EC heterotransplants.
A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report
Authors: Lin Kao-Min , Su Geng , Wang Fengpeng , Zhang Xiaobin , Wang Yuanqing , Ren Jun , Wang Xin , Yao Yi , Zhou Ying
Published: November 2019

Background

Epilepsy is a complex disorder caused by various factors, including genetic aberrance. Recent studies have identified an essential role of the sodium channel Nav1.6, encoded by the gene SCN8A, in epileptic encephalopathy.

Case presentation

Using parent-offspring trio targeted-exome sequencing, we identified a de novo heterozygous missense mutation c.3953A > G (p.N1318S) in SCN8A in a 3-year-and-9-month Chinese female patient with early infantile epileptic encephalopathy and a normal magnetic resonance imaging of the brain.

Conclusions

This de novo mutation was only detected in the patient but not in her parents. Bioinformatic analysis indicates the pathogenicity of this mutation. Administration of the sodium channel blocker well controlled seizures in the patient. Therefore, we recommend trio targeted-exome sequencing as a routine method for pathogenic variant screening in patients with intractable epilepsy and a normal MRI.
Research on the pathophysiology, treatment, and prevention of suicide: practical and ethical issues
Authors: Nugent Allison C. , Ballard Elizabeth D. , Park Lawrence T. , Zarate Carlos A.
Published: November 2019

Background

Despite decades of research, the rate of death from suicide is rising in the United States. Suicide is a complex and multifactorial phenomenon and, to date, no validated biomarkers that predict suicidal behavior have been identified. Only one FDA-approved drug to prevent suicide exists, and it is approved only for patients with schizophrenia. Although anti-suicide psychotherapeutic techniques exist, treatment takes time, and only preliminary data exist for rapid-acting therapies.

Discussion

While more research into suicidal ideation and acute suicidal behavior is clearly needed, this research is fraught with both practical and ethical concerns. As a result, many investigators and bioethicists have called for restrictions on the types of research that individuals with suicidal behavior can participate in, despite the fact that the available empirical evidence suggests that this research can be done safely. This manuscript presents background information on the phenomenology of suicide, discusses the current state of treatment and prevention strategies, and reviews the practical and ethical issues surrounding suicide research in the context of available empirical data.

Currently, the causes of suicide are poorly understood, in part due to the fact that very few studies have investigated the acute suicidal crisis. Although some biomarkers for predicting risk have been developed, none have been sufficiently validated. The most successful current interventions involve means restriction. However, while numerous hurdles face researchers, these are not insurmountable. The available evidence suggests that research into suicide can be conducted both safely and ethically.
An educational intervention to prevent overweight in pre-school years: a cluster randomised trial with a focus on disadvantaged families
Authors: Hodgkinson Alison , Abbott Janice , Hurley Margaret A. , Lowe Nicola , Qualter Pamela
Published: November 2019

Background

Early prevention is a promising strategy for reducing obesity in childhood, and Early Years settings are ideal venues for interventions. This work evaluated an educational intervention with the primary aim of preventing overweight and obesity in pre-school children.

Methods

A pragmatic, cluster randomised trial with a parallel, matched-pair design was undertaken. Interventions were targeted at both the cluster (Early Years’ Centres, matched by geographical area) and individual participant level (families: mother and 2-year old child). At the cluster level, a staff training intervention used the educational resource Be Active, Eat Healthy. Policies and provision for healthy eating and physical activity were evaluated at baseline and 12-months. The intervention at participant level was the Healthy Heroes Activity Pack: delivered over 6 months by Centre staff to promote healthy eating and physical activity in a fun, interactive way. Child and parent height and weight were measured at four time-points over 2 years. The trial primary outcome was the change in BMI z-score of the child between ages 2 and 4 years. Secondary outcomes consisted of parent-reported measures administered at baseline and two-year follow-up.

Results

Five pairs of Early Years’ Centres were recruited. Four pairs were analysed as one Centre withdrew (47 intervention families; 34 control families). At the cluster level, improvement in Centre policies and practices was similar for both groups (p = 0.830). At the participant level, the intervention group reduced their mean BMI z-score between age 2 and 4 years (p = 0.002; change difference 0.49; 95% CI 0.17 to 0.80) whereas the control group showed increasing BMI z-score throughout. Changes in parent-reported outcomes and parent BMI (p = 0.582) were similar in both groups.

