bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of association of genetic variant rs3918242 of matrix metalloproteinase-9 with hypertension, myocardial infarction and progression of ventricular dysfunction in Irish Caucasian patients with diabetes: a report from the STOP-HF follow-up programme
Authors: Watson Chris , Spiers J. Paul , Waterstone Max , Russell-Hallinan Adam , Gallagher Joseph , McDonald Kenneth , Ryan Cristin , Gilmer John , Ledwidge Mark
Published: February 2021

Background

Hypertension and/or myocardial infarction are common causes of heart failure in Type 2 diabetes. Progression to heart failure is usually preceded by ventricular dysfunction, linked to matrix metalloproteinase (MMP) mediated extracellular matrix changes. We hypothesise that the minor allele of genetic variant rs3918242 in the promoter region of the MMP-9 gene is associated with hypertension and/or myocardial infarction, with resultant progression of dysfunctional cardiac remodelling in patients with diabetes without symptomatic heart failure.

Methods

We genotyped 498 diabetes patients participating in the St Vincent’s Screening TO Prevent Heart Failure (STOP-HF) follow-up programme for the rs3918242 single nucleotide polymorphism and investigated associations with the co-primary endpoints hypertension and/or myocardial infarction using a dominant model. We also evaluated resulting cardiometabolic phenotype and progression of ventricular dysfunction and cardiac structural abnormalities over a median follow-up period of 3.5 years.

Results

The CT/TT genotype comprised 28.1% of the cohort and was associated with a twofold higher risk of myocardial infarction (17.9% vs 8.4%), a reduction in ejection fraction and greater left ventricular systolic dysfunction progression [adjusted OR = 2.56 (1.09, 6.01), p = 0.026] over a median follow-up of 3.5 years [IQR 2.6, 4.9 years]. Conversely, rs3918242 was not associated with hypertension, blood pressure, pulse pressure or left ventricular mass index at baseline or over follow up.

Conclusions

Diabetes patients with the minor T allele of rs3918242 in the STOP-HF follow up programme have greater risk of myocardial infarction, lower ejection fraction and greater progression of left ventricular systolic abnormalities, a precursor to heart failure. These data may support further work on MMP-9 as a biomarker of ventricular dysfunction and the investigation of MMP-9 inhibitors for heart failure prevention in diabetes, particularly in the post-infarction setting.

ClinicalTrials.gov Identifier: NCT00921960
Fibronectin mediates activation of stromal fibroblasts by SPARC in endometrial cancer cells
Authors: Yoshida Sachiko , Asanoma Kazuo , Yagi Hiroshi , Onoyama Ichiro , Hori Emiko , Matsumura Yumiko , Okugawa Kaoru , Yahata Hideaki , Kato Kiyoko
Published: February 2021

Background

Matricellular glycoprotein, SPARC is a secreted molecule, that mediates the interaction between cells and extracellular matrix. SPARC functions as a regulator of matrix organization and modulates cell behavior. In various kinds of cancer, strong SPARC expression was observed in stromal tissues as well as in cancer epithelial cells. The function of SPARC in cancer cells is somewhat controversial and its impact on peritumoral stromal cells remains to be resolved.

Methods

We investigated the effects of SPARC expression in endometrial cancer cells on the surrounding stromal fibroblasts using in vitro co-culture system. Changes in characteristics of fibroblasts were examined by analysis of fibroblast-specific markers and in vitro contraction assay.

Results

SPARC induced AKT phosphorylation and epithelial-to-mesenchymal transition, consistent with previous reports. Cancer-associated fibroblasts of endometrial cancer expressed higher levels of mesenchymal- and fibroblast-associated factors and had a stronger contraction ability. Unexpectedly, cancer-associated fibroblasts expressed comparable levels of SPARC compared with fibroblasts from normal endometrium. However, co-culture of normal fibroblasts with SPARC-expressing Ishikawa cells resulted in activation of the fibroblasts. Immunodepletion of SPARC did not affect the activation of fibroblasts.

Conclusions

Our data indicated that SPARC activated fibroblasts only in the presence of fibronectin, which was abundantly secreted from SPARC-expressing endometrial cancer cells. These results suggested that a SPARC-fibronectin-mediated activation of fibroblasts might be involved in enhanced mobility and invasion of cancer cells.
Preoperative nutritional risk index and postoperative one-year skeletal muscle loss can predict the prognosis of patients with gastric adenocarcinoma: a registry-based study
Authors: Kim Kyung Won , Lee Koeun , Lee Jung-Bok , Park Taeyong , Khang Seungwoo , Jeong Heeryeol , Ko Chang-Seok , Yook Jeong-Hwan , Kim Byung-Sik , Lee In-Seob
Published: February 2021

Background

Patients with gastric cancer have an increased nutritional risk and experience a significant skeletal muscle loss after surgery. We aimed to determine whether muscle loss during the first postoperative year and preoperative nutritional status are indicators for predicting prognosis.

Methods

From a gastric cancer registry, a total of 958 patients who received curative gastrectomy followed by chemotherapy for stage 2 and 3 gastric cancer and survived longer than 1 year were investigated. Clinical and laboratory data were collected. Skeletal muscle index (SMI) was assessed based on the muscle area at the L3 level on abdominal computed tomography.

