bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of global warming scenarios on life-history traits of Tetranychus evansi (Acari: Tetranychidae)
Authors: Ghazy Noureldin Abuelfadl , Gotoh Tetsuo , Suzuki Takeshi 
Published: November 2019

AbstractBackgroundThe tomato red spider mite,Tetranychus evansiBaker & Pritchard (Acari: Tetranychidae), is an agricultural pest of solanaceous crops. AlthoughT. evansiis of South American subtropical origin, it has recently expanded its distribution range to many tropical and temperate areas around the world. Its potential distribution range in response to scenarios of global warming was recently modeled, confirming its current and possible future distributions. Here, we experimentally investigated the biological traits ofT. evansiin the context of the current and future global warming (2100) scenarios. Using an environmental simulation system, we tested the life-history traits ofT. evansiunder current summer temperatures (as of June, July, and August 2016) and under expected temperature increases based on two IPCC scenarios: RCP2.6 (+ 1 °C) and RCP8.5 (+ 3.7 °C). The mites were introduced into each scenario on 1 June and their sequential progeny were used for testing in each following month.ResultsThe mite could develop and reproduce under all scenarios. There was a decrease in the duration of lifespan and female fecundity at RCP8.5 during June and August, but this may be compensated for by the high intrinsic rate of increase, which implies faster population growth and shorter generation time.ConclusionOur study and other reports reveal the high adaptability ofT. evansito a wide range of summer temperatures; this may explain its current distribution. We anticipate that global warming will favor the spread ofT. evansiand may further expand its distribution to a large area of the globe. These findings should be of ecological and practical relevance for designing prevention and control strategies.
Chitosan oligosaccharide inhibits skull resorption induced by lipopolysaccharides in mice
Authors: Guo Ke , Liu Zong Lin , Wang Wen Chao , Xu Wei Feng , Yu Shi Qi , Zhang Shan Yong 
Published: November 2019

Abstract
Background
Low-molecular-weight chitosan oligosaccharide (LMCOS), a chitosan degradation product, is water-soluble and easily absorbable, rendering it a popular biomaterial to study. However, its effect on bone remodelling remains unknown. Therefore, we evaluated the effect of LMCOS on lipopolysaccharide (LPS)-induced bone resorption in mice.

Methods
Six-week-old male C57BL/6 mice (n = five per group) were randomly divided into five groups: PBS, LPS, LPS + 0.005% LMCOS, LPS + 0.05% LMCOS, and LPS + 0.5% LMCOS. Then, the corresponding reagents (300 μL) were injected into the skull of the mice. To induce bone resorption, LPS was administered at 10 mg/kg per injection. The mice were injected three times a week with PBS alone or LPS without or with LMCOS and sacrificed 2 weeks later. The skull was removed for micro-computed tomography, haematoxylin-eosin staining, and tartrate-resistant acid phosphatase staining. The area of bone damage and osteoclast formation were evaluated and recorded.

Results
LMCOS treatment during LPS-induced skull resorption led to a notable reduction in the area of bone destruction; we observed a dose-dependent decrease in the area of bone destruction and number of osteoclasts with increasing LMCOS concentration.

Conclusions
Our findings showed that LMCOS could inhibit skull bone damage induced by LPS in mice, further research to investigate its therapeutic potential for treating osteolytic diseases is required.
Annual alveolar bone loss in older adults taking oral bisphosphonate: a retrospective cohort study
Authors: Helmi Mohammad , AlOsaimy Sara , Goodson J. Max , Hasturk Hatice , Natto Zuhair S. 
Published: November 2019

Abstract
Background
Although several studies assessed the effect of bisphosphonate (BIS) administration on alveolar bone loss, this relationship has not been fully investigated using longitudinal analysis. The aim of the this article is to predict annual alveolar bone loss in a subpopulation of older adults patients who were taking oral bisphosphonate (BIS), adjusting for systemic diseases and associated risk factors.

Methods
This is a retrospective cohort study. We identified all subjects who reported receiving oral bisphosphonate from 2008 to 2015 (N = 30) using the electronic health records of each patient to identify suitable radiographs for analysis. For the longitudinal data analysis, 26 subjects were eligible for inclusion, having at least two exposures of the complete mouth set or repeated bitewing radiographs at least a one-year interval; they were then matched on age and sex to another 26 patients who did not report receiving bisphosphonate at any point of their life.

Results
Mild periodontitis was higher in the BIS group compared to the no BIS group; however, moderate periodontitis was higher in the no BIS group. For those who did not take oral BIS, change over time was not significant after the two-year period. However, the BIS group had experienced 0.088 mm more bone loss compared to the no BIS group (95% CI: 0.001, 0.176. P-value = 0.048), adjusting for all other variables included in the model.

