bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINC00152 upregulates ZEB1 expression and enhances epithelial-mesenchymal transition and oxaliplatin resistance in esophageal cancer by interacting with EZH2
Authors: Zhang Shuyao , Liao Wei , Wu Qinshui , Huang Xiaoshan , Pan Zhen , Chen Wang , Gu Shuyi , Huang Zuojun , Wang Yiwen , Tang Xu , Liang Shanshan , Zhang Xiaoyan , Chen Yun , Chen Shuang , Chen Wanying , Jiang Yi , Chen Chen , Qiu Guodong 
Published: November 2020

Abstract
Background
Expression of the long non-coding mRNA LINC00152 has been reported to correlate with cancer cell resistance to oxaliplatin (L-OHP). However, little is known regarding the molecular mechanism of LINC00152 in esophageal cancer (EC). Hence, we intended to characterize the role of LINC00152 in EC, with a special focus on epithelial-mesenchymal transition (EMT) and L-OHP resistance.

Methods
We collected EC tissues and identified EC cell lines with higher L-OHP resistance, and then characterized expression patterns of LINC00152, Zeste Homologue 2 (EZH2), Zinc finger e-box binding homeobox (ZEB1) and EMT-related genes using RT-qPCR and Western blot analysis. Furthermore, their functional significance was identified by gain and loss-of-function experiments. The relationship among LINC00152, EZH2 and ZEB1 was examined using RIP, RNA pull-down and ChIP assays. Additionally, resistance of EC cells to L-OHP was reflected by CCK-8 assay to detect cell viability. Animal experiments were also conducted to detect the effects of the LINC00152/EZH2/ZEB1 on EMT and L-OHP resistance.

Results
LINC00152, EZH2 and ZEB1 were highly expressed in EC tissues and Kyse−150/TE-1 cells. As revealed by assays in vitro and in vivo, LINC00152 positively regulated ZEB1 expression through interaction with EZH2 to enhance EMT and L-OHP resistance in EC cells. In contrast, silencing of LINC00152 contributed to attenuated EMT and drug resistance of EC cells to L-OHP.

Conclusions
Our study demonstrates that LINC00152/EZH2/ZEB1 axis can regulate EMT and resistance of EC cells to L-OHP, thus presenting a potential therapeutic target for EC treatment.
Efficacy of extended release formulations of Natular™ (spinosad) against larvae and adults of Anopheles mosquitoes in western Kenya
Authors: Gimnig John E. , Ombok Maurice , Bayoh Nabie , Mathias Derrick , Ochomo Eric , Jany William , Walker Edward D. 
Published: November 2020

Abstract
Background
Larval source management is recommended as a supplementary vector control measure for the prevention of malaria. Among the concerns related to larviciding is the feasibility of implementation in tropical areas with large numbers of habitats and the need for frequent application. Formulated products of spinosad that are designed to be effective for several weeks may mitigate some of these concerns.

Methods
In a semi-field study, three formulations of spinosad (emulsifiable concentrate, extended release granules and tablet formulations) were tested in naturalistic habitats in comparison to an untreated control. Cohorts of third instar Anopheles gambiae (Diptera: Culicidae) were introduced into the habitats in screened cages every week up to four weeks after application and monitored for survivorship over three days. A small-scale field trial was then conducted in two villages. Two of the spinosad formulations were applied in one village over the course of 18 months. Immature mosquito populations were monitored with standard dippers in sentinel sites and adult populations were monitored by pyrethrum spray catches.

Results
In the semi-field study, the efficacy of the emulsifiable concentrate of spinosad waned 1 week after treatment. Mortality in habitats treated with the extended release granular formulation of spinosad was initially high but declined gradually over 4 weeks while mortality in habitats treated with the dispersable tablet formulation was low immediately after treatment but rose to 100% through four weeks. In the field study, immature and adult Anopheles mosquito populations were significantly lower in the intervention village compared to the control village during the larviciding period. Numbers of collected mosquitoes were lower in the intervention village compared to the control village during the post-intervention period but the difference was not statistically significant.

