bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients
Authors: Aoki Takuya , Akiba Takeshi , Nishiyama Jun , Tajiri Sakurako , Hayama Naoki , Takahashi Genki , Tanaka Jun , Sato Masako , Takiguchi Hiroto , Tomomatsu Hiromi , Tomomatsu Katsuyoshi , Takihara Takahisa , Niimi Kyoko , Oguma Tsuyoshi , Kohno Mitsutomo , Masuda Ryota , Urano Tetsuya , Itoh Hitoshi , Kajiwara Hiroshi , Nakamura Naoya , Kunieda Etsuo , Matsumae Mitsunori , Iwazaki Masayuki , Asano Koichiro
Published: November 2019

Background

Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years.

Methods

From our hospital database, 1,699 patients, registered as lung cancer between 1stMar 2004 and 30thApr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13thFeb 2017.

Results

There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response.

Conclusions

Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV.

This study was retrospectively registered on 16thJun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).
Strategies for measuring airway mucus and mucins
Authors: Atanasova Kalina R. , Reznikov Leah R.
Published: November 2019

Mucus secretion and mucociliary transport are essential defense mechanisms of the airways. Deviations in mucus composition and secretion can impede mucociliary transport and elicit airway obstruction. As such, mucus abnormalities are hallmark features of many respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Studying mucus composition and its physical properties has therefore been of significant interest both clinically and scientifically. Yet, measuring mucus production, output, composition and transport presents several challenges. Here we summarize and discuss the advantages and limitations of several techniques from five broadly characterized strategies used to measure mucus secretion, composition and mucociliary transport, with an emphasis on the gel-forming mucins. Further, we summarize advances in the field, as well as suggest potential areas of improvement moving forward.
Infective endocarditis according to type 2 diabetes mellitus status: an observational study in Spain, 2001–2015
Authors: de Miguel-Yanes José M. , Jiménez-García Rodrigo , Hernández-Barrera Valentín , de Miguel-Díez Javier , Méndez-Bailón Manuel , Muñoz-Rivas Nuria , Pérez-Farinós Napoleón , López-de-Andrés Ana
Published: November 2019

Background

The main aims of this study were to describe trends and outcomes during admission for infective endocarditis (IE) in people ≥ 40 years old with or without type 2 diabetes distributed in five time-periods (2001–2003; 2004–2006; 2007–2009; 2010–2012 and 2013–2015), using Spanish national hospital discharge data.

Methods

We estimated admission rates by diabetes status. We analyzed comorbidity, therapeutic procedures, and outcomes. We built Poisson regression models to compare the adjusted time-trends in admission rates. Type 2 diabetes cases were matched with controls using propensity score matching (PSM). We tested in-hospital mortality (IHM) in logistic regression analyses.

Results

We identified 16,626 hospitalizations in patients aged ≥ 40 years for IE in Spain, 2001–2015. The incidence of IE increased significantly from 6.0/100,000 per year to 13.1/100,000 per year (p < 0.001) in the population with type 2 diabetes, and from 3.9/100,000 per year to 5.5/100,000 per year (p < 0.001) in the population without diabetes, over the study period. The adjusted incidence of IE was 2.2-times higher among patients with diabetes than among those without diabetes (IRR = 2.2; 95% CI 2.1–2.3). People with type 2 diabetes less often underwent heart valve surgery than people without diabetes (13.9% vs. 17.3%; p < 0.001). Although IHM decreased significantly in both groups over time, it represented 20.8% of IE cases among diabetes patients and 19.9% among PSM matched controls (p = 0.337). Type 2 diabetes was not associated with a higher IHM in people admitted to the hospital for IE (OR = 1.1; 95% CI 0.9–1.2).

Conclusion

Incidence rates of IE in Spain, among those with and without T2DM, have increased during the period 2001–2015 with significantly higher incidence rates in the T2DM population. In our population based study and after PSM we found that T2DM was not a predictor of IHM in IE.
LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p
Authors: Ye Zhuo , Duan Jiachen , Wang Lihui , Ji Yanli , Qiao Baoping
Published: November 2019

Background

Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear.

Methods

LncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay.

Results

LncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors.

Conclusion

These findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.
MicroRNA-1269 promotes cell proliferation via the AKT signaling pathway by targeting RASSF9 in human gastric cancer
Authors: Liu Wen-Li , Wang Hu-xia , Shi Cheng-xin , Shi Fei-yu , Zhao Ling-yu , Zhao Wei , Wang Guang-hui
Published: November 2019

Background

MicroRNAs (miRNAs) play key roles in tumorigenesis and progression of gastric cancer (GC). miR-1269 has been reported to be upregulated in several cancers and plays a crucial role in carcinogenesis and cancer progression. However, the biological function of miR-1269 in human GC and its mechanism remain unclear and need to be further elucidated.