Conclusions

The Healthy Heroes educational resource deterred excess weight gain in pre-school children from poor socioeconomic areas. With training, Early Years’ staff can implement the Healthy Heroes programme.

Trial registration

ISRCTN22620137 Registered 21st December 2016.
Consequences of chronic diseases and other limitations associated with old age – a scoping review
Authors: Maresova Petra , Javanmardi Ehsan , Barakovic Sabina , Barakovic Husic Jasmina , Tomsone Signe , Krejcar Ondrej , Kuca Kamil
Published: November 2019

Background

The phenomenon of the increasing number of ageing people in the world is arguably the most significant economic, health and social challenge that we face today. Additionally, one of the major epidemiologic trends of current times is the increase in chronic and degenerative diseases. This paper tries to deliver a more up to date overview of chronic diseases and other limitations associated with old age and provide a more detailed outlook on the research that has gone into this field.

Methods

First, challenges for seniors, including chronic diseases and other limitations associated with old age, are specified. Second, a review of seniors’ needs and concerns is performed. Finally, solutions that can improve seniors’ quality of life are discussed. Publications obtained from the following databases are used in this scoping review: Web of Science, PubMed, and Science Direct. Four independent reviewers screened the identified records and selected relevant publications published from 2010 to 2017. A total of 1916 publications were selected. In all, 52 papers were selected based on abstract content. For further processing, 21 full papers were screened.”

Results

The results indicate disabilities as a major problem associated with seniors’ activities of daily living dependence. We founded seven categories of different conditions - psychological problems, difficulties in mobility, poor cognitive function, falls and incidents, wounds and injuries, undernutrition, and communication problems. In order to minimize ageing consequences, some areas require more attention, such as education and training; technological tools; government support and welfare systems; early diagnosis of undernutrition, cognitive impairment, and other diseases; communication solutions; mobility solutions; and social contributions.

Conclusions

This scoping review supports the view on chronic diseases in old age as a complex issue. To prevent the consequences of chronic diseases and other limitations associated with old age related problems demands multicomponent interventions. Early recognition of problems leading to disability and activities of daily living (ADL) dependence should be one of essential components of such interventions.
Promoting population health with public-private partnerships: Where’s the evidence?
Authors: Parker Lucy A. , Zaragoza Gustavo A. , Hernández-Aguado Ildefonso
Published: November 2019

Background

Although public-private partnerships have become common in the health sector, the evidence supporting their effectiveness is limited, and when the products or services provided by the private partner are harmful to health inherent conflicts of interest may be difficult to overcome. The objective of this study is to appraise the evidence describing process or effectiveness of public-private partnerships (PPPs) that aim to promote population health, and analyse how characteristics such as independence or competing interests influence the results of their evaluation.

Methods

We carried out a systematic search of Medline and Web of Science to identify scientific reports evaluating the process or effectiveness of PPPs that aim to promote population health. Two reviewers applied inclusion criteria, extracted and evaluated study quality. We classified PPPs according to the health problem tackled, the independence of the evaluation, and the potential for competition between business interests of the private partner and health promotion activity undertaken. We classified the conclusions of the evaluation as positive (supportive/tentatively supportive) or negative (semi-critical/critical).

Results

We identified 36 studies evaluating 25 PPPs. Evaluations that were favourable to the use of PPPs in health promotion were more frequently classed as “not independent” and of poor quality. On the other hand, negative evaluations were more common when the PPP involved a private partner with a high potential for competition between the health promotion activity undertaken and their financial interests. PPPs that sought to prevent non-communicable diseases were more frequently negatively evaluated compared to PPPs tackling infectious disease or other types of health problem. Almost all of the evaluations evaluated process, with only 2 papers reporting quantitative health related outcomes.

Conclusions

There is still a lack of sound evidence supporting the effectiveness of public-private partnerships in health promotion, and the evidence base is skewed by non-independent evaluations. Public health actors should abstain from engaging in agreements with industries whose business interests have a high potential for competition with the health promotion activity undertaken.
Study protocol to assess the impact of an integrated nutrition intervention on the growth and development of children under two in rural Bangladesh
Authors: Ara Gulshan , Sanin Kazi Istiaque , Khanam Mansura , Sarker Shafiqul Alam , Khan Sihan Sadat , Rifat Mahfuza , Chowdhury Imran Ahmed , Askari Sufia , Afsana Kaosar , Ahmed Tahmeed
Published: November 2019

Background

The period from birth to two years is the “critical window” for achieving optimal growth and development. An inadequate quality and quantities of complementary foods, poor child-feeding practices and infection negatively impact the growth of under-twos. Approximately one-third of under-fives in developing countries are stunted; many are also micronutrient deficient. An estimated 6% of mortalities among under-fives can be prevented by ensuring optimal complementary feeding. The objective of the study was to assess the ability of a 12-month integrated nutrition intervention to improve the nutritional status (length-for-age Z-score) of 6 to 12-month-old children in rural Bangladesh.

