bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple and low‐cost active dual‐axis solar tracker
Authors: Hammoumi Aboubakr El , Motahhir Saad , Ghzizal Abdelaziz El , Chalh Abdelilah , Derouich Aziz
Published: September 2018

This paper presents the design and practical implementation of a simple active dual‐axis solar tracker (DAST) to track the sun's movement by using fewer components and low‐cost as well. A dual‐axis mechanism is developed in order to tilt the PV panel by two servo motors facing the highest intensity of sunlight captured by LDR sensors, which are placed in the four corners of PV panel. The DAST prototype was constructed practically and tested using a real‐time virtual instrument based on Excel to determine its efficiency. Moreover, a comparison based on experimental results between the energy produced by the proposed smart DAST and a fixed panel shows that the smart DAST produces 36.26% more energy compared to the fixed panel. The proposed active DAST can be easily implemented without possessing deep knowledge about solar tracking technologies and electronic engineering.
Multiobjective optimization design of the solar field and reverse osmosis system with preheating feed water using Genetic algorithm
Authors: Ghoujdi Iman Ebrahimi , Hadiannasab Hasti , Bidi Mokhtar , Naeimi Abbas , Ahmadi Mohammad Hossein , Nazari Mohammad Alhuyi , Ming Tingzhen
Published: September 2018

In this article the solar energy is utilized to generate needed steam for a power generation cycle which in turn provides the required power of a RO system. Optimization was carried out on two levels. First, Economizer, Evaporator, Super heater in power generation cycle as well as the type of membrane, PV numbers and series were optimized. In addition, the optimum design of a solar field for the system was carried out and the collector specifications, number of branches, and flow rate were designed. Based on the first level, optimization was designed to reduce costs and increase the permeate water production and reduction in costs and pressure drop of the solar filed. Preheating of the RO feed water had different effects on the production of fresh water at various concentrations. For feed water with constant flow rate and concentration of 45 000 ppm, the maximum rate of permeate flow was obtained at 26°C, while for concentration of 35 000 ppm, the maximum permeate flow rate was achieved at 33°C. By using 5 parallel elements SW30XLE‐400 for RO system, in the optimized condition, permeate flow rate and recovery were 9494.19 (m3/day) and 59.5%, respectively. In this condition, the unit production cost of water was 0.6046 ($/m3).
Does River Restoration Increase Fish Abundance and Survival or Concentrate Fish? The Effects of Project Scale, Location, and Fish Life History
Authors: Roni Philip
Published: September 2018

Despite billions of dollars spent on various river restoration techniques, we still find ourselves debating whether habitat restoration increases fish abundance or concentrates fish. Based on the available literature, I discuss three important questions related specifically to the restoration of salmonid habitat: (1) “Does river restoration increase fish abundance or concentrate fish?”; (2) “Does river restoration increase fish survival or increase abundance?”; and (3) “Does the size or amount of river restoration influence fish response?” First, there is scant evidence to support the contention that river restoration leads to the concentration of fish at restoration projects. Second, the literature suggests that river restoration may lead to increased survival, increased abundance, or both. Third, recent studies have found little relationship between restoration project length and physical or biological response. The scientific literature does suggest that fish response to restoration varies greatly depending on the watershed template, location, and characteristics of the habitat restoration, and the life history of and limiting factors for a species. Thus, adequately determining whether changes in fish abundance observed in a restored area are due to increased movement, survival, or the amount of restoration will require detailed monitoring of these factors simultaneously.
Fluted projectile points in a stratified context at the Raven Bluff site document a late arrival of Paleoindian technology in northwest Alaska
Authors: Buvit Ian , Rasic Jeffrey T. , Kuehn Steven R. , Hedman William H.
Published: September 2018

Our understanding of the northern fluted point tradition, a critical early New World lithic assemblage, is constrained by limited data from stratified, datable contexts. Here, we report on the Raven Bluff site in northwest Alaska, where fluted projectile points, microblades, and a well‐preserved faunal assemblage have been recovered from datable sediments. Results show that prehistoric inhabitants occupied a stone‐sorted polygon where retooling, game processing, and raw material procurement occurred mostly between 12,720 and at least 11,340 cal. yr B.P. We argue that once polygon formation ended, the stratigraphic context remained relatively intact. Further studies focused on the site’s lithic and bone assemblages will help shape our understanding of the relationship between fluted point technology, microblades, and caribou hunting in northern Alaska.
Inferring disease risk genes from sequencing data in multiplex pedigrees through sharing of rare variants
Authors: Bureau Alexandre , Begum Ferdouse , Taub Margaret A. , Hetmanski Jacqueline B. , Parker Margaret M. , Albacha‐Hejazi Hasan , Scott Alan F. , Murray Jeffrey C. , Marazita Mary L. , Bailey‐Wilson Joan E. , Beaty Terri H. , Ruczinski Ingo
Published: September 2018