Methods

The expression of miR-1269 in GC tissues and cell lines was detected by quantitative real-time PCR (qRT-PCR). Target prediction programs (TargetScanHuman 7.2 and miRBase) and a dual-luciferase reporter assay were used to confirm that Ras-association domain family 9 (RASSF9) is a target gene of miR-1269. The expression of RASSF9 was measured by qRT-PCR and Western blotting in GC tissues. MTT and cell counting assays were used to explore the effect of miR-1269 on GC cell proliferation. The cell cycle and apoptosis were measured by flow cytometry. RASSF9 knockdown and overexpression were used to further verify the function of the target gene.

Results

We found that miR-1269 expression was upregulated in human GC tissues and cell lines. The overexpression of miR-1269 promoted GC cell proliferation and cell cycle G1-S transition and suppressed apoptosis. The inhibition of miR-1269 inhibited cell growth and G1-S transition and induced apoptosis. miR-1269 expression was inversely correlated with RASSF9 expression in GC tissues. RASSF9 was verified to be a direct target of miR-1269 by using a luciferase reporter assay. The overexpression of miR-1269 decreased RASSF9 expression at both the mRNA and protein levels, and the inhibition of miR-1269 increased RASSF9 expression. Importantly, silencing RASSF9 resulted in the same biological effects in GC cells as those induced by overexpression of miR-1269. Overexpression of RASSF9 reversed the effects of miR-1269 overexpression on GC cells. Both miR-1269 overexpression and RASSF9 silencing activated the AKT signaling pathway, which modulated cell cycle regulators (Cyclin D1 and CDK2). In contrast, inhibition of miR-1269 and RASSF9 overexpression inhibited the AKT signaling pathway. Moreover, miR-1269 and RASSF9 also regulated the Bax/Bcl-2 signaling pathway.

Conclusions

Our results demonstrate that miR-1269 promotes GC cell proliferation and cell cycle G1-S transition by activating the AKT signaling pathway and inhibiting cell apoptosis via regulation of the Bax/Bcl-2 signaling pathway by targeting RASSF9. Our findings indicate an oncogenic role of miR-1269 in GC pathogenesis and the potential use of miR-1269 in GC therapy.
Description of Plasmodium falciparum infections in central Gabon demonstrating high parasite densities among symptomatic adolescents and adults
Authors: Zoleko Manego Rella , Koehne Erik , Kreidenweiss Andrea , Nzigou Mombo Brice , Adegbite Bayode Romeo , Dimessa Mbadinga Lia Betty , Akinosho Malik , Matthewman Julian , Adegnika Ayola Akim , Ramharter Michael , Mombo-Ngoma Ghyslain
Published: November 2019

Background

Malaria remains a public health issue, particularly in sub-Saharan Africa with special features of seriousness in young children and pregnant women. Adolescents and adults are reported to have acquired a semi-immune status and, therefore, present with low parasitaemia. Children are understood to present with a much higher parasitaemia and severe malaria. It is a concern that effective malaria control programmes targeting young children may lead to a delay in the acquisition of acquired immunity and, therefore, causing a shift in the epidemiology of malaria. Prevalence and parasitaemia were explored in adolescents and adults with Plasmodium falciparum infections compared to young children in the area of Lambaréné, Gabon as an indicator for semi-immunity.

Methods

A cross-sectional study was conducted at the Centre de Recherches Médicales de Lambaréné (CERMEL) during a 6-month period in 2018. Symptomatic patients, of all ages were screened for malaria at health facilities in Lambaréné and Fougamou and their respective surrounding villages in the central region of Gabon. Plasmodium falciparum infections were determined either by rapid diagnostic test (RDT) or by microscopy. Descriptive analysis of data on parasite densities, anaemia, and fever are presented.

Results

1589 individuals screened were included in this analysis, including 731 (46%) adolescents and adults. Out of 1377 assessed, the proportion of P. falciparum positive RDTs was high among adolescents (68%) and adults (44%), compared to young children (55%) and school children (72%). Out of 274 participants assessed for malaria by microscopy, 45 (16%) had a parasite count above 10,000/µl of which 9 (20%) were adults.

