bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling Ga(III) phthalocyanine—a different photosensitizer in neuroblastoma cellular model
Authors: Constantin Carolina , Lupu Andreea‐Roxana , Fertig Tudor Emanuel , Gherghiceanu Mihaela , Pop Sevinci , Ion Rodica‐Mariana , Neagu Monica 
Published: November 2018

AbstractPhthalocyanines (Pc) and their metallated derivatives are strongly considered for photodynamic therapy (PDT) possessing unique properties as possible new photosensitizers (PS). We have used toxicological assessments, real‐time monitoring of cellular impedance, and imagistic measurements for assessing the in vitro dark toxicity and PDT efficacy of Ga(III)‐Pc in SHSy5Y neuroblastoma cells. We have established the non‐toxic concentration range of Ga(III)‐Pc, a compound which shows a high intracellular accumulation, with perinuclear distribution in confocal microscopy. By choosing Ga(III)Pc non‐toxic dose, we performed in vitro experimental PDT hampering cellular proliferation. Our proposed Ga(III)‐Pc could complete a future PS panel for neuroblastoma alternate therapy.
Intracellular reduction in ATP levels contributes to CYT997‐induced suppression of metastasis of head and neck squamous carcinoma
Authors: Zhao Xiangdong , Lang Liwei , He Leilei , Gao Lixia , Chyan David , Xiong Yuanping , Li Honglin , Peng Hong , Teng Yong 
Published: November 2018

AbstractThe incidence rate of head and neck squamous cell carcinoma (HNSCC) has steadily increased over the past decade. However, treatment options for metastatic HNSCC are often limited and the 5‐year survival rate has remained static. Therefore, the development and assessment of more efficient but less toxic therapeutic strategies is an unmet need for treatment of more extensive HNSCC. Here, we report that CYT997, a novel microtubule‐disrupting agent, exerts strong activity in inhibiting HNSCC cell invasion and metastasis. The loss of invasion capacity by CYT997 was accompanied by an associated increase in cell adhesion and the reversal of epithelial‐mesenchymal transition (EMT). Increased expression of E‐cadherin protein and decreased expression of Vimentin protein became evident in HNSCC cells following CYT997 exposure, which were consistently observed in HNSCC xenografts from the mice receiving CYT997. Moreover, the capacity of invasive HNSCC cells to form pulmonary metastases was significantly blocked with CYT997 treatment, indicating that the diminishment of EMT traits contributes to CYT997‐suppressed metastasis. Intriguingly, CYT997 impaired intracellular ATP levels in HNSCC cells, at least in part, through its inhibitory effect on the mitochondrial protein IF1. The addition of ATP attenuated CYT997‐induced suppression of cell invasion, coupled with down‐regulation of E‐Cadherin and up‐regulation of Vimentin. These findings support a critical role of ATP levels in cell invasion and metastasis under the influence of CYT997. Collectively, our data unveil the mechanism involved in mediating CYT997 action, and provide preclinical rationale for possible clinical application of CYT997 as a novel therapeutic strategy against aggressive HNSCC.
Two human MARs effectively increase transgene expression in transfected CHO cells
Authors: Li Qin , Zhao Chun‐peng , Lin Yan , Song Chao , Wang Fang , Wang Tian‐yun 
Published: November 2018

AbstractMatrix attachment regions (MARs) can enhance the expression level of transgene in Chinese hamster ovaries (CHO) cell expression system. However, improvements in function and analyses of the mechanism remains unclear. In this study, we screened two new and more functional MAR elements from the human genome DNA. The human MAR‐3 and MAR‐7 element were cloned and inserted downstream of the polyA site in a eukaryotic vector. The constructs were transfected into CHO cells, and screened under G418 to produce the stably transfected cell pools. The expression levels and stability of enhanced green fluorescent protein (eGFP) were detected by flow cytometry. The transgene copy number and transgene expression at mRNA level were detected by quantitative real‐time PCR. The results showed that the expression level of eGFP of cells transfected with MAR‐containing vectors were all higher than those of the vectors without MARs under transient and stably transfection. The enhancing effect of MAR‐7 was higher than that of MAR‐3. Additionally, we found that MAR significantly increased eGFP copy numbers and eGFP gene mRNA expression level as compared with the vector without. In conclusion, MAR‐3 and MAR‐7 gene can promote the expression of transgene in transfected CHO cells, and its effect may be related to the increase of the number of copies.
Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation
Authors: Weng Weidong , Yao Chenglun , Poonit Keshav , Zhou Xijie , Sun Chao , Zhang Feng , Yan Hede 
Published: November 2018