Results

Preoperative nutritional risk index (NRI) and postoperative decrement of SMI (dSMI) were significantly associated with overall survival (hazards ratio: 0.976 [95% CI: 0.962–0.991] and 1.060 [95% CI: 1.035–1.085], respectively) in a multivariate Cox regression analysis. Recurrence, tumor stage, comorbidity index were also significant prognostic indicators. Kaplan-Meier analyses exhibited that patients with higher NRI had a significantly longer survival than those with lower NRI (5-year overall survival: 75.8% vs. 63.0%, P <  0.001). In addition, a significantly better prognosis was observed in a patient group with less decrease of SMI (5-year overall survival: 75.7% vs. 66.2%, P = 0.009). A logistic regression analysis demonstrated that the performance of preoperative NRI and dSMI in mortality prediction was quite significant (AUC: 0.63, P <  0.001) and the combination of clinical factors enhanced the predictive accuracy to the AUC of 0.90 (P <  0.001). This prognostic relevance of NRI and dSMI was maintained in patients experiencing tumor recurrence and highlighted in those with stage 3 gastric adenocarcinoma.

Conclusions

Preoperative NRI is a predictor of overall survival in stage 2 or 3 gastric cancer patients and skeletal muscle loss during the first postoperative year was significantly associated with the prognosis regardless of relapse in stage 3 tumors. These factors could be valuable adjuncts for accurate prediction of prognosis in gastric cancer patients.
Prevalence trends of hypertension among 9–17 aged children and adolescents in Yunnan, 2017–2019: a serial cross-sectional surveillance survey
Authors: Yang Yunjuan , Min Jieqing , Chang Litao , Chai Jiajia , Song Zhizhong , Zha Shun , Zhang Min , Liu Hong , Yang Fan
Published: February 2021

Background

We aim to describe the prevalence and trends of hypertension among 9–17 school-aged students from 2017 to 2019 in Yunnan, China.

Methods

We conducted a cross-sectional study by using data from the Students’ Health Surveillance Surveys of 2017, 2018 and 2019 in Yunnan. The Students’ Health Surveillance Surveys in Yunnan collected date on physical fitness and health status of students in Yunnan through multistage-stratified sampling in 3 prefectures. In each prefecture, the study population were classified by gender and region (urban or rural), and each group had an equal size. Diagnosing criteria of hypertension was set with reference to Chinese age-specific and height-specific blood pressure (BP), to identify the abnormal status of boys and girls separately. ANOVA test was adopted to measure the differences in the mean BP stratified by gender, age, prefecture and area, and Chi-square test was used to compare the percentages of hypertension in different areas. For comparability, the age-standard and gender-standard population prevalence was calculated by directly using China Census in 2010 as a standard population. Totally 24,890 participants aged 9–17 years were included in this study.

Results

From 2017 to 2019, there were 24,872 students completed physical examinations and included in the analysis, of which 3288 were diagnosed with hypertension. The total prevalence of hypertension was 13.72, 12.49 and 13.45% among 9–17 years school-aged population in Yunnan, respectively. The total age-standardized hypertension prevalence trended to decrease from 13.82 to 13.48%. For urban population, the age-standardized hypertension prevalence decreased slightly from 11.24 to 10.13%. While, for rural population, it increased from 17.58 to 19.16%. The average annual growth rate in rural population was 0.53%.

Conclusions

From 2017to 2019, there was a significant and continuous increase in the prevalence of hypertension in 9–17 years school-aged population in Yunnan. Hypertension is epidemic among children and adolescents in Yunnan. We should take effective and comprehensive intervention measures to reduce its prevalence among school-aged children.
High-resolution mapping of reproductive tract infections among women of childbearing age in Bangladesh: a spatial-temporal analysis of the demographic and health survey
Authors: Feng Chenyang , Li Ruixue , Shamim Abu Ahmed , Ullah Md Barkat , Li Mengjie , Dev Rubee , Wang Yijing , Zhao Tingting , Liao Jing , Du Zhicheng , Ling Yuheng , Lai Yingsi , Hao Yuantao
Published: February 2021

Background

Reproductive tract infections (RTIs) have become major but silent public health problems devastating women’s lives in Bangladesh. Accurately and precisely identifying high-risk areas of RTIs through high-resolution risk maps is meaningful for resource-limited settings.

Methods

We obtained data reported with RTI symptoms by women of childbearing age in the years 2007, 2011 and 2014 from Bangladesh Demographic and Health Survey. High-spatial Environmental, socio-economic and demographic layers were downloaded from different open-access data sources. We applied Bayesian spatial-temporal models to identify important influencing factors and to estimate the infection risk at 5 km spatial resolution across survey years in Bangladesh.

Results

We estimated that in Bangladesh, there were approximate 11.1% (95% Bayesian credible interval, BCI: 10.5–11.7%), 13.9% (95% BCI: 13.3–14.5%) and 13.4% (95% BCI: 12.8–14.0%) of women of childbearing age reported with RTI symptoms in 2007, 2011 and 2014, respectively. The risk of most areas shows an obvious increase from 2007 to 2011, then became stable between 2011 and 2014. High risk areas were identified in the southern coastal areas, the western Rajshahi Division, the middle of Khulna Division, and the southwestern Chittagong Division in 2014. The prevalence of Rajshahi and Nawabganj District were increasing during all the survey years.

Conclusion

The high-resolution risk maps of RTIs we produced can guide the control strategies targeted to priority areas cost-effectively. More than one eighth of women of childbearing age reported symptoms suggesting RTIs and the risk of RTIs varies in different geographical area, urging the government to pay more attention to the worrying situation of female RTIs in the country.
The relationship between disability and parental status: a register study of the 1968 to 1970 birth cohorts
Authors: Namatovu Fredinah , Lundevaller Erling Häggström , Vikström Lotta
Published: February 2021

Background

Having children is a major life course event yet some disabilities could make it biologically challenging and some others could limit access to necessary socioeconomic resources. To date, there is relatively little data on disability and parental status and our study aimed to investigate this relationship.