Methods

In this community-based randomized controlled trial, the intervention group received a package of interventions that includes, food vouchers; to prepare egg-based nutritious snacks (suji firni for < 1-year-olds, suji halwa for > 1-year-olds), micronutrient powder to fortify children’s food at home, child feeding counselling and water, sanitation and hygiene (WASH), behaviour change communication. The control group received routine health messages provided by the government. Baseline and endline surveys were conducted; Data collection was performed monthly on children’s growth, food voucher utilization, child feeding and morbidity. In addition, we assessed the cognitive development of the children after 12 months of intervention.

Conclusion

This trial aims to explore whether an integrated nutrition intervention can mitigate childhood stunting during the critical window of opportunity in rural Bangladesh. The results may provide robust evidence to improve the linear growth of children in developing countries.

Trial registration

The study was retrospectively registered on August 17, 2018 and is available online at ClinicalTrials.gov (ID: NCT02768181).
Does community social capital buffer the relationship between educational disadvantage and cognitive impairment? A multilevel analysis in Japan
Authors: Murayama Hiroshi , Miyamae Fumiko , Ura Chiaki , Sakuma Naoko , Sugiyama Mika , Inagaki Hiroki , Okamura Tsuyoshi , Awata Shuichi
Published: November 2019

Background

This study explored the relationship between community social capital and cognitive impairment, with a focus on the buffering role of community social capital in the association between educational disadvantage and cognitive impairment in community-dwelling older adults in Japan.

Methods

We used data from two population-based, cross-sectional surveys targeting people aged ≥65 years in a suburban city of the Tokyo metropolitan area (n = 897; 49.8% men; average age = 74.4 years). Social capital included social support (emotional and instrumental support) and the strength of social networks (neighborly ties). To create district-level social capital indicators, we aggregated individual responses on social capital within each district. The Mini-Mental State Examination, Japanese version was used for the assessment of cognitive function.

Results

Using multilevel logistic regression analysis, we found that lower amounts of district-level emotional and instrumental support were associated with a greater likelihood of cognitive impairment among men. For women, district-level emotional support was associated with a greater likelihood of cognitive impairment. Additionally, a strong district-level social network buffered the relationship between low education and cognitive impairment in both sexes.

Conclusions

Community social capital appears to have a protective role in determining cognitive function in old age. Our findings may facilitate the development of new community-based strategies to combat dementia.
Associations of tobacco smoking with body mass distribution; a population-based study of 65,875 men and women in midlife
Authors: Graff-Iversen Sidsel , Hewitt Stephen , Forsén Lisa , Grøtvedt Liv , Ariansen Inger
Published: November 2019

Background

Studies indicate an effect of smoking toward abdominal obesity, but few assess hip and waist circumferences (HC and WC) independently. The present study aimed to assess the associations of smoking status and volume smoked with HC and WC and their ratio in a population with low prevalence of obesity together with high prevalence of smoking.

Methods

We used cross-sectional survey data from 11 of a total 19 Norwegian counties examined in 1997–99 including 65,875 men and women aged 39–44 years. Analysis of associations were adjusted for confounding by socioeconomic position, health indicators, and additionally for BMI.

Results

Compared with never-smokers, when adjusting for confounders and in addition for BMI, mean HC remained lower while mean WC and waist-hip-ratio (WHR) were higher in current smokers. The finding of a lower HC and higher WHR level among smokers was consistent by sex and in strata by levels of education and physical activity, while the finding of higher WC by smoking was less consistent. Among current smokers, BMI-adjusted mean HC decreased whereas WC and WHR increased by volume smoked. Compared with current smokers, former smokers had higher BMI-adjusted HC, lower WHR and among women WC was lower.

Conclusions

The main finding in this study was the consistent negative associations of smoking with HC. In line with the hypothesis that lower percentage gluteofemoral fat is linked with higher cardiovascular risk, our results suggest that smoking impacts cardiovascular risk through mechanisms that reduce the capacity of fat storage in the lower body region.