AbstractNeuropathic pain is a well‐known type of chronic pain caused by damage to the nervous system. Autophagy is involved in the development and/or progression of many diseases, including neuropathic pain. Emerging evidence suggests that metformin relieves neuropathic pain in several neuropathic pain models; however, metformin's cellular and molecular mechanism for pain relief remains unknown. In this study, we investigated the therapeutic effects of metformin on pain relief after spinal nerve ligation (SNL) and its underlying mechanism of autophagy regulation. Behavioural analysis, histological assessment, expression of c‐Fos and molecular biological changes, as well as ultrastructural features, were investigated. Our findings showed that the number of autophagosomes and expression of autophagy markers, such as LC3 and beclin1, were increased, while the autophagy substrate protein p62, as well as the ubiquitinated proteins, were accumulated in the ipsilateral spinal cord. However, metformin enhanced the expression of autophagy markers, while it abrogated the abundance of p62 and ubiquitinated proteins. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and analgesic effects of metformin on SNL. Taken together, these results illustrated that metformin relieved neuropathic pain through autophagy flux stimulation and provided a new direction for metformin drug development to treat neuropathic pain.
Glucose‐dependent insulinotropic polypeptide deficiency reduced fat accumulation and insulin resistance, but deteriorated bone loss in ovariectomized mice
Authors: Shimazu‐Kuwahara Satoko , Kanemaru Yoshinori , Harada Norio , Ikeguchi Eri , Ueda Yohei , Yamane Shunsuke , Murata Yuki , Yasoda Akihiro , Kieffer Timothy J , Inagaki Nobuya 
Published: November 2018

AbstractGiven the established roles of glucose‐dependent insulinotropic polypeptide (GIP) in promoting fat storage and bone formation, we assessed the contribution of GIP to obesity and osteopenia in ovariectomized mice with a gene encoding green fluorescent protein (GFP) inserted into the GIP locus, in which GIP was either reduced (GIPgfp/+) or absent (GIPgfp/gfp). In GIPgfp/gfp mice, weight gain, subcutaneous and visceral fat mass were reduced, and glucose intolerance was improved compared with wild‐type mice with the same magnitude of insulin responses. Cancellous bone mineral density and bone cortical thickness were reduced in GIPgfp/gfp mice compared with wild‐type mice. In GIPgfp/+ mice, weight gain, glucose intolerance and cancellous bone mineral density were not different from that of wild‐type mice. These results indicate that the total elimination of GIP ameliorates weight gain and adiposity in ovariectomized mice, but it enhances osteopenia, particularly in cancellous bone by partly suppressing bone formation.
Spatial distribution and sampling plan of the phytophagous stink bug complex in different soybean production systems
Authors: Fernandes Marcos Gino , Costa Eduardo Neves , Cavada Leonardo Hiroito , Mota Thiago Alexandre , da Fonseca Paulo Rogério Beltramin 
Published: November 2018

AbstractPhytophagous stink bugs are major soybean pests, and knowledge of spatial distribution models of the pest in the crop is fundamental to establishing an appropriate sequential sampling plan, and thus, allowing the correct utilization of control strategies. This work aimed to study the spatial distribution of phytophagous stink bugs in soybean grown in different cropping systems and determine a sequential sampling plan. The experiment was conducted in Maracaju, MS, Brazil, during the agricultural year of 2012/2013. Soybean cultivars BRS 284 and SYN 1163 RR were placed in an experimental area comprising six fields (two soybean cultivars × three cropping systems). Sampling was performed weekly, using a beat cloth per plot and counting the number of stink bugs found, virtually throughout the soybean reproductive period. Concerning the statistical analyses, we used the dispersion indexes (variance‐to‐mean ratio, Morisita's index, exponent k of the negative binomial and Green's coefficient) and probabilistic methods of frequency adjustment (negative binomial and Poisson). Adult and nymph phytophagous stink bugs showed aggregate disposition in the field regardless of the cropping system, and their numbers were adjusted to the negative binomial probability distribution. There was no difference in the behaviour of adult and nymphs considering the tested cultivars. We elaborated a practical sequential sampling plan for phytophagous stink bug complexes, considering crops intended for the production of grains and seeds.
Quality of hypertension care: An improvement initiative in two outpatient health care centers
Authors: Yusupov Eleanor , Krishnamachari Bhuma , Rand Sarah , Abdalla Mirette , Zwibel Hallie 
Published: November 2018