Conclusion
The group that reported receiving oral bisphosphonates showed no improvement in maintaining alveolar bone level, and the use of oral BIS may not be effective in reducing annual alveolar bone loss; however, emerging evidence is promising for the use of bisphosphonate as an adjunctive local delivery medication for the management of periodontal diseases.
Randomized, double-blind, placebo-controlled phase I dose escalation study of Dan Qi Tong Mai tablet in healthy volunteers
Authors: Gou Zhong-ping , Zhang Wei , Liang Xiu-fang , Wang Ying , Mou Ju-hong , Li Mei , Zhang Ya , Feng Ping 
Published: November 2019

Abstract
Background
This study aims to assess the tolerability and safety of DQTM tablet, which contains a complex mixture of Salvia miltiorrhiza salvianolic acids and Panax notoginseng saponins.

Methods
A double-blind, randomized, placebo-controlled phase I dose escalation study was conducted in 84 healthy volunteers. In a single ascending dose study, active ingredients were administered in various doses (90, 270, 540, 1080, 1800, 2880, 4320 or 5760 mg) to 60 subjects in cohorts 1–8. In a multiple ascending dose study, active ingredients were administered at doses of 360, 720 or 2160 mg twice daily to 24 subjects in cohorts 9–11 for 14 consecutive days. Safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiography, laboratory tests and adverse events.

Results
No serious adverse events or clinically significant changes in vital signs or electrocardiography were observed. One subject experienced mildly elevated levels of alanine aminotransferase and aspartate transaminase but recovered spontaneously. Five subjects experienced a small increase in the number of daily stools.

Conclusions
DQTM tablet was well tolerated at single doses of up to 5760 mg and twice-daily doses of up to 2160 mg for 14 consecutive days. The most frequent adverse event was an increase in the number of daily stools.
Comparative case studies in integrated care implementation from across the globe: a quest for action
Authors: Stadnick Nicole A. , Sadler Euan , Sandall Jane , Turienzo Cristina Fernandez , Bennett Ian M. , Borkan Jeffrey , Oladeji Bibilola , Gureje Oye , Aarons Gregory A. , Sklar Marisa 
Published: November 2019

AbstractBackgroundIntegrated care is the coordination of general and behavioral health and is a highly promising and practical approach to improving healthcare delivery and patient outcomes. While there is growing interest and investment in integrated care implementation internationally, there are no formal guidelines for integrated care implementation applicable to diverse healthcare systems. Furthermore, there is a complex interplay of factors at multiple levels of influence that are necessary for successful implementation of integrated care in health systems.MethodsGuided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework (Aarons et al., 2011), a multiple case study design was used to address two research objectives: 1) To highlight current integrated care implementation efforts through seven international case studies that target a range of healthcare systems, patient populations and implementation strategies and outcomes, and 2) To synthesize the shared and unique challenges and successes across studies using the EPIS framework.ResultsThe seven reported case studies represent integrated care implementation efforts from five countries and continents (United States, United Kingdom, Vietnam, Israel, and Nigeria), target a range of clinical populations and care settings, and span all phases of the EPIS framework. Qualitative synthesis of these case studies illuminated common outer context, inner context, bridging and innovation factors that were key drivers of implementation.ConclusionsWe propose an agenda that outlines priority goals and related strategies to advance integrated care implementation research. These goals relate to: 1) the role of funding at multiple levels of implementation, 2) meaningful collaboration with stakeholders across phases of implementation and 3) clear communication to stakeholders about integrated care implementation.Trial registrationNot applicable.
Comparative evaluation of drug information leaflets for non-steroidal anti-inflammatory drugs in Palestine: local versus imported products
Authors: Arandy Dina A. , Abu-Hashia Maysa W. , Al-hroub Bahaa M. , Qatmosh Sandra A. , Koni Amer A. , Qeeno Baraa G. , Al-Jabi Samah W. , Zyoud Sa’ed H. 
Published: November 2019