Conclusion

This study shows a high rate of P. falciparum infections in adolescents and adults associated with high-level parasitaemia similar to that of young children. Adolescents and adults seem to be an at-risk population, suggesting that malaria programmes should consider adolescents and adults during the implementation of malaria prevention and case management programmes with continuous care, since they also act as reservoirs for P. falciparum.
Correction to: Evidence of asymptomatic submicroscopic malaria in low transmission areas in Belaga district, Kapit division, Sarawak, Malaysia
Authors: Jiram Adela Ida , Ooi Choo Huck , Rubio José Miguel , Hisam Shamilah , Karnan Govindarajoo , Sukor Nurnadiah Mohd , Artic Mohd Mafe , Ismail Nor Parina , Alias Nor Wahida , Aziah Ismail
Published: November 2019

Please note that an author has been erroneously omitted from the author list of the published article [1].
Ongoing challenges in access to diabetes care among the indigenous population: perspectives of individuals living in rural Guatemala
Authors: Nieblas-Bedolla Edwin , Bream Kent D. W. , Rollins Allison , Barg Frances K.
Published: November 2019

Background

Indigenous persons living in Latin America suffer from a higher prevalence of type 2 diabetes compared to their non-indigenous counterparts. This difference has been attributed to a wide range of factors. Future interventions could be influenced by a deeper understanding of the challenges that impact care in rural regions and in other low-income settings.

Methods

This study was conducted using a modified grounded theory approach. Extended observations and fifteen interviews were performed with adult male and female residents of three rural Mayan towns in Sololá Department, Guatemala using purposive sampling. Questions focused on the perceptions of individuals living with type 2 diabetes and their caregivers regarding disease and treatment.

Results

Across interviews the most common themes that emerged included mistreatment by healthcare providers, mental health comorbidity, and medication affordability. These perceptions were in part influenced by indigeneity, poverty, and/or gender.

Conclusions

Both structural and cultural barriers continue to impact diabetes care for indigenous communities in rural Guatemala. The interviews in this study suggest that indigenous people experience mistrust in the health care system, unreliable access to care, and mental health comorbidity in the context of type 2 diabetes care. These experiences are shaped by the complex relationship among poverty, gender, and indigeneity in this region. Targeted interventions that are conscious of these factors may increase their chances of success when attempting to address similar health disparities in comparable populations.
Transcriptome-wide analysis of changes in the fetal placenta associated with prenatal arsenic exposure in the New Hampshire Birth Cohort Study
Authors: Winterbottom Emily F. , Ban Yuguang , Sun Xiaodian , Capobianco Anthony J. , Marsit Carmen J. , Chen Xi , Wang Lily , Karagas Margaret R. , Robbins David J.
Published: November 2019

Background

Increasing evidence suggests that prenatal exposure to arsenic, even at common environmental levels, adversely affects child health. These adverse effects include impaired fetal growth, which can carry serious health implications lifelong. However, the mechanisms by which arsenic affects fetal health and development remain unclear.

Methods

We addressed this question using a group of 46 pregnant women selected from the New Hampshire Birth Cohort Study (NHBCS), a US cohort exposed to low-to-moderate arsenic levels in drinking water through the use of unregulated private wells. Prenatal arsenic exposure was assessed using maternal urine samples taken at mid-gestation. Samples of the fetal portion of the placenta were taken from the base of the umbilical cord insertion at the time of delivery, stored in RNAlater and frozen. We used RNA sequencing to analyze changes in global gene expression in the fetal placenta associated with in utero arsenic exposure, adjusting for maternal age. Gene set enrichment analysis and enrichment mapping were then used to identify biological processes represented by the differentially expressed genes. Since our previous analyses have identified considerable sex differences in placental gene expression associated with arsenic exposure, we analyzed male and female samples separately.

Results

At FDR < 0.05, no genes were differentially expressed in female placenta, while 606 genes were differentially expressed in males. Genes showing the most significant associations with arsenic exposure in females wereLEMD1andUPK3B(fold changes 2.51 and 2.48), and in males,FIBINandRANBP3L(fold changes 0.14 and 0.15). In gene set enrichment analyses, at FDR < 0.05, a total of 211 gene sets were enriched with differentially expressed genes in female placenta, and 154 in male placenta. In female but not male placenta, 103 of these gene sets were also associated with reduced birth weight.

Conclusions

Our results reveal multiple biological functions in the fetal placenta that are potentially affected by increased arsenic exposure, a subset of which is sex-dependent. Further, our data suggest that in female infants, the mechanisms underlying the arsenic-induced reduction of birth weight may involve activation of stress response pathways.
Wrangling environmental exposure data: guidance for getting the best information from your laboratory measurements
Authors: Udesky Julia O. , Dodson Robin E. , Perovich Laura J. , Rudel Ruthann A.
Published: November 2019

Background

Environmental health and exposure researchers can improve the quality and interpretation of their chemical measurement data, avoid spurious results, and improve analytical protocols for new chemicals by closely examining lab and field quality control (QC) data. Reporting QC data along with chemical measurements in biological and environmental samples allows readers to evaluate data quality and appropriate uses of the data (e.g., for comparison to other exposure studies, association with health outcomes, use in regulatory decision-making). However many studies do not adequately describe or interpret QC assessments in publications, leaving readers uncertain about the level of confidence in the reported data. One potential barrier to both QC implementation and reporting is that guidance on how to integrate and interpret QC assessments is often fragmented and difficult to find, with no centralized repository or summary. In addition, existing documents are typically written for regulatory scientists rather than environmental health researchers, who may have little or no experience in analytical chemistry.