We previously demonstrated how sharing of rare variants (RVs) in distant affected relatives can be used to identify variants causing a complex and heterogeneous disease. This approach tested whether single RVs were shared by all sequenced affected family members. However, as with other study designs, joint analysis of several RVs (e.g., within genes) is sometimes required to obtain sufficient statistical power. Further, phenocopies can lead to false negatives for some causal RVs if complete sharing among affected is required. Here, we extend our methodology (Rare Variant Sharing, RVS) to address these issues. Specifically, we introduce gene‐based analyses, a partial sharing test based on RV sharing probabilities for subsets of affected relatives and a haplotype‐based RV definition. RVS also has the desirable feature of not requiring external estimates of variant frequency or control samples, provides functionality to assess and address violations of key assumptions, and is available as open source software for genome‐wide analysis. Simulations including phenocopies, based on the families of an oral cleft study, revealed the partial and complete sharing versions of RVS achieved similar statistical power compared with alternative methods (RareIBD and the Gene‐Based Segregation Test), and had superior power compared with the pedigree Variant Annotation, Analysis, and Search Tool (pVAAST) linkage statistic. In studies of multiplex cleft families, analysis of rare single nucleotide variants in the exome of 151 affected relatives from 54 families revealed no significant excess sharing in any one gene, but highlighted different patterns of sharing revealed by the complete and partial sharing tests.
The association between orthostatic hypotension and dementia: A meta‐analysis of prospective cohort studies
Authors: Min Min , Shi Tingting , Sun Chenyu , Liang Mingming , Zhang Yun , Wu Yile , Sun Yehuan
Published: September 2018

Objectives

As for the association between orthostatic hypotension (OH) and dementia, results of published studies are inconsistent; therefore, current substantive conclusions have yet been obtained. This meta‐analysis was conducted in hopes of producing progress in this topic.

Methods

A systematic database search was performed towards electronic databases including Chinese Biomedical Database, PubMed, Web of Science, Wiley Online Library, ScienceDirect, and the Cochrane Library. Five prospective cohort studies were included. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by random‐effects model. Statistical heterogeneity was assessed with the Cochran Q test and I2 statistic. A sensitivity analysis was also conducted in this meta‐analysis.

Results

A 22.4% higher prevalence of dementia in subjects with OH was obtained (adjusted pooled HR was 1.224; 95% CI: 1.106‐1.354; P < .001). This meta‐analysis also showed significant associations between OH and 2 dementia subtypes: Alzheimer disease (adjusted pooled HR was 1.175; 95% CI: 1.022‐1.351; P = .023) and Vascular dementia (adjusted pooled HR was 1.403; 95% CI: 1.042‐1.889; P = .026), respectively.

Conclusions

Orthostatic hypotension is positively associated with the overall prevalence of dementia, and it may contribute to the prevalence of Alzheimer disease and Vascular dementia as well.
The effect of reminiscence therapy on cognitive functions, depression, and quality of life in Alzheimer patients: Randomized controlled trial
Authors: Lök Neslihan , Bademli Kerime , Selçuk‐Tosun Alime
Published: September 2018

Background

Alzheimer is a disease leading to various neuropsychiatric behavioral disorders, and the most common symptom observed during the prognosis of Alzheimer's disease is dysmnesia. The aim of the present study is to investigate the effect of reminiscence therapy on cognitive functions, depression, and quality of life in Alzheimer's patients.

Methods

The present study was a randomized controlled single blind study with two groups, which was designed in the experimental pretest‐posttest pattern in the city of Konya, Turkey. It was decided to include a total of 60 elderly individuals. Information form that evaluated socio‐demographic characteristics and disease history of individuals in intervention and control groups and was developed by the researcher. Standardized Mini‐Mental State Examination (SMMSE), Cornell Scale for Depression in Dementia, and the Quality of Life in Alzheimer's Disease (QOL‐AD) Scale were used to collect the data. Reminiscence therapy was applied once a week and lasted for 8 weeks. Every session took 60 minutes. Groups consisted of six people.

Results

Mini‐Mental Test, depression, and quality of life mean scores of the elderly in intervention group before reminiscence therapy program increased after the administration, and the difference was statistically significant (P < 0.05). In the intergroup comparison, a significant difference was found between elderly individuals' posttest Mini‐Mental Test, depression, and quality of life mean scores (P < 0.05).

Conclusions

Our results suggest that regular reminiscence therapy should be considered for inclusion as routine care for the improvement of cognitive functions, depressive symptoms, and quality of life in elderly people with Alzheimer.
The place for dementia‐friendly communities in England and its relationship with epidemiological need
Authors: Woodward Michael , Arthur Antony , Darlington Nicole , Buckner Stefanie , Killett Anne , Thurman John , Buswell Marina , Lafortune Louise , Mathie Elspeth , Mayrhofer Andrea , Goodman Claire
Published: September 2018

Objectives

The dementia‐friendly community (DFC) initiative was set up to enable people living with dementia to remain active, engaged, and valued members of society. Dementia prevalence varies nationally and is strongly associated with the age and sex distribution of the population and level of social deprivation. As part of a wider project to evaluate DFCs, we examined whether there is a relationship between provision of DFCs and epidemiological need.