Methods

This longitudinal cohort study was based on register data obtained from all people born in Sweden from 1968 to 1970 (n = 440220). We performed descriptive analyses, graphical plots, logistic regression, and Cox regression analyses.

Results

Our findings from both logistic regression and Cox regression indicated that individuals that started to receive disability benefits at an early age had reduced chances of having children during the follow-up duration. Men with disabilities were less likely to have children when compared to women with disabilities and to men and women without disabilities.

Conclusions

We found evidence that disability during early adulthood was associated with reduced chances of having children. Findings support policies and programmes aimed at promoting optimal health during early adulthood, as this would promote continued labour force participation, reduce early use of disability benefits, and possibly improve chances of becoming a parent.
AITC inhibits fibroblast-myofibroblast transition via TRPA1-independent MAPK and NRF2/HO-1 pathways and reverses corticosteroids insensitivity in human lung fibroblasts
Authors: Yap Jennifer Maries Go , Ueda Takashi , Kanemitsu Yoshihiro , Takeda Norihisa , Fukumitsu Kensuke , Fukuda Satoshi , Uemura Takehiro , Tajiri Tomoko , Ohkubo Hirotsugu , Maeno Ken , Ito Yutaka , Oguri Testsuya , Ugawa Shinya , Niimi Akio
Published: February 2021

Background

Little is known on the role of transient receptor potential ankyrin 1 (TRPA1) in fibroblast—myofibroblast transition (FMT) that can lead to airway remodeling which is a major problem for severe asthma and fibrosis. Thus, this study investigated the effect of TRPA1 modulators on transforming growth factor beta 1(TGF-β1) -treated lung fibroblasts.

Methods

MRC-5 cells were preincubated with TGF-β1 for 24 h. TRPA1 agonist or antagonist were added and further incubated for 24 h. The changes in TRPA1 and alpha-smooth muscle actin (α-SMA) expressions by stimuli were evaluated using qRT-PCR, western blot and immunohistochemical analyses. Statistical significance was determined by using one- or two-way ANOVA, followed by Bonferroni’s post hoc analysis for comparison of multiple groups and paired 2-tailed Student’s t-test between 2 groups.

Results

MRC-5 cells treated by TGF-β1 significantly upregulated α-SMA mRNA expressions (P < 0.01), but downregulated TRPA1 gene expression (P < 0.001). Post-treatment of TRPA1 activator, allyl isothiocyanate (AITC), after TGF-β1 significantly downregulated the α-SMA gene induction (P < 0.01 at 24 h), protein expression (P < 0.05) and immunoreactivity with stress fibers (P < 0.05). On the other hand, TRPA1 antagonist HC-030031 did not prevent this effect, and instead tended to facilitate the suppressive effect of AITC when co-stimulated. AITC significantly increased phosphorylated- extracellular signal-regulated kinase (ERK) 1/2 and heme oxygenase (HO)-1 protein expressions (P < 0.05) in TGF-β1-treated cells. Combined inhibition with ERK1/2 mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor (NRF2) almost completely reversed AITC-induced α-SMA suppression (P < 0.05). Dexamethasone was not able to inhibit the upregulated α-SMA induction by TGF-β1. However, AITC improved dexamethasone-insensitive myodifferentiation in the presence of the corticosteroid (P < 0.01).

Conclusion

We found that AITC exerts protective effect on TGF-β1-induced α-SMA induction by activating ERK1/2 MAPK and NRF2/HO-1 pathways in lung fibroblasts. It also overcomes corticosteroids insensitivity in TGF-β1-induced α-SMA induction. TRPA1 antagonist modulates the suppressive effect, but not prevent it. AITC and TRPA1 antagonist may be therapeutic agents in treating chronic respiratory diseases.
Natural infections with different Plasmodium species induce antibodies reactive to a chimeric Plasmodium vivax recombinant protein
Authors: McCaffery Jessica N. , Singh Balwan , Nace Douglas , Moreno Alberto , Udhayakumar Venkatachalam , Rogier Eric
Published: February 2021

Background

As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns.

Methods

A bead-based multiplex antibody detection assay was used to evaluate a chimeric Plasmodium vivax MSP1 protein (PvRMC-MSP1), designed to be broadly immunogenic for use in vaccine studies, to act as a pan-malaria serological tool based on its ability to capture IgG in plasma samples obtained from naturally exposed individuals. Samples from 236 US travellers with PCR confirmed infection status from all four major Plasmodium species infecting humans, Plasmodium falciparum (n = 181), Plasmodium vivax (n = 38), Plasmodium malariae (n = 4), and Plasmodium ovale (n = 13) were tested for IgG capture using PvRMC-MSP1 as well as the four recombinant MSP1-19 kD isoforms representative of these Plasmodium species.