Objectives

We discuss approaches for implementing quality assurance/quality control (QA/QC) in environmental exposure measurement projects and describe our process for interpreting QC results and drawing conclusions about data validity.

Discussion

Our methods build upon existing guidance and years of practical experience collecting exposure data and analyzing it in collaboration with contract and university laboratories, as well as the Centers for Disease Control and Prevention. With real examples from our data, we demonstrate problems that would not have come to light had we not engaged with our QC data and incorporated field QC samples in our study design. Our approach focuses on descriptive analyses and data visualizations that have been compatible with diverse exposure studies with sample sizes ranging from tens to hundreds of samples. Future work could incorporate additional statistically grounded methods for larger datasets with more QC samples.

Conclusions

This guidance, along with example table shells, graphics, and some sample R code, provides a useful set of tools for getting the best information from valuable environmental exposure datasets and enabling valid comparison and synthesis of exposure data across studies.
Air pollution and mortality in a large, representative U.S. cohort: multiple-pollutant analyses, and spatial and temporal decompositions
Authors: Lefler Jacob S. , Higbee Joshua D. , Burnett Richard T. , Ezzati Majid , Coleman Nathan C. , Mann Dalton D. , Marshall Julian D. , Bechle Matthew , Wang Yuzhou , Robinson Allen L. , Arden Pope C.
Published: November 2019

Background

Cohort studies have documented associations between fine particulate matter air pollution (PM2.5) and mortality risk. However, there remains uncertainty regarding the contribution of co-pollutants and the stability of pollution-mortality associations in models that include multiple air pollutants. Furthermore, it is unclear whether the PM2.5-mortality relationship varies spatially, when exposures are decomposed according to scale of spatial variability, or temporally, when effect estimates are allowed to change between years.

Methods

A cohort of 635,539 individuals was compiled using public National Health Interview Survey (NHIS) data from 1987 to 2014 and linked with mortality follow-up through 2015. Modelled air pollution exposure estimates for PM2.5, other criteria air pollutants, and spatial decompositions (< 1 km, 1–10 km, 10–100 km, > 100 km) of PM2.5 were assigned at the census-tract level. The NHIS samples were also divided into yearly cohorts for temporally-decomposed analyses. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) in regression models that included up to six criteria pollutants; four spatial decompositions of PM2.5; and two- and five-year lagged mean PM2.5 exposures in the temporally-decomposed cohorts. Meta-analytic fixed-effect estimates were calculated using results from temporally-decomposed analyses and compared with time-independent results using 17- and 28-year exposure windows.

Results

In multiple-pollutant analyses, PM2.5 demonstrated the most robust pollutant-mortality association. Coarse fraction particulate matter (PM2.5–10) and sulfur dioxide (SO2) were also associated with excess mortality risk. The PM2.5-mortality association was observed across all four spatial scales of PM2.5, with higher but less precisely estimated HRs observed for local (< 1 km) and neighborhood (1–10 km) variations. In temporally-decomposed analyses, the PM2.5-mortality HRs were stable across yearly cohorts. The meta-analytic HR using two-year lagged PM2.5 equaled 1.10 (95% CI 1.07, 1.13) per 10 μg/m3. Comparable results were observed in time-independent analyses using a 17-year (HR 1.13, CI 1.09, 1.16) or 28-year (HR 1.09, CI 1.07, 1.12) exposure window.

Conclusions

Long-term exposures to PM2.5, PM2.5–10, and SO2 were associated with increased risk of all-cause and cardiopulmonary mortality. Each spatial decomposition of PM2.5 was associated with mortality risk, and PM2.5-mortality associations were consistent over time.
Global longitudinal strain is a hallmark of cardiac damage in mitral regurgitation: the Italian arm of the European Registry of mitral regurgitation (EuMiClip)
Authors: Santoro Ciro , Galderisi Maurizio , Esposito Roberta , Buonauro Agostino , Monteagudo Juan Manuel , Sorrentino Regina , Lembo Maria , Fernandez-Golfin Covadonga , Trimarco Bruno , Zamorano Josè Luis
Published: November 2019

Background

The search for reliable cardiac functional parameters is crucial in patients with mitral regurgitation (MR). In the Italian arm of the European Registry of MR, we compared the ability of global longitudinal strain (GLS) and left ventricular (LV) ejection fraction (LVEF) to detect cardiac damage in MR.