AbstractBackgroundDrug information leaflets (DILs) are written for patients and health care providers to show how to use the medications safely and effectively, in order to reach the required therapeutics outcomes. This comparative study was conducted to evaluate various DILs of non-steroidal anti-inflammatory drugs (NSAIDs) that are produced in Palestine, along with their imported equivalents.MethodsThirty-five DILs of NSAIDs were analyzed and evaluated in a cross-sectional comparative study. Thirty-one statements were obtained from literature and used; evaluation was performed on basis of both any presence or absence of these statements in the leaflets. 23 of the 31 statements that were available in both local and imported DILs were also evaluated in terms of total word-counts: the median (interquartile range) word-count for each statement was determined separately for the two groups and then compared. For the remaining 8 statements, this was not performed,either because they were not present in any leaflet, or because counting the number of words would not be meaningful.ResultsA total of 35 DILs for nine different active ingredients of NSAIDs were analyzed. In 97% of leaflets, “Instructions to convert medication into liquid forms” were missing and 94% did not provide any information about “Pharmacokinetics”. 83% of DILs provided no information about “Mechanism of action” and 74% did not mention any reliable references. 66% of the analyzed inserts did not include any instruction about the possibility of a tablet splitting. And in 63%, the “Date of last revision” was missing. Further, “Duration of using” and “Inactive ingredients” were not found in 51% of leaflets. In terms of word-count, the related sections of the 23 selected criteria were expressed with more words by imported leaflets compared with the local ones, significant differences were found in 12 categories, the highest significance of > 42.4-fold difference was found in “Geriatric considerations” category whereas 1.4-fold difference was found in “Shelf life,” being the lowest one.ConclusionsThis study shows that local products provide less information than imported products, so we recommend that appropriate measurements be taken by both Palestinian authorities and manufacturers to improve both quantity and quality of local DILs.
The intestinal microbiota regulates host cholesterol homeostasis
Authors: Le Roy Tiphaine , Lécuyer Emelyne , Chassaing Benoit , Rhimi Moez , Lhomme Marie , Boudebbouze Samira , Ichou Farid , Haro Barceló Júlia , Huby Thierry , Guerin Maryse , Giral Philippe , Maguin Emmanuelle , Kapel Nathalie , Gérard Philippe , Clément Karine , Lesnik Philippe 
Published: November 2019

AbstractBackgroundManagement of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale.ResultsWe depleted the intestinal microbiota of hypercholesterolemic femaleApoe−/−mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated toBetaproteobacteria,Alistipes,Bacteroides, andBarnesiellataxa.ConclusionsThese results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.
Identification and ranking of recurrent neo-epitopes in cancer
Authors: Blanc Eric , Holtgrewe Manuel , Dhamodaran Arunraj , Messerschmidt Clemens , Willimsky Gerald , Blankenstein Thomas , Beule Dieter 
Published: November 2019

Abstract
Background
Immune escape is one of the hallmarks of cancer and several new treatment approaches attempt to modulate and restore the immune system’s capability to target cancer cells. At the heart of the immune recognition process lies antigen presentation from somatic mutations. These neo-epitopes are emerging as attractive targets for cancer immunotherapy and new strategies for rapid identification of relevant candidates have become a priority.

Methods
We carefully screen TCGA data sets for recurrent somatic amino acid exchanges and apply MHC class I binding predictions.

Results
We propose a method for in silico selection and prioritization of candidates which have a high potential for neo-antigen generation and are likely to appear in multiple patients. While the percentage of patients carrying a specific neo-epitope and HLA-type combination is relatively small, the sheer number of new patients leads to surprisingly high reoccurence numbers. We identify 769 epitopes which are expected to occur in 77629 patients per year.

Conclusion
While our candidate list will definitely contain false positives, the results provide an objective order for wet-lab testing of reusable neo-epitopes. Thus recurrent neo-epitopes may be suitable to supplement existing personalized T cell treatment approaches with precision treatment options.
Vitamin D deficiency exacerbates bleomycin-induced pulmonary fibrosis partially through aggravating TGF-β/Smad2/3-mediated epithelial-mesenchymal transition
Authors: Li Se-Ruo , Tan Zhu-Xia , Chen Yuan-Hua , Hu Biao , Zhang Cheng , Wang Hua , Zhao Hui , Xu De-Xiang 
Published: November 2019

Abstract
Background
Our earlier report indicated that active vitamin D3 inhibited epithelial-mesenchymal transition (EMT) in bleomycin (BLM)-induced pulmonary fibrosis. The objective of this study was to further investigate whether vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis.

Methods
This study consists of two independent experiments. Experiment 1, male mice were fed with vitamin D deficient (VDD) fodder. Experiment 2, Cyp27b1+/+, Cyp27b1+/− and Cyp27b1−/− mice were fed with standard diet. For pulmonary fibrosis, mice were intratracheally instilled with a single dose of BLM (1.5 mg/kg). Serum 25(OH) D level was measured. Pulmonary collagen deposition was assessed by Sirius red staining. EMT was measured and transforming growth factor-beta (TGF-β)/Smad3 signaling was evaluated in the lungs of BLM-treated mice.