Methods

Dementia‐friendly communities were identified through the formal recognition process of DFC status by the Alzheimer's Society and mapped against areas defined by English Clinical Commissioning Groups. We tested whether provision of a DFC was associated with: (1) dementia prevalence, (2) number of known cases, and (3) known plus estimated number of unknown cases.

Results

Of the 209 English Clinical Commissioning Group areas, 115 had at least one DFC. The presence of a DFC was significantly associated with number of known dementia cases (mean difference = 577; 95% CI, 249 to 905; P = 0.001) and unknown dementia cases (mean difference = 881; 95% CI, 349 to 1413; P = 0.001) but not prevalence (mean difference = 0.03; 95% CI, −0.09 to 0.16; P = 0.61). This remains true when controlling for potential confounding variables.

Conclusions

Our findings suggest that DFC provision is consistent with epidemiological‐based need. Dementia‐friendly communities are located in areas where they can have the greatest impact. A retrospective understanding of how DFCs have developed in England can inform how equivalent international initiatives might be designed and implemented.
Resource use and its association to cognitive impairment, ADL functions, and behavior in residents of Swedish nursing homes: Results from the U‐Age program (SWENIS study)
Authors: Sköldunger Anders , Wimo Anders , Sjögren Karin , Björk Sabine , Backman Annica , Sandman Per‐Olof , Edvardsson David
Published: September 2018

Objectives

We aimed to investigate resource use and its association to cognitive impairment, activities of daily living, and neuropsychiatric symptoms in residents of Swedish nursing homes.

Methods

Data were collected in 2014 from a Swedish national sample of nursing home residents (n = 4831) and were collected by staff in the facility. The sample consists of all nursing homes in 35 of 60 randomly selected Swedish municipalities. Demographic data and data on resource use, cognitive and physical function as well as neuropsychiatric symptoms were collected through proxies. Descriptive statistics and regression modeling were used to investigate this association.

Results

We found that cognitive impairment, activities of daily living, and neuropsychiatric symptoms were associated with 23 hours per week increase in total resource use versus cognitively intact persons. This was also the case for being dependent in activities of daily living. Being totally dependent increased the amount of resource use by 25 hours per week. The sex of a resident did not influence the resource use. Annual costs of resource use with no functional dependency were 359 685 SEK, and in severely cognitive impaired resident, the cost was 825 081 SEK.

Conclusion

Being cognitively impaired as well as functionally dependent increases the resource use significantly in nursing homes. This has implications for differentiation of costs in institutional settings in health economic evaluations.
Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: A systematic review and meta‐analysis
Authors: Vacas Sara M. , Stella Florindo , Loureiro Julia C. , Simões do Couto Frederico , Oliveira‐Maia Albino J. , Forlenza Orestes V.
Published: September 2018

Background

Pharmacological and conventional nonpharmacological treatments for behavioural and psychological symptoms of dementia (BPSD) have only modest efficacy. Furthermore, pharmacotherapy carries the risk of important side effects. Noninvasive brain stimulation (repetitive transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS)) are valuable and safe for cognitive function in Alzheimer disease (AD). However, there have been few studies, and there is no consensus, regarding the use of these techniques to treat BPSD.

Methods

We performed a systematic review of the literature and meta‐analysis of studies reporting the effect of rTMS or tDCS on BPSD.

Results

Seven articles were included: five randomized, controlled clinical trials and two open‐label clinical trials. Five studies investigated the effects of rTMS and two the effects of tDCS. Both studies using tDCS reported no evidence of efficacy on BPSD, while two of the three RCTs using rTMS found statistically significant benefits. In an exploratory meta‐analysis with four of the RCT studies, we did not find evidence of efficacy of noninvasive brain stimulation techniques, with an overall effect of −0.02 (95% CI = −0.90, 0.94; I2 = 85%). However, when we used only the data from the studies that applied rTMS, we found a positive effect on BPSD, with an overall effect of −0.58 (95% CI = −1.02, −0.14; I2 = 0%). With regards to the adverse effects reported, these were mild and not clinically relevant.

Conclusions

Our results establish a tendency for efficacy of rTMS protocols on BPSD, while corroborating their safety and tolerability, suggesting the need for further research.
Acute Kidney Injury in Patients Undergoing Chronic Hepatitis C Virus Treatment With Ledipasvir/Sofosbuvir
Authors: Brown Patrick R. , Sadiq Omar , Weick Alexander , Lenhart Adrienne , Elbatta Mohammad , Fernandez Christopher , Kutait Anas , Pompa Robert , Jafri Syed‐Mohammed
Published: September 2018