Methods

Five hundred four consecutive patients with MR underwent a complete echo-Doppler exam. A total of 431, 53 and 20 patients had degenerative, secondary and mixed MR, respectively. The main echocardiographic parameters, including LV and left atrial (LA) size measurements, pulmonary artery systolic pressure (PASP) and GLS were compared between patients with mild MR (n = 392) vs. moderate to severe MR (n = 112).

Results

LVEF and GLS were related one another in the pooled population, and separately in patients with mild and moderate/severe MR (all p < 0.0001). However, a certain number of patients were above the upper or below the lower limits of the 95% confidence interval (CI) of the normal relation in the pooled population and in patients with mild MR. Only 2 patients were below the 95% CI in moderate to severe MR. After adjusting for confounders by separate multivariate models, LVEF and GLS were independently associated with LV and left atrial size in the pooled population and in mild and moderate/severe MR. GLS, but not LVEF, was also independently associated with PASP in patients with mild and moderate to severe MR.

Conclusions

Both LVEF and GLS are independently associated with LV and LA size, but only GLS is related to pulmonary arterial pressure. GLS is a powerful hallmark of cardiac damage in MR.
ΗΙF1α, EGR1 and SP1 co-regulate the erythropoietin receptor expression under hypoxia: an essential role in the growth of non-small cell lung cancer cells
Authors: Su Tianhong , Liu Pi , Ti Xinyu , Wu Shouzhen , Xue Xiaochang , Wang Zenglu , Dioum Elhardji , Zhang Qiuyang
Published: November 2019

Background

Overexpression of erythropoietin (EPO) and EPO receptor (EPO-R) is associated with poor prognosis in non-small-cell lung carcinoma (NSCLC). Hypoxia, a potent EPO inducer, is a major stimulating factor in the growth of solid tumors. However, how EPO-R expression is regulated under hypoxia is largely unknown.

Methods

The role of EPO-R in NSCLC cell proliferation was assessed by RNA interference in vitro. Luciferase reporter assays were performed to map the promoter elements involved in the EPO-R mRNA transcription. Nuclear co-immunoprecipitation and chromatin immunoprecipitation were performed to assess the interaction among transcription factors HIF1α, SP1, and EGR1 in the regulation of EPO-R under hypoxia. The expression of key EPO-R transcription factors in clinical specimens were determined by immunohistochemistry.

Results

Hypoxia induced a dosage and time dependent EPO-R mRNA expression in NSCLC cells. Knockdown of EPO-R reduced NSCLC cell growth under hypoxia (P < 0.05). Mechanistically, a SP1-EGR1 overlapped DNA binding sequence was essential to the hypoxia induced EPO-R transcription. In the early phase of hypoxia, HIF1α interacted with EGR1 that negatively regulated EPO-R. With the exit of EGR1 in late phase, HIF1α positively regulated EPO-R expression through additive interaction with SP1. In clinical NSCLC specimen, SP1 was positively while EGR1 was negatively associated with active EPO-R expression (P < 0.05).

Conclusions

HIF1α, SP1 and EGR1 mediated EPO-R expression played an essential role in hypoxia-induced NSCLC cell proliferation. Our study presents a novel mechanism of EPO-R regulation in the tumor cells, which may provide information support for NSCLC diagnosis and treatment.

Graphical abstract
Temporal features of sitting, standing and stepping changes in a cluster-randomised controlled trial of a workplace sitting-reduction intervention
Authors: Stephens Samantha K. , Winkler Elisabeth A. H. , Eakin Elizabeth G. , Clark Bronwyn K. , Owen Neville , Moodie Marj , La Montagne Anthony D. , Dunstan David W. , Healy Genevieve N.
Published: November 2019

Background

There is now a body of evidence on the effectiveness of interventions to reduce workplace sitting time. However, there has been limited reporting of how such interventions may impact behaviour both during and outside of work. Sitting, standing and stepping changes following a workplace intervention were examined across five timeframes (work time on work days; non-work time on work days; work days; non-work days; overall (i.e. work and non-work time on all days)), and the relationships between changes during and outside of work was assessed.

Methods

The cluster-randomised controlled trial, ‘Stand Up Victoria’, delivered a multi-component workplace-delivered intervention that successfully reduced workplace and overall sitting time (relative to controls). Separately, over the five timeframes, changes in device (activPAL3)-assessed outcomes — sitting; prolonged sitting (≥30 min bouts); standing; and, stepping — were compared between intervention (n = 114) and controls (n = 84), along with the time-course of sitting changes during work hours, using mixed models. The potential relationships of changes during work with changes outside of work were examined using compositional data analysis.