AbstractRationale, aims, and objectivesHypertension control is an important public health goal; however, significant barriers remain in primary care practice.Our objective was to identify areas for improvement in hypertension care and implement changes in management to improve outcomes. We also aimed to evaluate whether quality improvement influences physician attitudes towards and adherence to current hypertension guidelines.MethodWe conducted a non‐experimental pre‐ vs post‐ design quality improvement study for ambulatory patients with a history of hypertension. Specific measures of hypertension care were assessed at baseline and 3 months post‐implementation of the quality improvement initiative.De‐identified data were collected from 100 charts, randomly selected from the practice's electronic medical records, and compared with a national sample of peer data.The Intervention was based on the American Academy of Family Physicians METRIC Performance Improvement module. This consisted of creating a computerized registry, system improvements to the electronic medical records, and peer education workshops on best practices.A 7‐item survey was completed by primary care physicians pre‐ and post‐intervention.ResultsImprovement was demonstrated in several primary outcome measures: increased number of patients counselled on sodium intake (P = 0.005), physical activity (P = 0.001), alcohol consumption (P = 0.03), and weight reduction (P < 0.0001).Practice self‐assessment findings did not show a statistically significant change following the intervention.ConclusionsThis quality improvement increased provider compliance with hypertension guidelines. However, more effort is required to modify physician practices for full compliance with the 2017 updated hypertension guidelines.
Translation, cultural adaptation, validation, and reliability study of the Quick‐EBP‐VIK instrument: Chinese version
Authors: Zhou Chunlan , Wang Yanfang , Wang Siqi , Ou Jiexia , Wu Yanni 
Published: November 2018

AbstractRationale, aims, and objectivesValid and reliable instruments for measuring are needed. To add knowledge to the subject of tools of evidence‐based practice (EBP) evaluation in mainland China, the present study aims to translate the Quick‐EBP‐VIK into Chinese, which is an instrument for the assessment of nurses' value, knowledge, and implementation of EBP, and to evaluate the metric characteristics of the Chinese version.MethodsIn this methodological study, a total sample of 402 nurses from mainland China was applied. Construct validity was evaluated by using factor analysis and further supported through known‐group validity. A panel of experts examined the content validity. Internal consistency was determined using composite reliability and Cronbach alpha. The intraclass correlation coefficient (ICC) was calculated to assess test‐retest reliability.ResultsThe exploratory factor analysis revealed a three‐factor structure model same to the original instrument. The confirmatory factor analysis showed a good fit model with a comparative fit index of 0.957 and a root mean square error of approximation of 0.065. Significant differences were found in the item means of the tool between nurses who received EBP training and those who had not, which supported the known‐group validity. The Cronbach alpha and composite reliability for the three subscales were all higher than 0.70. The ICC ranged from 0.569 to 0.928 for the three subscales and from 0.494 to 0.903 for the items included in the instrument.ConclusionThe Chinese version of the Quick‐EBP‐VIK has evidence of acceptable reliability and validity and can be used to measure value, knowledge, and implementation of EBP for Chinese nurses.
Effect of different dry‐polishing regimens on the intrapulpal temperature assessed with pulpal blood microcirculation model
Authors: Ertugrul Ihsan Furkan , Orhan Ekim Onur , Yazkan Basak 
Published: November 2018