Conclusions
The extended release granular formulation and the dispersible tablet formulations of spinosad are effective against larval Anopheles mosquitoes for up to four weeks and may be an effective tool as part of larval source management programmes for reducing adult mosquito density and malaria transmission.
Prenatal exposure to perfluoroalkyl substances and thyroid hormone concentrations in cord plasma in a Chinese birth cohort
Authors: Liang Hong , Wang Ziliang , Miao Maohua , Tian Youping , Zhou Yan , Wen Sheng , Chen Yao , Sun Xiaowei , Yuan Wei 
Published: November 2020

Abstract
Background
Evidence of associations between prenatal exposure to perfluoroalkyl substances (PFASs) and fetal thyroid hormones (THs) is controversial, and few studies have estimated the associations, while addressing the high correlations among multiple PFASs. We aimed to examine the associations between prenatal PFAS exposure and thyroid hormone concentrations in cord blood.

Methods
A total of 300 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study were included. We measured the concentrations of eight PFASs in maternal plasma samples collected at 12–16 gestational weeks, as well as those of total thyroxine (T4), free T4 (FT4), total triiodothyronine (T3), free T3 (FT3), and thyroid stimulating hormone (TSH) in cord plasma. We estimated the associations between maternal PFAS concentrations and TH concentrations using linear regression and Bayesian kernel machine regression (BKMR) models.

Results
In BKMR models, higher PFAS mixture concentrations were associated with increased T3 concentrations, and there were suggestive associations with increased FT3 concentrations. For single-exposure effects in BKMR models, a change in PFDA, PFUdA, and PFOA concentrations from the 25th to 75th percentile was associated with a 0.04 (95%CrI: − 0.01, 0.09), 0.02 (95%CrI: − 0.03, 0.07), and 0.03 (95%CrI: − 0.001, 0.06) nmol/L increase in T3 concentrations, respectively. PFOA, PFNA, and PFDA were the predominant compounds in PFASs-FT3 associations, and the corresponding estimates were 0.11 (95% CrI: 0.02, 0.19), − 0.17 (95% CrI: − 0.28, − 0.07), and 0.12 (95% CrI: − 0.004, 0.24) pmol/L, respectively. A change in PFNA and PFOA concentrations from the 25th to 75th percentile was associated with a − 1.69 (95% CrI: − 2.98, − 0.41) μIU/mL decrease and a 1.51 (95% CrI: 0.48, 2.55) μIU/mL increase in TSH concentrations. The associations of PFOA and PFNA with T3/FT3 were more pronounced in boys, while those with TSH were more pronounced in girls.

Conclusion
Our results suggest that prenatal exposure to multiple PFASs was associated with thyroid hormones in cord blood. However, individual PFAS had varied effects—differing in magnitude and direction—on fetal thyroid hormones.
Looking back to look forward: a review of human resources for health governance in South Africa from 1994 to 2018
Authors: Van Ryneveld Manya , Schneider Helen , Lehmann Uta 
Published: November 2020