Results

On workdays, intervention participants significantly (p < 0.05) improved their activity profile relative to controls, with reduced sitting (− 117 min/8-h workday, 95% CI: − 141, − 93) and prolonged sitting (− 77 min/8 h workday, 95% CI: − 101, − 52); increased standing (114 min/8 h workday, 95% CI: 92, 136) and maintenance of stepping (3 min/8 h workday, 95% CI: − 7, 11, p = 0.576). Effects were nearly identical for time at work; similar but slightly weaker for overall; and, small and non-significant outside of work on workdays and non-work days. Improvements occurred at all times, but not equally, during work hours (p < 0.001). Correlations between changes during and outside of work on workdays were very weak in both the intervention group (r = − 0.07) and controls (r = − 0.09).

Conclusions

Sitting time was reduced almost exclusively during work hours (via replacement with standing), with reductions evident during all working hours, to varying degrees. There was no evidence of compensation, with minimal change in activity outside of work, in response to changes in activity at work. Future interventions may benefit from exploring how best to elicit change throughout the whole day, and across work and non-work domains.

Trial registration

This trial was prospectively registered with the Australian New Zealand Clinical Trials register (ACTRN12611000742976) on 15 July 2011
Current progress in hepatic tissue regeneration by tissue engineering
Authors: Hosseini Vahid , Maroufi Nazila Fathi , Saghati Sepideh , Asadi Nahideh , Darabi Masoud , Ahmad Saeed Nazari Soltan , Hosseinkhani Hosseini , Rahbarghazi Reza
Published: November 2019

Background

Liver, as a vital organ, is responsible for a wide range of biological functions to maintain homeostasis and any type of damages to hepatic tissue contributes to disease progression and death. Viral infection, trauma, carcinoma, alcohol misuse and inborn errors of metabolism are common causes of liver diseases are a severe known reason for leading to end-stage liver disease or liver failure. In either way, liver transplantation is the only treatment option which is, however, hampered by the increasing scarcity of organ donor. Over the past years, considerable efforts have been directed toward liver regeneration aiming at developing new approaches and methodologies to enhance the transplantation process. These approaches include producing decellularized scaffolds from the liver organ, 3D bio-printing system, and nano-based 3D scaffolds to simulate the native liver microenvironment. The application of small molecules and micro-RNAs and genetic manipulation in favor of hepatic differentiation of distinct stem cells could also be exploited. All of these strategies will help to facilitate the application of stem cells in human medicine. This article reviews the most recent strategies to generate a high amount of mature hepatocyte-like cells and updates current knowledge on liver regenerative medicine.
A prospective evaluation of thiamine and magnesium status in relation to clinicopathological characteristics and 1-year mortality in patients with alcohol withdrawal syndrome
Authors: Maguire Donogh , Talwar Dinesh , Burns Alana , Catchpole Anthony , Stefanowicz Fiona , Robson Gordon , Ross David P. , Young David , Ireland Alastair , Forrest Ewan , Galloway Peter , Adamson Michael , Colgan Eoghan , Bell Hannah , Orr Lesley , Kerr Joanna-Lee , Roussis Xen , McMillan Donald C.
Published: November 2019

Background

Alcohol withdrawal syndrome (AWS) is routinely treated with B-vitamins. However, the relationship between thiamine status and outcome is rarely examined. The aim of the present study was to examine the relationship between thiamine and magnesium status in patients with AWS.

Methods

Patients (n = 127) presenting to the Emergency Department with AWS were recruited to a prospective observational study. Blood samples were drawn to measure whole blood thiamine diphosphate (TDP) and serum magnesium concentrations. Routine biochemistry and haematology assays were also conducted. The Glasgow Modified Alcohol Withdrawal Score (GMAWS) measured severity of AWS. Seizure history and current medications were also recorded.

Results

The majority of patients (99%) had whole blood TDP concentration within/above the reference interval (275–675 ng/gHb) and had been prescribed thiamine (70%). In contrast, the majority of patients (60%) had low serum magnesium concentrations (< 0.75 mmol/L) and had not been prescribed magnesium (93%). The majority of patients (66%) had plasma lactate concentrations above 2.0 mmol/L. At 1 year, 13 patients with AWS had died giving a mortality rate of 11%. Male gender (p < 0.05), BMI < 20 kg/m2 (p < 0.01), GMAWS max ≥ 4 (p < 0.05), elevated plasma lactate (p < 0.01), low albumin (p < 0.05) and elevated serum CRP (p < 0.05) were associated with greater 1-year mortality. Also, low serum magnesium at time of recruitment to study and low serum magnesium at next admission were associated with higher 1-year mortality rates, (84% and 100% respectively; both p < 0.05).