Ledipasvir‐sofosbuvir, a once‐a‐day, oral combination pill, was approved in 2014 for the treatment of chronic hepatitis C infection. Initial trials did not comment on nephrotoxicity; however, recent data suggest a risk of acute kidney injury (AKI) with the use of the medication. We assessed the rates of AKI in patients undergoing ledipasvir‐sofosbuvir in a large, urban tertiary care center. This single‐center retrospective observation study included all patients undergoing therapy from October 1, 2014, to October 1, 2015. Rates of AKI, defined by more than a 0.3 mg/dL increase in serum creatinine level, were calculated. Patients were followed 12 weeks after therapy to assess for sustained viral response as well as to assess for improvement of AKI after completion of therapy, defined by less than 0.2 mg/dL above baseline serum creatinine. In total, 197 patients were included in the final analysis who had completed ledipasvir‐sofosbuvir therapy and completed laboratory values. Among the patients treated, 38 (19%) had AKI during therapy. An additional 4 (2%) had AKI at the end of therapy. Of the 38 patients who experienced AKI, 20 (53%) had improvement in serum creatinine to less than 0.2 mg/dL above their baseline. When comparing for chronic kidney disease (CKD) stage, those with CKD I or II experienced AKI 17% of the time compared with 47% of the time in CKD III or worse (P = 0.005). Conclusion: AKI was seen in nearly one‐fifth of our patients, and patients with CKD stage III or worse are at increased risk. Although ledipasvir‐sofosbuvir is generally safe in the general population, close monitoring of renal function is recommended.
Use of vitamin K antagonists and risk of prostate cancer: Meta–analysis and nationwide case–control study
Authors: Kristensen Kasper Bruun , Jensen Patricia Hjorslev , Skriver Charlotte , Friis Søren , Pottegård Anton
Published: September 2018

Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case–control study using Danish demographic and health data registries and summarized existing evidence in a meta‐analysis. The case–control study included all Danish men aged 40–85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age–matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long–term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95–1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97–1.10). We observed no dose–response relationship (e.g. OR for 5–10 years of use, 1.06 95% CI, 0.97–1.16). We included 8 studies in the meta–analysis reporting effect estimates from 0.51 (95% CI, 0.23–1.13) to 1.10 (95% CI, 0.94–1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70–1.05) was obtained; however, there was considerable across–study heterogeneity (I2: 93.9%). In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely.
Raman spectroscopy investigation of biochemical changes in tumor spheroids with aging and after treatment with staurosporine
Authors: Jamieson Lauren E. , Harrison David J. , Campbell Colin J.
Published: September 2018

There has been increasing use of in vitro cell culture models that more realistically replicate the three‐dimensional (3D) environment found in vivo. Multicellular tumor spheroids (MTS) using cell lines or patient‐derived organoids have become an important in vitro drug development tool, where cells are grown in a 3D “sphere” that exhibits many of the characteristics found in vivo. Significantly, MTS develop gradients in nutrients and oxygen, commonly found in tumors that contribute to therapy resistance. While MTS show promise as a more realistic in vitro culture model, there is a massive need to improve imaging technologies for assessing biochemical characteristics and drug response in such models to maximize their translation into useful applications such as high throughput screening (HTS). In this study, we investigate the potential for Raman spectroscopy to unveil biochemical information in MTS and have investigated how spheroid age influences drug response, shedding light on increased therapy resistance in developing tumors. The wealth of molecular level information delivered by Raman spectroscopy in a noninvasive manner, could aid translation of these 3D models into HTS applications.
Therapeutical effects of vaccine from Trypanosoma cruzi amastigote surface protein 2 by simultaneous inoculation with live parasites
Authors: Ribeiro Flávia Andressa Pidone  , Pontes Camila , Machado Alexandre De M.V. , Bruna‐Romero Oscar , Quintana Hananiah T. , De Oliveira Flávia , De Vasconcelos José Ronnie Carvalho , Ribeiro Daniel Araki
Published: September 2018

The aim of this study was to evaluate the efficacy of vaccine using replication‐deficient human recombinant Type 5 replication‐defective adenoviruses (AdHu5) carrying sequences of the amastigote surface protein 2 (ASP2) (AdASP2) in mice infected with the Trypanosoma cruzi (
T cruzi) Y strain. A total of 16 A/Sn mice female were distributed into four groups, as follows (n = 4 per group): Group 1 – Control Group (CTRL); Group 2 – Infected Group (TC): animals were infected by subcutaneous route with 150 bloodstream trypomastigotes of
T cruzi Y strain; Group 3 – Immunized Group (AdASP‐2): animals were immunized by intramuscular injection (im) route with 50 µL of AdSP‐2 (2 × 10
8 plaque forming units [pfu]/cam) at day 0; Group 4‐Immunized and Infected Group (AdASP‐2+TC): animals were immunized by im route with 50 µL of ASP‐2 (2 × 10
8 pfu/cam) and infected by
T cruzi at the same day (day 0). It was observed a significant decrease of nests in the group that was immunized with AdASP‐2 and infected on the same day. Tumor necrosis factor alpha (TNF‐α) and inducible nitric oxide synthase (iNOS) gene expressions showed a significant increase in the AdASP‐2+TC group when compared to TC group, but it was noted that Cyclooxygenase‐2 (Cox‐2) was increased in TC group when compared to AdASP‐2+TC group. Increase of matrix metalloproteinases‐2 (MMP‐2) and decrease of MMP‐9 immunoexpression in the AdASP‐2+TC group was noticed as well. Oxidative DNA damage was present in myocardium for AdASP‐2+TC group as a result of 8‐hydroxydeoxyguanosine immunoexpression. Taken together, our results highlighted an increased oxidative stress, MMP‐2 activity and inflammatory host response promoted by AdASP‐2 against
T cruzi infection.
PCSK9: A novel inflammation modulator in atherosclerosis?
Authors: Tang Zhi‐Han , Li Tao‐Hua , Peng Juan , Zheng Jie , Li Ting‐Ting , Liu Lu‐Shan , Jiang Zhi‐Sheng , Zheng Xi‐Long
Published: September 2018