AbstractWhile South Africa has had a fairly consistent record of producing national-level strategic plans for human resources for health in the past 25 years, the country continues to face major problems of affordability, availability, distribution and management of its health workforce. There are several factors contributing to the state of health human resources in the country, but problems with governance stand out as one area requiring further research, analysis and critique. This paper presents a retrospective analysis of the historical patterns in national health human resources governance in South Africa, based on a desktop policy review spanning 25 years after democracy. The authors took a multi-pronged, iterative approach, reviewing policy documents alongside grey and published literature. This led to a timeline showing key legislation, relevant health system and human resource policies, interventions, reviews and evaluations from 1994 to 2018. The review identified three distinct periods that help to characterise the terrain of human resources for health governance over the concerned 25 years. Firstly, a foundational period, in which much of the constitutional and legislative groundwork was laid. Secondly, the HIV epidemic period, which presented a major disruption to the development of system wide governance interventions and improvements. Thirdly, the launch of National Health Insurance discussions and policy processes, which signalled a gradual return to a comprehensive systems focus in line with the founding principles of the first period. Using this periodisation, as well as a conceptual framework of health human resources governance functions based on international literature, the authors argue that South Africa has experienced both progress and challenges in human resources for health governance. This has affected the successful implementation of its policy and strategic planning over the past 25 years. Good governance for human resources for health requires capable stewardship, underpinned by an appropriate mix of technical and administrative skills and explicit political support. The review findings suggest that strengthening human resources for health governance roles, including fostering purposeful stewardship by the National Department of Health, may be key to shifting the terrain in the availability and performance of South Africa’s health workforce going forwards.
Advancing the global physical activity agenda: recommendations for future research by the 2020 WHO physical activity and sedentary behavior guidelines development group
Authors: DiPietro Loretta , Al-Ansari Salih Saad , Biddle Stuart J. H. , Borodulin Katja , Bull Fiona C. , Buman Matthew P. , Cardon Greet , Carty Catherine , Chaput Jean-Philippe , Chastin Sebastien , Chou Roger , Dempsey Paddy C. , Ekelund Ulf , Firth Joseph , Friedenreich Christine M. , Garcia Leandro , Gichu Muthoni , Jago Russell , Katzmarzyk Peter T. , Lambert Estelle , Leitzmann Michael , Milton Karen , Ortega Francisco B. , Ranasinghe Chathuranga , Stamatakis Emmanuel , Tiedemann Anne , Troiano Richard P. , van der Ploeg Hidde P. , Willumsen Juana F. 
Published: November 2020

Abstract
Background
In July, 2019, the World Health Organization (WHO) commenced work to update the 2010 Global Recommendations on Physical Activity for Health and established a Guideline Development Group (GDG) comprising expert public health scientists and practitioners to inform the drafting of the 2020 Guidelines on Physical Activity and Sedentary Behavior. The overall task of the GDG was to review the scientific evidence and provide expert advice to the WHO on the amount of physical activity and sedentary behavior associated with optimal health in children and adolescents, adults, older adults (> 64 years), and also specifically in pregnant and postpartum women and people living with chronic conditions or disabilities.

Methods
The GDG reviewed the available evidence specific to each sub-population using systematic protocols and in doing so, identified a number of gaps in the existing literature. These proposed research gaps were discussed and verified by expert consensus among the entire GDG.

Results
Evidence gaps across population sub-groups included a lack of information on: 1) the precise shape of the dose-response curve between physical activity and/or sedentary behavior and several of the health outcomes studied; 2) the health benefits of light-intensity physical activity and of breaking up sedentary time with light-intensity activity; 3) differences in the health effects of different types and domains of physical activity (leisure-time; occupational; transportation; household; education) and of sedentary behavior (occupational; screen time; television viewing); and 4) the joint association between physical activity and sedentary time with health outcomes across the life course. In addition, we acknowledge the need to conduct more population-based studies in low- and middle-income countries and in people living with disabilities and/or chronic disease, and to identify how various sociodemographic factors (age, sex, race/ethnicity, socioeconomic status) modify the health effects of physical activity, in order to address global health disparities.

Conclusions
Although the 2020 WHO Guidelines for Physical Activity and Sedentary Behavior were informed by the most up-to-date research on the health effects of physical activity and sedentary time, there is still substantial work to be done in advancing the global physical activity agenda.
The effect of a school-based intervention on physical activity, cardiorespiratory fitness and muscle strength: the School in Motion cluster randomized trial
Authors: Kolle Elin , Solberg Runar Barstad , Säfvenbom Reidar , Dyrstad Sindre M. , Berntsen Sveinung , Resaland Geir K. , Ekelund Ulf , Anderssen Sigmund A. , Steene-Johannessen Jostein , Grydeland May 
Published: November 2020

Abstract
Background
Physical activity (PA) declines throughout adolescence, therefore PA promotion during this period is important. We analyzed the effect of two school-based PA interventions on daily PA levels, cardiorespiratory fitness (CRF) and muscle strength among adolescents.