Conclusion

The prevalence of low circulating thiamine concentrations were rare and it was regularly prescribed in patients with AWS. In contrast, low serum magnesium concentrations were common and not prescribed. Low serum magnesium was associated more severe AWS and increased 1-year mortality.
Stable, three degree-of-freedom myoelectric prosthetic control via chronic bipolar intramuscular electrodes: a case study
Authors: Dewald Hendrik Adriaan , Lukyanenko Platon , Lambrecht Joris M. , Anderson James Robert , Tyler Dustin J. , Kirsch Robert F. , Williams Matthew R.
Published: November 2019

Background

Modern prosthetic hands are typically controlled using skin surface electromyographic signals (EMG) from remaining muscles in the residual limb. However, surface electrode performance is limited by changes in skin impedance over time, day-to-day variations in electrode placement, and relative motion between the electrodes and underlying muscles during movement: these limitations require frequent retraining of controllers. In the presented study, we used chronically implanted intramuscular electrodes to minimize these effects and thus create a more robust prosthetic controller.

Methods

A study participant with a transradial amputation was chronically implanted with 8 intramuscular EMG electrodes. A K Nearest Neighbor (KNN) regression velocity controller was trained to predict intended joint movement direction using EMG data collected during a single training session. The resulting KNN was evaluated over 12 weeks and in multiple arm posture configurations, with the participant controlling a 3 Degree-of-Freedom (DOF) virtual reality (VR) hand to match target VR hand postures. The performance of this EMG-based controller was compared to a position-based controller that used movement measured from the participant’s opposite (intact) hand. Surface EMG was also collected for signal quality comparisons.

Results

Signals from the implanted intramuscular electrodes exhibited less crosstalk between the various channels and had a higher Signal-to-Noise Ratio than surface electrode signals. The performance of the intramuscular EMG-based KNN controller in the VR control task showed no degradation over time, and was stable over the 6 different arm postures. Both the EMG-based KNN controller and the intact hand-based controller had 100% hand posture matching success rates, but the intact hand-based controller was slightly superior in regards to speed (trial time used) and directness of the VR hand control (path efficiency).

Conclusions

Chronically implanted intramuscular electrodes provide negligible crosstalk, high SNR, and substantial VR control performance, including the ability to use a fixed controller over 12 weeks and under different arm positions. This approach can thus be a highly effective platform for advanced, multi-DOF prosthetic control.
Movement kinematics and proprioception in post-stroke spasticity: assessment using the Kinarm robotic exoskeleton
Authors: Mochizuki George , Centen Andrew , Resnick Myles , Lowrey Catherine , Dukelow Sean P. , Scott Stephen H.
Published: November 2019

Background

Motor impairment after stroke interferes with performance of everyday activities. Upper limb spasticity may further disrupt the movement patterns that enable optimal function; however, the specific features of these altered movement patterns, which differentiate individuals with and without spasticity, have not been fully identified. This study aimed to characterize the kinematic and proprioceptive deficits of individuals with upper limb spasticity after stroke using the Kinarm robotic exoskeleton.

Methods

Upper limb function was characterized using two tasks: Visually Guided Reaching, in which participants moved the limb from a central target to 1 of 4 or 1 of 8 outer targets when cued (measuring reaching function) and Arm Position Matching, in which participants moved the less-affected arm to mirror match the position of the affected arm (measuring proprioception), which was passively moved to 1 of 4 or 1 of 9 different positions. Comparisons were made between individuals with (n = 35) and without (n = 35) upper limb post-stroke spasticity.

Results

Statistically significant differences in affected limb performance between groups were observed in reaching-specific measures characterizing movement time and movement speed, as well as an overall metric for the Visually Guided Reaching task. While both groups demonstrated deficits in proprioception compared to normative values, no differences were observed between groups. Modified Ashworth Scale score was significantly correlated with these same measures.

Conclusions

The findings indicate that individuals with spasticity experience greater deficits in temporal features of movement while reaching, but not in proprioception in comparison to individuals with post-stroke motor impairment without spasticity. Temporal features of movement can be potential targets for rehabilitation in individuals with upper limb spasticity after stroke.
Australia’s overseas development aid commitment to health through the sustainable development goals: a multi-stakeholder perspective
Authors: Brolan Claire E. , McEwan Christopher A. , Hill Peter S.
Published: November 2019

Background

In 2018, the Australian Government, through a Senate-led Parliamentary Inquiry, sought the views of diverse stakeholders on Sustainable Development Goal (SDG) implementation both domestically and as part of Australia’s Overseas Development Assistance (ODA) program. One hundred and sixty-four written submissions were received. The submissions offered perspective and guidance from a rich cross-section of those involved, and with keen interest in, Australia’s ODA-SDG commitment. This article identifies and explores the submissions to that Inquiry which placed impetus on Australia’s ODA-SDG and health and development nexus. It then compares how the synthesized views, concerns and priorities of selected Inquiry stakeholders align with and reflect the Australian Government’s treatment of SDG 3 in its SDG Voluntary National Review (VNR), as well as with the final Inquiry report summarizing submission content.