Results

Regardless of infecting Plasmodium species, a large proportion of plasma samples from infected US travellers provided a high assay signal to the PvRMC-MSP1 chimeric protein, with 115 high responders out of 236 samples assessed (48.7%). When grouped by active infection, 38.7% P. falciparum-, 92.1% of P. vivax-, 75.0% P. malariae-, and 53.4% of P. ovale-infected individuals displayed high assay signals in response to PvRMC-MSP1. It was also determined that plasma from P. vivax-infected individuals produced increased assay signals in response to the PvRMC-MSP1 chimera as compared to the recombinant PvMSP1 for 89.5% (34 out of 38) of individuals. PvRMC-MSP1 also showed improved ability to capture IgG antibodies from P. falciparum-infected individuals when compared to the capture by recombinant PvMSP1, with high assay signals observed for 38.7% of P. falciparum-infected travellers in response to PvRMC-MSP1 IgG capture compared to just 1.1% who were high responders to capture by the recombinant PvMSP1 protein.

Conclusions

These results support further study of designed antigens as an approach for increasing sensitivity or broadening binding capacity to improve existing serological tools for determining population-level exposure to Plasmodium species. Including both broad-reacting and Plasmodium species-specific antigen-coated beads in an assay panel could provide a nuanced view of population-level exposure histories, an extensive IgG profile, and detailed seroestimates. A more sensitive serological tool for detection of P. vivax exposure would aid malaria elimination campaigns in co-endemic areas and regions where P. vivax is the dominant parasite.
Co-treatment with disulfiram and glycyrrhizic acid suppresses the inflammatory response of chondrocytes
Authors: Li Chao , Li Li , Lan Tian
Published: February 2021

Background

Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness. Nevertheless, due to the fact that OA can be triggered by multiple etiological factors, this disease is hard to be cured. Therefore, it is of great necessity for us to find novel targets or drugs for OA treatment.

Materials and methods

The chondrocytes were treated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to induce pyroptosis in OA. The cell proliferation was detected by Cell Counting Kit-8 assay (CCK-8 assay). Enzyme-linked immunosorbent assay (ELISA) was used for the detection of pyroptosis-related inflammatory factors. Then, the antagonists for gasdermin D (GSDMD) (disulfiram) and high mobility group box 1 (HMGB1) (glycyrrhizic acid) were used to treat the cell model to observe the effects of disulfiram and glycyrrhizic acid on the proliferation of chondrocytes in OA. The protein levels of pyroptosis-related inflammatory factors were measured by western blot, and the levels of aldehyde dehydrogenase (ALDH) and reactive oxygen species (ROS) were measured by corresponding commercial kits.

Results

After chondrocytes were induced by LPS and ATP, the cell proliferation was decreased and the expressions of pyroptosis-related inflammatory factors were increased. Disulfiram and glycyrrhizic acid treatment led to enhanced cell proliferation and increased expressions of pyroptosis-related inflammatory factors, while disulfiram showed better alleviative effects on the inflammation in chondrocytes in OA. However, co-treatment with disulfiram at a high concentration and glycyrrhizic acid did not result in higher proliferation of chondrocytes and alleviated inflammation, but led to oxidative stress.

Conclusion

In conclusion, co-treatment with disulfiram and glycyrrhizic acid at a standard concentration suppresses the inflammatory response of chondrocytes, which may provide guidance for the use of the drugs in the treatment of OA.
Contactless: a new personalised telehealth model in chronic pediatric diseases and disability during the COVID-19 era
Authors: Mercuri Eugenio , Zampino Giuseppe , Morsella Alisha , Pane Marika , Onesimo Roberta , Angioletti Carmen , Valentini Piero , Rendeli Claudia , Ruggiero Antonio , Nanni Lorenzo , Chiaretti Antonio , Vento Giovanni , Korn David , Meneschincheri Emilio , Sergi Paolo , Scambia Giovanni , Ricciardi Walter , Cambieri Andrea , De Belvis Antonio Giulio
Published: February 2021

Background

Suspending ordinary care activities during the COVID-19 pandemic made it necessary to find alternative routes to comply with care recommendations not only for acute health needs but also for patients requiring follow-up and multidisciplinary visits. We present the ‘Contactless’ model, a comprehensive operational tool including a plurality of services delivered remotely, structured according to a complexity gradient, aimed to cover diagnostic procedures and monitor disease progression in chronic pediatric patients.

Methods

A multidisciplinary and multiprofessional project team was recruited, in collaboration with patients’ associations, to map a panel of available Evidence-Based solutions and address individual needs in full respect of the concept of personalized medicine. The solutions include a number of services from videoconsultations to more structure videotraining sessions.

Results

A modular framework made up of four three Macro-levels of complexity - Contactless Basic, Intermediate and Advanced - was displayed as an incremental set of services and operational planning establishing each phase, from factors influencing eligibility to the delivery of the most accurate and complex levels of care.

Conclusion

The multimodal, multidisciplinary ‘Contactless’ model allowed the inclusion of all Units of our Pediatric Department and families with children with disability or complex chronic conditions. The strengths of this project rely on its replicability outside of pediatrics and in the limited resources needed to practically impact patients, caregivers and professionals involved in the process of care. Its implementation in the future may contribute to reduce the duration of hospital admissions, money and parental absence from work.
A floppy infant without lingual frenulum and kyphoscoliosis: Ehlers Danlos syndrome case report
Authors: Conti Rosaura , Zanchi Chiara , Barbi Egidio
Published: February 2021

Background

Ehlers-Danlos syndrome (EDS) represents a group of connective tissue disorders characterized by the fragility of the soft connective tissues resulting in widespread skin, ligament, joint, blood vessel and internal organ involvement. The clinical spectrum is highly variable in terms of clinical features, complications, severity, biochemical characteristics and genes mutations.

The kyphoscoliotic type EDS (EDS VIA) is a rare variant of the disease, with an incidence of 1:100.000 live births. EDS VIA presents at birth as severe muscular hypotonia, early onset of progressive kyphoscoliosis, marked hyperelasticity and fragility of the skin with abnormal scarring, severe joint hypermobility, luxations and osteopenia without a tendency to fractures. This condition is due to a mutation in the PLOD1 gene, and less commonly in FKBP14 gene, which results in the erroneous development of collagen molecules with consequent mechanical instability of the affected tissue.

Case presentation

A female newborn, found to be floppy at birth, presented a remarkable physical examination for joint hypermobility, muscle weakness, hyperelastic skin, a slight curve of the spine, the absence of the inferior labial and lingual frenulum. Due to severe hypotonia, neuromuscular disorders such as Spinal Muscular Atrophy (SMA), genetic diseases such as Prader Willi syndrome (PWS), myopathies and connective tissue disorders were considered in the differential diagnosis. Targeted gene sequencing were performed for SMN1, PLOD1, FKBP14, COL6A1, COL6A2, COL6A3. The urinary lysyl and hydroxy-lysyl pyridinoline ratio was diagnostic before discovering the homozygous duplication in the PLOD1 gene, which confirmed kyphoscoliotic EDS diagnosis.

Conclusion

In front of a floppy infant, a large variety of disorders should be considered, including some connective diseases. The presence at the birth of kyphoscoliosis, associated with joint hypermobility and the absence of the lingual and lower lip frenulum, should suggest an EDS.
Correction to: Understanding the impact of antibiotic perturbation on the human microbiome
Authors: Schwartz Drew J. , Langdon Amy E. , Dantas Gautam
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Alpha-enolase (ENO1), identified as an antigen to monoclonal antibody 12C7, promotes the self-renewal and malignant phenotype of lung cancer stem cells by AMPK/mTOR pathway
Authors: Shu Xiong , Cao Kai-Yue , Liu Hui-Qi , Yu Long , Sun Li-Xin , Yang Zhi-Hua , Wu Cheng-Ai , Ran Yu-Liang
Published: February 2021

Background

Tumor-associated antigens (TAAs) can be targeted in cancer therapy. We previously identified a monoclonal antibody (mAb) 12C7, which presented anti-tumor activity in lung cancer stem cells (LCSCs). Here, we aimed to identify the target antigen for 12C7 and confirm its role in LCSCs.

Methods

Immunofluorescence was used for antigen localization. After targeted antigen purification by electrophoresis and immunoblot, the antigen was identified by LC-MALDI-TOF/TOF mass spectrometry, immunofluorescence, and immunoprecipitation. The overexpression or silence of ENO1 was induced by lentiviral transduction. Self-renewal, growth, and invasion of LCSCs were evaluated by sphere formation, colony formation, and invasion assay, respectively. High-throughput transcriptome sequencing (RNA-seq) and bioinformatics analysis were performed to analyze downstream targets and pathways of targeted antigen.

Results

Targeted antigen showed a surface antigen expression pattern, and the 43–55 kDa protein band was identified as α-enolase (ENO1). Self-renewal, growth, and invasion abilities of LCSCs were remarkably inhibited by ENO1 downregulation, while enhanced by ENO1 upregulation. RNA-seq and bioinformatics analysis eventually screened 4 self-renewal-related and 6 invasion-related differentially expressed genes. GSEA analysis and qRT-PCR verified that ENO1 regulated self-renewal, invasion-related genes, and pathways. KEGG pathway analysis and immunoblot demonstrated that ENO1 inactivated AMPK pathway and activated mTOR pathway in LCSCs.

Conclusions

ENO1 is identified as a targeted antigen of mAb 12C7 and plays a pivotal role in facilitating self-renewal, growth, and invasion of LCSCs. These findings provide a potent therapeutic target for the stem cell therapy for lung cancer and have potential to improve the anti-tumor activity of 12C7.
Enhanced anti-inflammatory effects of mesenchymal stromal cells mediated by the transient ectopic expression of CXCR4 and IL10
Authors: Hervás-Salcedo Rosario , Fernández-García María , Hernando-Rodríguez Miriam , Quintana-Bustamante Oscar , Segovia Jose-Carlos , Alvarez-Silva Marcio , García-Arranz Mariano , Minguez Pablo , del Pozo Victoria , de Alba Marta Rodríguez , García-Olmo Damián , Ayuso Carmen , Lamana María Luisa , Bueren Juan A. , Yañez Rosa María
Published: February 2021

Background

Mesenchymal stromal cells (MSCs) constitute one of the cell types most frequently used in cell therapy. Although several studies have shown the efficacy of these cells to modulate inflammation in different animal models, the results obtained in human clinical trials have been more modest. Here, we aimed at improving the therapeutic properties of MSCs by inducing a transient expression of two molecules that could enhance two different properties of these cells. With the purpose of improving MSC migration towards inflamed sites, we induced a transient expression of the C-X-C chemokine receptor type 4 (CXCR4). Additionally, to augment the anti-inflammatory properties of MSCs, a transient expression of the anti-inflammatory cytokine, interleukin 10 (IL10), was also induced.

Methods

Human adipose tissue-derived MSCs were transfected with messenger RNAs carrying the codon-optimized versions of CXCR4 and/or IL10. mRNA-transfected MSCs were then studied, first to evaluate whether the characteristic phenotype of MSCs was modified. Additionally, in vitro and also in vivo studies in an LPS-induced inflamed pad model were conducted to evaluate the impact associated to the transient expression of CXCR4 and/or IL10 in MSCs.

Results

Transfection of MSCs with CXCR4 and/or IL10 mRNAs induced a transient expression of these molecules without modifying the characteristic phenotype of MSCs. In vitro studies then revealed that the ectopic expression of CXCR4 significantly enhanced the migration of MSCs towards SDF-1, while an increased immunosuppression was associated with the ectopic expression of IL10. Finally, in vivo experiments showed that the co-expression of CXCR4 and IL10 increased the homing of MSCs into inflamed pads and induced an enhanced anti-inflammatory effect, compared to wild-type MSCs.

Conclusions

Our results demonstrate that the transient co-expression of CXCR4 and IL10 enhances the therapeutic potential of MSCs in a local inflammation mouse model, suggesting that these mRNA-modified cells may constitute a new step in the development of more efficient cell therapies for the treatment of inflammatory diseases.
Systematic review on use, cost and clinical efficacy of automated decontamination devices
Authors: Dancer Stephanie J. , King Marco-Felipe
Published: February 2021

Background

More evidence is emerging on the role of surface decontamination for reducing hospital-acquired infection (HAI). Timely and adequate removal of environmental pathogens leads to measurable clinical benefit in both routine and outbreak situations.

Objectives

This systematic review aimed to evaluate published studies describing the effect of automated technologies delivering hydrogen peroxide (H202) or ultra-violet (UV) light on HAI rates.

Methods

A systematic review was performed using relevant search terms. Databases were scanned from January 2005 to March 2020 for studies reporting clinical outcome after use of automated devices on healthcare surfaces. Information collected included device type, overall findings; hospital and ward data; study location, length and size; antimicrobial consumption; domestic monitoring; and infection control interventions. Study sponsorship and duplicate publications were also noted.

Results

While there are clear benefits from non-touch devices in vitro, we found insufficient objective assessment of patient outcome due to the before-and-after nature of 36 of 43 (84%) studies. Of 43 studies, 20 (47%) used hydrogen peroxide (14 for outbreaks) and 23 (53%) used UV technology (none for outbreaks). The most popular pathogen targeted, either alone or in combination with others, was Clostridium difficile (27 of 43 studies: 63%), followed by methicillin-resistant Staphylococcus aureus (MRSA) (16 of 43: 37%). Many owed funding and/or personnel to industry sponsorship (28 of 43: 65%) and most were confounded by concurrent infection control, antimicrobial stewardship and/or cleaning audit initiatives. Few contained data on device costs and rarely on comparable costs (1 of 43: 2%). There were expected relationships between the country hosting the study and location of device companies. None mentioned the potential for environmental damage, including effects on microbial survivors.

Conclusion

There were mixed results for patient benefit from this review of automated devices using H202 or UV for surface decontamination. Most non-outbreak studies lacked an appropriate control group and were potentially compromised by industry sponsorship. Concern over HAI encourages delivery of powerful disinfectants for eliminating pathogens without appreciating toxicity or cost benefit. Routine use of these devices requires justification from standardized and controlled studies to understand how best to manage contaminated healthcare environments.
The relationship between political affiliation and beliefs about sources of “fake news”
Authors: Michael Robert B. , Breaux Brooke O.
Published: February 2021

The 2016 US Presidential campaign saw an explosion in popularity for the term “fake news.” This phenomenon raises interesting questions: Which news sources do people believe are fake, and what do people think “fake news” means? One possibility is that beliefs about the news reflect a bias to disbelieve information that conflicts with existing beliefs and desires. If so, then news sources people consider “fake” might differ according to political affiliation. To test this idea, we asked people to tell us what “fake news” means, and to rate several news sources for the extent to which each provides real news, fake news, and propaganda. We found that political affiliation influenced people’s descriptions and their beliefs about which news sources are “fake.” These results have implications for people’s interpretations of news information and for the extent to which people can be misled by factually incorrect journalism.
Approaches in cooling of resistive coil-based low-field Magnetic Resonance Imaging (MRI) systems for application in low resource settings
Authors: Natukunda Faith , Twongyirwe Theodora M. , Schiff Steven J. , Obungoloch Johnes
Published: February 2021

Magnetic Resonance Imaging (MRI), a non-invasive method for the diagnosis of diverse health conditions has experienced growing popularity over other imaging modalities like ultrasound and Computer Tomography. Initially, proof-of-concept and earlier MRI systems were based on resistive and permanent magnet technology. However, superconducting magnets have long held monopoly of the market for MRI systems with their high-field (HF) strength capability, although they present high construction, installation, and siting requirements. Such stringent prerequisites restrict their availability and use in low-middle income countries. Resistive coil-based magnet, albeit low-field (LF) in capacity, represent a plausible boost for the availability and use of MRI systems in resource constrained settings. These systems are characterized by low costs coupled with substantial image quality for diagnosis of some conditions such as hydrocephalus common is such regions. However, the nature of resistive coils causes them to heat up during operation, thus necessitating a dedicated cooling system to improve image quality and enhance system longevity. This paper explores a range of cooling methods as have been applied to resistive magnets, citing their pros and cons and areas for improvement.
Evaluation of an Interprofessional Training Program to Improve Cancer Drug Therapy Safety
Authors: Aebersold Michelle L. , Kraft Shawna , Farris Karen B. , Scherdt Marylee , Olsen MiKaela , Polovich Martha , Shelton Brenda K. , Montgomery Guy H. , Friese Christopher R.
Published: February 2021

PURPOSE:

Drug therapy for cancer is a high-risk, high-volume clinical intervention that requires interprofessional teams. Given the complexity of anticancer drug therapy and safety concerns, an interdisciplinary team developed a novel training program for oncology registered nurses and pharmacists to improve cancer drug safety.

METHODS:

Participants completed preworkshop learning assessments and received access to web-based modules on six topics: hazardous drug handling, drug extravasation, hypersensitivity reaction management, sepsis recognition, immune checkpoint inhibitor toxicities, and oral oncolytic adherence. In a 7-hour workshop, participants applied module content in interactive exercises and high-fidelity simulations. Preworkshop and postworkshop questionnaires assessed changes in knowledge and confidence in each topic. Program satisfaction and changes to clinical practice or policies were assessed 3 months after the workshop.

RESULTS:

Two hundred ninety-two nurses and 82 pharmacists applied to participate, and 103 (35%) and 44 (54%) have participated, respectively. Long-term follow-up data were available on 133 (90%) participants. Change scores in confidence to meet program objectives increased between pre- and postworkshop (range of increase 0.6-0.8, P < .01). Knowledge scores increased significantly between pre- and postworkshop (average improvement of 3.2 points, P < .01). Overall program satisfaction was high (mean 5.0, standard deviation [0.2] on a five-point scale). Seventy-seven (60%) reported that they had made at least one clinical practice or institutional policy change at 3 months.

CONCLUSION:

An interprofessional education program with online modules, in-person interactive sessions, and simulation activities is a promising strategy to deliver cancer drug safety content to practicing oncology clinicians.
An In-situ Brine Solution in Salt-cavern Supported Redox-flow Battery Using Iron/Organic Materials
Authors: Wang Hui , Ke Wang , Wei Zhang , Li Dan , Chen Liuping
Published: February 2021

Salt cavern redox flow batteries with a large salt-cavern storing electrolyte are a promising large-scale energy storage technology. Here a low-cost iron/organic redox material system was proposed to explore salt cavern redox flow batteries. To avoid the formation of ferric hydroxide, ligand threonine was used to enhance the stability of the ferric ion in aqueous solution. Paired with a two electron viologen catholyte and saturated brine solution as supporting electrolyte, the battery delivered a high battery efficiency and cycling stability, 99% CE, 80% EE, and an average 99.5% capacity retention per cycle. The impressive battery performance provides a promising strategy for developing large-scale salt-cavern redox flow batteries.
Social prescribing for autistic people: A framework for service provision
Authors: Charlton Rebecca A. , Crompton Catherine J. , Roestorf Amanda , Torry Christopher ,   The Autistica Physical Health and Ageing Study Group
Published: February 2021

Social Prescribing (SP) is the referral of patients to non-clinical services for practical, physical or psychosocial support. Recent guidelines from the National Health Service England mean that SP will become commonplace for people with complex healthcare needs. Autistic adults make up over 1% of the population and commonly have co-existing physical and mental health conditions, therefore they are likely to be referred to SP services. As yet, no studies have examined the efficacy of SP for autistic adults. In this letter, we review the existing literature examining the efficacy of SP in the general population. We further examine the factors that should be considered when offering SP to autistic adults in order to optimise outcomes for physical and mental well-being.
Concerns about testing
Authors: Ford Vicky
Published: February 2021

eye, MA Education Ltd, St Jude's Church, Dulwich Road, London, SE24 0PB or email: karen.faux@markallengroup.com
Action for change
Authors: Archer Nathan
Published: February 2021

In the current climate of pressing concerns, the early years sector continues to strive for a stronger voice. While lobbying often shouts the loudest, ‘quiet activism’ can be equally powerful.
A prospective longitudinal study investigating outcomes including patient-reported outcome measures after surgery for metastatic bone disease
Authors: Downie Samantha , Stillie Alison , Moran Matthew , Sudlow Catherine , Simpson A. Hamish R. W.
Published: February 2021

Aims

Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD.

Methods

This will be a prospective, longitudinal study across six UK orthopaedic centres powered to identify the influence of ten patient variables on quality of life at three months after surgery for MBD. Adult patients managed for bone metastases will be screened by their treating consultant and posted out participant materials. If they opt in to participate, they will receive questionnaire packs at regular intervals from three to 24 months post-surgery and their electronic records will be screened until death or five years from recruitment. The primary outcome is quality of life as measured by the European Organisation for Research and the Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ) C30 questionnaire. The protocol has been approved by the Newcastle & North Tyneside 2 Research Ethics Committee (REC ref 19/NE/0303) and the study is funded by the Royal College of Physicians and Surgeons of Glasgow (RCPSG) and the Association for Cancer Surgery (BASO-ACS).