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the secretory serine protease family. It binds to low‐density lipoprotein receptor (LDLR) for endocytosis and lysosome degradation in the liver, resulting in an increasing in circulating LDL‐cholesterol (LDL‐c) level. Since a PCSK9 induced increase in plasma LDL‐c contributes to atherosclerosis, PCSK9 inhibition has become a new strategy in preventing and treating atherosclerosis. However, in addition to the effect of PCSK9 on elevating blood LDL‐c levels, accumulating evidence shows that PCSK9 plays an important role in inflammation, likely representing another major mechanism for PCSK9 to promote atherosclerosis. In this review, we discuss the association of PCSK9 and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy.
Deglycosylation of epithelial cell adhesion molecule affects epithelial to mesenchymal transition in breast cancer cells
Authors: Liu Xue , Yang Liu , Zhang Dandan , Liu Tingjiao , Yan Qiu , Yang Xuesong
Published: September 2018

The transmembrane glycoprotein epithelial cell adhesion molecule (EpCAM) is overexpressed in most epithelial cancers including breast cancer, where it plays an important role in cancer progression. Previous study has demonstrated that knockdown of EpCAM inhibits breast cancer cell growth and metastasis via inhibition of the Ras/Raf/ERK signaling pathway and matrix metallopeptidase‐9 (MMP‐9). Although glycosylation is believed to be associated with the function of EpCAM, the contribution of N‐glycosylation to this function remains unclear. We constructed the N‐glycosylation mutation plasmid of EpCAM and used it to treat breast cancer cells. Loss of N‐glycosylation at all three sites EpCAM had no effect on its level of expression or membrane localization. However, mutation at glycosylation sites significantly reduced the ability of EpCAM to promote epithelial to mesenchymal transition in breast cancer. N‐glycosylation mutation of EpCAM led to decrease phosphorylation of Raf, ERK, and Akt, and inhibited the Ras/Raf/ERK and PI3K/Akt signaling pathways. Furthermore, we demonstrated that N‐glycosylation mutation of EpCAM‐mediated invasion and metastasis of breast carcinoma cells required the downregulation of MMP‐9 via inhibition of these two signaling pathways. Our results identified the characteristics and function of EpCAM glycosylation. These data could illuminate molecular regulation of EpCAM by glycosylation and promote our understanding of the application of glycosylated EpCAM as a target for breast cancer therapy.
Potentiating apoptosis and modulation of p53, Bcl2, and Bax by a novel chrysin ruthenium complex for effective chemotherapeutic efficacy against breast cancer
Authors: Roy Souvik , Sil Anweshan , Chakraborty Tania
Published: September 2018

Breast cancer is the most frequent cause of cancer in women. In the current study, transition metal ruthenium was complexed with flavonoid chrysin to evaluate the chemotherapeutic potential of this compound in Michigan Cancer Foundation‐7 (MCF‐7) human mammary cancer cell line and 7,12‐dimethylbenz(α)anthracene‐induced mammary cancer in female Sprague–Dawley rats. The characterizations of the complex were accomplished through UV–visible, NMR, IR, Mass spectra, and XRD techniques and antioxidant activity was assessed by DPPH, FRAP, and ABTS methods. In vitro studies included cell viability, cell cycle analysis, DNA fragmentation, and marker analysis by western blot analysis and found that complex treatment suppressed cell growth‐induced cell cycle arrest and enhanced the induction of apoptosis in cancer cells. Moreover, complex treatment modulated signaling pathways including mTOR, VEGF, and p53 in the MCF‐7 cells. Acute and subacute toxicity was performed in rats to determine the therapeutic doses. Breast cancer in rats was initiated by the administration of 7,12‐dimethylbenz(α)anthracene (0.5 mg/100 g body weight) via single tail vein injection. The histopathological analysis after 24 weeks of carcinogenesis study depicted substantial repair of hyperplastic lesions. Immunohistochemical analysis revealed upregulation of Bax and p53 and downregulation of Bcl2 proteins and TUNEL assay showed an increase in apoptotic index in ruthenium–chrysin‐treated groups as compared to the carcinogen control. Our findings from the in vitro and in vivo study support the continued investigation of ruthenium–chrysin complex possesses a potential chemotherapeutic activity against breast cancer and was efficient in reducing hyperplastic lesions in the mammary tissues of rats by inducing apoptosis.
The miR‐15a/16 gene cluster in human cancer: A systematic review
Authors: Liu Ting , Xu Zhenru , Ou Daming , Liu Jing , Zhang Ji
Published: September 2018