Results
The relative weight of lungs was elevated in BLM-treated mice. Col1α1 and Col1α2, two collagen protein genes, were upregulated, and collagen deposition, as determined by Sirius red staining, was observed in the lungs of BLM-treated mice. E-cadherin, an epithelial marker, was downregulated. By contrast, vimentin and α-SMA, two EMT markers, were upregulated in the lungs of BLM-treated mice. Pulmonary TGF-β/Smad3 signaling was activated in BLM-induced lung fibrosis. Further analysis showed that feeding VDD diet, leading to vitamin D deficiency, aggravated elevation of BLM-induced relative lung weight. Moreover, feeding VDD diet aggravated BLM-induced TGF-β/Smad3 activation and subsequent EMT in the lungs. In addition, feeding VDD diet exacerbated BLM-induced pulmonary fibrosis. Additional experiment showed that Cyp27b1 gene knockout, leading to active vitamin D3 deficiency, exacerbated BLM-induced pulmonary fibrosis. Moreover, Cyp27b1 gene knockout aggravated pulmonary TGF-β/Smad2/3 activation and subsequent EMT in BLM-induced lung fibrosis.

Conclusion
Vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis partially through aggravating TGF-β/Smad2/3-mediated EMT in the lungs.
Effect of beta blocker use and type on hypoglycemia risk among hospitalized insulin requiring patients
Authors: Dungan Kathleen , Merrill Jennifer , Long Clarine , Binkley Philip 
Published: November 2019

Abstract
Background
Although beta blockers could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied. This study sought to determine the relationship between type of beta blocker and incidence of hypoglycemia and mortality in hospitalized patients.

Methods
We retrospectively identified non-critically ill hospitalized insulin requiring patients who were undergoing bedside glucose monitoring and received either carvedilol or a selective beta blocker (metoprolol or atenolol). Patients receiving other beta blockers were excluded. Hypoglycemia was defined as any glucose < 3.9 mmol/L within 24 h of admission (Hypo1day) or throughout hospitalization (HypoT) and any glucose < 2.2 mmol/L throughout hospitalization (Hyposevere).

Results
There were 1020 patients on carvedilol, 886 on selective beta blockers, and 10,216 on no beta blocker at admission. After controlling for other variables, the odds of Hypo1day, HypoT and Hyposevere were higher for carvedilol and selective beta blocker recipients than non-recipients, but only in basal insulin nonusers. The odds of Hypo1day (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.28, 3.09, p = 0.0002) and HypoT (OR 1.38, 95% CI 1.02, 1.86, p = 0.03) but not Hyposevere (OR 1.90, 95% CI 0.90, 4.02, p = 0.09) were greater for selective beta blocker vs. carvedilol recipients in basal insulin nonusers. Hypo1day, HypoT, and Hyposevere were all associated with increased mortality in adjusted models among non-beta blocker and selective beta blocker recipients, but not among carvedilol recipients.

Conclusions
Beta blocker use is associated with increased odds of hypoglycemia among hospitalized patients not requiring basal insulin, and odds are greater for selective beta blockers than for carvedilol. The odds of hypoglycemia-associated mortality are increased with selective beta blocker use or nonusers but not in carvedilol users, warranting further study.
Phosphate regulator PhoP directly and indirectly controls transcription of the erythromycin biosynthesis genes in Saccharopolyspora erythraea
Authors: Xu Ya , You Di , Yao Li-li , Chu Xiaohe , Ye Bang-Ce 
Published: November 2019

Abstract
Background
The choice of phosphate/nitrogen source and their concentrations have been shown to have great influences on antibiotic production. However, the underlying mechanisms responsible for this remain poorly understood.

Results
We show that nutrient-sensing regulator PhoP (phosphate regulator) binds to and upregulates most of genes (ery cluster genes) involved in erythromycin biosynthesis in Saccharopolyspora erythraea, resulting in increase of erythromycin yield. Furthermore, it was found that PhoP also directly interacted with the promoter region of bldD gene encoding an activator of erythromycin biosynthesis, and induced its transcription. Phosphate limitation and overexpression of phoP increased the transcript levels of ery genes to enhance the erythromycin production. The results are further supported by observation that an over-producing strain of S. erythraea expressed more PhoP than a wild-type strain. On the other hand, nitrogen signal exerts the regulatory effect on the erythromycin biosynthesis through GlnR negatively regulating the transcription of phoP gene.

Conclusions
These findings provide evidence that PhoP mediates the interplay between phosphate/nitrogen metabolism and secondary metabolism by integrating phosphate/nitrogen signals to modulate the erythromycin biosynthesis. Our study reveals a molecular mechanism underlying antibiotic production, and suggests new possibilities for designing metabolic engineering and fermentation optimization strategies for increasing antibiotics yield.
Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway
Authors: Zhang Huan-yu , Xing Mao-qing , Guo Jing , Zhao Jin-chuan , Chen Xin , Jiang Zhong , Zhang Hong , Dong Qian 
Published: November 2019

Abstract
Background
Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved.

Methods
Through mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo.

Results
We identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain‐derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence.

Conclusion
Overall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.