Results

Four key themes were synthesized and drawn from the thirty-one stakeholder submissions included in our analysis. Disconnect was then found to exist between the selected stakeholder views and the Australian Government’s SDG-VNR’s treatment of SDG 3, as well as with the content of the Parliamentary Inquiry’s final report with respect to the ODA-SDG and health and development nexus.

Conclusions

We situate the findings of our analysis within the wider strategic context of the Australian Government’s policy commitment to “step up” in the Pacific region. This research provides an insight into both multi-stakeholder and Federal Government views on ODA in the Indo-Pacific region, especially at a time when Australia’s Pacific engagement has come to the forefront of both foreign and security policy. We conclude that the SDG agenda, including the SDG health and development agenda, could offer a unique vehicle for enabling a paradigm shift in the Australian Government’s development approach toward the Pacific region and its diverse peoples. This potential is strongly reflected in stakeholder perspectives included in our analysis. However, study findings remind that the political determinants of health, and overlapping political determinants of SDG achievement, will be instrumental in the coming decade, and that stakeholders from different sectors need to be genuinely engaged in SDG-ODA policy-related decision-making and planning by governments in both developed and developing countries alike.
Building the capacity of users and producers of evidence in health policy and systems research for better control of endemic diseases in Nigeria: a situational analysis
Authors: Onwujekwe Obinna , Etiaba Enyi , Mbachu Chinyere , Ezenwaka Uchenna , Chikezie Ifeanyi , Arize Ifeyinwa , Nwankwor Chikezie , Uzochukwu Benjamin
Published: November 2019

Background

There is a current need to build the capacity of Health Policy and Systems Research + Analysis (HPSR+A) in low and middle-income countries (LMICs) as this enhances the processes of decision-making at all levels of the health system. This paper provides information on the HPSR+A knowledge and practice among producers and users of evidence in priority setting for HPSR+A regarding control of endemic diseases in two states in Nigeria. It also highlights the HPSR+A capacity building needs and interventions that will lead to increased HPSR+A and use for actual policy and decision making by the government and other policy actors.

Methods

Data was collected from 96 purposively selected respondents who are either researchers/ academia (producers of evidence) and policy/decision-makers, programme/project managers (users of evidence) in Enugu and Anambra states, southeast Nigeria. A pre-tested questionnaire was the data collection tool. Analysis was by univariate and bivariate analyses.

Results

The knowledge on HPSR+A was moderate and many respondents understood the importance of evidence-based decision making. Majority of researcher stated their preferred channel of dissemination of research finding to be journal publication. The mean percentage of using HPSR evidence for programme design & implementation of endemic disease among users of evidence was poor (18.8%) in both states. There is a high level of awareness of the use of evidence to inform policy across the two states and some of the respondents have used some evidence in their work.

Conclusion

The high level of awareness of the use of HPSR+A evidence for decision making did not translate to the significant actual use of evidence for policy making. The major reasons bordered on lack of autonomy in decision making. Hence, the existing yawning gap in use of evidence has to be bridged for a strengthening of the health system with evidence.
Global scientific trends on aflatoxin research during 1998–2017: a bibliometric and visualized study
Authors: Zyoud Sa’ed H.
Published: November 2019

Background

Aflatoxins are fungal metabolites associated with contaminated food products. Intake of aflatoxin-contaminated food results in serious health hazards and even death. Therefore, the aim of this study is to evaluate the global scientific output of research of aflatoxin by using bibliometric techniques.

Methods

This bibliometric study was conducted using Scopus database and classified the retrieved publications were classified from different aspects, including the countries/region of focus, journals, authors, institutes, citations, and content analysis to discover any hot and emerging topics. In addition, the bibliometric analysis of the international collaborative network and hot research topics were generated by VOSviewer© software version 1.6.10. The publication period was restricted in the search for two decades (1998–2017).

Results

The search engine of the Scopus database found 9845 documents published in the field of aflatoxin. The USA is the top publishing source in the world (22.85%), followed by China (11.85%), India (9.32%), and Italy (5.25%). In earlier years, researchers focused on terms related to the topics of “sources and biosynthesis of aflatoxin”, “health effects by aflatoxin”, and “detoxification and treatment of aflatoxin”. However, in recent years, researchers pay more attention to the topic of detection and quantification of aflatoxin.

Conclusions

The quantity of research in global aflatoxin has substantially increased over the past two decades. The evaluation of the historical status and development trend in aflatoxin scientific research can guide future research, and ultimately provide the basis for improving management procedures for governmental decisions, healthcare, industries, and educational institutions.