MicroRNAs (miRNAs) are an important class of endogenous small noncoding single‐stranded RNAs that suppress the expression of their target genes through messenger RNA (mRNA) degradation to inhibit transcription and translation. MiRNAs play a crucial regulatory role in many biological processes including proliferation, metabolism, and cellular malignancy. miR‐15a/16 is an important tumor suppressor gene cluster with a variety of factors that regulate its transcriptional activity. It has been discovered that a relative reduction of miR‐15a/16 expression in various cancers is closely related to the occurrence and progression of tumors. miR‐15a/16 takes part in a wide array of biological processes including tumor cell proliferation, apoptosis, invasion, and chemoresistance by binding to the 3′‐untranslated region of its target gene's mRNA. In this review, we will examine the complex regulatory network of miR‐15a/16 gene expression and its biological functions in human cancers to further elucidate the molecular mechanisms of its antitumor effects.
USP49 inhibits ischemia–reperfusion‐induced cell viability suppression and apoptosis in human AC16 cardiomyocytes through DUSP1–JNK1/2 signaling
Authors: Zhang Wei , Zhang Yangyang , Zhang Hengbing , Zhao Qian , Liu Zheng , Xu Yawei
Published: September 2018

Dual‐specificity protein phosphatases (DUSP) also known as mitogen‐activated protein kinase (MAPK) phosphatases (MKPs) can dephosphorylate MAPKs, including extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase (JNK), and p38. DUSP1‐mediated JNK dephosphorylation has been found to play an antiapoptotic role against cardiac ischemia–reperfusion (I/R) injury. However, the regulation of DUSP1–JNK pathway remains unclear. In the current study, ubiquitin‐specific peptidase 49 (USP49) expression in human AC16 cardiomyocytes following I/R injury was measured by real‐time polymerase chain reaction and western blot analysis. Cell viability, apoptosis, the Bax, Bcl‐2, and DUSP1 expression, and the activity of MAPKs in AC16 cardiomyocytes following indicated treatment was measured by CCK‐8, flow cytometry, and western blot analysis. The direct interaction between USP49 and DUSP1 was measured by coimmunoprecipitation and ubiquitination analysis. The effect of USP49 on apoptosis and JNK activity in rat cardiomyocytes following I/R injury was also measured by TUNEL and western blot analysis. Here, we found that USP49 expression was time‐dependently increased in AC16 cardiomyocytes following I/R. I/R‐induced cell apoptosis and JNK1/2 activation both in in vivo and in vitro reversed by USP49 overexpression in AC16 cardiomyocytes. Inhibiting JNK1/2 activation significantly inhibited USP49 knockdown‐induced the cell viability inhibition, apoptosis and the JNK1/2 activation in AC16 cardiomyocytes. Moreover, USP49 positively regulated DUSP1 expression through deubiquitinating DUSP1. Overall, our findings establish USP49 as a novel regulator of DUSP1–JNK1/2 signaling pathway with a protective role in cardiac I/R injury.
Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR‐125b/STAT3 axis
Authors: Jin Xue‐J. , Chen Xiang‐J. , Zhang Zhi‐F. , Hu Wen‐S. , Ou Rong‐Y. , Li Shi , Xue Ji‐S. , Chen Lu‐L. , Hu Yan , Zhu Hua
Published: September 2018

Increasing evidence showed that long noncoding RNAs (lncRNAs) played an important role in the occurrence and development of tumors. To date, lncRNA small nucleolar RNA host gene 12 (SNHG12) has revealed an oncogenic role in various tumors. However, the role of SNHG12 in cervical cancer is still unclear. Therefore, we focused on the biological function and molecular mechanism of SNHG12 in the tumorigenesis of cervical cancer. In this study, the expression of miR‐125b was observably downregulated in cervical cancer cells. Meanwhile, the expression of SNHG12 was obviously upregulated in cervical cancer cell lines (HeLa, SiHa, Caski, C4‐1, and C33A) compared with the immortalized cervical epithelial cells. The further assay showed that miR‐125b was a target of SNHG12 in cervical cancer. Moreover, a negative relationship between miR‐125b and SNHG12 was found in cervical cancer. In addition, SNHG12 inhibition restrained the proliferation, migration, and invasion of cervical cancer cells. Meanwhile, miR‐125b mimics repressed the expression of signal transducer and activator of transcription 3 (STAT3). The further assay showed that STAT3 was a target of miR‐125b in cervical cancer. In addition, sh‐STAT3 repressed the migration and invasion of cervical cancer cells. Furthermore, it showed that miR‐125b inhibitors reversed STAT3 expression restrained by the reduction of SNHG12 expression. In general, SNHG12 modulated STAT3 by sponging miR‐125b in cervical cancer and played an important role in the development of cervical cancer.
Pediatric Obesity: Influence on Drug Dosing and Therapeutics
Authors: Ameer Barbara , Weintraub Michael A.
Published: September 2018

Obesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of U.S. children and adolescents. Severe obesity (≥120% of the 95th percentile of body mass index (BMI) for age, or a BMI ≥ 35 kg/m2) is the fastest‐growing subgroup and now approaches 6% of all U.S. youth. Health consequences (eg, type 2 diabetes, coronary heart disease) are related in a dose‐dependent manner to severity of obesity. Because therapeutic interventions are less effective in severe obesity, prevention is a high priority. Treatment plans involving combinations of behavioral therapy, nutrition, and exercise achieve limited success. Only one drug, orlistat, is U.S. Food and Drug Administration approved for long‐term obesity management in adolescents 12 years and older. As part of comprehensive medication management, clinicians should consider the propensity for a given drug to aggravate weight gain and to consider alternatives that minimize weight impact. Medication management must take into account developmental changes as well as the pathophysiology of obesity and comorbidities. Despite expanding insight into obesity pathophysiology, there are gaps in its translation to therapeutic application. The historical construct of obesity as simply a fat‐storage disorder is fundamentally inaccurate. The approach to adjusting doses based solely on body size and extrapolating from therapeutic knowledge of adult obesity may be based on assumptions that are not fully substantiated. Classes of drugs commonly prescribed for comorbidities associated with obesity should be prioritized for clinical research evaluations aimed at optimizing dosing regimens in pediatric obesity.
Analgesics and Sedatives in Critically Ill Newborns and Infants: The Impact on Long‐Term Neurodevelopment
Authors: Schiller R.M. , Allegaert K. , Hunfeld Maayke , van den Bosch G.E. , van den Anker John , Tibboel D.
Published: September 2018

Inadequate pain and/or stress management in preterm‐ and term‐born infants has been associated with increased morbidity and even mortality. However, exposure to analgosedatives during early infancy may also be one of the risk factors for subsequent neurodevelopmental impairment, at least in animal studies. Because infants admitted to neonatal or pediatric intensive care units may receive high amounts of these drugs for prolonged periods of time and the majority of these infants nowadays survive to discharge, this is of major concern. A balanced approach that incorporates the assessment and quantification of both wanted effects as well as unwanted side effects is therefore needed. In this article, the optimal dose determination of commonly used analgosedative drugs as well as their potential long‐term effects on the developing human brain and neuropsychological functioning are reviewed.
Pharmacometric Modeling and Simulation Is Essential to Pediatric Clinical Pharmacology
Authors: Neely Michael , Bayard David , Desai Amit , Kovanda Laura , Edginton Andrea
Published: September 2018

Pediatric clinical pharmacology now encompasses a wide range of activities, including drug pharmacokinetic and pharmacodynamic modeling and simulation, also known as pharmacometrics. Pediatric clinical pharmacologists may be physicians but are more likely to be pharmacists or PhD scientists, and pediatric clinical pharmacology today is largely a research specialty rather than a subspecialty for direct patient care. Pharmacometrics, including “top‐down” population modeling and “bottom‐up” physiologically based pharmacokinetic modeling, has become an indispensable tool for pharmaceutical industry scientists, government regulators, academic researchers, and even a handful of patient‐oriented practitioners. This review summarizes the application of pharmacometrics within each of these domains and predicts future trends of further applications across the spectrum of pediatric clinical pharmacology from drug development to patient care.
Elucidating the binding efficacy of β‐galactosidase on polyaniline–chitosan nanocomposite and polyaniline–chitosan–silver nanocomposite: activity and molecular docking insights
Authors: Khan Maryam , Husain Qayyum , Ahmad Nafees
Published: September 2018

BACKGROUND

Aspergillus oryzae β‐galactosidase (β‐gal; EC 3.2.1.23) was physically adsorbed on polyaniline–chitosan nanocomposite (PANI‐CS‐NC) and polyaniline–chitosan–silver nanocomposite (PANI‐CS‐Ag‐NC). Stability and kinetic studies were assessed, along with reusability and molecular docking interactions.

RESULTS

According to transmission electron microscopy images, the sizes of the respective NCs were found to be in the range of 23–39 and 6–18 nm. The η (effectiveness factor) values for PANI‐CS‐NC‐ and PANI‐CS‐Ag‐NC‐bound β‐gal were calculated to be 0.89 and 1.23, respectively, suggesting an enhancement in the activity of the enzyme in the presence of silver ions. Significant broadening was observed in pH and temperature profiles. Kinetic properties of PANI‐CS‐NC‐ and PANI‐CS‐Ag‐NC‐bound β‐gal showed lower Km, and two‐ and fourfold higher Vmax, respectively, compared to free enzyme. PANI‐CS‐Ag‐NC‐bound β‐gal was able to retain 94% of its initial activity after 10 repeated uses. Circular dichroism analysis revealed conformational changes in the secondary structure of protein upon immobilization. The genotoxic assessment revealed non‐toxic behaviour of both free and enzyme‐bound NC. The rate of lactose hydrolysis at 50 °C exhibited by PANI‐CS‐‐Ag‐NC bound β‐gal was 7% higher than that for the native enzyme. In‐silico analysis showed efficient binding of β‐gal on PANI‐CS‐ NCs due to interaction with residues that were exclusive of the active site of the enzyme.