Discussion

This will be the first powered study internationally to investigate patient-reported outcomes after orthopaedic treatment for bone metastases. We will assess quality of life, function, and pain relief at three to 24 months post-surgery and identify which patient variables are significantly associated with a good outcome after MBD treatment. Cite this article: Bone Jt Open 2021;2(2):79–85.
REKOMENDASI SEMILOKA NASIONAL KONSERVASI BIODIVERSITAS UNTUK PERLINDUNGAN DAN PENYELAMATAN PLASMA NUTFAH DI PULAU JAWA, SURAKARTA 17-20 JULI 2000
Authors: BIODIVERSITAS SISIPAN
Published: February 2021

Dengan mengucap syukur alhamdulillah, bersama ini kami sampaikan rumusan rekomendasikegiatan â€œSEMILOKA NASIONAL KONSERVASI BIODIVERSITAS UNTUK PERLINDUNGAN DANPENYELAMATAN PLASMA NUTFAH DI PULAU JAWAâ€, yang diselenggarakan oleh PanitiaKonservasi Biodiversitas Flora dan Fauna di Gunung Lawu, Jurusan Biologi FMIPA UNSSurakarta, Kegiatan Seminar dilaksanakan pada tanggal 17-18 Juli 2000, dilanjutkan Lokakaryapada tanggal 19-20 Juli 2000
Correlation and path analysis for agronomic traits contributing to yield in 30 genotypes of soybean
Authors: Karyawati Anna Satyana , PUSPITANINGRUM ENO SINTHIA VINKY
Published: February 2021

Abstract. Karyawati AS, Puspitaningrum ESV. 2021. Correlation and path analysis for agronomic traits contributing to yield in 30 genotypes of soybean. Biodiversitas 22: 1146-1151. To obtain more productive soybean genotypes, it is essential to know the contribution of each agronomic trait to the productivity of soybeans. The purpose of this study was to analyze the correlation and path analysis in thirty genotypes of soybeans (Glycine max (L.) Merrill) for eleven traits. The study was conducted in March-June 2019, in an experimental area located at Agro Techno Park, which belongs to Universitas Brawijaya, Malang, East Java Province, Indonesia. The experimental design was a randomized complete block design with three replications. Analysis of correlation showed that the number of branches, number of filled pods, number of seeds per plant, weight of 100 seeds, and weight of seeds per plant had a positive correlation value to the yield. Path analysis showed that the number of seeds per plant had a high positive, direct effect on the yield. The plant height, number of branches, fresh weight and dry weight had an indirect effect on the yield. Based on the result, the number of seeds per plant can be selected as one of the selection criteria in a soybean breeding program to obtain a high-yield soybean variety.
Normalized Difference Vegetation Index (NDVI) analysis for vegetation cover in Leuser Ecosystem area, Sumatra, Indonesia
Authors: Hartoyo Adisti Permatasari Putri , SUNKAR ARZYANA , RAMADANI RAHMATULLOH , FALUTHI SYAHLAN , HIDAYATI SYAFITRI
Published: February 2021

Abstract. Hartoyo APP, Sunkar A, Ramadani R, Faluthi S, Hidayati S. 2021. Normalized Difference Vegetation Index (NDVI) analysis for vegetation cover in Leuser Ecosystem area, Sumatra, Indonesia. Biodiversitas 22: 1160-1171. About 2 Mha of 24.3 Mha degraded area in Indonesia is inside conservation area. The Leuser Ecosystem Area (LEA) is the largest conservation area in Malesian forest that plays essential role in biodiversity and ecosystem services conservation efforts. It is the last habitat on earth where Sumatran tigers, elephants, orangutans, and rhinoceros are found together. However, LEA faces many threats, such as infrastructure development, and industrial palm oil plantation. Additionally, vegetation cover data as an approach to monitor forest cover changes in LEA is still lacking and baseline data regarding composition, structure as well as vegetation diversity in LEA is very limited. The objectives of this study were to analyze vegetation cover using Normalized Difference Vegetation Index (NDVI) in LEA and its relation to agroforestry structure, composition and diversity in Agusen Village, Gayo Lues District and Alur Durin Village, East Aceh District, Aceh Province belonging to LEA. Based on the NDVI analysis, the largest area in LEA belonged to class 5, meaning that the most area in LEA was dominated by high dense vegetation (1,870,116.40 ha). The average accuracy and standard error of NDVI analysis were 83.33% and 2.62. LEA is an effective buffer for maintaining forest ecosystems and increasing the local communities' welfare through agroforestry system. Agroforestry structures in agroforestry practices, both in Agusen Village and Alur Durin Village did not reflect reverse-J curve, meaning that enrichment planting for increasing numbers of individual and species was necessary. Management of agroforestry system depends on the landowners or managers and their selection of shade tree species with high economic value with market demand such as C. arabica, T. cacao with A. moluccanus, L. leucocephala, H. brasiliensis, D. zibethinus, etc. Trees that produce non-timber products are also an alternative way for conservation strategy and sustainable utilization.
GAMBARAN SUBJECTIVE WELL-BEING DOSEN DAN TENAGA PENDIDIK
Authors: Suari Dewi Anak Agung Sagung
Published: February 2021

Being a lecturer and educational staffs are a noble task because they aimed to build a greater young generation for the nation, so that their welfare should be well-attended. Well-being or is divided into two types, which are objective well-being (OWB) and subjective well-being (SWB). This is a descriptive survey research and focused more on SWB. The respondent criteria were lecturer and educational staff at the EB and P faculty, thus obtaining 74 respondents. The scale used in this study is SWB scale adapted from the Subjective Well-Being Inventory (SUBI) (Nagpal & Sell, 1992), using an interval scale, and presented in statements. Examining the results, it can be seen that more than half (71.62%) of the respondents considered that their life had been positive, both physically and mentally, which was indicated by a high SWB level. As many as 20 respondents (27.03%) were at moderate level, and only 1.35% or 1 respondent had a low SWB level. Perceived ill-health dimension is the most contributor to the low level of SWB, which related to physical complaints experienced by individuals, such as pain, a racing heart, frequent dizziness, easily tired, sleep disturbed, and worrying about their health.