Methods
For the nine-month School in Motion intervention study (ScIM), we cluster-randomized 30 Norwegian secondary schools (N = 2084, mean age [SD] = 14 [0.3] years) to one of three study arms. The physically active learning (PAL) intervention included 30 min physically active learning, 30 min PA and a 60 min physical education (PE) lesson per week. The Don’t worry-Be happy (DWBH) intervention included a 60 min PA lesson and a 60 min PE lesson per week, both tailored to promote friendships and wellbeing. Both intervention arms were designed to engage the adolescents in 120 min of PA per week in addition to recess and mandatory PE lessons. The control group continued as per usual, including the standard amount of mandatory PE. PA (main outcome) was assessed by accelerometers, CRF and muscle strength (secondary outcomes) were assessed by an intermittent running test and selected tests from the Eurofit test battery.

Results
Daily PA and time spent in moderate- to vigorous-intensity PA (MVPA) decreased in all groups throughout the intervention. The mean difference in PA level and MVPA for participants in the PAL-intervention arm was 34.7 cpm (95% CI: 4.1, 65.3) and 4.7 min/day (95% CI: 0.6, 8.8) higher, respectively, compared to the control arm. There were no significant intervention effects on daily PA level, MVPA or time spent sedentary for adolescents in the DWBH-intervention arm. Adolescents in the PAL-intervention arm increased distance covered in the running test compared to controls (19.8 m, 95% CI: 10.4, 29.1), whilst a negative intervention effect was observed among adolescents in the DWBH-intervention arm (− 11.6 m, 95% CI: − 22.0, − 1.1).

Conclusion
The PAL-intervention resulted in a significantly smaller decrease in daily PA level, time spent in MVPA, and increased CRF compared to controls. Our results indicate that a teacher-led intervention, including three unique intervention components, is effective in curbing the decline in PA observed across our cohort and improving CRF.

Trial registration
ClinicalTrials.gov ID nr: NCT03817047. Registered 01/25/2019 ‘retrospectively registered’.
Functional characteristics of Th1, Th17, and ex-Th17 cells in EAE revealed by intravital two-photon microscopy
Authors: Loos Julia , Schmaul Samantha , Noll Theresa Marie , Paterka Magdalena , Schillner Miriam , Löffel Julian T. , Zipp Frauke , Bittner Stefan 
Published: November 2020

AbstractBackgroundT helper (Th) 17 cells are a highly plastic subset of T cells, which in the context of neuroinflammation, are able to acquire pathogenic features originally attributed to Th1 cells (resulting in so called ex-Th17 cells). Thus, a strict separation between the two T cell subsets in the context of experimental autoimmune encephalomyelitis (EAE) is difficult. High variability in culture and EAE induction protocols contributed to previous conflicting results concerning the differential contribution of Th1 and Th17 cells in EAE. Here, we systematically evaluate the role of different T cell differentiation and transfer protocols for EAE disease development and investigate the functional dynamics of encephalitogenic T cells directly within the inflamed central nervous system (CNS) tissue.MethodsWe compiled the currently used EAE induction protocols reported in literature and investigated the influence of the different Th1 and Th17 differentiation protocols as well as EAE induction protocols on the EAE disease course. Moreover, we assessed the cytokine profile and functional dynamics of both encephalitogenic Th1 and Th17 cells in the inflamed CNS using flow cytometry and intravital two-photon laser scanning microscopy. Lastly, we used astrocyte culture and adoptive transfer EAE to evaluate the impact of Th1 and Th17 cells on astrocyte adhesion molecule expression in vitro and in vivo.ResultsWe show that EAE courses are highly dependent on in vitro differentiation and transfer protocols. Moreover, using genetically encoded reporter mice (B6.IL17A-EGFP.acRFP x 2d2/2d2.RFP), we show that the motility of interferon (IFN)γ-producing ex-Th17 cells more closely resembles Th1 cells than Th17 cells in transfer EAE. Mechanistically, IFNγ-producing Th1 cells selectively induce the expression of cellular adhesion molecules I-CAM1 while Th1 as well as ex-Th17 induce V-CAM1 on astrocytes.ConclusionsThe behavior of ex-Th17 cells in EAE lesions in vivo resembles Th1 rather than Th17 cells, underlining that their change in cytokine production is associated with functional phenotype alterations of these cells.
Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2′s main protease
Authors: Mahdi Mohamed , Mótyán János András , Szojka Zsófia Ilona , Golda Mária , Miczi Márió , Tőzsér József 
Published: November 2020