CONCLUSION

PANI‐CS‐Ag‐NC‐bound β‐gal preparation proved to be a robust nano‐biocatalyst due to remarkable enhancement in catalytic activity along with excellent stability and reusability characteristics, which could be further utilized for efficient construction of nano‐biosensors for producing lactose‐free dairy products to feed lactose‐intolerant patients. © 2018 Society of Chemical Industry
A note on the maximum number of triangles in a C5‐free graph
Authors: Ergemlidze Beka , Methuku Abhishek , Salia Nika , Győri Ervin
Published: September 2018

We prove that the maximum number of triangles in a ‐free graph on vertices is at most , improving an estimate of Alon and Shikhelman.
19F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments
Authors: Couch Marcus J. , Ball Iain K. , Li Tao , Fox Matthew S. , Biman Birubi , Albert Mitchell S.
Published: September 2018

Fluorine‐19 (19F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19F lung images are typically acquired in a single breath‐hold, or in a time‐resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19F lung MRI is expected to complement existing proton‐based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic.

Level of Evidence: 3

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;49:343–354.
Evaluation of TMPA 3B42V7, GPM IMERG and CMPA precipitation estimates in Guangdong Province, China
Authors: Wang Dashan , Wang Xianwei , Liu Lin , Wang Dagang , Huang Huabing , Pan Cuilin
Published: September 2018

Three satellite rainfall products (3B42V7, IMERGV05/V04/V03, and China hourly Merged Precipitation Analysis product) are evaluated using measurements from a dense rain gauge network as reference in Guangdong Province, China from April 2014 to December 2016. The three products are compared with gauges in annual, monthly, daily and hourly accumulation, and at gridded, sub‐regional and regional scales. An error decomposition approach is employed to separate the total bias into Hit, Miss and False components. Overall, the CMPA estimate is the best in agreement with gauge observations. The improvement of IMERGV05 over 3B42V7 is notable, especially in reducing the hit bias and missed precipitation, resulting in better detection of the light rain and heavy rain. The enhancement of IMERG is more significant at the 3‐hr scale than daily scale. IMERGV05 shows better performance than its previous versions especially for IMERGV03, which had an abnormal blocky pattern mainly from July to September over the Pearl River Delta area. The three products have different error characteristics and show large spatial variations. 3B42V7 and IMERG have large areas of overestimation in the mountainous areas and underestimation in the coastal areas, while CMPA is characterized by an alternate distribution of small positive and negative values. The overestimation of precipitation is partially attributed to the positive hit biases that falsely estimate the precipitation from moderate intensity to heavy rainfall by the three products.
The association between frailty and medicines use over time: an analysis using the Australian Longitudinal Study on Ageing population
Authors: Widagdo Imaina S. , Pratt Nicole L. , Roughead Elizabeth E.
Published: September 2018

Background

Frailty and medicine‐related problems are common among the elderly and have been associated with an increased risk of adverse outcomes. However, there has been limited research on the association between frailty and medicines use.

Aim

To determine the distribution of frailty among older people who used medicines and to examine the difference in frailty scores over time with continuation or discontinuation of specific medicines.

Methods

The study population was from the Australian Longitudinal Study of Ageing (ALSA). The data used in the analysis were collected in 1992 (wave 1) and in 1995 (wave 3). Frailty scores were assessed at both waves using a modified version of the Frailty Index. Non‐parametric tests were used to examine the difference in the distribution of frailty scores in relation to medicines used at baseline. Medicine use was categorised into continued or stopped by comparing use at wave 3 to use at baseline. A t‐test was used to compare the mean changes in frailty scores between the two groups, with a p‐value of <0.05 considered to be significant.

Results

Data from 2087 participants were included. At baseline, a higher number of medicines used was associated with higher frailty scores (p < 0.0001). Stopping any preventive medicines, as well as beta‐blockers, or potassium‐sparing diuretics, was associated with a higher increase in mean frailty score changes than continuing these medicines, p = 0.01, p = 0.03 and p = 0.004, respectively.

Conclusions

There was an association between frailty and medicines use. Further study is needed to assess whether the progression of frailty was due to medicine cessation or vice versa.
Joint sparse representation and denoising method for Raman spectrum
Authors: Fang Zheng , Tao Yu , Wang Wen , Zhang Wenxin , Duan Lingfeng , Liu Ying , Yan Changchun , Qu Lulu , Han Caiqin
Published: September 2018

A new method based on joint sparse representation is developed to recover the peak information from high‐noise Raman signal. This method used the sparsity of Raman spectrum to recover the signals and preserve its useful peak information. The peak information is then reconstructed by using an orthogonal matching pursuit algorithm. The joint sparse representation method is found to be an effective approach to analyze the Raman spectrum, especially Raman spectrum that have high noise, thus improving the detection limit of Raman spectroscopy. Experimental results demonstrate that this approach is better than other approaches in case of low signal‐to‐noise ratios.