AbstractObjectiveThe aim of the study was to evaluate the effect of different dry‐polishing regimens on the intrapulpal temperature assessed using a pulpal blood microcirculation model.Materials and MethodsEighty extracted human mandibular premolar teeth were used. Standardized class V cavity preparations were performed and were then restored. Teeth were divided into four main groups (n = 20): Fine polishing disc (SSF; 3M Sof‐Lex, 3M ESPE, Minnesota); Super‐fine polishing disc (SSS; 3M Sof‐Lex); Spiral finishing wheel (SSW; 3M Sof‐Lex); Enhance PoGo—One step diamond micro‐polisher cup (EPO; Dentsply Sirona, Inc, Delaware). The main groups were divided: the low‐load pressure (0.4N) and the high‐load pressure (0.8N). The average change in intrachamber temperatures (Δt), from initial to highest, were measured.ResultsThe highest temperature increase was recorded in SSF08 (9.55°C). The lowest value was recorded in EPO04 (1.9°C). SSS08, SSW08, and EPO08 demonstrated significantly higher Δt values than the low‐load mode in SSS04, SSW04, and EPO04, respectively (P < .0001).ConclusionsTemperature was the least affected by the diamond cup in both pressure modes, and it was also less affected by the spiral finishing wheel in the low‐load mode than in the high‐load mode. Fine and super‐fine discs had the greatest effect on intrachamber temperatures.Clinical SignificanceThe present study suggests intrachamber temperature can rise among different dry‐polishing regimes. Dental practitioners should pay attention to dry‐polishing regimens and pressures for reducing heat‐related dental problems.
Management of Acute Changes in Condition in Skilled Nursing Facilities
Authors: Ouslander Joseph G. , Engstrom Gabriella , Reyes Bernardo , Tappen Ruth , Rojido Carolina , Gray‐Miceli Deanna 
Published: November 2018

OBJECTIVESTo describe the presentation and management of acute changes in condition in skilled nursing facilities (SNFs) during implementation of a program designed to reduce unnecessary emergency department visits and hospitalizations.DESIGNSecondary analysis of data from a randomized controlled trial involving 264 SNFs.PARTICIPANTSOne hundred thirty‐three of the 264 participating SNFs that provided data on acute changes in condition: 55 in the intervention group, 78 in the control group.INTERVENTIONSDuring a 12‐month period, intervention SNFs received training and support for implementation of the Interventions to Reduce Acute Care Transfers program. Control SNFs were offered training and implementation support after the end of the 12‐month trial.MEASURESProject champions used a structured online tool to describe acute changes in condition that did not result in a hospital transfer within 72 hours of the change.RESULTSMost of the 7,689 episodes of acute change in condition reported involved multiple changes that were not disease specific. Ten percent resulted in hospital transfer between 72 hours and 7 days after the change. Five acute changes had odds ratios for transfer greater than 2 (mental status change, abnormal vital signs, bleeding, shortness of breath, and unresponsiveness). Most transfers were for reasons other than the initial change in condition.CONCLUSIONSA wide variety of acute changes in condition can be managed in SNFs without hospital transfer. Most of these changes are nonspecific and multiple, and when they are associated with hospital transfer, the reasons for the transfer are most often different from the initial acute change in condition. These data highlight the multifactorial nature of acute changes in condition in the SNF population and suggest that disease‐specific protocols and assessment tools may not be the most appropriate approach to managing acute changes in condition in the SNF setting. J Am Geriatr Soc 66:2259–2266, 2018.
Multifactorial Examination of Caregiver Burden in a National Sample of Family and Unpaid Caregivers
Authors: Riffin Catherine , Van Ness Peter H. , Wolff Jennifer L. , Fried Terri 
Published: November 2018

OBJECTIVESTo examine factors associated with caregiver burden from a multifactorial perspective by examining caregiver and care recipient characteristics and a full range of caregiving tasks.DESIGNNationally representative surveys of community‐dwelling older adults and their family caregivers residing in the United States.SETTING2011 National Health and Aging Trends Study and National Study of Caregiving.PARTICIPANTSCommunity‐dwelling older adults and their family caregivers.MEASUREMENTSCaregiver burden, comprising emotional, physical, and financial difficulties associated with caregiving.RESULTSAn estimated 14.9 million caregivers assisted 7.6 million care recipients. More than half of caregivers reported burden related to caregiving. In a multivariable regression model, caregivers who assisted with more activities of daily living and instrumental activities of daily living, health management tasks, and health system logistics were more likely to experience burden, as were female caregivers, adult child caregivers, caregivers in poor health, caregivers with anxiety symptoms, and those using respite care. Dementia was the only care recipient characteristic associated with burden.CONCLUSIONCaregiver characteristics and provision of caregiving tasks determine caregiver burden more than care recipient characteristics. Absence of an association between type of a care recipient's chronic conditions and burden, except for dementia, suggests that the tasks that caregivers who assist older adults with a variety of health conditions undertake shape the experience of caregiving. J Am Geriatr Soc 67:277–283, 2019.
Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients
Authors: Li Jianjia , Wang Runting , Ge Yihong , Chen Danhong , Wu Buling , Fang Fuchun 
Published: November 2018

Background and ObjectiveThis study aimed to discover the distinctive MicroRNAs (miRNA) functioning in the pathogenesis of periodontal inflammation, which might be potential therapy targets of chronic periodontitis.Material and MethodsmiRNA profiles of human inflamed gingival tissue from three previous microarrays were re‐analysed. Gingival tissues were collected for the validation of overlapping miRNAs, and a network was constructed to show regulatory connection between overlapping miRNAs and periodontitis‐associated target genes. Potential miRNAs were screened based on their expression levels and predicted target genes. Correlation analysis and binding site prediction were conducted to reveal the relationship between the potential miRNAs and their target genes.ResultsmiR‐144‐5p, found to be upregulated in all three studies, showed the greatest upregulation (P < 0.0001). Another 16 miRNAs (10 upregulated and six downregulated) overlapped between any two of the three studies. All overlapping miRNAs had expected expression levels except for miR‐203 during validation. Ten miRNAs (six upregulated and four downregulated) were found to have periodontal inflammation‐associated targets. Cyclooxygenase 2 (COX2) and interleukin‐17F (IL17F), predicted target genes of upregulated miR‐144‐5p, showed significant decreases and were negatively correlated with miR‐144‐5p in the periodontitis group (r = −0.742 for COX2, r = −0.615 for IL17F).ConclusionThis re‐analysis of miRNA signatures has implied the potential regulatory mechanism of miR‐144‐5p and its potential for exploring alternative therapeutic approaches, especially those that use miRNA delivery systems to treat chronic periodontitis. Nevertheless, further study based on larger sample size and homogenous cells is needed to reveal the exact roles of miRNAs in chronic periodontitis.
Dynamic changes in innate immune responses during direct‐acting antiviral therapy for HCV infection
Authors: Holmes Jacinta A. , Carlton‐Smith Charles , Kim Arthur Y. , Dumas Emily O. , Brown Joelle , Gustafson Jenna L. , Lauer Georg M. , Silva Sakuni T. , Robidoux Maxwell , Kvistad Daniel , Alatrakchi Nadia , Tonnerre Pierre , Cohen Daniel E. , Zhang Hongtao , Shulman Nancy S. , Chung Raymond T. 
Published: November 2018

SummaryThe role of the endogenous interferon (IFN) system has been well characterized during IFN‐based therapy for chronic hepatitis C virus (HCV) infection; less is known for direct‐acting antivirals (DAAs). In this phase 3b open‐label study, we assessed changes in IFN‐stimulated genes (ISGs) in non‐cirrhotic treatment‐naïve or pegIFN/RBV‐experienced HCV‐GT1a‐infected patients receiving paritaprevir/ritonavir/ombitasvir + dasabuvir + ribavirin (PrOD + R) for 12 weeks. ISG expression was quantified from peripheral blood mononuclear cells at baseline, treatment weeks (TW)2, TW4, TW8, end of treatment (EOT) and at post‐treatment week 12. Paired sera were used to assess IFN‐α/IFN‐related chemokines/cytokines. Twenty‐five patients were enrolled. Overall sustained virologic response (SVR)12 was 92% (no virologic failure [VF]) and 100% for those completing the study protocol. Two patients were excluded from the ISG analysis due to lack of post‐treatment samples. The majority of ISGs were downregulated at TW2‐TW4 (nadir TW4); however, a relative increase was observed at TW8‐EOT, although levels were lower than baseline. This downregulation was accompanied by increases in IFN‐α/IFN‐related chemokines, a finding not observed with TH1/2‐related cytokines. Following SVR, ISG expression returned to TW2 levels. In conclusion, PrOD + R for 12 weeks was well‐tolerated with no VF. Our data demonstrate dynamic alterations in innate immune profiles during highly potent IFN‐free DAA therapy. The downregulation of ISG post‐therapy suggests reversal of the “exhausted” ISG phenotype following SVR, and the rise in ISGs and IFN‐α/IFN‐responsive chemokines late during therapy suggests resetting of IFN responsiveness that may be relevant in determining duration of or immunological sequelae from DAA therapy, including HBV reactivation.