Abstract
Background
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of infections worldwide. While the search for an effective antiviral is still ongoing, experimental therapies based on repurposing of available antivirals is being attempted, of which HIV protease inhibitors (PIs) have gained considerable interest. Inhibition profiling of the PIs directly against the viral protease has never been attempted in vitro, and while few studies reported an efficacy of lopinavir and ritonavir in SARS-CoV-2 context, the mechanism of action of the drugs remains to be validated.

Methods
We carried out an in-depth analysis of the efficacy of HIV PIs against the main protease of SARS-CoV-2 (Mpro) in cell culture and in vitro enzymatic assays, using a methodology that enabled us to focus solely on any potential inhibitory effects of the inhibitors against the viral protease. For cell culture experiments a dark-to-bright GFP reporter substrate system was designed.

Results
Lopinavir, ritonavir, darunavir, saquinavir, and atazanavir were able to inhibit the viral protease in cell culture, albeit in concentrations much higher than their achievable plasma levels, given their current drug formulations. While inhibition by lopinavir was attributed to its cytotoxicity, ritonavir was the most effective of the panel, with IC50 of 13.7 µM. None of the inhibitors showed significant inhibition of SARS-CoV-2 Mpro in our in vitro enzymatic assays up to 100 µM concentration.

Conclusion
Targeting of SARS-CoV-2 Mpro by some of the HIV PIs might be of limited clinical potential, given the high concentration of the drugs required to achieve significant inhibition. Therefore, given their weak inhibition of the viral protease, any potential beneficial effect of the PIs in COVID-19 context might perhaps be attributed to acting on other molecular target(s), rather than SARS-CoV-2 Mpro.
Elevated l-threonine is a biomarker for Lassa fever and Ebola
Authors: Gale Trevor V. , Schieffelin John S. , Branco Luis M. , Garry Robert F. , Grant Donald S. 
Published: November 2020

Abstract
Background
Lassa fever and Ebola are characterized by non-specific initial presentations that can progress to severe multisystem illnesses with high fatality rates. Samples from additional subjects are examined to extend and corroborate biomarkers with prognostic value for these diseases.

Methods
Liquid Chromatography Mass Spectrometry metabolomics was used to identify and confirm metabolites disrupted in the blood of Lassa fever and Ebola patients. Authenticated standards are used to confirm the identify of key metabolites.

Results
We confirm prior results by other investigators that the amino acid l-threonine is elevated during Ebola virus infection. l-Threonine is also elevated during Lassa virus infection. We also confirmed that platelet-activating factor (PAF) and molecules with PAF moiety are reduced in the blood of patients with fatal Lassa fever. Similar changes in PAF and PAF-like molecules were not observed in the blood of Ebola patients.

Conclusions
Metabolomics may provide tools to identify pathways that are differentially affected during viral hemorrhagic fevers and guide development of diagnostics to monitor and predict outcome.
Neuropathology changed by 3- and 6-months low-level PM2.5 inhalation exposure in spontaneously hypertensive rats
Authors: Chuang Hsiao-Chi , Chen Hsin-Chang , Chai Pei-Jui , Liao Ho-Tang , Wu Chang-Fu , Chen Chia-Ling , Jhan Ming-Kai , Hsieh Hui-I , Wu Kuen-Yuh , Chen Ta-Fu , Cheng Tsun-Jen 
Published: November 2020

Abstract
Background
Epidemiological evidence has linked fine particulate matter (PM2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM2.5 in spontaneously hypertensive (SH) rats.

Results
SH rats were exposed to S-, K-, Si-, and Fe-dominated PM2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 μg/m3 for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM2.5 exposure (p < 0.05). We observed that 3 months of exposure to PM2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p < 0.05) but not in other brain regions. Beclin 1 was overexpressed in the hippocampus with 3 months of PM2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM2.5 exposure.

Conclusions
Chronic exposure to low-level PM2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension.